text:
Tech India Transformation Convention salutes key industry innovators
September 24 2021: The Tech India Transformation Convention (TITC), was concluded successfully on September 18, in the virtual presence of industry veterans and thought leaders. Conceptualized by Industry Live, the convention witnessed participation from over 500 brands from the tech industry along with more than 800 delegates.
Presented by KartmaX by GreenHonchos, supported by VR/AR Association, with Sugarbox Networks and Ambab Infotech as the session partners, the unique TITC forum brought together all the stakeholders across the industry on one platform to deliberate on trends, areas of growth and innovation, and the future course of action to revive and thrive in the post-COVID times.
The media partners for the convention were CIO Review India, Digital Terminal, DeviceNext, Electronics Maker, NFA Post, BIS Infotech, Smart State India, Techmezine, IndiaTechOnline, Proche & Telecomtoday.in
The convention kick-started with a keynote address by Jagdish Mitra, Chief Strategy Officer & Head of Growth, Tech Mahindra who shared his thoughts on Connecting India to Bharat through AI - Leveraging AI to Create a $5 trillion Economy.
The day was replete with a power-packed agenda distributed over eleven different sessions on various topics such as Silver lining for the tech industry in India in the New Normal; AI, IoT, Machine Learning - Powering the Digital Future; Drones & Robotics - An Emerging Solution in the New Normal; Transforming Health Care with a Jab of Technology; The Serious Business of Digital Gaming; Pandemic Fuels Tech Inclusion in the Financial Sector; How AR/VR technology is helping in addressing the challenges posed by the COVID Pandemic?; Building the Digital Trust (Cyber Curve); How ecommerce is leveraging deep tech to unlock seamless growth? and Challenges to solve while scaling up your D2C business online.
The event concluded with Tech India Transformation Awards. Celebrating the best in the Indian tech and the allied industries, the entire fraternity joined hands to celebrate excellence and to raise a toast to outstanding achievements in the industry so far and keep the businesses going in the difficult times of the pandemic. A jury panel comprising Mr Amit Malik, MD, Global Service Provider Segment, Cisco Asia Pacific, Japan & Greater China; Mr Saurabh Saha, Head Product Management, NASSCOM FutureSkills and Mr Pradeep Khanna, Executive Director Asia Pacific & CEO, VR AR Association (VRARA) & Global Mindset judged winners across 40+ categories. Few of the renowned Winners at the ceremony were – Amazon Web Services was conferred with the "Best Cloud Service Provider of the Year" award; upGrad won the "EdTech of the Year" award; CropIn was awarded the "Agri Tech of the Year"; GreenHonchos was conferred with the "D2C Enabler of the Year" award; Khatabook won the "App of the Year" award; MOTOVOLT was awarded the "Best in Innovation"; RESET was conferred with the "Best Tech Start-Up of the Year (Fitness & Wellness)" award; CCAvenue (Infibeam Avenues Ltd) won the "Fintech of the Year" award; Zensar Technologies was awarded the "Tech Company of the Year"; KartmaX by GreenHonchos was conferred with the "Best Tech Start-up of the Year- Ecommerce" award; Altorum Leren won the "Best Tech Start-Up of the Year (IOT)" award; MY JEN AI PVT. LTD was awarded the "Best Tech Start-Up of the Year- Artificial Intelligence"; Samaaro was conferred with the "Best Tech of the Year (Web Conferencing/Virtual Meeting Platform)" award; Orion Security Solutions Private Limited won the "Best Tech of the Year (Security)" award; Nexus Engineering was awarded the "Best Tech of the Year (Manufacturing)"; Mr. Manan Shah; Founder & CEO; Avalance Global Solutions was conferred with the "Young Trailblazer of the Year" award; Dr. Geetha Manjunath, Founder, CEO & CTO, NIRAMAI won the "Difference Maker of the Year" award to name a few.


text:
import { createSlice, PayloadAction } from '@reduxjs/toolkit';

import { Team, TeamGroup, TeamMember, TeamsState, TeamState } from 'app/types';

export const initialTeamsState: TeamsState = { teams: [], searchQuery: '', searchPage: 1, hasFetched: false };

const teamsSlice = createSlice({
  name: 'teams',
  initialState: initialTeamsState,
  reducers: {
    teamsLoaded: (state, action: PayloadAction<Team[]>): TeamsState => {
      return { ...state, hasFetched: true, teams: action.payload };
    },
    setSearchQuery: (state, action: PayloadAction<string>): TeamsState => {
      return { ...state, searchQuery: action.payload, searchPage: initialTeamsState.searchPage };
    },
    setTeamsSearchPage: (state, action: PayloadAction<number>): TeamsState => {
      return { ...state, searchPage: action.payload };
    },
  },
});

export const { teamsLoaded, setSearchQuery, setTeamsSearchPage } = teamsSlice.actions;

export const teamsReducer = teamsSlice.reducer;

export const initialTeamState: TeamState = {
  team: {} as Team,
  members: [] as TeamMember[],
  groups: [] as TeamGroup[],
  searchMemberQuery: '',
};

const teamSlice = createSlice({
  name: 'team',
  initialState: initialTeamState,
  reducers: {
    teamLoaded: (state, action: PayloadAction<Team>): TeamState => {
      return { ...state, team: action.payload };
    },
    teamMembersLoaded: (state, action: PayloadAction<TeamMember[]>): TeamState => {
      return { ...state, members: action.payload };
    },
    setSearchMemberQuery: (state, action: PayloadAction<string>): TeamState => {
      return { ...state, searchMemberQuery: action.payload };
    },
    teamGroupsLoaded: (state, action: PayloadAction<TeamGroup[]>): TeamState => {
      return { ...state, groups: action.payload };
    },
  },
});

export const { teamLoaded, teamGroupsLoaded, teamMembersLoaded, setSearchMemberQuery } = teamSlice.actions;

export const teamReducer = teamSlice.reducer;

export default {
  teams: teamsReducer,
  team: teamReducer,
};

redpajama_set_name: RedPajamaGithub


text:
Support: Language Acquisition: PhD, Carnegie Mellon University
From: Vera Lampley <vl2pandrew.cmu.edu>
Subject: Language Acquisition: PhD, Carnegie Mellon University, USA
Department: Modern Languages
Web Address: https://www.cmu.edu/dietrich/modlang/
Institution/Organization: Carnegie Mellon University
Duties: Research,Teaching
Specialty Areas: Language Acquisition
Required Language(s): Arabic, Standard (arb)
Chinese, Mandarin (cmn)
French (fra)
German (deu)
Italian (ita)
Japanese (jpn)
Russian (rus)
Spanish (spa)
The Department of Modern Languages, at Carnegie Mellon University invites applications for its PhD program in Second Language Acquisition.
The ideal candidate will
- Hold an MA in linguistics, a foreign language, cognitive science or a related field.
- Be proficient in a second language such that the candidate can teach language
courses offered through the department (e.g., Arabic, Chinese, French, German, Italian,
Japanese, Russian, Spanish).
- Have an interest in one (or more) of the program's four major research areas: 1) literacy development in a second language; 2) social dimensions of learning a second language; 3)
instruction and learning of a second language; 4) cognitive aspects of a second language.
Applications must be submitted online and include
- Current GRE scores
- Current TOEFL scores (if applicable)
- Transcripts of undergraduate and previous graduate studies
- Three letters of recommendation
- A statement of research area interest and career goals
- A writing sample
Carnegie Mellon University recognizes the power of a diverse community and encourages applications
from individuals with varied experiences, perspectives, and backgrounds.
Application Deadline: see below
Applications Deadline: 01-Dec-2019
Web Address for Applications: https://apply-dc-mcs.mcs.cmu.edu/apply/?sr=2c2c8534-1c5b-4eb6-9ff5-2e57a29913b1
Vera Lampley
vl2pandrw.cmu.edu
Page Updated: 07-Oct-2019

redpajama_set_name: RedPajamaCommonCrawl


text:
LAOIS GAA - Timahoe speak out as Quigley joins Fingallians
Timahoe GAA club have hit out strongly at "the trend of top players being poached from rural clubs" after losing Laois senior player Brendan Quigley to Dublin club Fingallians last week.
Quigley has taken up a job near the Swords-based club and will become the latest Laois player to throw his lot in with a Dublin club.
While Timahoe signed Quigley's transfer form, they have urged the GAA to address the issue of players leaving their home clubs for bigger outfits in the capital.
"Timahoe GAA is a small rural club," read a statement issued by the club. "And like other clubs of our size, the GAA traditions are an essential element to the fabric of community life. We have a catchment of approximately 170 households and will never be able to compete with the attraction of large urban centre clubs like Fingallians.
"In times where employment opportunities are so difficult to come across throughout the country, these large urban centre clubs also face the reality of having players out of employment.
"While we in Timahoe GAA club have signed Brendan's transfer request, not wanting to stand in the way of preventing a player from earning a livelihood, this trend of top players being poached from rural clubs to the Dublin area needs to be seriously addressed by the GAA hierarchy."
The hard-hitting statement went on to say that the cream of Laois footballers have exited the club scene in the county and this latest transfer comes at a time when Dublin players are blocked from transferring between clubs within their own county.
"The powers that be in the GAA ... need to consider the long term implication that this has on sustaining a viable future for rural clubs," it added.
"To maintain the tradition of rural communities and their GAA clubs, the GAA would be better advised to raise this as a priority on their agenda rather than focusing on fantasies such as winter training bans."
Quigley's move to Fingallians will see the number of Laois players in the 2011 Dublin SFC rise to nine although the presence of John O'Loughlin and Donie Kingston with UCD doesn't prevent them playing with their home clubs.
Parnells had four Laois players on their books last year as Colm Parkinson, Darren Rooney, Colm Begley and Michael Tierney played with them while David Sweeney was with Oliver Plunkett's and Stephen Lawlor was with St Vincent's.
Parkinson has been linked with a move back to Portlaoise but a number of other Laois players have been linked with switches to Dublin.
Fingallians is the home club of current Dublin player Paul Flynn and former player Kieran Duff but they aren't currently one of the stronger senior teams in Dublin having only finished ninth in Division 2 of the league last year. They were also knocked out of the championship at an early stage.
His loss will hit Timahoe hard however as they bid to make an impact on their return to the senior grade following last year's Laois IFC triumph.


text:
Семюель Уенделл Уіллістон (,  — ) — американський палеонтолог і педагог. Автор гіпотези про те, що предки птахів розвинули здатність до польоту поступово за допомогою бігу, а не шляхом перестрибування з однієї гілки дерева на іншу.

Народився у Бостоні, але в ранньому дитинстві з сім'єю переїхав до Канзасу, де закінчив школу, а потім державний аграрний колледж (нині Університет штату Канзас) в 1872 році із ступенем магістра мистецтв. Після закінчення коледжу він поступив в Єльський університет вивчати палеонтологію, з 1874 року брав участь у палеонтологічних розкопках і дослідженнях. У 1890 році він повернувся в Канзас, де став професором геології і анатомії в Канзаському університеті. У 1902 році він відправився в університет Чикаго в якості завідувача кафедрою палеонтології.

Також відомий як ентомолог, що займався вивченням мух, хоча ця його діяльність завжди носила аматорський характер.

Джерела

Бібліографія

Примітки

Палеонтологи США

redpajama_set_name: RedPajamaWikipedia


text:
Q: How to set value of one service from one controller, and update value of another controller with this service I am new in this field and want to write a app, now I meet some problems. Here is a simple version of my code, what I want is the API only show signUp first. After I press signUp and press submit the button shown should be only signout
I think my way is not all right, because after I change the value in service, another controller can't update its value. Could you tell me that?
please use this.logged if possible, thanks!
The process is not necessary to be same to my title. OK if it can implement my function.
https://plnkr.co/edit/1ptaVzmD7EwPZ6dU23gR?p=preview
(function(){
    angular.module('myApp',['myApp.dashboard','myApp.value','myApp.signUp']);
})();

(function(){
    angular.module('myApp.dashboard',[]);
})();

(function(){
    angular.module('myApp.value',[]);
})();

(function(){
    angular.module('myApp.signUp',[]);
})();

(function(){
    'use strict';
    angular.module('myApp.dashboard').controller('mainControl',mainControl);

    mainControl.$inject = ['whichToShow'];
    function mainControl(whichToShow){
        this.logged=whichToShow.getVar();
        alert(this.logged);
    }
})();

(function(){
    'use strict';
    angular.module('myApp.value').factory('whichToShow',function(){
        alert("running2");
        var logged=false;
        return {
            getVar: function(){
                return logged;
            },
            setVar: function(value){
                logged=value;
            }

        };
    });
})();

(function(){
    'use strict';
    angular.module('myApp.signUp').controller('signUpControl',signUpControl);
    signUpControl.$inject = ['whichToShow'];
    function signUpControl(whichToShow){
        alert("haha");
        this.logIn=function(){
            whichToShow.setVar(true);
            alert("running set!");
        };
    };
})();

partial html:

                <button type="button" class="btn" data-toggle="modal" data-target=".signUp">Sign Up</button>

                <button>Sign Out</button>

sigh up

                        <button type="button" class="close" data-dismiss="modal" aria-label="Close">×</button>

                        <form id="signUpForm" name="signUpForm" ng-submit="sc.logIn()">

                                email:
                                <input type="email" name="email">

                            <button class="submit" id="signUpSubmit" type="submit" value="signUp">submit</button>
                        </form>

A: You need watch for the changes on the logged value from the service.
That is all you need to do.

(function() {
  angular.module('myApp', ['myApp.dashboard', 'myApp.value', 'myApp.signUp']);
})();

(function() {
  angular.module('myApp.dashboard', []);
})();

(function() {
  angular.module('myApp.value', []);
})();

(function() {
  angular.module('myApp.signUp', []);
})();

(function() {
  'use strict';
  angular.module('myApp.dashboard').controller('mainControl', mainControl);

  mainControl.$inject = ['$scope', 'whichToShow'];

  function mainControl($scope, whichToShow) {
    $scope.$watch(() => whichToShow.getVar(), (newValue, oldValue) => this.logged = newValue)
  }
})();

(function() {
  'use strict';
  angular.module('myApp.value').factory('whichToShow', function() {

    var logged = false;
    var service = {};

    return {
      getVar: function() {
        return logged;
      },
      setVar: function(value) {
        logged = value;
      }

    }
  });
})();

(function() {
  'use strict';
  angular.module('myApp.signUp').controller('signUpControl', signUpControl);
  signUpControl.$inject = ['whichToShow'];

  function signUpControl(whichToShow) {
    this.logIn = function() {
      whichToShow.setVar(true);
    };
  };
})();

<link href="https://cdnjs.cloudflare.com/ajax/libs/twitter-bootstrap/3.3.7/css/bootstrap.min.css" rel="stylesheet" />

        <button type="button" class="btn" data-toggle="modal" data-target=".signUp">Sign Up</button>

        <button>Sign Out</button>

sigh up

            <button type="button" class="close" data-dismiss="modal" aria-label="Close">×</button>

            <form id="signUpForm" name="signUpForm" ng-submit="sc.logIn()">

                email:
                <input type="email" name="email">

              <button class="submit" id="signUpSubmit" type="submit" value="signUp">submit</button>
            </form>

Working solution on Codepen

A: Basically you are setting values in factory object after user clicks on submit but that doesn't reflect in UI as you have not updated the scope object this.logged.So to tell main controller fromsign up controller that change the this.logged $scope value we can use $emit or $broadcast
Apart from $watch approach you can even use $broadcast to achieve this.
Working DEMO
Just add this below code in your JS file controllers
signUpControl
(function(){
    'use strict';
    angular.module('myApp.signUp').controller('signUpControl',signUpControl);
    signUpControl.$inject = ['whichToShow','$rootScope'];
    function signUpControl(whichToShow,$rootScope){
        alert("haha");
        this.logIn=function(){
            whichToShow.setVar(true);
            $rootScope.$broadcast('login');//broadcasting that user has logged in
            //alert("running set!");
        };
    };
})

mainControl
(function(){
    'use strict';
    angular.module('myApp.dashboard').controller('mainControl',mainControl);

    mainControl.$inject = ['whichToShow','$rootScope'];

    function mainControl(whichToShow,$rootScope){
        var mc = this;
        mc.main ={};
        mc.main.logged=whichToShow.getVar();
        alert(mc.main.logged);

       // below code will listen to the broadcast and do the necessary process..
        $rootScope.$on('login',function(event,args){
                mc.main.logged=whichToShow.getVar();
        });
    }
})

A: You are still trying to set the value of primitives here, rather than object properties.  In JavaScript, primitives are passed byValue, not byReference, so whichToShow.getVar(); is returning true or false rather than returning a reference to logged.  Therefore, you won't see changes to logged unless you call .getVar() again, to get the new value.  This is why most answers you have seen so far have had some form of $watch, $broadcast, or similar, to alert your mc that it should ask again for the logged variable's current value.
If you want to avoid using a $watch, you should use an object instead of a primitive.  by using an object, you can pass the object byReference, which will allow angular to see the changes to the properties wherever there is a reference set.
In your factory, return an object:
(function() {
  'use strict';
  angular.module('myApp.value').factory('whichToShow', function() {
    alert("running2");
    var status = {
      logged: false
    };
    var logged = false;
    return {
      getVar: function() {
        return status;
      },
      setVar: function(value) {
        status.logged = value;
      }

    };
  });
})();

In mainControl, use a reference to this object:
(function() {
  'use strict';
  angular.module('myApp.value').factory('whichToShow', function() {
    alert("running2");
    var status = {
      logged: false
    };
    return {
      getVar: function() {
        return status;
      },
      setVar: function(value) {
        status.logged = value;
      }

    };
  });
})();

And finally, use the object property in the HTML:

...

...

https://plnkr.co/edit/Pindt2LYxDxyk8C5Axp1?p=preview
I might even go one step further and just return the object directly by the service, and skip the getVar and setVar functions.

A: You can put some variable globally or in your rootcontroller,lets says isLoggedIn
now with one service you can set this variable on signingIn
and use it like this
{
}Sign In
Sign Out

redpajama_set_name: RedPajamaStackExchange


text:
The Rose and Crown is a well-known local landmark that has been owned by the same family since 1985. Rebuilt in the early 1930's at 199 Stoke Newington Church St, right across the road from its original location, the Rose and Crown was designed for Truman's Brewery by the highly respected pub architect A.E. Sewell, and now lies adjacent to the 13th century St. Mary's Church, and proudly overlooking Clissold Park and fashionable Stoke Newington Church Street, with its eclectic mix of boho shops, cafes, bars and restaurants.
from £198 1-4 person
Our Suite is spacious, beautifully presented and comes with a flat screen TV, newly fitted Air Con, WiFi and en-suite facilities.
from £96 1-2 person
Single | Our Single room is spacious, beautifully presented and comes with a flat screen TV, newly fitted Air Con, WiFi and en-suite facilities.
Double; Our Standard Double room is spacious, beautifully presented and comes with a flat screen TV, newly fitted Air Con, WiFi and en-suite facilities.
Twin: Our Standard Twin room is spacious, beautifully presented and comes with a flat screen TV, newly fitted Air Con, WiFi and en-suite facilities.
Superior Double; Our Superior Double room is spacious, beautifully presented and comes with a flat screen TV, newly fitted Air Con, WiFi and en-suite facilities.
Junior Deluxe
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Deluxe; Our Deluxe room is spacious, beautifully presented and comes with a flat screen TV, newly fitted Air Con, WiFi and en-suite facilities.
Need Something?
For reservation and questions.


text:
State: Gastonia assisted living center hit hard by COVID-19
Adam Orr
aorr@shj.com
Over the past month, one Gastonia assisted living facility has been hit hard by COVID-19.
According to data released late last week by North Carolina health officials, Brian Center Health and Rehabilitation in Gastonia has recorded a cumulative total of 111 confirmed cases of COVID-19, and 10 virus related deaths, including one staff worker.
That death toll is higher than all but 10 other assisted living facilities statewide, according to data released Friday by the North Carolina Department of Health and Human Services.
The facility's website is currently reporting 44 active cases of COVID-19.
Outbreaks of COVID-19 were first reported in mid-July in multiple congregate care facilities across Gaston County.
That includes Alexandria Place, which has reported a total of five confirmed cases, Carolina Care in Cherryville, which has reported six total cases, Peak Resources in Cherryville which has recorded 13 total cases and two deaths, and Stanley Total Living Center with five total cases.
Gaston County Public Health Director Steve Eaton said Tuesday that cases and deaths at Brian Center reflect an ongoing, month-long outbreak.
"Those totals have not come overnight," Eaton said. "It was one of our first congregate living facility outbreaks and they have been working hard, taking every precaution that they can."
Last month officials with Brian Center's parent company, SavaSeniorCare Consulting, described heightened precautions, including providing appropriate protective equipment, screening the health of staff before every shift, and restricting visitation to the center.
Eaton said the facility has tested each of its employees and clients and said the majority of positive cases were asymptomatic and have recovered.
"(Brian Center) has been great to work with and they've been providing updates to us every single day and they've also done a great job communicating what's happening there to families," Eaton said.
"It's unfortunate but this is what we're seeing across the nation," he continued. "When COVID gets in, especially among vulnerable populations, this is what it looks like. It spreads easily and vulnerable populations are hit hard."
Gaston County health officials reported 1,341 active cases of COVID-19 on Monday, with 46 hospitalizations. The virus has claimed a total of 52 lives to date.
Eaton said Tuesday there is reason for cautious optimism. Between May 2 and July 11, the percentage of positive tests per week increased from less than 5% to nearly 13.5%.
Since then, county officials have reported that metric as falling to 11.9% on Aug. 1.
The total number of confirmed cases per week has also shown signs of falling. For the week ending July 11, officials reported 438 confirmed cases. That fell to 362 confirmed cases for the week ending on July 18, 360 cases on July 25, and 300 confirmed cases on Aug. 1.
"We've started to see the positive impacts of mitigation efforts that the community is taking seriously, wearing masks, washing hands and social distancing," Eaton said
"The efforts are working," he continued, " and it has started to level off. We're still at a high percentage, 11.9% and we want to get back down below 5%, but we're showing signs of heading in the right direction."
Reach Adam Orr at 704-869-1828 or aorr@gastongazette.com


text:
Immaculate Conception High School
A Message from our Head of School
A Message from our Associate Head of School - Dean of Student Life
About ICHS
Greetings from the Enrollment Office
Visit ICHS
ICHS Flip Book
Message from the Dean of Academics
Collegiate Academy Program
ICHS Email Login
PlusPortals Login
ICHS Gala
Strategic Plan / Executive Summary
The Fund for ICHS
Adopt-A-Scholar
The Spirit Magazine
ICHS Reunions
Taste of...
Alumnae Directory
Donate PlusPortals Login ICHS Email Login
ICHS Presents... Shrek the Musical
Based on the Oscar-winning DreamWorks Animation film,Shrek The Musical is a Tony Award-winning fairy tale adventure that brings all the beloved characters you know from the film to life on stage and proves there's more to the story than meets the ears. "Once upon a time, there was a little ogre named Shrek...." And thus begins the tale of an unlikely hero who finds himself on a life-changing journey alongside a wisecracking Donkey and a feisty princess who resists her rescue. Throw in a short-tempered bad guy, a cookie with an attitude and over a dozen other fairy tale misfits, and you've got the kind of mess that calls for a real hero. Luckily, there's one on hand... and his name is Shrek. Irreverently fun for the whole family,Shrek proves that beauty is truly in the eye of the ogre. The show runs April 12th - 14th. Tickets are selling fast, so purchase yours today!
http://ichs.eventbrite.com
Immaculate Conception High School 258 S. Main St., Lodi, NJ 07644


**Article proposed must cover artists or other culture-related topics lying outside mainstream coverage.We would like articles to follow CUE's mission of providing a platform for new experiences and encounters with the arts.
Documents must be pdf format and titled beginning with writer's last name, then type of document (i.e. Brown_Sample).


Apache Geode Native is an Apache Geode client that has both C++ and .NET interfaces. Geode Native is set to make its first release as part of the Apache Geode 1.8 release later this year. Last week, I did a getting started guide for the C++ interface, now it's time for some .NET.
The video starts off by setting up a Windows Developer VM based on the Microsoft provided image.
Once you have the image up and running, open Powershell as Admin and install Chocolately.
Inside the Geode Native repo, run install-dependencies.ps1 to install all build dependencies.
Set Apache Geode Environment Variable. This let's the system know where to find the Apache Geode Server.
I like to put everthing in my workspace, so C:\workspace\geode-native-install is what I'm going to be using for the rest of the post.
Copy the examples directory to workspace using ths below Powershell command.
Next, we will use CMake to configure and build the examples.
In C:\workspace\examples\build, open the generated solution file in Visual Studio and build the example you are interested in.
Back in the examples directory, run the startserver.ps1 powershell script to start the Apache Geode server.
Lastly, use Visual Studio to run the built example. Don't forget to run stopserver.ps1.
Hit me up on Twitter or in the comments below if you have any questions.


text:
Harville is a commune in Meuse, France.

Harville may also refer to:

 Chad Harville (born 1976), U.S. baseball player
 Louis-Auguste Juvénal des Ursins d'Harville, Count of Harville (1749–1815) General of France
 Captain Harville, a fictional character from the 1817 Jane Austen novel Persuasion

See also
 Harville Hendrix (born 1935) self-help book author


text:
Individual patient data meta-analysis on continued use of glucocorticoids after their initiation as bridging therapy in patients with rheumatoid arthritis
http://orcid.org/0000-0001-8036-950XLotte van Ouwerkerk1,
http://orcid.org/0000-0002-6969-283XMaarten Boers2,3,
http://orcid.org/0000-0002-7429-8482Paul Emery4,
http://orcid.org/0000-0001-6628-6222Pascal HP de Jong5,
http://orcid.org/0000-0002-0577-6620Robert BM Landewé3,6,
http://orcid.org/0000-0002-6885-3953Willem Lems3,
Josef S Smolen7,
http://orcid.org/0000-0002-0340-3580Patrick Verschueren8,
http://orcid.org/0000-0001-7033-7520Tom WJ Huizinga1,
Cornelia F Allaart1,
http://orcid.org/0000-0002-7136-5248Sytske Anne Bergstra1
1Department of Rheumatology, Leiden Universitair Medisch Centrum, Leiden, The Netherlands
2Epidemiology & Data Science, Amsterdam UMC Locatie VUmc, Amsterdam, The Netherlands
3Rheumatology and Immunology Center, Amsterdam UMC, Amsterdam, The Netherlands
4Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
5Department of Rheumatology, Erasmus Medical Center, Rotterdam, The Netherlands
6Department of Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, The Netherlands
7Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Wien, Austria
8Division of Rheumatology, KU Leuven University Hospitals Leuven, Leuven, Belgium
Correspondence to Dr Lotte van Ouwerkerk, Rheumatology, Leiden Universitair Medisch Centrum, Leiden, 2333, The Netherlands; l.van_ouwerkerk{at}lumc.nl
Objectives To investigate whether patients with rheumatoid arthritis (RA) can discontinue glucocorticoids (GC) after GC 'bridging' in the initial treatment step and to identify factors that may affect this.
Methods Data from 7 clinical trial arms (with 1653 patients) that included a GC bridging schedule, previously identified in a systematic literature search, were combined in an individual patient data meta-analysis. Outcomes were GC use (yes/no) at predefined time points (1/3/6/12/18 months after bridging had ended), cumulative GC dose and continuous (≥3 months) GC use after bridging had ended. Age, sex, ACPA status, initial GC dose, duration of bridging schedule, oral versus parenteral GC administration and initial co-treatment were univariably tested with each outcome.
Results The probability of using GC 1 month after bridging therapy had ended was 0.18, decreasing to 0.07 from 6 until 18 months after bridging had ended. The probability of continuous GC use after bridging had ended was 0.18 at 1 year and 0.30 at 2 years of follow-up. In oral GC bridging studies only, the probabilities of later and continuous GC use and the cumulative GC doses were higher compared to the combined analyses with also parenteral GC bridging studies included. A higher initial dose and a longer GC bridging schedule were associated with higher cumulative GC doses and more patients on GC at 18 months after bridging had ended.
Conclusions Based on these RA clinical trial arms with an initial GC bridging schedule, the probability of subsequent ongoing GC use following bridging is low.
Data are available on reasonable request.
Glucocorticoids (GC) are commonly used as bridging therapy in patients with rheumatoid arthritis to rapidly suppress inflammation and relieve symptoms, in the period before slower-acting conventional synthetic disease modifying antirheumatic drugs (such as methotrexate) exert their effect.
There are concerns that patients cannot discontinue GC after the intended bridging time and that continued GC use may cause (serious) adverse events.
So far, success rates of GC discontinuation after bridging therapy have only rarely been reported, Also, the factors influencing successful discontinuation are unknown.
This is the first study to combine individual patient data from clinical trial arms where patients with rheumatoid arthritis were treated with protocolised GC bridging schedules.
In these patients, the probability for continued GC use after bridging was found to be low, further decreasing over time.
A shorter oral bridging schedule and a lower initial dose were associated with lower cumulative GC doses and less patients on GC at 18 months after bridging.
We conclude that most patients with rheumatoid arthritis who start a GC bridging schedule to suppress inflammation rapidly, successfully discontinue GC.
This directly addresses the concern that patients cannot stop GC after bridging.
It remains to be determined if these results can be copied in daily practice, which may deviate from the protocolised treatment in the clinical trials available for this study, requiring to taper and stop GC when started as bridging therapy.
Glucocorticoids (GC) are often part of the initial treatment of early rheumatoid arthritis (RA).1 2 Before slower-acting conventional synthetic disease modifying antirheumatic drugs (csDMARDs) are effective, GC are used as 'bridging' therapy as they rapidly suppress inflammation and symptoms and prevent radiographic damage progression.3–5 Because long-term use of GC has been associated with serious adverse effects,6–9 the EULAR 2019 recommendations for the management of RA suggest to taper and stop GC as quickly as possible, preferably within 3 months after initiation.10 The American College of Rheumatology (ACR) 2021 guidelines for the treatment of RA include a conditional recommendation to avoid GC and only use a csDMARD as initial treatment, based on concerns that patients will not be able to subsequently stop GC.11
In our previous systematic literature review (SLR) on continued use of GC after initial 'bridging' therapy in patients with RA was shown that there is limited information available on this topic. We identified 10 clinical trials with at least one trial arm applying GC bridging therapy,12 long-term GC use was not among the main outcomes in these trials and details about continued GC use were rarely reported. Due to the insufficient reported data, an aggregated meta-analysis could not be performed on all outcomes. Therefore, in the current study, an individual patient data (IPD) meta-analysis was performed on patients in GC bridging arms of the clinical trials that were identified in the aforementioned SLR.12 With these data, we aimed to establish how often patients continue to use GC after initial GC bridging and we investigated factors that may affect continuation of GC use after bridging.
To acquire details on GC use following bridging therapy in the trials identified in the SLR, the 10 senior researchers of the trials were approached to contribute anonymised individual-level patient data for an IPD meta-analysis. All were invited to participate in an advisory board, composed the statistical analysis plan (unpublished) for an IPD meta-analysis and contributed original data for each patient in a study arm including initial GC bridging. The provided detailed data on GC use over time plus patient characteristics allowed us to study multiple outcome measures and indicators which were not reported earlier on. All analyses were conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of IPD (PRISMA-IPD) guidelines and the Cochrane handbook.13 14 The advisory board was consulted in the SLR phase to discuss if potentially suitable trials existed that were not identified by the SLR, they also clarified trial eligibility and integrity and provided clarity regarding data uncertainties during the analysing process (ie, clarification of missing data in the included trials). Study selection, search strategy and risk of bias of the included trials were described and assessed in the SLR and can be found in those supplementary files.12
Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Outcome measures and indicators
In the workplan standardised outcome definitions were defined and conversion of GC dose into an equivalent oral prednisone dose (mg) was agreed. Primary outcomes were: GC status (yes/no still using) at predefined time points after bridging had ended, continuous GC use defined as use for ≥3 months at any time after initial bridging (yes/no) and cumulative GC dose (including the bridging schedule). Secondary outcomes were: occurrence of a disease activity flare (yes/no, flare defined as: Disease Activity Score based on 28 Joints (DAS28) increase >1.2 or ∆DAS28 >0.6 if DAS28 at previous visit was ≥3.2) after stopping GC bridging and after GC were stopped following initial restart ('second flare'), and intensification of DMARD treatment in case of a flare following stopping GC. These outcomes were assessed for the studies separately and also combined with a one-stage IPD meta-analysis. Age, sex, anti-citrullinated protein antibodies (ACPA) status, oral or parenteral GC bridging, initial GC dose, duration of GC bridging schedule and the initial csDMARD co-treatment were tested for associations with both the primary and secondary outcomes.
IPD from the included study arms (in effect, separate cohorts of patients treated with GC bridging) were analysed with one stage model mixed effects regression analyses with study arm as random effect to account for differences between study arms. For dichotomous outcomes, this was based on a mixed effects logistic regression model, resulting in odds which were recalculated into probabilities. Such a model can provide the odds that patients who started GC bridging, continue or restart GC (at several time points) after bridging had ended, taking into account differences between the included study arms. Continuous outcomes were combined with mixed effects linear regression models resulting as betas. These models can provide cumulative GC doses at certain time points, considering differences between studies. Subsequently, in separate univariable models, age, sex, ACPA status, oral or parenteral GC bridging, initial co-treatment, initial GC dose and duration of bridging schedule were added as independent variables to the fixed effects parts of the model, to investigate whether the outcomes varied by study characteristics. For all outcomes, 95% CIs are presented as an indication of between-study variation. Sensitivity analyses were performed after excluding studies with parenteral administration of GC (the IDEA study and arm 1 of the tREACH study). Given the number of analyses performed in this study, a correction for multiple testing was made with the method of Benjamini-Hochberg taking into account all models performed.15 16 Statistical analyses were performed with Stata V.16.1.
The senior researchers of the 10 clinical trials previously identified by the SLR were approached to participate in this study.12 One declined because the requested data were not yet published for that individual trial.17 Two others did not respond despite repeated requests.18 19 Combining the data of the 7 available trials resulted in 1653 patients with newly diagnosed RA (1987 or 2010 classification criteria) or undifferentiated arthritis (IMPROVED) or a high-risk profile for persistent arthritis by the Visser risk model20 (tREACH) treated with GC bridging therapy (oral, intramuscular or intravenous administration) as part of the initial treatment.21–27 The baseline characteristics collected for the purpose of this study are presented in table 1. The mean DAS28 at baseline ranged from 4.8 (tREACH) to 6.5 (COBRA). The majority of the patients in all studies were female, ACPA and/or rheumatoid factor positive and around 50 years of age.
Baseline characteristics of the participants with GC bridging therapy from the included trials (n=7)
In total, 13 study arms from the 7 trials started with GC bridging therapy. Two study arms (IDEA arm 1 and tREACH arm 1) used single-dose intravenous (IDEA) or intramuscular GC (tREACH), the other trial arms started bridging therapy with oral GC, initially with a high dose (30 or 60 mg/day) and rapidly tapered to 5 or 7.5 mg/day as maintenance dose for a fixed duration. An extensive description of the bridging schedules is shown in table 2.
Overview of clinical trials*
Primary outcomes
Use of GC at various time points after bridging therapy ended, mean cumulative GC dose at 6 and 12 months from baseline (ie, bridging included) and continuous use of GC for ≥3 months at any point after end of bridging therapy (yes/no) are reported for all seven studies separately, and by treatment arm, as shown in table 3. The proportions of patients using GC decreased over time or remained low in all trials except for IMPROVED, where GC restart (in arm 'early remission', if remission was lost) and/or 4 months continuation (arm 1) was required per protocol. The mean cumulative dose was highest in the BeSt study and arm 1 of the COBRA light study whereas in all arms of the tREACH study and the IDEA study it was relatively low. Percentage of patients using continuous GC (for ≥3 months) was higher in the BeSt study, COBRA light study, IMPROVED early remission group and IMPROVED arm 1 than in IMPROVED arm 2, the tREACH, CareRA and the IDEA studies.
Primary and secondary outcomes in patients starting with GC in the included trials
In table 4, the pooled results for the primary outcomes are shown. The probability of ongoing use or restart of GC 1 month after GC bridging ended is 0.18, decreasing to 0.07 at 6, 12 and 18 months after bridging ended. The probability of continuous GC use for ≥3 months after bridging was 0.18 at 12 months from baseline and 0.30 at 24 months from baseline. In the oral GC bridging studies (ie, excluding IDEA and arm 1 of the tREACH study), the probabilities of GC use following bridging were higher (0.30 at 1 month and 0.14 at 18 months after GC bridging ended), and to a lesser extent also the probabilities for continuous GC use ≥3 months were higher (table 4). The mean cumulative doses were also higher in this sensitivity analysis without parenteral GC bridging.
IPD meta-analysis results of GC use after the initial GC bridging schedule in patients starting with GC bridging
Based on the combined data of the seven studies, the probability of a flare was low, both after stopping the initial GC bridging therapy (0.11) and after stopping a second course of GC (0.07) (table 5). In the models including only oral GC use these flare probabilities were higher (0.13 and 0.16, respectively). Also, the probabilities of starting an extra DMARD due to a flare after stopping GC bridging are low, 0.11 in all studies and 0.12 in the studies with oral GC bridging only. The secondary outcomes for each study separately are displayed in table 3. Flares, defined as a DAS28 increase of >1.2 or a DAS28 increase of >0.6 with the DAS28 on the previous visit being ≥3.2, were rare, except in the COBRA study, where in almost 50% of patients a flare occurred after the first attempt to stop GC bridging, and in the BeSt and CareRA studies, where in some arms up to 20% of patients had a flare. Across the trials, flares appeared to occur less often after a second course of GC was stopped. However, percentages may have been affected by small numbers. Compared with the other studies, a higher proportion of patients started a new DMARD after a flare following stop of GC bridging therapy in arm 1 of the IMPROVED study and arms 2 and 3 of the tREACH study (all by study protocol design).
Secondary outcomes in patients starting with GC bridging (n=1653)
Associations with bridging schedule and patient characteristics
Oral GC bridging (compared with parenteral bridging) was significantly associated with more patients on GC at all assessments following bridging therapy, before multiple testing correction. The cumulative GC dose was higher for oral than for parenteral GC bridging, with significance reached only at 12 months (table 6) as more studies provided data for this time point compared with 18 months. Due to limited variation in the included groups and thereby collinearity, not all analyses provided results and those without results were therefore 'omitted'. In online supplemental table 1, the number of patients per analysis is depicted.
Associations of several indicators of patient characteristics and bridging schedules with each outcome measure
A longer duration of the bridging schedule in the studies with oral GC bridging only, was associated with more patients on GC following bridging at 3 and 18 months and a higher mean cumulative GC dose (all significant after correction for multiple testing) (table 7). At 6 months, this translates for instance to an increase in the mean cumulative dose of 76 mg (95% CI 46 to 105) with each additional week of GC use in the GC bridging therapy schedule. In the primary analysis, initial GC dose was not related to any of the outcomes (table 6). However, in the studies with oral GC bridging only, a higher initial oral GC dose was associated with significantly more GC use at 12 and 18 months and a higher mean cumulative dose (table 7). At 6 months, this translates for instance to an increase in the mean cumulative dose of 41 mg (95% CI 30 to 53) with each milligram increase in initial GC dose. A higher initial oral GC dose and a longer duration of the bridging schedule were both also associated with higher flare rates after discontinuation of GC bridging therapy (table 7). Neither initial co-treatment with multiple csDMARDs, nor age, gender or APCA status were associated with the primary or secondary outcomes (table 6).
Associations in database without parenteral GC bridging with primary (upper 3) and secondary (bottom 3) outcomes
This novel study combining IPD from trial-based cohorts showed that most patients with RA treated with initial bridging successfully discontinued GC. Additional analyses suggested that lower dosing and shorter schedules were associated with more successful discontinuation.
In both the first EULAR recommendations (2010) as well as the first ACR guidelines (1996) for treatment of RA, GC were considered part of the initial treatment because of their rapid efficacy in suppressing disease activity where a treatment gap exists as csDMARDs are more slow-acting.28 29 However, there have always been concerns about the adverse events related to long-term GC use, and therefore it has been stated in every recommendation or guideline since, to taper GC as rapidly as clinically feasible. Unfortunately, we found that published data on the successes of tapering GC after their use as bridging therapy as part of the initial treatment step in patients with RA are scarce.12 The majority of the clinical trials which used GC bridging therapy focused on presenting data on its rapid efficacy and early safety. We presume that GC use beyond a short course of bridging therapy is triggered by a disease activity relapse after GC are tapered or stopped. This was investigated in the BeSt study and the IMPROVED study, which used GC bridging therapy combined with respectively two and one csDMARD as first treatment step.30 It was found that 40% of the patients experienced a disease activity flare following GC discontinuation 3–4 months after the start of GC bridging therapy, despite continued use of the csDMARD(s). In the BeSt and IMPROVED studies, other treatments were required to avoid restart of GC. An effort to identify predictors of successful discontinuation of GC bridging showed that a lower DAS at both baseline and stop visit and male gender were associated with more successful GC discontinuation but in general both were poor predictors.30 In the current univariable analysis, we did not find an association between sex and GC discontinuation after bridging.
All trials in this analysis used a treatment protocol with fixed rules for GC discontinuation and with alternative treatment steps in case of a disease activity flare, either restarting GC or switching to other DMARDs. In arm 2 of the IMPROVED study, for instance, in case of a flare, restart of GC was prohibited and a switch to a biologic DMARD was required, whereas in arm 1, GC had to be restarted while at the same time sulfasalazine (SSZ) and hydroxychloroquine (HCQ) were added to methotrexate (MTX). In CareRA, patients in the COBRA slim arm received leflunomide on top of MTX in case of insufficient response or a flare, whether this was after stopping GC or not. Also an intramuscular injection of GC or temporary oral GC as bridging was allowed in case of flares after the induction period. The protocolised treatment in the trials may have resulted in more GC discontinuation than in daily practice, where fixed treatment steps and alternative treatments such as biologic DMARD may not always be available. Patients included in trials may differ from patients who were not included in trials or from patients in daily practice, as patients in trials need to fulfil inclusion and exclusion criteria and are willing to participate in a protocol-driven study. The inclusion and exclusion criteria of the studies selected in our analyses resulted in a selection of patients with early RA, who were DMARD naïve, had active disease at the moment of inclusion and limited comorbidities. One observational study has compared GC use over time in 19 patients who received initial double csDMARD therapy with GC bridging, and 52 who started on MTX monotherapy. Subsequent treatment steps, including tapering and drug discontinuation, were protocolised, aimed at low disease activity and GC discontinuation after initial GC bridging therapy.31 The initial GC bridging patients did better over time, had fewer DMARD changes and there was a trend for less GC use in the second year, compared with the initial monotherapy patients.
In our previous SLR and meta-analysis on this subject only information from the publications about the trials instead of raw data were used, therefore we could only focus on two outcomes: GC use at 12 months and GC use at 24 months. The information on these outcomes were available from 4 and 2 trials, respectively, despite the extensive number of publications which are available from the included trials.12 In this IPD analysis, we were able to look into GC use after bridging in more detail. A limitation of using combined data of several trials remains the heterogeneity that exists between the trials, in duration of bridging schedules and concomitant therapy. A sensitivity analysis in only-oral-GC-bridging trials was therefore conducted, showing slightly greater probabilities than in the analysis including also parenteral administration of bridging therapy. Not all studies provided raw data on GC use after 12 months of follow-up, which caused a reduction in patient number for analyses at subsequent time points. Also, the bridging schedules of almost all included trials except for the tREACH trial, were longer than the recommended 3 months (in both EULAR recommendations and ACR guidelines), which limits the generalisability to daily practice. However, in daily practice it may be more difficult to taper and stop GC bridging within these recommended 3 months as protocolised tapering rules are lacking. Furthermore, we did not receive data from three eligible trials.17–19 The study by Hua et al was a single-centre randomised double-blind clinical trial. They compared MTX combined with HCQ and GC (started at 10 mg for 3 months, then 5 mg for 2 months and stopped thereafter) with MTX combined with HCQ and placebo. The NORD-STAR trial, a randomised open-label (but blind assessor) clinical trial compared four study arms. Each arm started with MTX, combined with either GC orally (started at 20 mg, tapered to 5 mg in 9 weeks and stopped at week 36), HCQ plus SSZ and intra-articular GC, certolizumab pegol, abatacept or tocilizumab. The ARCTIC trial was a randomised controlled strategy trial, primarily focused on the comparison of two monitoring strategies within a treat-to-target design, namely ultrasound versus a conventional approach. All patients started with MTX plus GC (15 mg at start and tapered in 7 weeks). Since the bridging schedules of these three studies all used lower starting doses compared with the arms included in this analysis and two of them also stopped earlier than most of the included trials, it could have influenced the results if they were involved in this IPD meta-analysis. In the SLR, we did not search trial registries to identify unpublished trials and therefore publication bias might have played a role in our study selection.
To conclude, this IPD analysis showed that in the setting of clinical trials with fixed treatment protocols, the chances of long-term GC use after bridging therapy are low and decreasing over time. A shorter bridging schedule and lower initial GC dose decrease the chance of GC use after bridging has ended.
All trials were approved by the medical ethics committees and all data were collected after patients had given informed consent.
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. Daily practice effectiveness of a step-down treatment in comparison with a tight step-up for early rheumatoid arthritis. Rheumatology 2008;47:59–64.doi:10.1093/rheumatology/kem288pmid:http://www.ncbi.nlm.nih.gov/pubmed/18039681
Handling editor Kimme L Hyrich
Contributors All authors contributed to the analysis plan. MB, PHPdJ, WL, PV and CFA have provided the data. SAB, CFA and LvO analysed the data and drafted the manuscript. All authors revised the drafted manuscript. SAB, CFA and LvO are responsible for the overall content as guarantor (accepting full responsibility for the finished work and the conduct of the study, had access to the data, and controlled the decision to publish).
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests LvO, MB, PHPdJ, RBML, JSS and TWJH declare no competing interests. PV: holds the Pfizer Chair Early Rheumatoid Arthritis Management at KU Leuven and received consultancy and/or speaker honoraria from AbbVie, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Roularta and Sidekick Health within the last 24 months. SAB: received an ASPIRE grant from Pfizer. CFA: received study grants for BeSt and IMPROVED from Centocor (now Janssen) and AbbVie, respectively. PE: provided expert advice to AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Janssen, MSD, Lilly, Novartis, Pfizer, Roche, Samsung. And clinical trials: AbbVie, BMS, Lilly, Novartis, Pfizer, Roche, Samsung. WL received study grants from Pfizer, and consultancy speaker fees from Eli Lilly, Pfizer, Amgen, Galapagos and UCB.


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Our Little Earth – December 21, 2007
Lots happening in South Korea
South Korea has been a very busy country these last couple of weeks. First, on Dec 7th, there was a huge
oil spill (10,000 tons – that is more than 3 Olympic-size swimming pools) near its coast. The spill was caused when the oil tanker was hit by a drifting barge carrying a crane. There has been a huge effort to clean up this oil – over 40,000 people have helped!
On Dec 10th, history was made when the first regular rail service started between North and South Korea after
more than 50 years! The cargo trains will make a round-trip run every week day. North and South Korea were created in 1948 when Korea was split into two countries. Soon after the split, the two countries got into a war with each other and have barely talked to each other since. So a regular train service is a huge step towards becoming friends again.
Lastly, on December 19th, South Koreans elected a new president for their country – Lee Myung-bak. Lee will take over the presidency in February, 2008 (until then, he will be known as the President-elect). For many years, Lee ran one of the companies of the Hyundai Group, one of South Korea's largest corporations. Hyundai is the world's largest ship builder and one of the largest auto makers.
Russia's President Putin is "Person of the Year"
Time magazine named Russian President Vladimir Putin its "Person of the Year" for 2007. Putin took over as President of Russia in 2000, replacing Boris Yeltsin. He has helped Russia's economy recover steadily and has brought Russia back as a prominent world power.
The Person of the Year award by Time Magazine has been awarded since 1927. The award is given to individuals (or sometimes groups of people or even things) that significantly influence the world, for better or worse. There have been some interesting winners in the past that were not individuals. Last year, the Person of the Year was "You", as in all of us. This was to recognize the impact that user-generated information has caused because of the internet. In 1982, the award went to the computer for the impact it was having on us. In 1988, planet Earth was the winner because our environment and its protection became a significant subject.
One of the runners-up for the award this year is someone you all know – J. K. Rowling, who has touched a large portion of the human race with Harry Potter and other figments of her imagination!
You can browse through all the winners of this award at : http://www.time.com/time/2007/poy/.
W00t for W00t!
Merriam-Webster, one of the world's largest publisher of dictionaries, has announced its choice of the word of 2007 – "w00t". That's spelt with two zeroes! W00t is a word that has been used by people playing online games and by people in online chat rooms. The definition for w00t given by Merriam Webster is "expressing joy".
The origins of w00t are not clear. Some attribute it to the phrase "We Owned the Other Team", used by online gamers. Others say that it comes from a combination of the words "wow" and "loot". W00t belongs to a language called "leet" that has been created by internet users and has become part of the internet culture. It combines alphabet and numbers to form words. For example, "3" represents "E", "0" represents "O", "4 represents "A", and 7 represents "T". This is why "leet" itself is also referred to as "l337" and "l33t".
W00t is the word of the year but that doesn't make it an official word in the Merriam-Webster dictionary just yet. For a word to become official, it needs to be used often, over a period of time, by several communities of people, and with a consistent meaning. "Blog" was the word of the year in 2004, and has since become an official word in the Merriam-Webster dictionary.
By the way, the American version of the Oxford English Dictionary chose "locavore" as its word of 2007. The definition given to locavore is "someone who only eats locally grown food"!
SOMETHING FAMOUS
Let's play Taekwondo! Taekwondo is a form of martial arts that originates from Korea. The word Taekwondo is often translated as 'the way of hand and foot'. It is known for its fast, high, and spinning kicks.
Taekwondo's origins are in ancient martial arts practiced in Korea over 2000 years ago. Various forms of this sport have been practiced over the centuries. When the Japanese occupied Korea, they had forbidden the practice of any martial arts, but it was still done in secret. After the Japanese left in the 1940s, the martial arts started thriving again, but there were several different forms being followed. An army general by the name of General Choi helped unify and standardize these forms in 1955 and gave it the name Taekwondo. So for a 2000 year old art, Taekwondo has a very young name!
Russia is home to the longest continuous rail line in a country! The Trans-Siberian railroad takes you from Moscow in the West to Vladivostok to the East – a journey of almost six thousand miles (about ten thousand kilometers). That is about the distance from San Francisco to Paris! This ride takes 7 days. There are two longer train rides that both use the Trans-Siberian railroad – one starts in the Ukraine, and the other goes all the way to North Korea. Both of these roughly take 9 days each!
The world's thinnest cellular phone is the Samsung Ultra Edition II – just 0.2 in (5.9mm) thick. The handset has a 3-megapixel camera and 11 hours of music play time. Samsung is one of South Korea's largest corporations.
FUNNY BONE
An English teacher was lecturing to his class one day. "In English," he said, "a double negative forms a positive. In some languages, though, such as Russian, a double negative is still a negative. However, there is no language where a double positive can form a negative."
A voice from the back of the room piped up, "Yeah, right."
Three musicians travel together to New York. When they arrive in the city, they go to the hotel to check in. They plan to share the same room. The desk clerk quotes a rate of $30 for the night. They pay him and go to their room.
But, then the clerk remembers there is a weekend special room rate of $25 a night. Trying to correct the situation, he gives five one dollar bills to the bellboy to take to the guests' room. On the way there, the bellboy says to himself, "Three people can't divide five dollars evenly amongst them." So he takes two dollars for himself and when he gets to the room, he gives each musician a one dollar refund.
So now each of the three musicians paid nine dollars and the bellboy kept two dollars for himself. That totals $29. So where did the extra dollar go?
What word, when written in capital letters, is the same forwards, backwards and upside down?
FIGURED OUT
Puzzle from last edition: Andy and John (from the Chocolate truck story) are driving through four countries to get from the UK to Mali. Which countries are these? Their names begin with the letters F, S, M, and M.
Solution: The four countries are France, Spain, Morocco, and Mauritania.
Puzzle from last edition: Jack has a 5 liter bucket, a 3 liter bucket, and an unlimited supply of sand. He needs to get exactly 4 liter of sand into one of the buckets. How can he go about doing that?
Solution: There are several solutions. The main trick to this is to use "remaining" sand – the sand left over in one bucket when you are done filling the other. Here is one solution:
– Start with empty buckets.
– Fill the 3 liter bucket and pour it into the 5 liter one.
– Fill the 3 liter bucket again and keep pouring until the 5 liter bucket is filled. This will leave 1 liter in the 3 liter bucket.
– Empty out the 5 liter bucket, pour the 1 liter into it. Fill the 3 liter bucket again and pour it all into the 5 liter bucket. This gives us 4 liters of sand in that bucket.
Talking of liters, here is an interesting fact. "Liter" is the American English spelling of the word. In British English, it is spelt "Litre". Try finding a couple more words that have similar spelling differences.
Credits: Harvard for Korea map picture, Kremlin's press material for Putin's picture, Red Star Taekwando club for Taekwando picture, Merriam Webster for dictionary photo.
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This is an excellent property for a number of uses. Much of the ground has been covered with gravel, there is a 50'x50' unheated quonset hut, and this property also has its own gravel pit/pond. The zoning is GU-1 with no covenants, located on newly paved Hollowell Road. This would be a great property for a trucking operation, small farm, even multi-family uses. It is easily large enough to accommodate multiple 4 plex's etc.


Everything we do and every decision we make will be for the purpose of improving service for our customers, making ColorNet more profitable, and improving the standard of living of our employees.
We are in the business of printing. However, we feel that ColorNet produces something much larger than ink and toner on paper. Our company produces success. We take pride in the fact that the products we create help to make your business more successful. We make every effort to be successful, and recognize that we can accomplish this only if we can help you be successful.


Parkinson's Disease is a type of motor system disorder, which is characterized by a decrease in dopamine-producing brain cells. The four main symptoms of PD are tremors in the legs, arms, face and jaw; limb stiffness; reduced movement; and balance and coordination problems. Secondary symptoms include problems swallowing, speaking or chewing; depression; skin and urinary issues; and trouble sleeping. Symptoms appear mild at first, but as they progress, can cause difficulty walking or completing everyday tasks.
Below you will find alternative and natural treatment options including those from a Chinese Medicine perspective for Parkinson's Disease.
What Patterns Are Related To Parkinson's Disease (PD)?
The Chinese Medicine treatment of parkinson's disease (pd) generally involves arriving at the appropriate TCM diagnosis or pattern. This pattern within the individual is what treatment is based on not the general condition (see treating the cause and not the symptoms).
Which Tam Healing and Tongren Therapy Protocols Apply To Parkinson's Disease (PD)?
Tong Ren Therapy is the energy healing/medical qi gong aspect of the Tam Healing System. The areas of focus for parkinson's disease (pd) that we would use in Tong Ren techniques form the basis for our acupuncture treatments as well. Generally you would mix these primary points with points specific to the patients underlying TCM pattern and then our tuina (medical massage) would be largely focused on these points as well.


Dallas, TX (RestaurantNews.com) Thanks to a new Pronto Pick-Up ordering option, Cowboy Chicken has made it easier than ever to enjoy authentic, wood-fired rotisserie chicken and homemade sides on the go. No more standing in line to pick up and pay – guests can simply walk in, grab their prepaid order from the Pronto Pick-Up shelf and be on their way.
The process is simple. Busy diners order and pay online via CowboyChicken.com or on the popular Cowboy Chicken app. Team members prepare and package the order and place it on the conveniently located Pronto Pick-Up shelf, allowing guests to walk in, find the order under their name and walk back out. The Cowboy Chicken app gives users the added bonus of earning rewards for each purchase and is available through the Apple App Store and Google Play Store.
For more than 30 years, Cowboy Chicken has been serving all-natural, hormone-free rotisserie chickens that are hand-seasoned in store, marinated for 24 hours and then slowly roasted for two hours over a real wood-burning fire. Other dishes include signature sour cream tomatillo chicken enchiladas, abundant scratch-made sides such as Twice Baked Potaters™, Baked Mac & Cheese, Ranchero Beans and seasonal cobblers baked in-house daily. Cowboy Chicken's hearty and healthy dishes are available during lunch and dinner for dine-in, take out, catering and delivery.
Cowboy Chicken is currently seeking qualified franchisees to help build the brand in select markets across the U.S. For more information, visit www.cowboychicken.com or contact Kathy Davidson at kdavidson@cowboychicken.com.


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Tag Archives: SRT3190
The eggshell has an in vivo model system for extracellular matrix
The eggshell has an in vivo model system for extracellular matrix assembly, in which programmed gene expression, cell migrations, extracellular protein trafficking, proteolytic processing, and cross-linking are all required to generate a multi-layered and regionally complex architecture. structural features of the eggshell. Of particular notice are the putative enzymes, some likely to be involved in matrix cross-linking (two yellow family members previously implicated in eggshell integrity, a heme peroxidase, and a small-molecule oxidoreductase) among others possibly involved with matrix proteolysis or adhesion (proteins linked to cathepsins B and D). This ongoing work offers a Eltd1 framework for future molecular studies of eggshell assembly. eggshell offers a extraordinary in vivo model for procedures involved with assembly of complicated extracellular matrix architectures (analyzed by Waring, 2000). During the last 30 hours of oogenesis, somatic follicle cells overlying the oocyte secrete a series of eggshell elements that together type five eggshell levels, like the oocyte-proximal vitelline membrane, the lipid polish level, the crystalline internal chorionic level (ICL), the tripartite endochorion formulated with a flooring, pillars, and roofing, as well as the non-proteinaceous exochorion (Margaritis et al., 1980). This sequential secretion consists of precise legislation of gene appearance and, in the entire case from the main chorion genes, gene amplification to allow synthesis of needed levels of chorion protein in under 5 hours (Petri et al., 1976; Mahowald and Spradling, 1980). Eggshell morphogenesis consists of follicle cell migrations, of primary body follicle cells to create a continuing columnar epithelium within the oocyte (Schulz et al., 1993; Thomas and Zarnescu, 1999), of boundary cells that take part in developing an anterior sperm-entry framework, the micropyle (Montell et al., 1992), and of dorsal anterior follicle cells that migrate right out of the oocyte while synthesizing the matched respiratory appendages (Dorman et al., 2004). Cell signaling between your follicle oocyte and cells is normally very important to these migration occasions, as well for building and preserving polarity from the oocyte and eggshell (for testimonials, see Raftery and Dobens, 2000; Montell, 2003; van St and Eeden. Johnston, 1999). A job for the eggshell in embryonic patterning in addition has been shown with the anchoring in the vitelline membrane of Torsolike, a spatial cue involved with patterning the embryo termini (Stevens et al., 2003); very similar anchoring continues to be suggested, however, not proven, for an as-yet-unknown spatial cue involved with building the SRT3190 embryonic dorsoventral axis (Anderson et al., 1992). Regardless of the orderly secretion to begin vitelline membrane protein (sV23, sV17, VM32E, VM34C) in the mid-oogenesis Levels 8?10, and chorion protein C these split into early (s36, s38 in Levels 11?12), middle (s16, s19 SRT3190 in Stage 13), and past due (s15, s18 in Stage 14) classes C immunolocalization and American blot studies have got revealed a surprising intricacy in what goes on to these protein after their secretion. These occasions include temporally governed trafficking of proteins between levels and their proteolytic handling after deposition. For instance, a big percentage of the secreted s36 chorion protein in the beginning localizes to the SRT3190 vitelline membrane, with only a small fraction present on the forming chorion, then late in oogenesis it cannot be recognized in the vitelline membrane and instead is distributed throughout the endochorion (Pascucci et al., 1996); related behavior is seen for the s36 and s38 homologues in (Trougakos and Margaritis, 1998). SRT3190 Conversely, while the vitelline membrane proteins sV23 and sV17 appear to localize exclusively to the vitelline membrane (Pascucci et al., 1996), VM32E shows partial relocalization to the inner chorionic coating and endochorion late in oogenesis (Andrenacci et al., 2001). The major chorion proteins do not undergo proteolytic processing, while the sV23 and sV17 vitelline membrane proteins do appear to undergo sequential N- and C-terminal processing after their SRT3190 secretion (Manogaran and Waring, 2004; Pascucci et al., 1996). Products of the complex Pxd (Peroxidase) gene has recently been demonstrated.
June 14, 2017 Colleen Sims	Eltd1, SRT3190	Leave a comment
Background Enlargement of hematopoietic stem cells represents an important objective for
Background Enlargement of hematopoietic stem cells represents an important objective for improving cell and gene therapy protocols. by 3 to 6 SRT3190 occasions and significantly enhances the level of engraftment. Comparative transcriptome analysis of CD34+ cells subjected or not to HOXB4 or HOXC4 showed that both homeoproteins regulate the same group of genes, a few of which encode essential hematopoietic elements and signaling substances. Specific substances discovered herein are elements reported to be engaged in stem cell extension or destiny in various other versions, such as for example MEF2C, EZH2, DBF4, DHX9, YPEL5 and Pumilio. Conclusions Today's study can help to identify brand-new HOX downstream essential factors potentially involved in hematopoietic stem cell growth or in leukemogenesis. growth of human being hematopoietic cells currently relies on the use of high concentrations of cytokines and growth factors. However, the value of this practice is limited since it often prospects to irreversible differentiation of HSC in the tradition. An alternative approach is made up in using transcription factors involved in HSC self-renewal or maintenance. Among them, the HOXB4 homeoprotein was identified as a major growth element of mouse and human being HSC after retroviral transduction of the coding sequence.1C3 Although that gene was first described as non-leukemogenic, a recent study revealed that transduction of into the HSC of large animals could lead to the late emergence of acute myeloid leukemias.4 Thus, retrovirus-mediated genetic alterations of HSC along with constitutive expression of human being can be hazardous for therapeutic applications. To overcome this problem, we established an alternative growth method taking advantage of the house of homeoproteins to translocate spontaneously and reversibly through membranes and reach the cytoplasm and nucleus.5,6 Long-term lifestyle of individual CD34+ immature cells in the current presence of the homeoprotein induces expansion of HSC and hematopoietic progenitors from the myeloid and lymphoid lineages. Extended cells have a sophisticated capability to repopulate also to maintain their pluripotentiality.7C9 Nevertheless, no matter the technology used, the HOXB4-mediated expansion of HSC and progenitors is somewhat low in humans than in mice generally. We, therefore, made a decision to examine whether using HOXC4 would improve extension efficacy. In fact, retroviral transduction of gene, have been shown to trigger the extension of individual hematopoietic progenitors.10 In today's research, we demonstrate that HOXC4 protein transfer into human Compact disc34+ hematopoietic cells by method of co-culture Mouse monoclonal to Plasma kallikrein3 with MS-5 stromal cells engineered to actively secrete this homeoprotein, induces 3- to 6-fold expansion of HSC and hematopoietic progenitors. The human genes regulated by homeoproteins during hematopoiesis are unknown mainly. We, therefore, thought we would seek out potential effectors of HOXB4 and HOXC4 using comparative transcriptome evaluation of Compact disc34+ individual cells following exposure to these factors. We reasoned that, since HOXB4 and HOXC4 display important molecular analogies and have related SRT3190 temporal and spatial manifestation patterns during embryogenesis, both molecules should influence the manifestation of the same set of genes. We display herein the transcriptomes from CD34+ cells exposed to HOXB4 or HOXC4 are virtually identical. Gene appearance profiling uncovered that various pieces of genes encoding essential hematopoietic elements and signaling pathway substances (KLF10, HNRPDL, IKZF, and hypoxia, myc, IGF-1, 14-3-3 and angiopoietin-1 signaling) had been either turned on or repressed after cell contact with these homeoproteins. Furthermore, certain molecules discovered herein (MEF2C, EZH2, DBF4, DHX9, YPEL5, Pumilio) are participating with stem cell destiny SRT3190 or extension in other versions, matching to important focuses on for even more research thus. Style and Strategies Structure from the HOXC4 vector The cDNA was something special from Dr. Daga.10 The mouse immunoglobulin -chain leader sequence for protein secretion was inserted upstream of the HoxC4 sequence. That create was cloned into the TRIP vector plasmid then, as described somewhere else.11 Lentiviral vector transduction and creation cDNA, known as control), MS-5/HOXC4 and MS-5/HOXB4 (MS-5 transduced with vectors containing the human being or cDNA, respectively) were grown in alpha-minimum important medium (-MEM) containing 10% fetal leg serum (FCS) (Invitrogen, Cergy Pontoise, France). Isolation, immuno-labeling and ethnicities of Compact disc34+ cells Human being immature hematopoietic cell isolation, labeling, tradition and SRT3190 cloning assays had been performed as currently referred to, 7C9 and fully presented in the section. Cell expansion analysis The relative fold expansion was calculated as the fold-increase in HSC expansion in the presence of MS-5/HOXC4 or MS-5/HOXB4 cells, divided by that in the presence of MS-5/GFP cells. The absolute fold expansion was calculated as the total number of HSC recovered per culture at day X, divided by that at day.
May 30, 2017 Colleen Sims	Mouse monoclonal to Plasma kallikrein3, SRT3190	Leave a comment