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Secret FBI Informant Breaks Silence on Uranium One Scandal — Says Proof of Wrongdoing 'Exists'
By Joshua Caplan
Published November 16, 2017 at 1:54pm
For the first time, the FBI informant on the Clinton-Uranium One deal has broken his silence to the media. The informant revealed he is eager to testify because of his "concerns about Russia's activities in the United States, but declined to comment further," reports Reuters.
Independent Journal Review reports:
The witness, identified by Reuters as William D. Campbell, worked as a lobbyist for a Russian firm.
Hillary Clinton claims no wrongdoing with Uranium One, though.
"If they send a signal that we're going to be like some dictatorship, like some authoritarian regime, where political opponents are going to be unfairly, fraudulently investigated, that rips at the fabric of the contract we have, that we can trust our justice system," she said during an interview with Mother Jones.
Campbell, on the other hand, refuses to stay silent about the issue and plans to testify in front of Congress. But he doesn't just have his testimony, and he claims to have evidence.
"I have worked with the Justice Department undercover for several years, and documentation relating to Uranium One and political influence does exist, and I have it," he told Reuters.
As The Gateway Pundit previously reported, Victoria Toensing, the lawyer representing the FBI informant says there is "on-the-record quid pro quo" surrounding the Uranium One scandal with Bill Clinton receiving a $500,000 speaking fee from a Russian backed bank and the Clinton Foundation receiving millions of dollars from people involved on the deal.
As previously reported, not only was the FBI informant working on the Russian bribery case threatened by the Obama administration, he was blocked by the DOJ under then-AG Loretta Lynch from testifying to Congress.
Toensing said her client "is not only afraid of the Russian people, but he is afraid of the US government because of the threats the Obama administration made against him."
In a major win for the American people, the DOJ lifted the informant's gag order which means he will be able to testify to Congress.
Joshua Caplan
Fruit Of The Poisonous Tree? Longtime Hillary Clinton Advisor Lays Out Why Mueller Probe Is "Corrupt" (VIDEO)
FOX NEWS: Justice Department IG Horowitz Asked To Testify As Clinton Probe Report Looms
Former FBI Assistant Director Rips James Comey Over 'Salacious' ABC Interview
McCabe, Hillary And The Steele Dossier: Excellent Questions ABC's George Stephanopoulos Failed To Ask James Comey
'What A Self-Centered Jacka**': FBI Insiders Are Savaging James Comey's Interview With ABC


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Official Foreign Reserves
Refers to the gross official reserves held by the Monetary Authority of Singapore (MAS). The data include gold and foreign exchange, Special Drawing Rights (SDR) and Singapore's reserve position in the International Monetary Fund (IMF). Prior to May 1999, Singapore's official foreign reserves were valued at book cost. With effect from May 1999, the book value of foreign reserve assets are translated at market exchange rates prevailing at the end of each reporting month.
© 2019 Government of Singapore Last Updated: 15 Apr 2018

redpajama_set_name: RedPajamaCommonCrawl


We were commissioned by Alistair Currie Events to take an annual corporate Christmas Party and blast it into outer space, our response was to 'make it so'. Our wonderful workshop created a spaceship that even Scotty would be proud of. Our Captain Smirk and his crew took the guests to a drive that warped their minds and left them beaming. We created six fictional characters that entertained the guests from their arrival, throughout dinner, and until they were gyrating to the best hits from around the galaxy. Creatively costumed creatures from other planets greeted guests aboard the international space station, while our hilarious interstellar Security Guard put them through their paces (and the X-ray machine). The guests boarded the 'spaceship' and were entertained throughout dinner by a fully scripted and rehearsed stage show, with high drama and strong links to every sci-fi film ever made! The destination? Planet X Mas, which was successfully reached at around midnight thanks to the help of the extremely entertained crew.
"Thank you so much for Friday's performance we were so happy with how everything looked. It was wonderful to see it appear just as we'd wanted it to, the end result was just amazing! " Alice Peacock, Alastair Currie Events.


Peter Zafriz is the author of the My Monster Books Boxed Set. We are in the process of adding the books to the database. If you would like copies of the books, give us a call and we will be glad to hold copies for you.


Rugged silhouettes, durable details and a little less refined are what make this collection so masculine. Equal parts fashion and function, this style brings a warm, relaxed elegance to any room, including that man cave.
Antique Farmhouse's gift ideas for him include the 4 Tier Metal Shelving Unit, perfect to highlight a collection or organize a room. Our Genuine Leather Men's Messenger Bag and Gun Case are handsome accessories and the Pool Ball Candle Holders are the perfect accent item for the recreation or billiard room. Enjoy the rest of the collection of men's gift ideas.


The Noordzeeloket receives a great variety of questions. Here you can find a number of frequently asked questions.
How does the emergency response organisation for the North Sea work?
The disaster and incident control takes place under the operational command of the Coastguard (Kustwacht) Director. The Coastguard is a partnership and is a cooperative organisation of government services (five departments) for the operational implementation of Coastguard tasks.
The responsibility for the policy of the Coastguard is shared by the Ministry of Infrastructure and the Environment and the Permanent Contact Group Enforcement North Sea (Permanente Kontaktgroep Handhaving Noordzee, PKHN).
Am I allowed to spread the ashes of my deceased loved one at sea?
Where is dredging allowed and how do I obtain a permit?
The government has designated certain locations where dredging is allowed. You can get this information and obtain a permit from the Ministry of Infrastructure and the Environment, Rijkswaterstaat Sea and Delta.
Where can I find more information on water levels, currents and wave heights?
Where at sea do military exercises take place?
You can find this information in the Notice to Mariners (Bericht aan Zeevarenden) of the Royal Netherlands Navy's Hydrographic Service.
I am looking for a map with the cables and pipelines and drilling platforms in the North Sea.
I found a bird covered in oil. Where can I report this?
Which permits do I need to install a cable at sea?
In principle, you will need a Water Permit. According to the Water Act (Wtw), you should apply for a permit for anything installed on or in the seabed of the North Sea. Exceptions are the cables that come with mining installations which are covered by the permit granted under the Mining Law of the Ministry of Economic Affairs.


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Breaking: Trump and Melania Make Surprise Visit to Iraq for Special Moment with Troops
By Ben Marquis December 26, 2018 at 1:35pm
In the eyes of his supporters, President Donald Trump's unabashed admiration, love and respect for the men and women who serve our nation in uniform is clearly evident.
Naturally, Trump's critics see things quite differently, and assert that the president really doesn't care that much about military service members or the great sacrifices they make.
A key anti-Trump talking point in that regard that critics have hyped incessantly was the fact that the president had yet to visit any of our nation's troops stationed in a war zone, ostensibly because he was too fearful to travel to a dangerous area and just didn't care about the risks his soldiers faced in a combat zone while under his command.
But CNBC reported that that particular anti-Trump narrative died an inglorious death on the day after Christmas, as it was revealed that the president and first lady had made a surprise trip to Iraq to visit with U.S. airmen, soldiers and Marines deployed in the war-torn nation.
President Trump and the First Lady traveled to Iraq late on Christmas night to visit with our troops and Senior Military leadership to thank them for their service, their success, and their sacrifice and to wish them a Merry Christmas. pic.twitter.com/s2hntnRwpw
— Sarah Sanders (@PressSec) December 26, 2018
White House press secretary Sarah Sanders tweeted, "President Trump and the First Lady traveled to Iraq late on Christmas night to visit with our troops and Senior Military leadership to thank them for their service, their success, and their sacrifice and to wish them a Merry Christmas."
CNBC noted that this was the president's first visit to a war zone since becoming the president. He and the first lady secretly left the White House and Washington D.C. Tuesday evening for an overnight flight on Air Force One to a military airbase west of the Iraqi capital of Baghdad.
Once the president and first lady had arrived and began to meet with military leaders, officers and enlisted personnel, pictures soon began to circulate among the media.
President Trump makes previously unannounced visit to Iraq to meet with troops, Press Secretary Sarah Huckabee Sanders announced Wednesday https://t.co/4fsrzQN4TP pic.twitter.com/GQzbkA9MJ7
— CBS News (@CBSNews) December 26, 2018
It was noted that the return trip from Iraq would make a stop at Ramstein Air Base in Germany, where the Trumps will also visit with U.S. troops who are stationed there.
The surprise visit to Iraq came just days after Trump had announced that he was withdrawing the roughly 2,000 U.S. troops deployed to neighboring Syria to combat the Islamic State group, a heavily criticized decision by all sides that likely led to the announced resignation of Defense Secretary James Mattis.
Coinciding with rumored troop withdrawals from Afghanistan, speculation ran wild among analysts and "experts" in the media who suggested that Trump was pulling the entirety of the U.S. military presence out of the Middle East … which isn't really the case at all.
The stated fear among the media and Trump's critics was that the troop withdrawal from Syria would essentially undermine all of the gains made over the past two years and abandon our Kurdish allies to fend for themselves against their enemies and rivals in the region.
Are you glad to see the president and first lady visit our troops in Iraq?
Yes: 100% (2703 Votes)
However, CNBC reported that the president made it clear to those he spoke with in Iraq that he had "no plans at all" to draw down and remove the more than 5,000 troops currently deployed there.
Left unsaid by that outlet is the obvious fact that, should there be a need for the U.S. to engage our nation's enemies or protect our allies in Syria once again, we have thousands of troops literally right next door who could move in at a moment's notice to handle whatever task is assigned them.
Trump also reportedly addressed the impending departure of Mattis while he was in Iraq, and offered up high praise for Deputy Secretary Patrick Shanahan, who will soon transition to be the acting defense secretary in the absence of Mattis, a post Trump suggested Shanahan could fill "for a long time."
Trump's critics had made great hay out of the fact that he hadn't visited any U.S. troops in a war zone since becoming president, but they'll have to drop that talking point now that both the president and first lady have paid a visit to our men and women in uniform in Iraq.
Christmas, Iraq, Iraq War, Islamic State group, Melania Trump, politics, Syria
Ben Marquis
Ben Marquis is a writer who identifies as a constitutional conservative/libertarian. He has written about current events and politics for The Western Journal since 2014. His focus is on protecting the First and Second Amendments.
Ben Marquis has written on current events and politics for The Western Journal since 2014. He reads voraciously and writes about the news of the day from a conservative-libertarian perspective. He is an advocate for a more constitutional government and a staunch defender of the Second Amendment, which protects the rest of our natural rights. He lives in Little Rock, Arkansas, with the love of his life as well as four dogs and four cats.
Topics of Expertise
Mississippi AG Shoots Down Order from Mayor Who Made the Mistake of Banning Open Carry
To Save His Town, Mayor Defies Shutdown Order, Dares New Mexico Governor To Send in State Police
FBI Halting Gun Sales? Reportedly Breaking Law, Keeping Americans from Arming Selves
Biden Disrespects Wisconsin Ventilator Plant Workers, Dismisses Their Visit with Pence as 'Photo Op'
WaPo Tries To Fact Check Trump on WHO Claim, Misses The Point Entirely


text:
package dotty
package tools
package vulpix

import scala.language.unsafeNulls

import java.io.{ File => JFile, InputStreamReader, BufferedReader, PrintStream }
import java.nio.file.Paths
import java.nio.charset.StandardCharsets
import java.util.concurrent.atomic.AtomicBoolean
import java.util.concurrent.TimeoutException

import scala.concurrent.duration.Duration
import scala.concurrent.{ Await, Future }
import scala.concurrent.ExecutionContext.Implicits.global
import scala.collection.mutable

/** Vulpix spawns JVM subprocesses (`numberOfSlaves`) in order to run tests
 *  without compromising the main JVM
 *
 *  These need to be orchestrated in a safe manner with a simple protocol. This
 *  interface provides just that.
 *
 *  The protocol is defined as:
 *
 *  - master sends classpath to for which to run `Test#main` and waits for
 *    `maxDuration`
 *  - slave invokes the method and waits until completion
 *  - upon completion it sends back a `RunComplete` message
 *  - the master checks if the child is still alive
 *    - child is still alive, the output was valid
 *    - child is dead, the output is the failure message
 *
 *  If this whole chain of events is not completed within `maxDuration`, the
 *  child process is destroyed and a new child is spawned.
 */
trait RunnerOrchestration {

  /** The maximum amount of active runners, which contain a child JVM */
  def numberOfSlaves: Int

  /** The maximum duration the child process is allowed to consume before
   *  getting destroyed
   */
  def maxDuration: Duration

  /** Destroy and respawn process after each test */
  def safeMode: Boolean

  /** Running a `Test` class's main method from the specified `dir` */
  def runMain(classPath: String, toolArgs: ToolArgs)(implicit summaryReport: SummaryReporting): Status =
    monitor.runMain(classPath)

  /** Kill all processes */
  def cleanup() = monitor.killAll()

  private val monitor = new RunnerMonitor

  /** The runner monitor object keeps track of child JVM processes by keeping
   *  them in two structures - one for free, and one for busy children.
   *
   *  When a user calls `runMain` the monitor makes takes a free JVM and blocks
   *  until the run is complete - or `maxDuration` has passed. It then performs
   *  cleanup by returning the used JVM to the free list, or respawning it if
   *  it died
   */
  private class RunnerMonitor {

    def runMain(classPath: String)(implicit summaryReport: SummaryReporting): Status =
      withRunner(_.runMain(classPath))

    private class Runner(private var process: Process) {
      private var childStdout: BufferedReader = _
      private var childStdin: PrintStream = _

      /** Checks if `process` is still alive
       *
       *  When `process.exitValue()` is called on an active process the caught
       *  exception is thrown. As such we can know if the subprocess exited or
       *  not.
       */
      def isAlive: Boolean =
        try { process.exitValue(); false }
        catch { case _: IllegalThreadStateException => true }

      /** Destroys the underlying process and kills IO streams */
      def kill(): Unit = {
        if (process ne null) process.destroy()
        process = null
        childStdout = null
        childStdin = null
      }

      /** Did add hook to kill the child VMs? */
      private val didAddCleanupCallback = new AtomicBoolean(false)

      /** Blocks less than `maxDuration` while running `Test.main` from `dir` */
      def runMain(classPath: String)(implicit summaryReport: SummaryReporting): Status = {
        if (didAddCleanupCallback.compareAndSet(false, true)) {
          // If for some reason the test runner (i.e. sbt) doesn't kill the VM, we
          // need to clean up ourselves.
          summaryReport.addCleanup(() => killAll())
        }
        assert(process ne null,
          "Runner was killed and then reused without setting a new process")

        // Makes the encapsulating RunnerMonitor spawn a new runner
        def respawn(): Unit = {
          process.destroy()
          process = createProcess
          childStdout = null
          childStdin = null
        }

        if (childStdin eq null)
          childStdin = new PrintStream(process.getOutputStream, /* autoFlush = */ true)

        // pass file to running process
        childStdin.println(classPath)

        // Create a future reading the object:
        val readOutput = Future {
          val sb = new StringBuilder

          if (childStdout eq null)
            childStdout = new BufferedReader(new InputStreamReader(process.getInputStream, StandardCharsets.UTF_8))

          var childOutput: String = childStdout.readLine()

          // Discard all messages until the test starts
          while (childOutput != ChildJVMMain.MessageStart && childOutput != null)
            childOutput = childStdout.readLine()
          childOutput = childStdout.readLine()

          while (childOutput != ChildJVMMain.MessageEnd && childOutput != null) {
            sb.append(childOutput).append(System.lineSeparator)
            childOutput = childStdout.readLine()
          }

          if (process.isAlive && childOutput != null) Success(sb.toString)
          else Failure(sb.toString)
        }

        // Await result for `maxDuration` and then timout and destroy the
        // process:
        val status =
          try Await.result(readOutput, maxDuration)
          catch { case _: TimeoutException =>  Timeout }

        // Handle failure of the VM:
        status match {
          case _: Success if safeMode => respawn()
          case _: Success => // no need to respawn sub process
          case _: Failure => respawn()
          case Timeout => respawn()
        }
        status
      }
    }

    /** Create a process which has the classpath of the `ChildJVMMain` and the
     *  scala library.
     */
    private def createProcess: Process = {
      val url = classOf[ChildJVMMain].getProtectionDomain.getCodeSource.getLocation
      val cp = Paths.get(url.toURI).toString + JFile.pathSeparator + Properties.scalaLibrary
      val javaBin = Paths.get(sys.props("java.home"), "bin", "java").toString
      new ProcessBuilder(javaBin, "-Dfile.encoding=UTF-8", "-Duser.language=en", "-Duser.country=US", "-Xmx1g", "-cp", cp, "dotty.tools.vulpix.ChildJVMMain")
        .redirectErrorStream(true)
        .redirectInput(ProcessBuilder.Redirect.PIPE)
        .redirectOutput(ProcessBuilder.Redirect.PIPE)
        .start()
    }

    private val freeRunners = mutable.Queue.empty[Runner]
    private val busyRunners = mutable.Set.empty[Runner]

    private def getRunner(): Runner = synchronized {
      while (freeRunners.isEmpty && busyRunners.size >= numberOfSlaves) wait()

      val runner =
        if (freeRunners.isEmpty) new Runner(createProcess)
        else freeRunners.dequeue()
      busyRunners += runner

      notify()
      runner
    }

    private def freeRunner(runner: Runner): Unit = synchronized {
      freeRunners.enqueue(runner)
      busyRunners -= runner
      notify()
    }

    private def withRunner[T](op: Runner => T): T = {
      val runner = getRunner()
      val result = op(runner)
      freeRunner(runner)
      result
    }

    def killAll(): Unit = {
      freeRunners.foreach(_.kill())
      busyRunners.foreach(_.kill())
    }

    // On shutdown, we need to kill all runners:
    sys.addShutdownHook(killAll())
  }
}

redpajama_set_name: RedPajamaGithub


Gaiters come at all different price points, and while they're usually less than $100, that can be more than some people want to spend on gaiters. Fortunately, it's possible to find a good pair of cheap gaiters, provided that you know what you're looking for. A sale will make things a lot easier, but even without that, it's not impossible to find a cheap pair of gaiters that you will be happy with. All you have to do is educate yourself a bit on what your options are.
What to look for if you want cheap gaiters.
eVent – If you want waterproof gaiters then the obvious choice is Gore Tex. The problem, however, is that Gore Tex can be a rather expensive fabric. eVent, however, is a very similar waterproof fabric that is often quite a bit cheaper. It's not as common as Gore Tex, but if you're looking to save money it's worth searching for it.
Ankle Gaiters – Bigger, taller gaiters tend to cost more. So if you can make do with shorter ankle gaiters you will be able to save some money. If you're looking for winter gaiters, to protect you from downpours or for walking through snow, then you don't have much of a choice, you need the tall gaiters, but for everything else, you can likely make ankle gaiters work.
Some of the very best of the cheap gaiters out there.
Rab Hispar Gaiters - If you want a full length, waterproof gaiters, there aren't any better choices than the Hispar gaiters from Rab. They use 3 layer eVent, which is a fabric similar to Gore Tex, though known to be more breathable, which is never a bad thing for gaiters. The bottom section is 600D ballistic polyester, which is more than enough to prevent damage from boot rubbing and whatever other abuse your gaiters endure. The top is just a drawcord enclosure, but for the low price that's hardly something to complain about.
Rab Latok Mid Gaiters - The Rab Latok gaiters are fairly similar to the Hispar gaiters above, but are ankle length, rather than calf length. They use the same 3 layer eVent for the top portion, and a slightly different 500D cordura nylon for the bottom. The eVent will keep you dry, of course, and if you don't mind the ankle length, these are a fantastic pair of cheap gaiters for bad weather.
REI Desert Gaiters - The Desert gaiters are just a basic nylon gaiter with no waterproofing or water resistance. In fact as the name suggests, these are really made more for warm weather, when you're likely to be more worried about rocks, sticks and dirt filling your shoes up. And these are actually designed to work with smaller hiking shoes and running shoes, as opposed to boots. The nylon wont keep you dry, but it will at least dry fast if it does get wet, and also offers UPF 30 protection from the sun.


The Siberia 650 has rich 50mm speaker drivers, uses Dolby's ProLogic IIx and Dolby Headphone tech, and has a 10-band EQ. There's also a microphone mute and volume dial built right into each earcup.
The suspension headband and memory foam earcups have been engineered to make the Siberia 650 one of our most comfortable headsets ever. The earcups inner openings have been widened on the Siberia 650 for a nice, roomy fit on your ears.
With SteelSeries Engine 3, you can choose from 16.8 million colors, displayed on the vivid LEDs that encircle the earcups. With the external sound card, you can customize your sound options, too. Options like the 10-band equalizer, noise cancellation, mic feedback, and much more.
The Siberia 650 USB gaming headset features customizable RGB illumination with 16.8 million colors. It delivers best-in-class sound and comfort. With SteelSeries Engine, gamers can take full control over the Siberia 650's performance. Customize the illumination within SteelSeries Engine 3, including the colors, brightness and various effects (Trigger, Breathing, ColorShift).


text:
Argument essay prompts gre
There has been a substantial decline in the numbers of amphibians worldwide, and global pollution of water and air is clearly implicated. Therefore, we recommend maintaining Grove College's tradition of all-female education. To further revitalize the city, we should now take similar action in a declining residential area on the opposite side of the city. Since we are famous for our special bargains, raising our rental prices is not a viable way to improve profits. Watch courses on your mobile device without an internet connection. The following is a recommendation from the Board of Directors of Monarch Books. The buildings were erected by two different construction companies Alpha and Zeta. While the Department of Education in the state of Attra recommends that high school students be assigned homework every day, the data from a recent statewide survey of high school math and science teachers give us reason to question the usefulness of daily homework. We recommend building a similar golf course and resort hotel in Brindleburg. Be sure to explain how the answers to these questions would help to evaluate the advice. Improving vocabulary and reading comprehension skills.
GRE, argument, essay : Practice Sample, prompts - Kaplan Test Prep
Therefore, the new Captain Seafood restaurant that specializes in seafood should be quite popular and profitable. When our researchers conducted a poll of area residents, 88 percent of those who responded indicated that they would welcome the opening of a hobby shop in southeastern Grilldon. "In a laboratory study of liquid antibacterial hand soaps, a concentrated solution of UltraClean produced a 40 percent greater reduction in the bacteria population than did the liquid hand soaps currently used in our hospitals. The following appeared in a letter to argument essay prompts gre the school board in the town of Centerville. Vocabulary and sentence formations could also be enhanced through preparative materials such as Barron's wordlist, flashcards, and continuous revision. Such regulation is necessary to ensure fair prices for consumers." Write a response in which you discuss what questions would need to be answered in order to decide whether the recommendation is likely to have the predicted result. The following appeared in a memo from the vice president of a company that builds shopping malls around the country. Arrange all of the above points from the introduction to the conclusion in your scratch paper in order and develop a rough draft. Their habitat is limited to areas warm enough to sustain the plants on which they feed and cold enough, at least some of the year, for the ice to cover the sea separating the islands, allowing the deer to travel over.
The council currently predicts that the proposed measure, if passed, will result in a significant increase in housing prices in Maple County. "A ten-year nationwide study of the effectiveness of wearing a helmet while bicycling indicates that ten years ago, approximately 35 percent of all bicyclists reported wearing helmets, whereas today that number is nearly 80 percent. The following appeared in the summary of a study on headaches suffered by the residents of Mentia. GRE Arithmetic Integers: Factors, multiples, and remainders 2m 7s Integers: Even and odd and primes 3m 29s Order of operations 2m Number properties 3m 46s Adding and subtracting fractions 3m 36s Multiplying and dividing fractions 1m 22s Decimals. Fifteen years ago, Omega University implemented a new procedure that encouraged students to evaluate the teaching effectiveness of all their professors. We predict that instituting these online degree programs will help Humana both increase its total enrollment and solve its budget problems." Write a response in which you discuss what questions would need to be answered in order to decide. Hard work never fails, and with all these guidelines you cannot fail to score high on this part of the GRE. During the summer, then, the town council of Balmer Island should decrease the maximum number of moped rentals allowed at each of the island's six moped and bicycle rental companies from 50 per day to 30 per day. Currently, the nearest jazz club is 65 miles away; thus, the proposed new jazz club in Monroe, the C-Note, would have the local market all to itself. GRE Algebra Operations with expressions 3m 46s Multiplying expressions 1m 42s Algebraic identities 3m 5s Linear equations 2m 1s Linear equations with two variables 3m 33s Quadratic equations 4m 5s Linear inequalities 1m 37s Functions 4m 6s Symbol functions 58s. We therefore predict that the C Note cannot help but make money." Write a response in which you discuss what questions would need to be answered in order to decide whether the prediction and the argument on which it is based are reasonable. The following appeared in a recommendation from the President of the Amburg Chamber of Commerce. Keeping the college all female will improve morale among students and convince alumnae to keep supporting the college financially." Write a response in which you examine the stated and/or unstated assumptions of the argument.
Even though the two buildings had identical floor plans, the building constructed by Zeta cost 30 percent more to build, and its expenses for maintenance last year were twice those of the building constructed by Alpha. Adams has 40 real estate agents; in contrast, Fitch has 25, many of whom work only part-time. Next analyze the given argument with the eye of a critique while giving importance to the following clues: The evidence used by the author to help support the claim made in the essay. Home tests Exam gRE, the GRE Argument Essay is crucial as it tests the ability of the students to take part in a presented argument, analyze it critically without letting their opinions get in the way. But a long-term study of a large number of people found that those who consistently consumed dairy products throughout the years of the study have a higher rate of bone fractures than any other participants in the study.
GRE, sample, essays, Analyzed (Issue, argument )
But this claim is undermined by a recent report on the Elthyrian economy, which found that since 1999 far more jobs have been created than have been eliminated, bringing the unemployment rate in Elthyria to its lowest level in decades. Develop a thesis for the issue essay 2m 15s Issue essay examples 1m 57s Argument essay flaws 2m 44s Language, grammar, and writing mechanics 1m 44s Analyze an issue essay 2m 55s Analyze an argument essay 2m 42s. Question Type: Sentence Equivalence Sentence equivalence overview 4m 2s Difficult vocabulary in sentence equivalence 1m 37s Review sentence equivalence 57s. Thus, if the Rialto intends to hold on to its share of a decreasing pool of moviegoers, it must offer the same features as Apex." Write a response in which you discuss what questions would need to be answered. The following appeared in an article written. Specifically, dog owners tend to have a lower incidence of heart disease. By replacing its children's books section with a caf?, Monarch Books can increase profits and ward off competition from Book and Bean." Write a response in which you discuss what specific evidence is needed to evaluate the argument. Welcome to the GRE. In the past two years, however, there has been only a small increase in the number of visitors to Central Plaza, and litter and vandalism are still problematic.
Last year, however, private contributions to the symphony increased by 200 percent, and attendance at the symphony's concerts-in-the-park series doubled. Newsbeat's editor, however, opposes the proposed shift in editorial policy, pointing out that very few magazines offer extensive political coverage anymore. In an effort to improve our employees' productivity, we should implement electronic monitoring of employees' Internet use from their workstations. Moreover, Clearview's mayor promises many new programs to improve schools, streets, and public services. The following appeared in a health newsletter. Write a response in which you discuss what questions would need to be answered in order to decide whether the recommendation is likely to have the predicted result. The buildings were erected by different construction companies Alpha and Zeta. A recent government study reports that fatigue and sleep deprivation among workers are significant contributing factors in many on-the-job accidents. Therefore, it can be concluded that the respondents in the first study had misrepresented their reading preferences. Therefore, in order to increase profits without jeopardizing our reputation for offering great movies at low prices, we recommend implementing similar changes in our other nine Movies Galore stores." Write a response in which you discuss what questions. The following is a letter to the head of the tourism bureau on the island of Tria. The following appeared as a recommendation by a committee planning a ten-year budget for the city of Calatrava. They search for food by moving over ice from island to island during the course of the year.
Introduction to the, gRE, argument, task (For Test Takers)
In addition, the energy consumption of the Zeta building has been lower than that of the Alpha building every year since its construction. Come up with the alternative and missed out explanations to the presented argument without proving argument essay prompts gre the conclusion to be wrong. Inadequate and missed out evidence. Thus, to increase enrollment and solve the problem of budget deficits at Humana University, we should initiate and actively promote online degree programs like those at Omni." Write a response in which you examine the stated and/or unstated assumptions of the argument. Installing software on company computers to detect employees' Internet use is the best way to prevent employees from wasting time on the job. Two years ago the nearby Avon Repertory Company started a 'Free Plays in the Park' program, and its profits have increased 10 percent since then. "Recently, butter has been replaced by margarine in Happy Pancake House restaurants throughout the southwestern United States. For these reasons, we recommend that the city eliminate funding for the Grandview Symphony Orchestra from next year's budget.
It would be better to follow the example of the nearby city of Garville. To reduce the number of accidents involving mopeds and pedestrians, the town council of Balmer Island plans to limit the number of mopeds rented by each of the island's six moped rental companies from 50 per day to 30 per day during the summer season. However, Groveton College has successfully reduced student cheating by adopting an honor code, which calls for students to agree not to cheat in their academic endeavors and to notify a faculty member if they suspect that others have cheated. Therefore, we recommend that the city of Grandview eliminate its funding for the Grandview Symphony from next year's budget. Karp decided that. We should therefore build one of our new stores in Plainsville, which clearly has many such residents. Finally, Plainsville's schoolchildren argument essay prompts gre represent a new generation of potential customers: these schoolchildren are required to participate in a fitness-for-life program, which emphasizes the benefits of regular exercise at an early age. Many Central Plaza store owners believe that the decrease in their business is due to the number of skateboard users in the plaza.
"Last week, all the showerheads in the first three buildings of the Sunnyside Towers complex were modified to restrict maximum water flow to one-third of what it used. We discovered that there are currently no hobby shops in southeastern Grilldon. Consequently, students will find it increasingly difficult to afford off-campus housing. Welcome 1m 3s, what you should know 1m 30s. Question Type: Text Completion Overview of text completions 2m 30s Learn the text completion technique 3m 41s Use signposts 2m 23s Double-blank text completions 2m 15s Triple-blank text completion 4m 22s Analyze complex sentences 2m 23s Difficult vocabulary in text. Each Argument topic consists of a passage that presents an argument followed by specific task instructions that tell you how to analyze the argument. Since some houses and apartments in existing nearby neighborhoods are currently unoccupied, alternate housing for those displaced by this action will be readily available." Write a response in which you discuss what specific evidence is needed to evaluate the. "Several factors indicate that know radio can no longer succeed as a rock-and-roll music station. Also, a number of well-known jazz musicians own homes in Monroe. Several years ago, Groveton College adopted an honor code, which calls for students to agree not to cheat in their academic endeavors and to notify a faculty member if they suspect that others have cheated. Thus the number of students enrolled in our public schools will soon decrease dramatically, and we can safely reduce the funds budgeted for education during the next decade. Duration 529,757, views, show More Show Less.
Essay, writing - Reference Page, Footnotes in APA and MLA Formats
Despite receiving less frequent homework assignments, Marlee students earn better grades overall and are less likely to be required to repeat a year of school than are students in Sanlee. In contrast, over the past three years, enrollment at Humana University has failed to grow, and the cost of maintaining buildings has increased along with our budget deficit. We have always advertised our use of the Endure process, but the new study shows argument essay prompts gre that despite the socks' durability, our customers, on average, actually purchase new Dura-Socks every three months. "Last October the city of Belleville installed high-intensity lighting in its central business district, and vandalism there declined within a month. The following is a recommendation from the personnel director to the president of Acme Publishing Company. Their stores saw sales increase by 15 percent. Thus it follows that the so-called Palean baskets were not uniquely Palean. Moreover, Adams' revenue last year was twice as high as that of Fitch and included home sales that averaged 168,000, compared to Fitch's 144,000.
The chemists did find small amounts of the three remaining suspected chemicals but pointed out that these occur naturally in all canned foods." Write a response in which you discuss what questions would need to be addressed in order. The following appeared argument essay prompts gre in a memorandum from the manager of wwac radio station. The following appeared in a recommendation from the president of Amburg's Chamber of Commerce. Experts believe that a significant contributing factor in many accidents is fatigue caused by sleep deprivation among workers. This change is sure to result in a dramatic decline in cheating among college students.
Family meals were also associated with higher grades, better self-esteem, and lower rates of depression. Arctic deer live on islands in Canada's arctic regions. The following appeared as part of an article in a Dillton newspaper. "Of the two leading real estate firms in our town Adams Realty and Fitch Realty Adams Realty is clearly superior. Woven baskets characterized by a particular distinctive pattern have previously been found only in the immediate vicinity of the prehistoric village of Palea and therefore were believed to argument essay prompts gre have been made only by the Palean people. "Recently, there have been discussions about ending Grove College's century-old tradition of all-female education by admitting male students into our programs.
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Internal Control is responsible for reconciliation and daily monitoring of all of NM Tech's bank accounts. Primary contact for any issues regarding bank activity.
This office also monitors all internet payments and is responsible for maintainence and collection of student Perkins loans.


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Confused about O365 SharePoint's Classic vs. Modern? Let us help.
If your organization utilizes O365 SharePoint as a part of its technology toolbelt you must have experienced or heard through the grapevine about Microsoft's Modern UI previews and updates. Microsoft completed its integration of modern SharePoint Team Sites with O365 groups in August of 2016 and the new integration brings many questions for administrators and end users alike about classic versus modern UI. It can be a lengthy and arduous process to sort through all the marketing campaigns from Microsoft and feedback from users so allow us to lead the way in your journey through Office 365.
WHAT IS CLASSIC VERSUS MODERN?
It's important to note that at its core, SharePoint has not changed much from versions of the past. Each update brings users a pool of new features or updates on existing components you know and love. The Modern UI is an example of an improvement Microsoft is making to their web-based collaboration platform. The classic experience refers to the SharePoint you know and love and it is not going away (at least not anytime soon). The core concept of sites, pages, web parts, lists and libraries remains but the look and feel of it is changing with the modern UI. Let's review the top three reasons for the appearance of the modern UI.
1. Classic SharePoint is not mobile responsive
A non-responsive site with a lot of content creates a horizontal scrollbar for devices with smaller screens. This makes SharePoint a difficult pill to swallow during the age of on-the-go collaboration and easy-access mobile devices. Classic SharePoint can be responsive as well, but it does require development and SharePoint infrastructure knowledge to implement which can be a difficult process to embark on alone.
2. SharePoint administration requires a healthy dose of training and knowledge
Your average user would be far more comfortable adopting an administrator hat for their workplace if training and support is made available. For your organization, this means additional overhead for your IT team, multiple tickets opened to create/manage new content areas with training sessions and guidance applied.
3. Out of the box page layouts and flexibility in design
Classic SharePoint has a good variety of layouts, but they are not mobile responsive and creating SharePoint sites may not be a good solution for a fast pace collaboration team. Modern UI allows users to quickly create pages and components but branding capabilities of the modern UI has room for improvement.
SHOULD YOU WAIT ON SHAREPOINT'S MODERN UI?
There is a long list of pros and cons that we can review but the number one reason to wait on the modern SharePoint UI is that it's in its early stages of development, it's still a baby. It's a growing baby with a lot of potential but larger organizations may want to wait until it matures before they make their move. Our message today is not to tell everyone to run from the modern UI but to review its pros and cons and make an informed decision. The modern UI has an intuitive interface and some great new web parts and features for you to check out and determine if it fits your needs. Also features that exist in the classic experience may not exist in the modern UI at this time so take the time to research both the benefits of the modern UI, what may be missing and how long you will have to wait for the features you need.
NEED HELP DECIDING WHETHER YOU ARE READY?
Are you curious what the extended list of pros and cons are? Would you like to learn more about our experience with the modern UI versus classic? Reach out and we can schedule a deep dive into modern SharePoint's current features, capabilities and any active bugs we've discovered which may prove troublesome in a transition to the modern UI. SharePoint is one of our core services and we'd love to partner with you on your journey through Office 365.


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Sign-inContactSearch
Self Care Programme
Have I Got IBS?
Could it be anything else?
Is this IBS?
What is the cause of IBS
Does IBS Run in the family
Have I a got food allergy?
Is it Food Intolerance?
So what can I eat?
It's Not What You Eat
Food and Mood
What's Really Going On
What Can I Do About It
Reducing Anxiety Preventing Panic
Dealing with Despair
What else could it be?
Nutritional and Herbal Therapies
Causes of Constipation
Developing a Good Bowel Habit
Diet and Life Style
Colonic Therapies
Constipation Medicines
What's Causing My Diarrhoea
How can I manage my diarrhoea?
Urgency and Faecal Incontinence
What Causes Bloating
How can I relieve Bloating
Other Causes
Pain in the bottom
How can I manage the pain
AccountContact
IBS awareness month
During IBS Awareness Month, The IBS Network charity supported the promotion of ASDA Pharmacy's digestive health campaign nationwide. This was to provide easy-to-understand advice and tips that people can take away with them whilst they were in-store for their weekly shop. The campaign aimed to open-up the conversation about IBS - how to spot the symptoms and what steps you can take to alleviate it, so we can all better understand how to make life easier for those who need the support. ASDA Pharmacy's digestive health event ran in-store from 1 – 24 April. A series of radio interviews and press coverage with ASDA and The IBS Network spokespeople has been generated, as a result.
Irritable Bowel Syndrome (IBS) Sufferers Miss Nine Days of Work a Year Due to "Debilitating" Illness
4 in 10 IBS sufferers regularly take time off work, with an average of nine days a year
Almost three-quarters (70%) say IBS is a "debilitating" medical condition that occupies their lives daily
Almost 1 in 3 people in the UK say they suffer from IBS, more than the current estimate
6 in 10 have never sought professional help due to embarrassment
ASDA Pharmacies to hold a digestive health event instore from 1-24 April to mark IBS Awareness Month in April
New research by ASDA has brought to light just how common irritable bowel syndrome (IBS) is in the UK, with almost 1 in 3 people suffering from the condition – more than the current estimates.
The study revealed that 4 in 10 IBS sufferers regularly take time off work for their condition, with an average of nine days a year due to the symptoms brought on by IBS, which includes abdominal pain or cramping, bloating, flatulence and constipation.
In addition to the physical impact of not being able to attend work, sufferers disclosed the extent to which the condition impacts other areas of their daily lives, with the avoidance of certain activities until a more suitable time:
Fitness activities (26%)
Travelling on a plane or train (24%)
Being intimate with a partner (23%)
Attending a social event e.g. party, festival (19%)
Going on a date (17%)
Sufferers also highlighted the hidden mental stress associated with their symptoms and cited the thoughts that most occupy their minds daily:
Having total privacy (completely enclosed spaces) in the bathroom (28%)
Timing meals around times when there is easy access to facilities (21%)
Having to avoid certain foods, especially in situations where choice is unavailable (17%)
Finding time in the day to avoid work or high-stress situations that can bring on symptoms without managers noticing absence (11%)
Not being able to take painkillers in situations (i.e. meetings, presentations) when a bout of symptoms come on
Anxiety and stress is a key factor in triggering IBS with almost three-quarters stating that it exacerbates their symptoms.
Despite 7 in 10 sufferers stating that they find their condition "debilitating", 6 in 10 have never sought professional help through a GP, instead choosing to manage the condition as best they can themselves. Over half (57%) said that the embarrassment of talking about it has held them back, even causing them to keep the condition hidden from friends and colleagues.
Alison Reid, CEO of The IBS Network comments:
"IBS affects between 10 and 20% of the population, that's about 12 million people. The condition can mean feelings of isolation through an inability to leave the house for fear of an accident, cancelled holidays, and days off work. The stress caused by the distress of these symptoms, worry of losing job, the humiliation of an accident, can make the condition worse; which creates a vicious circle. Pharmacists play a key role in signposting people with IBS symptoms to see their GP for a diagnosis. Our members have reported that talking openly about their condition with people who understand really helps them break this cycle supporting them in taking control of their IBS. Through our work, the charity is challenging the 'poo taboo'."
Faisal Tuddy, Asda's Superintendent Pharmacist Pharmacy comments:
"As with any health condition, removing the stigma and embarrassment associated with it is important in encouraging sufferers to seek help so they can better manage and cope with their symptoms. IBS symptoms can be managed with a few easy-to-incorporate lifestyle changes so it needn't be a stressful experience.
To mark IBS Awareness Month in April, ASDA Pharmacies, backed by The IBS Network, the national charity supporting people living with IBS, will be hosting a digestive health campaign nationwide to provide easy-to-understand advice and tips that people can conveniently take away with them whilst they're in-store for their weekly shop. It's key to open up the conversation about IBS - how to spot the symptoms and what steps you can take to alleviate it, so we can all better understand how to make life easier for those who need the support. ASDA Pharmacy's digestive health event will run in-store from 1 – 24 April."
IBS is a long-standing illness consisting of frequent abdominal discomfort and bowel symptoms which cannot be explained by any other disease. Symptoms can be complex and conflicting but include constipation, diarrhoea, abdominal cramps and pain and bloating. Other common symptoms that may be associated with IBS include tiredness, nausea, heartburn and indigestion, backache, needing to pass urine frequently, headaches, muscle pain, anxiety and depression. It can lead to feelings of isolation and cause major problems in people's working and personal lives.
Independent research commissioned by Asda Pharmacy, conducted by Atomik Research. 2,003 people aged 18-65 in the UK were surveyed in March 2017.
To Read More Join today to access Members' Exclusive Content
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Acknowledging your Illness, Supporting your Journey, Transforming your Life
The IBS Network is a registered charity in England and Wales. Charity No. 1173208
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Las dos doncellas es una de las Novelas ejemplares de Miguel de Cervantes Saavedra.

Argumento

En un pueblo cerca de Sevilla, un hombre misterioso acude a una posada y pide un cuarto para él solo, para el cual paga generosamente a la posadera. Sin embargo, se ve obligado a ceder su cama a otro visitante, el cual se ve interesado en compartir el cuarto con esa persona al saber que era un hombre hermoso, al punto de sobornar al alguacil del pueblo para que obligue al primer huésped a compartir su habitación.

Durante la noche el primer huésped, creyendo que su compañero de cuarto esta dormido, comienza a lamentar en voz alta las desventuras amorosas que ha pasado revelando que es una mujer. El segundo huésped pronto decide ayudarle pero no sin antes escuchar las razones de sus lamentos.

La mujer revela entonces su nombre como Teodosia, quien fue abandonada por su marido Marco Antonio justo dos días de haberse casado con él, entonces usando la ropa de su hermano y cortándose el cabello decide ir a Salamanca a buscarlo, a sabiendas que sus padres, e incluso su propio hermano puede encontrarlo, pero sabe que su marido caerá en razón especialmente por un anillo de diamantes que le dio como prenda de matrimonio.

Un silencio incómodo se genera, y Teodosia piensa que el hombre intentará aprovecharse de ella (o simplemente se quedó dormido), así que decide empuñar su daga y abrir las ventanas del lugar para revelar la identidad de su acompañante, quien no es más que su hermano Rafael.

Rafael, comprendiendo la situación de su hermana, decide ayudarle con su búsqueda y le sugiere que tome el nombre de Don Teodoro y pronto recibe la ayuda de su paje para continuar la búsqueda de Marco Antonio, de quien revela Rafael, no lo ha visto desde ese entonces. Pronto tienen noticias de un grupo de personas que fueron atrapadas por unos ladrones y deciden investigar si Marco Antonio está ahí, pero no lo encuentran, sino a un hombre con un rostro hermoso. Usando la capa del paje, lo llevan a la posada para ayudarle.

Pronto se enteran de que el hombre se hace llamar Don Leonardo, pero pronto Teodosia se da cuenta de que es otra doncella, Leocadia, la cual fue otro amor de Marco Antonio que también fue abandonada y, al igual que Teodosia, está dispuesto a encontrarlo.

El trío prosigue su búsqueda y encuentran a Marco Antonio en Barcelona teniendo una disputa con otras personas, para lo cual Don Teodoro y Don Leonardo acuden a defenderlo y dispersan la disputa. Confundido Marco Antonio es pronto confrontado por los dos hombres, quienes revelan su verdadera identidad. Marco Antonio termina aceptando que decidió ir a enrolarse al ejército para poder tener las riquezas necesarias para hacer a Teodosia feliz y que no ha dejado de amarla.

Esta reunión desilusiona a Leocadia que quiere alejarse de ellos y cometer suicidio, pero Rafael, enamorado de Leocadia, decide declararle su amor. Leocadia decide corresponderle y acepta casarse con él.

Escenario

Esta novela se desarrolla en España. Habla de las ciudades de Sevilla y Barcelona.

Personajes

Personajes principales

Teodosia: Esposa de Marco Antonio. Es matada por su esposo, pero cuenta con un anillo de diamantes con sus nombres grabado como prueba de su matrimonio. Decide robar la ropa de su hermano e ir disfrazado como Don Teodoro para buscar a su pareja en Salamanca.

Leocadia: Enamorada de Marco Antonio. Éste la abandona por Teodosia. Ella era una bella mujer que también decide buscar a Marco Antonio cuando le abandona por Teodosia. Es atrapada cerca de Salamanca por unos ladrones y su belleza impresiona a Rafael, pese a vestir como un hombre. Pese a mostrar cierto odio por Teodosia, decide seguirlos para poder aclarar las cosas con Marco Antonio. Al ver que este ya no la ama, intenta abandonar al grupo para cometer suicidio, pero se da cuenta de que en el fondo ama a Rafael, el hermano de Teodosia no acepta casarse con el

Marco Antonio: Hombre que desdicha a las dos mujeres. Abandona a Rafael  al saberse pobre y decide intentar enrolarse al ejército en busca de fortuna. Es encontrado en Andalucía por las dos doncellas quienes lo salvan en una disputa. Finalmente demuestra que ama a Teodosia.

Personajes secundarios

Rafael: Hermano de Teodosia y enamorado de Leocadia. Rafael siente interés por el misterioso caballero que encuentra en una posada y que lamenta su amor perdido mientras finge estar dormido y se impresiona con la belleza del otro caballero que fue atrapado por unos ladrones a las afueras de Salamanca.

Calvete, mozo de mulas: Sirve a Rafael. Le acompañaría al fin del mundo, tal como dice en un momento de la historia.

Enlaces externos

Información sobre el libro
Libro

Véase también

La fuerza de la sangre
Miguel de Cervantes

Novelas ejemplares
Novelas de 1613
Novelas en español

redpajama_set_name: RedPajamaWikipedia


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Африканская региональная организация промышленной собственности (АРОПС) Кения Южная Африка
Египет Иордания Марокко Саудовская Аравия Тунис
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1. (WO2019050903) METHODS FOR TREATING SLEEP DISORDERS, SLEEP DISTURBANCES, AND RELATED SYMPTOMS USING AMINOSTEROL COMPOSITIONS
Библиограф. данные PCT
Национальная фаза
Примечание: Текст, основанный на автоматизированных процессах оптического распознавания знаков. Для юридических целей просьба использовать вариант в формате PDF
WHAT IS CLAIMED
1. A method of treating or preventing a sleep disorder, sleep disturbance, or related symptom in a subject comprising administering to the subject a composition comprising a pharmaceutically acceptable grade of at least one aminosterol, or a pharmaceutically acceptable salt or derivative thereof, in an amount sufficient to produce a beneficial effect.
(a) determining a dose of an aminosterol or a pharmaceutically acceptable salt or derivative thereof for the subject, wherein the aminosterol dose is determined based on the effectiveness of the aminosterol dose in improving or resolving a sleep disorder, sleep
disturbance, or related symptom being evaluated,
(b) followed by administering the aminosterol dose to the subject for a period of time, wherein the method comprises:
(i) identifying a sleep disorder, sleep disturbance, or related symptom to be evaluated;
(ii) identifying a starting aminosterol dose for the subject; and
(iii) administering an escalating dose of the aminosterol to the subject over a period of time until an effective dose for the sleep disorder, sleep disturbance, or related symptom being evaluated is identified, wherein the effective dose is the aminosterol dose where improvement or resolution of the sleep disorder, sleep disturbance, or related symptom is observed, and fixing the aminosterol dose at that level for that particular sleep disorder, sleep disturbance, or related symptom in that particular subject.
3. The method of claim 1 or 2, wherein the composition is administered orally, intranasally, or a combination thereof.
4. The method of any one of claims 1-3, wherein the composition is administered orally and:
(a) the starting aminosterol dose ranges from about 1 mg up to about 175 mg/day;
(b) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof for the subject following escalation is fixed at a range of from about 1 mg up to about 500 mg/day; and/or
(c) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is escalated in about 25 mg increments.
5. The method of any one of claims 1-3 wherein the composition is administered
intranasally and:
(a) the starting dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof ranges from about 0.001 mg to about 3 mg/day;
(b) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof for the subject following escalation is fixed at a range of from about 0.001 mg up to about 6 mg/day;
(c) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof for the subject following escalation is a dose which is subtherapeutic when given orally or by injection; and/or
(d) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is escalated in increments of about 0.1, about 0.2, about 0.25, about 0.3, about 0.35, about 0.4, about 0.45, about 0.5, about 0.55, about 0.6, about 0.65, about 0.7, about 0.75, about 0.8, about 0.85, about 0.9, about 0.95, about 1, about 1.1, about 1.2, about 1.3, about 1.4, about 1.5, about 1.6, about 1.7, about 1.8, about 1.9, or about 2 mg.
6. The method of any one of claims 1-5, wherein:
(a) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is escalated every about 3 to about 5 days;
(b) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is escalated every about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, or about 14 days;
(c) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is escalated about lx/week, about 2x/week, about every other week, or about lx/month;
(d) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is given once per day, every other day, once per week, twice per week, three times per week, four times per week, five times per week, six times per week, every other week, or every few days;
(e) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative
thereof is given for a few weeks, followed by skipping a few weeks, followed by restarting aminosterol treatment;
(f) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is incrementally reduced after the fixed dose of aminosterol or a pharmaceutically acceptable salt or derivative thereof has been administered to the subject for a period of time;
(g) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is varied plus or minus a defined amount to enable a modest reduction or increase in the fixed dose;
(h) the dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is varied plus or minus a defined amount to enable a modest reduction or increase in the fixed dose, and the fixed aminosterol dose is increased or decreased by about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%; and/or
(i) the starting dose of the aminosterol or a pharmaceutically acceptable salt or derivative thereof is higher if the symptom being evaluated is severe.
7. The method of any one of claims 2-6, wherein the sleep disorder, sleep disturbance, or related symptom to be evaluated is selected from the group consisting of:
(1) total sleep time;
(2) total number of hours of uninterrupted sleep, per day;
(3) sleep efficiency;
(4) presence or frequency of a change in sleeping patterns;
(5) presence or frequency of a change in Circadian rhythm;
(6) developing a normal Circadian (i.e., diurnal) rhythm;
(7) presence of a sleep-wake cycle that is not 24 hours;
(8) sleeping at night rather than during the day, when night would is the preferred sleeping period;
(9) presence and/or frequency of awakenings during sleep period;
(10) presence and/or frequency of nonrestorative sleep;
(11) presence and/or frequency of a difficulty maintaining sleep;
(12) presence and/or frequency of sleep fragmentation;
(13) presence and/or frequency of hallucinations during sleep period;
(14) presence and/or frequency of thrashing or limb movement during sleep period;
(15) presence and/or frequency of nightmares and/or vivid dreams;
(16) presence and/or frequency of delayed sleep onset;
(17) presence and/or frequency of day time sleepiness;
(18) presence and/or frequency of clinical or sub-clinical "sleep attacks";
(19) cognitive impairment and/or improvement in memory as a result of better memory consolidation during sleep;
(20) presence and/or frequency of disturbances in sleep architecture;
(21) time of awakening following sleep period, with a later time correlated with improved sleep;
(22) presence and/or frequency of sleep problems;
(23) presence and/or frequency of sleep disturbances and/or sleep disruption;
(24) REM disturbed sleep;
(25) presence and/or frequency of apnea;
(26) presence and/or frequency of narcolepsy;
(27) poor psychomotor coordination;
(28) presence and/or frequency of headaches;
(29) presence and/or frequency of gastrointestinal distress;
(30) presence and/or frequency of insomnia;
(31) presence and/or frequency of parasomnias;
(32) diurnal skin temperature oscillations;
(33) a symptom from the Horne-Ostberg Morningness-Eveningness Questionnaire
(MEQ) selected from the group consisting of difficulty waking up in the morning, difficulty falling asleep at night, falling asleep earlier than normal at night, dependence on alarm to wake in morning, lack of alertness in morning, appetite upon waking in morning, feeling tired after waking in the morning, going to bed later than normal when subject has no commitments the following day, inability to fall back to sleep upon waking in the morning, lack of willingness to engage in physical activity in the morning, and lack of willingness to engage in cognitively challenging tasks in the morning;
(34) a symptom from the Epworth Sleepiness Scale (ESS) selected from the group
consisting of dozing or sleeping when sitting and reading, dozing or sleeping when watching television (TV), dozing or sleeping when sitting while inactive in public, dozing or sleeping when riding as a passenger in a car for greater than 1 hour, dozing or sleeping when lying down in the afternoon, dozing or sleeping when talking to another person, dozing or sleeping when sitting quietly after lunch, and dozing or sleeping when driving and stopped in traffic;
(35) REM behavior disorder (RBD);
(36) circadian rhythm dysfunction;
(37) Restless leg syndrome;
(38) jet lag;
(39) hypersomnia; and/or
(40) personal judgement of restful sleep.
(a) administration of the composition decreases the occurrence of at least one symptom of the sleep disorder or sleep disturbance;
(b) progression or onset of the sleep disorder, sleep disturbance or related symptom is slowed, halted, or reversed over a defined time period following administration of the composition, as measured by a medically-recognized technique, tool or scale; and/or
(c) the sleep disorder, sleep disturbance or related symptom is positively impacted by administration of the composition, as measured by a clinically-recognized technique, tool or scale.
9. The method of claim 8, wherein:
(a) the progression or onset of the sleep disorder, disturbance or related symptom is slowed, halted, or reversed by about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%, as measured by a medically-recognized technique, tool or scale; and/or
(b) the positive impact on the sleep disorder, disturbance, or related symptom is at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%), at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%>, at least about 90%, at least about 95%, or at least about 100%, as measured using a clinically recognized scale, tool, or technique.
10. The method of any one of claims 1-9, wherein the sleep disorder, disturbance or related symptom:
(a) comprises a dyssomnia, parasomnia, and/or circadian rhythm sleep disorder;
(b) comprises a loss of diurnal rhythm (Circadian rhythm);
(c) comprises a delay in sleep onset, sleep fragmentation, REM-behavior disorder (RBD), sleep-disordered breathing including snoring and apnea, day-time sleepiness, micro-sleep episodes, narcolepsy, hallucinations, hypersomnia, Restless leg syndrome (RLS), Periodic limb movement disorder (PLMD), insomnia, gastrointestinal distress, headache, narcolepsy, REM disturbed sleep, clinical or sub-clinical "sleep attacks", thrashing or limb movement during sleep period, nonrestorative sleep, awakenings during sleep period, cognitive impairment, sleep problems, poor psychomotor coordination, bruxism, catathrenia, cataplexy, sleep walking, Delayed sleep phase disorder (DSPD), advanced sleep phase disorder (ASPD), non-24-hour sleep-wake disorder (non-24) in the sighted or in the blind, irregular sleep wake rhythm, Shift work sleep disorder (SWSD), Hypopnea syndrome, Idiopathic hypersomnia, Kleine-Levin syndrome, sleep terror disorder, nocturia, sleep paralysis, somniphobia, or any combination thereof; and/or
(d) comprises or is associated with a neurodegenerative disorder or disease.
11. The method of claim 10, wherein: :
(a) the loss of diurnal rhythm is caused by dysfunction of the suprachiasmatic nucleus, and administration of the composition reverses the dysfunction of the suprachiasmatic nucleus, restores the diurnal rhythm, and treats the sleep disorder, sleep disturbance, or related symptom;
(b) the loss of diurnal rhythm is caused by dysfunction of the enteric nervous system, and administration of the composition reverses the dysfunction of the enteric nervous system, restores the diurnal rhythm, and treats the sleep disorder, sleep disturbance, or related symptom;
(c) the loss of diurnal rhythm is caused by dysfunction of the olfactory nervous system, and administration of the composition reverses the dysfunction of the olfactory nervous system, restores the diurnal rhythm, and treats the sleep disorder, sleep disturbance, or related symptom;
(d) the loss of diurnal rhythm is caused by visual loss, and administration of the composition reverses the dysfunction of the circadian rhythm caused by visual loss;
(e) the loss of diurnal rhythm is caused by jet lag, and administration of the composition reverses the dysfunction of circadian rhythm caused by jet lag; and/or
(f) the loss of diurnal rhythm is caused by night-shift work, and administration of the composition reverses the dysfunction of the circadian rhythm caused by night-shift work.
12. The method of claim 10, wherein:
(a) treating the sleep disorder, sleep disturbance, or related symptom prevents or delays the onset or progression of the neurodegenerative disorder; and/or
(b) the neurodegenerative disorder is selected from the group consisting of
Parkinson's disease, Alzheimer's disease, Huntington's chorea and/or Disease, schizophrenia, multiple sclerosis, dementia, degenerative processes associated with aging, dementia of aging, multi-system atrophy (MSA), fronto-temporal dementia, autism, progressive nuclear palsy, Guadeloupian Parkinsonism, spinocerebellar ataxia, Amyotorphic Lateral Sclerosis (ALS), Friedreich's ataxia, vascular dementia, Lewy Body dementia or disease, spinal muscular atrophy, supranuclear palsy, fronto temperal dementia, neuropathy of diabetes, peripheral sensory neuropathy, cerebral palsy, epilepsy, diabetic neuropathy, and depression.
13. The method of any one of claims 1-12, wherein:
(a) the method results in a positive change in the sleeping pattern of the subject;
(b) the method results in a positive change in the sleeping pattern of the subject, wherein the positive change is defined as an increase in the total amount of sleep obtained of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%;
(c) the method results in a positive change in the sleeping pattern of the subject, and the positive change is defined as a percent decrease in the number of awakenings during the night selected from the group consisting of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%;
(d) as a result of the method the subject obtains the total number of hours of sleep recommended by a medical authority for the age group of the subject.
14. The method of any one of claims 1-13, wherein the aminosterol:
(a) is isolated from the liver of Squalus acanthias;
(b) is squalamine or a pharmaceutically acceptable salt thereof;
(c) is a squalamine isomer or derivative;
(d) is aminosterol 1436 or a pharmaceutically acceptable salt thereof;
(e) is an aminosterol 1436 isomer or derivative;
(f) comprises a sterol nucleus and a polyamine attached at any position on the sterol, such that the molecule exhibits a net charge of at least + 1;
(g) comprises a bile acid nucleus and a polyamine, attached at any position on the bile acid, such that the molecule exhibits a net charge of at least + 1;
(h) is a derivative of squalamine or aminosterol 1436 modified through medical chemistry to improve bio-distribution, ease of administration, metabolic stability, or any combination thereof;
(i) is a derivative of a natural aminosterol modified through medical chemistry to improve bio-distribution, ease of administration, metabolic stability, or any combination thereof;
(j) is a synthetic aminosterol; or
(k) is a derivative modified to include one or more of the following:
(i) substitutions of the sulfate by a sulfonate, phosphate, carboxylate, or other anionic moiety chosen to circumvent metabolic removal of the sulfate moiety and oxidation of the cholesterol side chain;
(ii) replacement of a hydroxyl group by a non-metabolizable polar substituent, such as a fluorine atom, to prevent its metabolic oxidation or conjugation; and/or
(iii) substitution of one or more ring hydrogen atoms to prevent oxidative or reductive metabolism of the steroid ring system.
15. The method of claim 14, wherein the aminosterol is squalamine or a pharmaceutically acceptable salt thereof or aminosterol 1436 or a pharmaceutically acceptable salt thereof.
16. The method of any one of claims 1-15, wherein the aminosterol is a phosphate salt.
17. The method of any one of claims 1-16, wherein the composition further comprises one or more of the following: (a) an aqueous carrier; (b) a buffer; (c) a sugar; and/or (d) a polyol compound.
(a) each aminosterol dose is taken on an empty stomach, optionally within two hours of the subject waking; and/or
(b) no food is taken after about 60 to about 90 minutes of taking the aminosterol dose.
19. The method of any one of claims 1-18, wherein the aminosterol or a pharmaceutically acceptable salt or derivative thereof is administered in combination with at least one additional active agent to achieve either an additive or synergistic effect.
(a) the additional active agent is administered via a method selected from the group consisting of concomitantly, as an admixture, separately and simultaneously or concurrently, and separately and sequentially;
(b) the additional active agent is a different aminosterol from that administered in the method of any one of claims 1-19;
(c) the method comprises a first aminosterol which is aminosterol 1436 or a pharmaceutically acceptable salt or derivative thereof administered intranasally and a second aminosterol which is squalamine or a salt or derivative thereof administered orally;
(d) the additional active agent is an active agent used to treat sleep disorders, sleep disruption, or a related symptom;
(e) the additional active agent is selected from the group consisting of an orexin receptor antagonist such as suvorexant (Belsomra®), supplements such as melatonin, valerian, 5-htp, magnesium or glycine; a benzodiazepine such as clonazepam (Klonopin®), diazepam (Valium®), chlorodiazepoxide (Librium®), flurazepam (Dalmine®); and/or a Z-drug such as zopiclone (Imovane®), zaleplon (Sonata®) and Zolpidem (Ambien®).
21. The method of any one of claims 1-20, wherein the subject is a human.
22. A composition comprising a pharmaceutically acceptable grade of at least one aminosterol, or a pharmaceutically acceptable salt or derivative thereof, for use in a method of treating or preventing a sleep disorder, sleep disturbance, or related symptom in a subject.
23. The composition of claim 22, for use in a method according to any one of claims 1-21.