text:
let fs = require('fs');
let PNG = require('pngjs').PNG;
let config = require('../configs/epsonConfig');

let buffer = null;
function append(buff) {
  if (buffer) buffer = Buffer.concat([buffer, buff]);
  else buffer = buff;
}

module.exports = {

  // ------------------------------ Epson QR ------------------------------
  printQR: function (str, settings) {
    settings = settings || {};

    // [Name] Select the QR code model
    // [Code] 1D 28 6B 04 00 31 41 n1 n2
    // n1
    // [49 x31, model 1]
    // [50 x32, model 2]
    // [51 x33, micro qr code]
    // n2 = 0
    // https://reference.epson-biz.com/modules/ref_escpos/index.php?content_id=140
    if(settings.model) {
      if(settings.model === 1) append(config.QRCODE_MODEL1);
      else if(settings.model === 3) append(config.QRCODE_MODEL3);
      else append(config.QRCODE_MODEL2);
    } else {
      append(config.QRCODE_MODEL2);
    }

    // [Name]: Set the size of module
    // 1D 28 6B 03 00 31 43 n
    // n depends on the printer
    // https://reference.epson-biz.com/modules/ref_escpos/index.php?content_id=141
    if(settings.cellSize) {
      var i = "QRCODE_CELLSIZE_".concat(settings.cellSize.toString());
      append(config[i]);
    } else {
      append(config.QRCODE_CELLSIZE_3)
    }

    // [Name] Select the error correction level
    // 1D 28 6B 03 00 31 45 n
    // n
    // [48 x30 -> 7%]
    // [49 x31-> 15%]
    // [50 x32 -> 25%]
    // [51 x33 -> 30%]
    // https://reference.epson-biz.com/modules/ref_escpos/index.php?content_id=142
    if(settings.correction) {
      var i = "QRCODE_CORRECTION_".concat(settings.correction.toUpperCase());
      append(config[i]);
    } else {
      append(config.QRCODE_CORRECTION_M)
    }

    // [Name] Store the data in the symbol storage area
    // 1D 28  6B pL pH 31 50 30 d1...dk
    // https://reference.epson-biz.com/modules/ref_escpos/index.php?content_id=143
    var s = str.length + 3;
    var lsb = parseInt(s % 256);
    var msb = parseInt(s / 256);
    append(new Buffer([0x1d, 0x28, 0x6b, lsb, msb, 0x31, 0x50, 0x30]));
    append(new Buffer(str));

    // [Name] Print the symbol data in the symbol storage area
    // 1D 28 6B 03 00 31 51 m
    // https://reference.epson-biz.com/modules/ref_escpos/index.php?content_id=144
    append(config.QRCODE_PRINT);

    // Dont forget to clean the buffer
    let buff = buffer;
    buffer = null;
    return buff;
  },

  // ------------------------------ Epson PDF417 ------------------------------
  pdf417: function(data, settings) {
    settings = settings || {};

    // Set error correction ratio 1 - 40
    if(settings.correction){
      append(config.PDF417_CORRECTION);
      append(new Buffer([settings.correction]))
    } else {
      append(config.PDF417_CORRECTION);
      append(new Buffer([0x01]))
    }

    // Set row height 2 - 8
    if(settings.rowHeight){
      append(config.PDF417_ROW_HEIGHT);
      append(new Buffer([settings.rowHeight]))
    } else {
      append(config.PDF417_ROW_HEIGHT);
      append(new Buffer([0x03]))
    }

    // Set width of module 2 - 8
    if(settings.width){
      append(config.PDF417_WIDTH);
      append(new Buffer([settings.width]))
    } else {
      append(config.PDF417_WIDTH);
      append(new Buffer([0x03]))
    }

    // Manually set columns 1 - 30
    if(settings.columns){
      append(config.PDF417_COLUMNS);
      append(new Buffer([settings.columns]))
    } else {
      // Default to auto
      append(config.PDF417_COLUMNS);
      append(new Buffer([0x00]))
    }

    // Standard or truncated option
    if(settings.truncated) append(config.PDF417_OPTION_TRUNCATED);
    else append(config.PDF417_OPTION_STANDARD);

    // Set PDF417 bar code data
    var s = data.length + 3;
    var lsb = parseInt(s % 256);
    var msb = parseInt(s / 256);

    append(new Buffer([0x1d, 0x28, 0x6b, lsb, msb, 0x30, 0x50, 0x30]));
    append(new Buffer(data.toString()));

    //Print barcode
    append(new Buffer(config.PDF417_PRINT));

    // Dont forget to clean the buffer
    let buff = buffer;
    buffer = null;
    return buff;
  },

  // ------------------------------ Epson CODE128 ------------------------------
  maxiCode: function(data, settings){
    settings = settings || {};

    // Maxi Mode
    // 2 - Formatted data/structured Carrier Message with a numeric postal code. (US)
    // 3 - Formatted data/structured Carrier Message with a numeric postal code. (International)
    // 4 - Unformatted data/Standard Error Correction.
    // 5 - Unformatted data/Enhanced Error Correction.
    // 6 - Used for programming hardware devices.

    if(settings.mode) {
      if(settings.mode == 2) append(config.MAXI_MODE2);
      else if(settings.mode == 3) append(config.MAXI_MODE3);
      else if(settings.mode == 5) append(config.MAXI_MODE5);
      else if(settings.mode == 6) append(config.MAXI_MODE6);
      else append(config.MAXI_MODE4)
    } else {
      append(config.MAXI_MODE4)
    }

    // Setup size of MaxiCode data
    var s = data.length + 3;
    var lsb = parseInt(s % 256);
    var msb = parseInt(s / 256);

    // Send Data
    append(new Buffer([0x1d, 0x28, 0x6b, lsb, msb, 0x32, 0x50, 0x30]));
    append(new Buffer(data.toString()));

    // Print barcode
    append(config.MAXI_PRINT);

    // Don't forget to clean the buffer
    let buff = buffer;
    buffer = null;
    return buff;
  },

  // ------------------------------ Epson BARCODE ------------------------------
  printBarcode: function(data, type, settings){
    settings = settings || {};

    //Set HRI characters Position, 0-3 (none, top, bottom, top/bottom)
    if(settings.hriPos){
      append(new Buffer([0x1d, 0x48])); // GS H
      append(new Buffer([settings.hriPos]))
    } else {
      append(new Buffer([0x1d, 0x48, 0x00]))
    }

    // Set HRI character font. 0-4, 48-52, 97, 98 (depending on printer, 0 and 1 available on all), default 0
    if(settings.hriFont){
      append(new Buffer([0x1d, 0x66])); // GS f
      append(new Buffer([settings.hriFont]))
    } else {
      append(new Buffer([0x1d, 0x66, 0x00]))
    }

    // Set width 2-6, default 3
    if(settings.width){
      append(new Buffer([0x1d, 0x77])); // GS W
      append(new Buffer([settings.width]))
    } else {
      append(new Buffer([0x1d, 0x77, 0x03]))
    }

    // Set height 1 - 255 default 162
    if(settings.height){
      append(new Buffer([0x1d, 0x68])); // GS h
      append(new Buffer([settings.height]))
    } else {
      append(new Buffer([0x1d, 0x68, 0xA2]))
    }

    // Print Barcode
    append(new Buffer([0x1d, 0x6b])); // GS k
    // Select type and bit length of data
    append(new Buffer([type, data.length]));
    // Data
    append(new Buffer(data));

    // Don't forget to clean the buffer
    let buff = buffer;
    buffer = null;
    return buff;
  },

  // ----------------------------------------------------- PRINT IMAGE EPSON -----------------------------------------------------
  // https://reference.epson-biz.com/modules/ref_escpos/index.php?content_id=88
  printImageEpson: function(image, callback){
    let png = new PNG({
      filterType: 4
    });

    fs.createReadStream(image)
      .pipe(png)
      .on('parsed', function() {
        module.exports._printImageBufferEpson(this.width, this.height, this.data, function(buff){
          callback(buff);
        });
      })
      .on('error', function(err) {
        console.error(err);
      });
  },

  _printImageBufferEpson: function(width, height, data, callback){
    // Get pixel rgba in 2D array
    var pixels = [];
    for (var i = 0; i < height; i++) {
      var line = [];
      for (var j = 0; j < width; j++) {
        var idx = (width * i + j) << 2;
        line.push({
          r: data[idx],
          g: data[idx + 1],
          b: data[idx + 2],
          a: data[idx + 3]
        });
      }
      pixels.push(line);
    }

    var imageBuffer_array=[];
    for (var i = 0; i < height; i++) {
      for (var j = 0; j < Math.ceil(width/8); j++) {
        var byte = 0x0;
        for (var k = 0; k < 8; k++) {
          var pixel = pixels[i][j*8 + k];

          // Image overflow
          if(pixel === undefined){
            pixel = {
              a: 0,
              r: 0,
              g: 0,
              b: 0
            };
          }

          if(pixel.a > 126){ // checking transparency
            var grayscale = parseInt(0.2126 * pixel.r + 0.7152 * pixel.g + 0.0722 * pixel.b);

            if(grayscale < 128){ // checking color
              var mask = 1 << 7-k; // setting bitwise mask
              byte |= mask; // setting the correct bit to 1
            }
          }
        }

        imageBuffer_array.push(byte);
        // imageBuffer = Buffer.concat([imageBuffer, new Buffer([byte])]);
      }
    }

    let imageBuffer = Buffer.from(imageBuffer_array);

    // Print raster bit image
    // GS v 0
    // 1D 76 30	m	xL xH	yL yH d1...dk
    // xL = (this.width >> 3) & 0xff;
    // xH = 0x00;
    // yL = this.height & 0xff;
    // yH = (this.height >> 8) & 0xff;
    // https://reference.epson-biz.com/modules/ref_escpos/index.php?content_id=94

    // Check if width/8 is decimal
    if(width%8 != 0) {
      width += 8;
    }

    append(new Buffer ([0x1d, 0x76, 0x30, 48]));
    append(new Buffer ([(width >> 3) & 0xff]));
    append(new Buffer ([0x00]));
    append(new Buffer ([height & 0xff]));
    append(new Buffer ([(height >> 8) & 0xff]));

    // append data
    append(imageBuffer);

    // Don't forget to clean the buffer
    let buff = buffer;
    buffer = null;
    callback(buff);
    return buff;
  },

};

redpajama_set_name: RedPajamaGithub


text:
Q: Generate unigrams from google books that start with a number, using regex The code below, generates pickle dictionaries of unigrams of google books.
It generates 26 dictionaries like dictionary of words starting with a, b, c, ..., z.
p = re.compile(r'^[a-z]*$', re.IGNORECASE)
el = 'abcdefghijklmnopqrstuvwxyz'

for l in el:
    fname, url, records = next(readline_google_store(ngram_len=1, indices=l))
    unigrams = {}
    count = 0
    for r in records:
        if (r.year >=2000):
            w = r.ngram.lower()
            if p.match(w):
                if w in unigrams:
                    unigrams[w] += np.array([r.match_count, r.volume_count])
                else:
                    unigrams[w] = np.array([r.match_count, r.volume_count])
    with open(str(l)+'_unigram_dict.pickle', 'w') as f:
        pickle.dump(unigrams, f)

The output is like {'word':[total_match_count, total_volume_count]}
I want to change it to have only dictionary of words that start with a number.
The regex should catch a pattern that start with a number (from 0 to 9) followed by any character.
I tried re.compile(r'^(?:\d*\.)?\d+$', re.IGNORECASE) but it only catches numeric words. It does not capture words like:
"00161_VERB" or "002,200_NUM" or "01-73", etc
Edit: input is (a record) in this format:
ngram TAB year TAB match_count TAB page_count NEWLINE

I want the output to be a dictionary with key ngrams that start with '0' and
value a list ['sum of match_count over the years', 'sum of page_count over the years'] like this:
{'ngrams':['sum of match_count over the years', 'sum of page_count over the years']}

A: Issue resolved,
re.compile(r'^\d\S+') worked.

redpajama_set_name: RedPajamaStackExchange


It's going to be end of mine day, but before ending I am reading this wonderful paragraph to increase my know-how.
articles or blog posts on this kind of space . Exploring in Yahoo I ultimately stumbled upon this site.


The global Sodium Chlorite Market was worth USD 132.45 billion in 2014 and is expected to reach approximately USD 228.18 billion by 2023, while registering itself at a compound annual growth rate (CAGR) of 6.23% during the forecast period. Rising demand for the chemical in wastewater treatment and water filtration applications inferable from its biocidal and antimicrobial properties is foreseen to fuel the interest for sodium chlorite over the estimate time frame. The business has the existence of countless and medium scale makers, which are fundamentally situated in China. Sodium chlorite costs change over the business grades with 80% concentrated being the highest expended review among all. Raw material and operational and transportation cost are the key components characterizing the last estimation of the products.
Rising interest for antimicrobial operators in the food processing sector to enhance the time span of usability of packaged products is foreseen to positively affect industry development. An acidic type of the substance does not hamper the healthful nature of sustenance in this manner driving its application in food & beverage applications. The interest for the compound as a blanching specialist is foreseen to develop at a significant CAGR in the following years, inferable from its predominant oxidizing properties.
The chemical finds an extensive variety of usage scope in pulp & paper, electronics, fertilizer, textiles, water treatment, and electronics. The developing interest for the synthetic to create chlorine dioxide at pulp preparing and material bleaching plants is foreseen to drive the business development throughout the following years. The rising demand for the product in paper industry remained for USD 242 million in 2016 and is anticipated to develop significantly in the following years.
In 2016 Asia Pacific was the biggest market investor of the worldwide sodium chlorite market, representing 38.7% of the general market income in 2016. The rising pulp & paper industry application in the locale is anticipated to boost the market. The market in North America is foreseen to be driven by high usage levels of sodium chlorite for water treatment. The usage of the synthetic in Europe is high when contrasted with the residential generation. The request in the area was USD 30.85 million in 2016, which was fundamentally met through the imports from Asian producers.
The market is extensively competitive with the existence of leading players like Alfa Aesar, ABI Chemicals LLC, Sigma, CONIER CHEM AND PHARMA, DuPont, ERCO Worldwide Inc, Finetech Industry Limited, Jalor Chem and Oxy Chemical Corp.
7.4. Dongying Shengya Chemical Co., Ltd.
7.6. Shandong Gaomi Gaoyuan Chemical Industry Co., Ltd.
*You can glance through the list of Tables and Figures when you view the sample copy of Sodium Chlorite Market.


Wilmington ; the City Antique Touch.
Our Limousine Services for Wilmington is like a household name-through our prompt response; safety on the road; decency to customers, friendliness and being very conversant with not only Wilmington city but the environ besides all locations and sites that are recognized as tourist points. This is not a small achievement. The Knowledge of the city; the accompanying earnest service to our esteemed clients made us valued performers in Limo service provider in the city. We are the most preferred limo service. Breaking-off from job monotony or some commerce excursion to Wilmington? Talk to us .We do not act; our service does the miracle- certainly you will agree that we are the very best, in city and neighborhoods. Our limos are unequaled; yes they are same vehicles you might have seen, but the consistency is the service offered by providers. We are ultimate limo services Wilmington.
Wedding is a big time consumer and stressful. We have solved that for you. At Globallimos.com Services for Wilmington all the stress is healed. You partner with us; no regrets or wedding headaches anymore. Our limos are designed for such jobs - for your peace.
Globallimos.com offers a huge range of fleet for this city. Some of our most preferred vehicles include Hummer, Escalade, Lincoln town car, Rolls limousine, Range rover stretch Limousine which can accommodate up to 14 passengers. If you are planning to travel with more friends you can hire our party buses that can accommodate up to 40 passengers. These cars would be a vehicle of choice for all kinds of your events, such as weddings, birthdays, Night outs, proms and formals, wine tours etc.
So just contact globallimos.com and hire yourself a perfect limousine from our limousines service for Wilmington.


text:
package arbitrator
/*
* File Generated by enaml generator
* !!! Please do not edit this file !!!
*/
type GaleraHealthcheck struct {

	/*Port - Descr: Port used by sidecar process to listen on Default: 9200
*/
	Port interface{} `yaml:"port,omitempty"`

	/*EndpointUsername - Descr: Username used by the sidecar endpoints for Basic Auth Default: <nil>
*/
	EndpointUsername interface{} `yaml:"endpoint_username,omitempty"`

	/*EndpointPassword - Descr: Password used by the sidecar endpoints for Basic Auth Default: <nil>
*/
	EndpointPassword interface{} `yaml:"endpoint_password,omitempty"`

}


The Institute of Apprenticeships are an independent public body that works with employer groups to develop the apprenticeship standards and assessment plans to the best they can be.
Developing and maintaining quality criteria for the approval of apprenticeship standards and assessment plans.
Supporting the development of standards and assessment plans by employer groups.
Publishing approved standards and assessment plans.
Advising maximum amount of government funding that can be drawn down by employers for individual apprenticeship standards.
Ensuring all end-point assessments are quality assured.
A traineeship is a course with work experience that gets you ready for work or an apprenticeship. It can last up to 6 months.


Daniel and Majella kayaking in Enniskillen.
AS Daniel and Majella O'Donnell come to the end of the road, their final stop sees them take in the sights of the North stopping at Enniskillen before heading to Newtownabbey.
The hugely successful series, 'Daniel and Majella's B&B Road Trip', concludes with the final episode broadcasting on Monday, November 30, at 8pm on UTV.
Daniel and Majella's first stop is with Joan and Tom Foster owners of Willowbank B&B in Enniskillen.
Willowbanks tranquil setting with un-spoilt views of the lake from nearly every room in the house and Joan's superb homemade treats including potato farls, hash browns, scones, and compote make the B&B a special experience for guests.
Daniel and Majella find their sea legs as they kayak around Enniskillen taking in some breath taking scenery before hitting the road once again to their final road trip destination in Newtownabbey Co. Antrim.
Sponsored by John Mulholland Skoda, Daniel and Majella's B&B Road Trip concludes on Monday at 8pm on UTV.
Viewers can join in the conversation using the hashtag #BnBRoadTrip.


text:
Holbeck is een wijk in Leeds, West Yorkshire, Engeland.
De wijk ligt aan de zuidelijke rand van het centrum van de stad Leeds.
De Leeds and Liverpool Canal loopt door Holbeck.

Leeds

redpajama_set_name: RedPajamaWikipedia


Setting a location for your advertisements will allow you to center the broadcast area of your ads; naturally, this should be your site location. Patients will likely not be interested in driving too far out of their way to participate in your study, so limiting your ad radius to a reasonable driving distance (30-40 miles) around your site will help you reach a relevant audience and maximize ROI. It is beneficial to switch this broadcast setting to "People who live in this location." This way, you will only target Facebook users who live near your research site, rather than visitors to the area.
Facebook provides a unique opportunity to help you effectively reach an audience of any age-- whether that's 18+, 50+, or less than 18 years old. Of all internet users, 79% aged 30-49 use Facebook, and surprisingly, 56% of internet users ages 65 and up are active on the site. If your site has seen particular successes with a certain age range within your study's qualification criteria-- let's say you've noticed that people aged 25-40 are more likely to participate in a study than 18-25-year-olds-- feel free to narrow your broadcast age range. This change can help you get a larger ROI when advertising on Facebook.
When recruiting children for a study, you can use Facebook as an advertising tool to reach the decision makers in the child's household. If your study is designed to help young children, you might have the highest likelihood of connecting with the right patients if your target audience is defined as young adult, perhaps between the ages of 25-35 years.
Facebook's audience targeting tools specify three gender selections: "Men," "Women," and "All." Of course, this can be kept consistent with the qualifying criteria for your study. Keep in mind that studies designed to help children are most successful in recruiting patients when ads are broadcast to the person in charge of the child's healthcare. Statistically speaking, this tends to be a female parent or guardian, but selecting "All" will account for all family structures. Choose the option that makes the most sense for your study.
These options offer the most detailed selections when choosing an audience, and can be extremely effective in helping you find the specific patients who will benefit from your study. For example, if you are running a Cancer Study, you might set your advertisement to broadcast to Facebook users interested in "Cancer Research," "Investigational Medicine," etc. These settings will target users who have indicated interest or behaved like your desired audience to ensure your advertisements reach the most relevant audience, allowing patients to find your study and maximizing ROI.
With over 1 billion users on the site, selecting a relevant audience for your Facebook ad can seem daunting. When using Facebook's detailed audience selection tools, considering an audience consistent with the qualification criteria for your study will help you reach the right patients, allowing you to get the most out of your investment.


Did you know gratitude has health benefits?
I'm grateful for these two.
I try to have an attitude of gratitude. I didn't realize how many benefits being grateful brings to your life until I read "Gratitude yields health and social benefits" by Jenni Stahlmann and Jody Hagaman in the Sarasota Herald Tribune.
Positive emotions such as gratitude open our minds.
With Thanksgiving having passed, we may want a jump start on our New Year's resolutions. Research shows such a long list of health and social benefits that families might want to focus on cultivating an attitude of gratitude all year long.
Researchers at Northeastern University found that grateful people are more likely to be patient and make wiser decisions.
Gratitude also makes us more likely to take better care of ourselves. In one psychology journal, a study showed that a grateful attitude correlated to a greater willingness to eat healthier foods, exercise more and go to the doctor. Some research even shows that being appreciative boosts willpower.
Counting our blessings before bedtime can also translate to better sleep. One researcher said it may help soothe the nervous system. Not only can gratitude improve our quality of sleep, it can also help us fall asleep faster and sleep longer.
The health benefits of gratitude can't be overstated. It's been shown to decrease physical pain, reduce symptoms associated with depression, decrease blood pressure and boost energy levels. In fact, simply cultivating a lifestyle of gratitude can add an average of seven years to your lifespan.
Being grateful also makes us more resilient, less envious, more optimistic, kinder and more social. It's no wonder that the more grateful a person is, the more likely the person is to have strong social connections, healthier marriages, larger friendship circles and improved networking skills.
Not only does gratitude have the power to transform our health, our social lives and our careers, it can transform our personalities. Research shows that gratitude contributes to a wide range of positive character traits. It makes us humble and it makes us more generous. Together, these traits combat entitlement and self-centeredness. Grateful people are more willing and able to focus on others and can therefore contribute more broadly to their communities.
We the parents have both the opportunity and the obligation to raise children who will have a positive and transformative effect on the future. As we focus on grooming an attitude of gratitude in our kids, we are not only improving their own quality of life but we are helping to change the world one child at a time.
I do believe it's our duty as parents to instill gratitude as a trait our kids should embrace. One way is to start a gratitude journal. Another tip is to ask your children at dinner or bedtime to name three things they're grateful for. In the book I'm reading called "Finding Water: The Art of Perseverance" by Julia Cameron, has exercises to list 10 things you cherish. Another day there I was asked to write 10 things I'm thankful for. It's not a bad thing to do. By the way, I gave my husband a journal of gratitude and he's enjoying writing a few things each day.
As parents, I think we need to let our kids and family know how much they mean to us. It's that time of year!
Would you change your parenting if you could travel back in time?
That makes me look at my children today and wonder what would I change if I could? I'd have given them more chores, not picked up after them and let them make more decisions and mistakes. I wouldn't worry so much about grades, homework, or focus on performance. Would that have changed who they are today? Probably not. My kids are kind people with character. They have compassion and they care for their environment and other people. It would be a little tweak on my part to help them be more self-sufficient and a little steadier on their feet as they explore the years post college graduation.
How would we talk to them, and what kinds of choices would we make if we were completely aware that we are raising the future parents of our grandkids and someone's future employee or boss and a future spouse and next door neighbor and someone's friend — maybe (hopefully) our own future friend and possibly even the person who will one day take care of us when we can't take care of ourselves.
Beach walk with my daughter this summer.
What would you do differently if you could look back in time?


text:
Gaming is more than just button bashing and Fortnite. These articles cover everything from Nintendo to video games and their effect in the brain.
7 Game Boy Accessories You May Not Have Heard Of
Gaming May 28 September 13
Here's a list of some of the strangest Gameboy add-ons you'll ever see. The Nintendo Gameboy celebrated its 30th birthday this year (something I wrote about for Distant Arcade). There were plenty of official accessories made for the device, like the Gameboy Camera. But there were some oddities in its history and I've compiled a …
Continue reading "7 Game Boy Accessories You May Not Have Heard Of"
8 Games I'd Love To See On The Nintendo Switch
Gaming October 21 July 3
The Nintendo Switch is set for release next year. Here are 8 games I'd love to see join it on the shelves. Nintendo announced their newest console today, the Nintendo Switch. It will be released in March 2017 and acts as a "hybrid device": both a tablet-like portable console and a home console placed in a docking station (complete with satisfying "click" sound). The …
Continue reading "8 Games I'd Love To See On The Nintendo Switch"
Bored Of Crossword Puzzles? Try Nonograms.
My mother once got a free subscription to The Times newspaper for 6 months. This is how I got into Sudoku. My first puzzle took 2 days to complete and it felt amazing to finish. After a while, I got bored of the varying levels of difficulty. I could never do the 3D puzzles but …
Continue reading "Bored Of Crossword Puzzles? Try Nonograms."

redpajama_set_name: RedPajamaCommonCrawl


SOAR Funding and Sustainability Overview | SOAR Works!
There is no dedicated source of funding for SSI/SSDI Outreach, Access and Recovery (SOAR) programs. However, states and communities have been very resourceful in tapping a wide variety of funding sources - here are some examples.
There is no dedicated source of funding for SOAR programs. And yet, all 50 states participate in SOAR at some level by reallocating existing resources; by securing funding through federal and state grants or foundation funding; or by establishing collaborations with hospitals and criminal justice systems. Still, the major reason that SOAR services are severely limited in some communities and nonexistent in others is the difficulty that communities have finding funds to pay the salaries of SOAR benefits specialists.
Despite these difficulties, SOAR's impact to date and untapped potential for ending and preventing homelessness is compelling and communities have been resourceful in tapping a wide variety of funding sources some of which are highlighted below.
Projects for Assistance in Transition from Homelessness (PATH) - funds provide outreach and supportive services for adults with serious mental illness or substance use disorders who are experiencing or at risk of homelessness. PATH funds support dedicated SOAR benefits specialists, SOAR training, and statewide leadership and coordination in many states.
Cooperative Agreements to Benefit Homeless Individuals (CABHI) – funds dedicated SOAR benefits specialists and access to mainstream benefits programs in Colorado, Connecticut, Michigan, Nebraska, and New Mexico.
Adult Treatment Drug Courts– Nevada utilizes this grant to fund a SOAR benefits specialist in the court system.
Community Mental Health Services Block Grant (MHBG) funds priority treatment and support services not covered by Medicaid, Medicare or private insurance for low income individuals that demonstrate success in improving outcomes and/or supporting recovery.
A flexible program that provides communities with resources to address unique community development needs, and distributes annual grants on a formula basis to local governments and states. SOAR programs have used these funds to support dedicated benefits specialists.
AmeriCorps State members can provide direct outreach, engagement, and assistance with SSI/SSDI applications using the SOAR process.
State and community organizations can apply for a grant to support AmeriCorps State members through their governor-appointed State Service Commission.
AmeriCorps VISTA members can identify potential SOAR collaborations, organize local SOAR planning meetings, fundraise for dedicated SOAR staff, collect data, and coordinate future trainings.
State and community organizations can apply to sponsor an AmeriCorps VISTA member through their State Corporation for National and Community Service Office.
State or County General Assistance (GA) and Temporary Assistance for Needy Families (TANF) Incentives For individuals with severe disabilities who cannot work, transitioning from GA or TANF to SSI/SSDI provides them with greater benefits and saves state funds when individuals transition to federal benefits. Programs in Minnesota, Pennsylvania, Vermont and Utah have documented savings to state programs and leveraged funding for SOAR programs.
GA funds offer time-limited cash benefits to adults without dependents who have limited or no income. These benefits are not available in every state. Through an Interim Assistance Reimbursement (IAR) agreement, SSA can reimburse state or local public assistance funds when individuals begin receiving SSI/SSDI.
TANF is a block grant from the Department of Health and Human Services for states to provide time-limited assistance to families with dependent children to help them become self-sufficient through employment. For parents who cannot meet the TANF work requirements, assessment of eligibility for SSI/SSDI may better meet their needs and save state funds for others in need.
State or Local Plans to End Homelessness have funded SOAR leadership, coordination, and dedicated benefits specialists.
In Nashville, Tennessee, the Mayor's office funds three dedicated benefits specialists through the city's 10-year Plan to End Homelessness.
Foundation and Other Private Funding – National and local companies and foundations fund SOAR coordination, training, and dedicated SOAR benefits specialists.
Hospital Collaborations – Hospitals can benefit from SOAR collaborations by recouping payments for previously uncompensated care when individuals approved for SSI obtain Medicaid. SOAR providers may receive funding from hospitals for dedicated SOAR benefits specialists to help individuals access SSI/SSDI and health insurance.
In Atlanta, Georgia, First Step collaborated with Grady Memorial Hospital to help get individuals on SSI/SSDI and Medicaid/Medicare. First Step shared a percentage of the funds that Grady was able to recover from Medicaid for previously uncompensated care.
Criminal Justice System Collaborations – SOAR programs collaborate with jails and prisons through in-reach initiatives, re-entry planning, and training corrections staff to complete SSI/SSDI applications. These efforts reduce recidivism and prevent incarceration through jail diversion, which in turn saves money for states and communities.
The Miami-Dade Jail Diversion Program helps individuals apply for SSI/SSDI using SOAR while they are incarcerated. Documenting reductions in recidivism, they estimated a cost-savings to the state of $7 million in 2009. These results helped leverage on-going funding for their SOAR program.
U.S. Department of Veterans Affairs (VA) – The Supportive Services for Veteran Families (SSVF) grant promotes housing stability for low-income Veterans. Funds may be used to increase access to SSI/SSDI and to support dedicated SOAR benefits specialists.


text:
Q: Gettig user input and storing it/using it c# I've been learning for a little over a month now in c# and I have a little problem.
I want to get user input and store it into variables then do some operations with it, and then get an answer, but I can't even get it to print anything nor let me write. Could someone please tell me what I did wrong and how to fix it?
{
    Console.Write("Enter Mass1 ");
    string Mass1 = Console.ReadLine();

    Console.Write("Enter Lil Numbers ");
    int LilNum = Console.ReadLine();

    Console.Write("Enter Mass2 ");
    int Mass2 = Console.ReadLine();

    Console.Write("Enter Lil Numbers ");
    int LilNum2 = Console.ReadLine();

    Console.Write("Enter Distance between Mass1 & 2 ");
    int distance = Console.ReadLine();
}
    int Mass3 = Mass/Mass2;

}

A: I have rewrote your program and added inline comments which will help you understand what you did wrong..
Console.Write("Enter Mass1 ");
int Mass1 = int.Parse(Console.ReadLine());

// Console.ReadLine() method returns the `string`
// hence you need to parse it to specific type before assigning it
Console.Write("Enter Lil Numbers ");
int LilNum = int.Parse(Console.ReadLine());

// same here
Console.Write("Enter Mass2 ");
int Mass2 = int.Parse(Console.ReadLine());

// same here
Console.Write("Enter Lil Numbers ");
int LilNum2 = int.Parse(Console.ReadLine());

// same here
Console.Write("Enter Distance between Mass1 & 2 ");
int distance = int.Parse(Console.ReadLine());

// You are using `Mass` which is not present
// `Mass1` was `string` type on which you can not do division
int Mass3 = Mass1 / Mass2;

hope this helps.

A: First, you should be receiving an error when trying to read directly from the Console to an int, as the Console.ReadLine function returns a string.
That aside, you'll want to utilize the TryParse static functions of the type you want to convert the string to.
For example, using your code, we can loop while the user input is invalid, like if they enter "x" for a number, using the TryParse function:
string val;
int Mass1, LilNum, Mass2, LilNum2, distance;

do {
    Console.Write("Enter Mass1 ");
    val = Console.ReadLine();
} while (!int.TryParse(val, out Mass1));

do {
    Console.Write("Enter Lil Numbers ");
    val = Console.ReadLine();
} while (!int.TryParse(val, out LilNum));

do {
    Console.Write("Enter Mass2 ");
    val = Console.ReadLine();
} while (!int.TryParse(val, out Mass2));

do {
    Console.Write("Enter Lil Numbers ");
    val = Console.ReadLine();
} while (!int.TryParse(val, out LilNum2));

do {
    Console.Write("Enter Distance between Mass1 & 2 ");
    val = Console.ReadLine();
} while (!int.TryParse(val, out distance));

Or, you could put this loop in a function, like so:
public static void ParseUserInput(string msg, out int outval)
{
    string val;
    do {
        Console.Write(msg);
        val = Console.ReadLine();
    } while (!int.TryParse(val, out outval));
}

public static void Main()
{
    int Mass1, LilNum, Mass2, LilNum2, distance;
    ParseUserInput("Enter Mass1 ", out Mass1);
    ParseUserInput("Enter Lil Numbers ", out LilNum);
    ParseUserInput("Enter Mass2 ", out Mass2);
    ParseUserInput("Enter Lil Numbers ", out LilNum2);
    ParseUserInput("Enter Distance between Mass1 & 2 ", out distance);
    Console.WriteLine("Mass 3: {0}", Mass1/Mass2);
}

This code utilizes the int.TryParse function, but there is also a TryParse for all of the other primitive numeric types, like long, double, etc. The TryParse function will return false if the string is an invalid numeric value, and true if the parse succeeded; if the parse succeeds, the value will be put in the out value.
You can also use the Parse function of the type you are converting, like int.Parse, however, you'll need to take into account that the Parse function will throw an Exception if the parsing failed, for example:
try {
    Console.Write("Enter a number: ");
    int val = int.Parse(Console.ReadLine());
    Console.WriteLine("Number: {0}", val);
} catch (Exception ex) {
    Console.WriteLine("There was an error parsing the number: {0}", ex);
}

Just remember you cannot trust user input and must validate the value's entered are within the ranges that are valid for your program. As an example, your Mass2 cannot be a 0 value since you divide Mass1 into it for Mass3 (int Mass3 = Mass1/Mass2;). Additionally, you'd likely want to cast the int values to a float for your Mass3, e.g. float Mass3 = (float)Mass1/Mass2;
I hope that can help.


Burdensome; wearing: a taxing business schedule.
wearingly burdensome: the taxing duties of a hotel manager.
Adj. 1. taxing - not easily borne; wearing; "the burdensome task of preparing the income tax return"; "my duties weren't onerous; I only had to greet the guests"; "a taxing schedule"
adjective demanding, trying, wearing, heavy, tough, tiring, punishing, exacting, stressful, sapping, onerous, burdensome, wearisome, enervating You won't be asked to do anything too taxing.
arduous, backbreaking, burdensome, demanding, difficult, effortful, exacting, exigent, formidable, hard, heavy, laborious, onerous, oppressive, rigorous, rough, severe, tough, trying, weighty.
Therefore, supposing there are six millions of tax-payers in easy circumstances (Rabourdin proved their existence, including the rich) is it not better to make them pay a duty on the consumption of wine, which would not be more offensive than that on doors and windows and would return a hundred millions, rather than harass them by taxing the thing itself.
Monsieur Gabelle was the Postmaster, and some other taxing functionary united; he had come out with great obsequiousness to assist at this examination, and had held the examined by the drapery of his arm in an official manner.
109 as the "new rock stars in tax"; see Frieswick, "Too Taxing," CFO Magazine (11/1/05), p.
Conservatives have always been interested in taxing consumption as a way of encouraging savings and investment, and liberals in need of revenue will have no alternative but to reconsider their historical aversion to consumption taxes as regressive.
TEI is concerned that proposed legislation to implement a new regime for taxing Foreign Investment Entities (FIEs) and Non-Resident Trusts (NRTs) would upset the careful policy balance that has been struck by the current foreign affiliate rules.
The project is seeking an equitable method for taxing electronic commerce.
In other words, the feds are very successful at taxing the rich, too.
Instead of taxing saving, we must tax consumption of goods and services.
But the government spending lobby, assuming that greater cost equals greater benefit, argues that California is not taxing its residents enough because Californians contribute a lower share of our incomes to government than taxpayers in places like North Dakota, Iowa, Utah, Idaho, Louisiana, and South Carolina (states with low incomes).
However, the assets and liability for each tax-paying component of an enterprise within each taxing jurisdiction are offset for presentation in the balance sheet.


Hello! My name is Mieko and I am the founder/organizer/host/promoter/digital storyteller of Vermont Womenpreneurs. This endeavor is a digital content and event production of Radiance Studios, promoting the stories of women owned businesses in the Green Mountain State.
Radiance Studios began as a side hustle in 2013, focused on career development and personal branding. Today, it has evolved into a business dedicated to distinguishing the voice, presence, and brand story of individuals and small organizations through digital marketing, website and content strategy, and event production.
I took the initiative to organize the showcase when my friend Bethany mentioned in one of our VTW meetings that she wished there was a "science fair" type of event where she got to talk about her business to an audience. So I did some informal research to see if there was such a space for women entrepreneurs in the state. Resoundingly, I heard women business owners express interest in participating in an event to promote their businesses. While there are many great business and particularly women organizations in our community, there wasn't a place outside of tabling at an expo or being in the food and beverage industry to promote a small, often times solopreneur, business. Between business pitch contests and panel discussions that select a pool of notable women business owners to speak, it is tough to get heard amidst the noise. Vermont is a place where word of mouth about a business means something over the mass marketing we are inundated with on a daily basis.
Our intent for the evening is for you to put a face to a woman-owned business. Whether or not you use their product or their services, we hope by meeting these 20 women business owners and our sponsors that you refer their business to a friend, colleague, family member, etc. If you are an aspiring entrepreneur, get inspired to take your first step by taking business development classes at local organizations such as Mercy Connections and Center for Women & Enterprise.
Read on about #herstory and get to know these businesses.


text:
The Drive-By Execution of Honduras Activist Walter Trochez
By Queerty Staff December 15, 2009 at 10:12am · 8 comments
Walter Trochez, the LGBT activist in Honduras who pushed back against the military coup's torment of queers and all citizens there, was reportedly murdered during a drive-by assassination while walking home in Tegucigalpa. He was 25. Relays Direland:
Trochez, who had already been arrested and beaten for his sexual orientation after participating in a march against the coup, had been very active recently in documenting and publicizing homophobic killings and crimes committed by the forces behind the coup, which is believed to have been the motive for his murder. He had been trailed for weeks before his murder by thugs believed to be members of the state security forces.
There are demands — though doubtful to come to fruition — from Amnesty International for a full investigation into his death.
Walter Trochez told Amnesty International on Friday that he had escaped a kidnapping attempt on 4 December after suffering several hours of beatings and threats by masked men. They had interrogated Walter Trochez about individuals opposed to the de facto authorities who seized power following the 28 June coup d'état.
"The murder of Walter Trochez must be investigated immediately and those responsible brought to justice." said Kerrie Howard, Americas Deputy Director at Amnesty International. "It is essential that human rights defenders and opposition activists are able to exercise freedom of expression without fearing threats or attacks."
activists Amnesty International Crime deaths honduras Murder walter trochez
Subscribe to Queerty for a daily dose of #activists #amnestyinternational #crime stories and more
I'm so glad you are helping to get the word out about Walter's assassination. He was a colleague and friend of mine and his death is a shocking reminder of the price of advocating for equity. Unfortunately Walter's killing is only a symptom of the downward spiral in Honduras, and activists for all varieties of human rights are being killed and disappeared there with increasing frequency. Only by making these kind of tragic deaths known can we hope to put a stop to these abuses.
One small correction, in spite of what's being published, he was actually 27–still far too young to die.
December 15, 2009 at 11:12am
Jaroslaw
This is truly sad, but I hope it motivates people to do SOMETHING, anything on behalf of Gay Rights everywhere. Make a telephone call, write a letter, donate some money, volunteer at the Gay community center. Don't let this death be for nothing.
December 15, 2009 at 12:12pm
So sad… As they say: mourn his death, celebrate his life. I agree, Jaroslaw. Let's not let his death be in vain, his life should inspire us to more action.
FakeName
Within 24 hours of the death of a gay-for-pay porn star there were over 30 comments, including several that accused the police of murder.
Here we have an actual assassination of an actual gay activist and it garners three responses.
Nice priorities, Queerty readers. Outrage for the porn star, silence for the hero.
Hyhybt
Where did you get the idea that the number of comments was a good indicator of "priorities?" There's just not much to say on this one yet, and, for this audience at least, it's completely noncontroversial, so nothing to argue about either.
December 16, 2009 at 3:12pm
I just find it fascinating that the voices calling for life in prison for the sheriff's deputies in Florida for "murder" are silent here. The first comment out of the box called the police executioners and the second called for them to be imprisoned for life for the "murder of a gay man". Yet none of those who worked themselves up into a froth over the death of a porn star seem to be bothered enough by the assassination of a gay activist to vent with equal vigor, or at all. I do think it says something about the priorities of some members of the community when they go ballistic over the former and don't even appear to notice the latter.
Make a donation to the Alianza Centroamericana (Alianza CA) which is the regional LGBT group covering Nicaragua, Honduras, Guatemala, El Salvador, Panama, and Costa Rica. You can reach them through the IDSDH – Iniciativa Desde la Diversidad Sexual por los Derechos Humanos (Sexual Diversity Initiative for Human Rights) – the national group in Nicaragua (http://idsdh.org).
HYHYBT: I agree with Fakename here. (although I do understand what you mean about this being n/c for people who read here) however, People could be commenting on how sad this is, or what they are going to do or even ASKING what can be done. (see post#7) I don't know how you verify if that is legit, but surely we could donate someplace. PS- Queerty used to show how many people viewed items -THAT would be a great indicator. Wonder why they stopped?
December 18, 2009 at 9:12am


it snowed last night. there is lots and lots of snow. i had to drive in it for the first time ever (well, i've been in cars on the snow, but i've never been the one driving). had to drive on the highway. took it really slow. didn't die, didn't kill anyone, didn't wreck Audrey. will get better at it with time.
at least the snow should stop before I have to drive home.


Prime numbers keeps reducing with its range. 0-100, 100-200 (100-200 will have less number of primes than 0-100) If you want to know the number of prime numbers in any given range and the list, check M4apt's fastest tool.
There is only one prime number which is even - that is 2 - and it also happens to be less than 100. All other prime numbers are odd.
A prime number (or prime) is a natural number greater than 1 that has no positive divisors other than 1 and itself. By Euclid's theorem, there are an infinite number of prime numbers. Subsets of the prime numbers may be generated with various formulas for primes.
This c++ code prints out the following prime numbers: 3 5 7 11 13 17 19 23 29 31 37 41 43 47 53 59 61 67 71 73 79 83 89 97. But I don't think that's the way my book wants it to be written. It mentions something about square root of a number.
Thus, when generating a bounded sequence of primes, when the next identified prime exceeds the square root of the upper limit, all the remaining numbers in the list are prime. In the example given above that is achieved on identifying 11 as next prime, giving a list of all primes less than or equal to 80.
Home Search Site Largest The 5000 Top 20 Finding How Many? Mersenne Glossary Prime Curios! Prime Lists FAQ e-mail list Titans Submit primes. What is small? Depends on your context, but since this site focuses on titanic primes (those with more than 1000 digits), any prime with less than 1000 digits is small.


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Glaucoma | August 2017
Establishment and Characterization of an Acute Model of Ocular Hypertension by Laser-Induced Occlusion of Episcleral Veins
Liwei Zhang; Guangyu Li; Meng Shi; Hsin-Hua Liu; Shaokui Ge; Yvonne Ou; John G. Flanagan; Lu Chen
Author Affiliations & Notes
Liwei Zhang
Center for Eye Disease and Development, Vision Science Graduate Program, University of California, Berkeley, California, United States
School of Optometry and Vision Science, University of California, Berkeley, California, United States
Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, China
Guangyu Li
Meng Shi
Hsin-Hua Liu
Shaokui Ge
Yvonne Ou
Department of Ophthalmology, University of California, San Francisco, California, United States
John G. Flanagan
Lu Chen
Correspondence: Lu Chen, 689 Minor Hall, University of California, Berkeley, CA 94720, USA; chenlu@berkeley.edu.
Investigative Ophthalmology & Visual Science August 2017, Vol.58, 3879-3886. doi:10.1167/iovs.16-20807
This feature is available to authenticated users only.
Liwei Zhang, Guangyu Li, Meng Shi, Hsin-Hua Liu, Shaokui Ge, Yvonne Ou, John G. Flanagan, Lu Chen; Establishment and Characterization of an Acute Model of Ocular Hypertension by Laser-Induced Occlusion of Episcleral Veins. Invest. Ophthalmol. Vis. Sci. 2017;58(10):3879-3886. doi: 10.1167/iovs.16-20807.
© ARVO (1962-2015); The Authors (2016-present)
Purpose: This study was designed to develop and characterize a laser-induced model of acute intraocular hypertension that permits the study of the anterior segment of the eye.
Methods: CD1 mice aged 5 and 8 weeks were examined for elevation of IOP induced by laser photocoagulation. We compared between occlusion of episcleral veins alone and when combined with 270° limbal vessel occlusion. Anterior chamber angle, corneal thickness, and retinal nerve fiber layer (RNFL) thickness were evaluated by anterior- and posterior-segment optical coherence tomography (OCT). Additionally, at day 7 post-procedure, the anterior segment was evaluated for inflammatory cellular presentation by histologic analysis and OCT, and limbal vessels and whole-mount retina were immunostained for CD31 and Brn3a, respectively. Brn3a-positive retinal ganglion cells (RGCs) were quantified with ImageJ software.
Results: After single or combined laser treatment in mice aged 5 or 8 weeks, IOP was significantly elevated for 5 to 6 days before returning to the baseline by day 7 post-procedure. Anterior segment assessment indicated less synechiae in the anterior chamber angle and better preserved limbal vessels with single versus combined laser treatment. Corneal thickness was significantly increased after single or combined treatment. No inflammatory cells were detected in the anterior chamber. The thickness of the RNFL and the density of RGCs were both significantly reduced after single or combined treatment.
Conclusions: Laser photocoagulation of episcleral veins alone in CD1 mice aged 5 to 8 weeks may be used to induce ocular hypertension resulting in RNFL thinning and ganglion cell loss. This model permits the study of the anterior as well as the posterior segment of the eye.
Glaucoma is a leading cause of irreversible blindness. It is estimated that 111.8 million people will be affected by this disease worldwide in 2040.1 Given its importance and multifacets, the mechanisms underlying glaucoma have been studied extensively but are not yet fully understood.2–7 We recently reported the first evidence that Schlemm's canal, a critical structure involved in aqueous humor drainage, expresses Prox-1, the master control gene for lymphatic development.8 This novel finding aligns well with several succeeding reports showing that Schlemm's canal is a VEGF-C/VEGFR-3 responsive lymphatic-like vessel and Prox-1 determines its integrity and identity.9,10 We are therefore interested in studying the structures located at the anterior chamber angle and exploring possible new mechanisms and therapeutic targets for glaucoma.
The purpose of this study was to develop a mouse model of acute intraocular hypertension that permits the study of the anterior segment of the eye. While a variety of mouse models have been developed to establish elevated IOP for glaucoma research, it is acknowledged that they are all bound by limitations. Nevertheless, depending on the subject of interest, it is possible to choose or develop a specific model to best approach individual research goals. Recently, an animal model of elevated IOP and glaucoma was developed by injection of microbeads into the anterior chamber with subsequent blockage of the aqueous humor outflow pathway.11–13 While this model best suits studies of the posterior segment of the eye, its application to the anterior segment is limited by blockade and damage of the angle structures. Laser photocoagulation is another method to induce ocular hypertension. This method was first developed in rats using a hand-held ophthalmic cautery to induce chronic hypertension.14 It was later reported that chronic hypertension can also be achieved in mice using laser photocoagulation by targeting both the limbus and the episcleral veins,15 by targeting the limbus following anterior chamber cannulation,16 by targeting the trabecular meshwork through the limbus,17 or by targeting the trabecular meshwork and the episcleral veins.18 Fu et al.19 reported a mouse model of acute ocular hypertension by laser photocoagulation of both limbal and episcleral vessels, and with this model, IOP elevation returns to normal within 1 week post-procedure. All these models, whether of the acute or chronic type, cause damage to the anterior chamber angles and are thus not ideal for our research purpose.
In this paper, we present an acute ocular hypertension model in CD1 mice using laser-induced occlusion of the episcleral veins alone. This model, avoiding direct cautery on limbal vessels or nearby structures, overcomes barriers of other mouse models that hinder the study of the anterior chamber angle. By comparative analysis between occlusion of episcleral veins alone and when combined with 270° limbal vessel occlusion, we show that occlusion of episcleral veins alone in CD1 mice is effective in inducing IOP elevation for 1 week, and this insult also leads to thinning of the retinal nerve fiber layer (RNFL) and loss of retinal ganglion cells (RGCs). More importantly, this model is associated with less synechiae of the anterior chamber angle and thereby permits the study of both anterior and posterior segments of the eye. Because the structures of the iridocorneal angles of the mice mature by postnatal days 35 to 42,20 we studied mice as early as 5 weeks of age. In addition, mice aged 8 weeks that are more commonly used for adult stage study, were also investigated. Our study revealed similar results between the groups. Taken together, we have demonstrated that this model of laser-induced occlusion of the episcleral veins alone can be used to study both anterior and posterior segments of the eye, and it can be used in CD1 mice aged 5 to 8 weeks. Further investigations using this new model may facilitate the discovery and development of new mechanisms and treatment for glaucoma.
Five- and eight-week-old male CD1 mice (Charles River Laboratories, Wilmington, MA, USA) were used in the study. All animals were treated according to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research, and all protocols were approved by the animal care and use committee at the University of California, Berkeley. Mice were anesthetized using a mixture of ketamine, xylazine, and acepromazine (50 mg, 10 mg, and 1 mg/kg body weight, respectively) for each surgical procedure. This was complemented with topical anesthesia using 0.5% proparacaine hydrochloride ophthalmic solution (Bausch & Lomb, Rochester, NY, USA). Antibiotic ointment was applied after laser treatment.
Measurement of Intraocular Pressure
Intraocular pressure was measured by a noninvasive TonoLab tonometer (Icare Lab, Helsinki, Finland) under light general anesthesia with 2% isoflurane. The measurement was performed three times for each eye, with each instrument-generated average derived from six effective IOP measurements.
Laser Photocoagulation
Mice were randomized to receive unilateral laser photocoagulation (532 nm, OcuLight TX; IRIDEX Corporation, Mountain View, CA, USA) on the right eye using the parameter settings of power, treatment duration, and spot number. As illustrated in Supplementary Figure S1, for episcleral veins occlusion, the setting is 300 mW × 0.5 seconds × 70 to 80 spots; for combined laser photocoagulation with 270° limbal vessels (sparing nasal 90° aspect and long posterior ciliary artery), the setting is 300 mW × 0.5 seconds × 110 to 120 spots. The left eye was used as control. Intraocular pressure was measured pre- and post-laser treatment for 7 consecutive days in both eyes. Mice with IOP between 30 and 50 mm Hg in the right eye at day 1 after laser treatment were included in subsequent experiments. Mice of technical failure (i.e., hyphema) with IOP above 50 mm Hg, which occurred rarely (4/153), were excluded from the study.
Anterior and Posterior Segment Optical Coherence Tomography
The analysis was performed as previously reported.21–24 For evaluation of central corneal thickness and peripheral anterior synechiae, an anterior-segment optical coherence tomography (OCT; Visante OCT MODEL 1000; Carl Zeiss Meditec, Dublin, CA, USA) was used. Quadrant-scans along four axes (0°–180°, 45°–225°, 90°–270°, and 135°–315°) were performed to ensure scanning through the central cornea and data along the 0° to 180° axis were used for analysis. For evaluation of RNFL thickness, upon pupil dilation with 1% tropicamide ophthalmic solution (Akorn, Inc., Lake Forest, IL, USA), a posterior segment OCT (Envisu R2300; Bioptigen, Inc., Morrisville, NC, USA) was used to capture retinal cross-section images. A rectangular scanning sequence (3 × 3 mm) produced a single en face image of the retina using a customized mouse lens (50° field of view), which consisted of 100 B-scan images (each B-scan comprised 1000 A-scans). The B-scan images were analyzed with the manufacturer's InVivoVue Clinic software (Bioptigen, Inc.). Retinal nerve fiber layer thickness was measured in 4 quadrants (nasal, temporal, superior, and inferior) of the en face image by masked observers. Measurements at 400 μm from the center of the optic nerve head were performed within each quadrant. Consequently, a total of four readings were averaged to return a single thickness value. For evaluation of inflammatory cells in the anterior chamber, eyes pre- and 7 days after laser treatment were examined by high-resolution OCT and cellular presentation was evaluated as opaque dots that did not adhere to the cornea, iris, or lens, as previously reported.21,23
Hematoxylin and Eosin Stain
The experiment was performed as described previously.23,25–27 Laser-treated eyes at day 7 post-procedure were harvested and embedded in optimal cutting temperature compound (Tissue-Tek; Sakura Finetek, Torrance, CA, USA). Frozen sections (6 μm) were fixed with 4% paraformaldehyde and stained with hematoxylin (Fisher Scientific, Pittsburgh, PA, USA) and eosin (Leica Biosystems, Richmond, IL, USA) (H&E). Five to six sections per animal were evaluated for the presence of inflammatory cells in the anterior chamber.
Assessment of Limbal Vessels
The experiment was performed as described previously.24 Briefly, whole-mount limbal tissues were harvested at day 7 post-procedure, fixed in 4% paraformaldehyde, and immunostained with primary rat-anti-mouse CD31 antibody (BD Pharmingen, San Diego, CA, USA) that was visualized by Cy3-conjugated donkey anti-rat secondary antibody (Jackson-Immuno Research Laboratories, West Grove, PA, USA). Samples were mounted with Vectashield mounting medium (Vector Laboratories, Burlingame, CA, USA) and examined by an AxioImager M1 epifluorescence deconvolution microscope with AxioVision 4.8 software (Carl Zeiss AG, Göttingen, Germany).
Assessment of Retinal Ganglion Cell Density
The experiment was performed as described previously.28 Briefly, whole-mount retinae were harvested at day 7 post-procedure, fixed in methanol, and immunostained with primary goat-anti-mouse Brn3a antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA), which was recognized by Cy3-conjugated donkey anti-goat secondary antibody (Abcam, Cambridge, MA, USA). Samples were mounted with Vectashield mounting medium (Vector Laboratories) and examined by the AxioImager M1 epifluorescence deconvolution microscope with AxioVision 4.8 software (Carl Zeiss AG). For each retina, eight areas were randomly selected at a distance of 850 μm from the optical disc for data analysis.29 Digital images were analyzed to quantify the density of Brn-3a+ cells in each area (688 × 545 μm) using ImageJ software (http://imagej.nih.gov/ij/; provided in the public domain by the National Institutes of Health, Bethesda, MD, USA). The percentage scores were obtained by normalizing to control condition defined as being 100%.24
Data were reported as mean ± SEM. The statistical significance between two groups was assessed by Student's t-test with Prism software (GraphPad, La Jolla, CA, USA). Mann-Whitney U test was performed for Figures 5 and 6. Fisher' exact test was used for Figure 2C and 3C with R Studio software (R Studio Inc., Boston, MA, USA). P less than 0.05 was considered significant.
View OriginalDownload Slide
Intraocular pressure measurement with single or combined laser treatment in mice of 5 or 8 weeks of age. (A) Intraocular pressure elevation after single or combined laser treatment, as compared with control contralateral eyes, in mice aged 5 (n = 13–17/group) or 8 (n = 10–12/group) weeks. ***P < 0.001, **P < 0.01. (B) No significant difference was found between 5 (n = 13–17/group) and 8 (n = 10–12/group) weeks of age with single versus combined treatment. n.s., not significant.
Anterior-segment OCT evaluation of central corneal thickness and anterior chamber angles in mice age 5 weeks. (A) Representative OCT images showing central corneal thickness and anterior chamber angles pre- (Day 0) and post-laser treatment on days 1 and 7 after the single or combined procedure. White circle indicates normal anterior chamber angle; red circle indicates synechiae at the angle with iris flattening; blue bar indicates site of measurement for central corneal thickness. Scale bar: 1 mm. (B) Summarized data showing significantly lower rate of synechiae in single than combined treatment. *P < 0.05 (n = 13–17/group). (C) Summarized and comparative data showing increased central corneal thickness at day 1 after single or combined treatment. No significant difference was found at day 7 after the procedures. ***P < 0.001. n.s., not significant (n = 10–12/group).
Anterior-segment OCT evaluation on central corneal thickness and anterior chamber angles in mice aged 8 weeks. (A) Representative OCT images showing central corneal thickness and anterior chamber angles pre- (Day 0) and post-laser treatment on days 1 and 7 after the single or combined procedure. White circle indicates normal anterior chamber angle; red circle indicates synechiae at the angle with iris flattening; blue bar indicates site of measurement for central corneal thickness. Scale bar: 1 mm. (B) Summarized data showing significantly lower rate of synechiae in single than combined treatment. *P < 0.001 (n = 10–12/group). (C) Summarized and comparative data showing increased central corneal thickness at day 1 after single or combined treatment. No significant difference was found at day 7 after the procedures. ***P < 0.001. n.s., not significant (n = 10–12/group).
Posterior-segment OCT evaluation on the thickness of RNFL after single or combined laser treatment in mice aged 5 or 8 weeks. (A) Representative OCT image showing a normal retina of a CD1 mouse. Yellow cross shows the measurement location at 400-μm distance from the optic nerve head. Scale bar: 500 μm. (B) Representative posterior-segment OCT image of the RNFL layer and total retina in a normal CD1 mouse. Scale bar: 100 μm. (C) Summarized data showing significant reduced RNFL thickness at day 7 post procedure in mice aged 5 or 8 weeks in both single and combined treatment settings. *P < 0.05 (n = 16–18/group). IPL, inner plexiform layer; ONL, outer nuclear layer.
Immunofluorescent microscopic analysis of retinal ganglion cell loss after single or combined treatment in mice aged 5 weeks. (A) Representative images showing reduced Brn3a+ cells (red) in the retina 7 days after single (upper panels) or combined (lower panels) laser treatment, as compared with untreated contralateral retina. Scale bar, 100 μm. Summarized data are presented in (B) and (C) for single and combined treatment, respectively. ***P < 0.001 (n = 9/group).
Immunofluorescent microscopic analysis of RGC loss after single or combined treatment in mice aged 8 weeks. (A) Representative images showing reduced Brn3a+ cells (red) in the retina 7 days after single (upper panels) or combined (lower panels) laser treatment, as compared with untreated contralateral retina. Scale bar: 100 μm. Summarized data are presented in (B) and (C) for single and combined treatment, respectively. ***P < 0.001 (n = 9/group).
Comparative Analysis of Elevation of Intraocular Pressure Between Single and Combined Laser Treatment and Between Mice Aged 5 and 8 Weeks
Intraocular pressure is an important risk factor of glaucoma. We first set out to assess whether IOP elevation can be induced by laser photocoagulation of the episcleral veins alone, and how it compared with the combined treatment including limbal vessels. Because structures of the iridocorneal angles typically mature by postnatal day 35 to 42,20 we also compared the results between CD1 mice at 5 or 8 weeks of age. Our results on day 1 post-procedure showed that for mice 8 weeks of age, the success rates for mice reaching IOP between 30 and 50 mm Hg after the single and combined treatment are 60% and 63%, respectively, and the corresponding rates for mice 5 weeks of age are 61% and 70%, respectively. The mice with IOP between 30 and 50 mm Hg were included for further analysis.
As presented in Figure 1A, after single or combined laser treatment with mice aged 5 or 8 weeks, IOP was significantly elevated for 5 to 6 days before returning to the baseline by day 7 post-procedure. No significant difference was observed at each time point between mice aged 5 or 8 weeks in single or combined treatment (Fig. 1B). Our further analysis on short-term IOP changes at 4, 10, and 24 hours after laser treatment showed that IOP of the treated eyes was significantly elevated at 4 hours post-procedure and it remained above that of the control eyes at 10 and 24 hours post-procedure. No significant difference was observed between the single or combined treatment (Supplementary Fig. S2).
Comparative Analysis of Peripheral Anterior Synechiae Between Single and Combined Laser Treatment and Between Mice Aged 5 and 8 Weeks
We next examined peripheral anterior synechiae (PAS) in the anterior chamber angle with anterior segment OCT,17 and compared the results between single and combined laser treatment, and between mice of 5 and 8 weeks of age. The presence of PAS with flattening iris,30 as demonstrated by representative OCT images in Figures 2A and 3A (red circles in lower panels), indicates laser-induced adherence of iris tissue to the nearby angle structures after the insult. As summarized in Figure 2B and 3B, our results from mice aged 5 weeks showed significantly higher incidence of PAS in the combined versus single treatment setting (82.35% vs. 7.69%), and this dramatic difference was also observed in mice aged 8 weeks (91.67% vs. 10.0%). Taken together, these data suggest that single laser treatment results in fewer PAS than the combined treatment.
Comparative Analysis of Central Corneal Thickness Between Single and Combined Laser Treatment and Between Mice Aged 5 and 8 Weeks
We also evaluated the thickness of the central cornea using anterior-segment OCT, an important parameter associated with IOP elevation and corneal edema. Our results in mice of 5 and 8 weeks of age (Figs. 2C and 3C, respectively) showed a similar pattern where corneal thickness was significantly increased with peak IOP at day 1 after single or combined treatment. By day 7 when IOP returned to baseline, no significant difference was detected with corneal thickness between treated and control eyes, in all experimental settings.
Assessment of Inflammatory Cells in the Anterior Chamber
Previously, it was reported that black Swiss mice after laser treatment at the limbus showed no evidence of inflammation in the anterior segment.26 In this study with the CD1 mice, we performed histologic analysis of laser-treated eyes on day 7 post-procedure with H&E staining, as previously reported.23 While our results confirmed the presence of PAS with combined laser treatment, no inflammatory cells were detected in the anterior chamber after single or combined laser treatment in mice aged 5 or 8 weeks (Supplementary Fig. S3). This negative result was also confirmed by high-resolution OCT where no cellular presentation, defined as opaque dots that did not adhere to the cornea, iris, or lens,21,23 was detected in the anterior chamber (Supplementary Fig. S4).
To assess the condition of limbal vessels after single or combined laser treatment, we performed immunofluorescent microscopic analysis using specific antibody against CD31, a panendothelial cell marker. As shown in Supplementary Figure S5, compared with combined treatment that resulted in significant loss of limbal vessels upon laser photocoagulation, single treatment better preserved these vessels, and this effect was observed in mice aged 5 and 8 weeks.
Comparative Analysis of Loss of Retinal Nerve Fibers Between Single and Combined Laser Treatment and Between Mice Aged 5 and 8 Weeks
The above data indicate that single laser occlusion of episcleral veins alone is effective in inducing acute IOP elevation and meanwhile preserving the anterior segment. Because glaucoma is a disease associated with optic nerve damage, we next assessed thinning of the RNFL by posterior segment OCT, and compared the results between single and combined laser treatment, and between mice of 5 and 8 weeks of age. As presented in Figure 4, this set of experiments again revealed a similar pattern between single and combined treatment, and between 5 and 8 weeks of age. The RNFL thickness at day 7 post-procedure was significantly reduced compared with day 0 in all experimental groups.
Comparative Analysis of Loss of Retinal Ganglion Cells Between Single and Combined Laser Treatment and Between Mice Aged 5 and 8 Weeks
Finally, we performed immunofluorescent microscopic assays with whole-mount retina and analyzed RGC loss with single and combined treatment, and with mice of 5 and 8 weeks of age (Figs. 5, 6). As demonstrated in Figures 5A and 6A, our results showed a significant reduction of Brn3a+ cells in all experimental settings. In mice 5 weeks of age, the density of Brn3a+ cells after single or combined treatment was decreased by 33.02% and 36.67%, respectively, compared with control. A similar pattern was observed with mice 8 weeks of age, and the corresponding reduction rates are 30.04% and 36.8%, respectively.
In summary, we have presented in this study a new mouse model of laser photocoagulation with occlusion of the episcleral veins alone. This model is effective in the induction of acute intraocular hypertension, RNFL thinning, and RGC loss. Compared with the combined model of laser photocoagulation that requires additional occlusion of the limbal vessels, this single treatment model is of smaller scale and less invasive. More importantly, because this procedure spares the limbal area, it reduces the incidence of PAS and leave the anterior chamber angles open. This study thus offers a new model that permits the study of the anterior segment of the eye in addition to the posterior segment.
In this study, we assessed age as a factor and compared mice 5 and 8 weeks of age. Because structures of iridocorneal angles of mice mature by postnatal day 35 to 42,20 and our results demonstrate elevated IOP in both age groups, the laser model should be effective with mice aged 5 to 8 weeks. Considering a previous study demonstrating that there is no significant difference in IOP between CD1 mice 2- and 10-months old,31 it may be possible to extend the working range of this laser model to 10 months of age, which warrants further investigation.
Our model of single or combined treatment is able to induce IOP elevation within the first day before it returns to baseline levels in 1 week. This week-long period of IOP elevation causes a significant reduction of RGCs by 30% to 40%. Previously, hand-held cautery models were reported in rats and CD1 mice, respectively, by surgical incision through the conjunctiva and Tenon's capsule. Intraocular pressure elevation was achieved within the first day and remained elevated for 2.5 months in rats and 4 weeks in CD1 mice, respectively.14,32 While these models induce sustained IOP elevation, it is a more challenging procedure with invasive surgery that is associated with damage of surrounding tissues. In this study, as suggested by a previous report on combined laser treatment, we spared nasal 90° of the limbal vessels and the long posterior ciliary artery to avoid acute IOP spikes (>70 mm Hg within 12 hours) that could lead to severe ischemic changes, and we did not repeat the laser treatment to extend the period of IOP elevation to avoid ocular inflammation.19 Our model of week-long elevation of IOP is already successful in inducing RGC loss and RNFL thinning. Our week-long duration of IOP elevation is consistent with the previous reports on combined laser treatment in albino CD1 or Swiss mice.19,33 While one study19 reports no significant loss of RGCs at 1 week post-procedure though a trend of decrease is observed, the other study33 shows significant loss of RGCs around 1 week post-procedure. The disparity among the studies may be due to different thresholds used in analysis. We set a threshold value of IOP at 30 mm Hg on day 1 after laser treatment because our preliminary experiments indicate no significant loss of RGCs in mice with IOP below this threshold. Our data on loss of RGCs align well with thinning of the RNFL, which is also apparent at 1 week post-procedure. In this study, we also observed pupil dilation upon IOP elevation, as reported previously.18 This may be due to compromised pupil sphincter upon IOP elevation because iris blood vessels are not autoregulated.34,35 This phenomenon is also seen in patients of acute glaucoma.
Taken together, we have developed a new mouse model of laser coagulation that can be used to study both the anterior and posterior segment of the eye and can be employed in mice aged 5 to 8 weeks, and possibly older. This model recapitulates key parameters associated with acute glaucoma and can potentially be used to study this disease from various aspects.
The authors thank the Core Translational Module at Vision Science Graduate Program and School of Optometry, University of California at Berkeley, for statistical assistance.
Supported in part by grants from National Institutes of Health and the University of California at Berkeley (LC; Berkeley, CA, USA).
Disclosure: L. Zhang, None; G. Li, None; M. Shi, None; H.-H. Liu, None; S. Ge, None; Y. Ou, None; J.G. Flanagan, None; L. Chen, None
Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014; 121: 2081–2090.
Wiggs JL. Glaucoma genes and mechanisms. Prog Mol Biol Transl Sci. 2015; 134: 315–342.
Wax MB. The case for autoimmunity in glaucoma. Exp Eye Res. 2011; 93: 187–190.
Dibas A, Yorio T. Glucocorticoid therapy and ocular hypertension. Eur J Pharmocol. 2016; 787: 57–71.
Davis BM, Crawley L, Pahlitzsch M, Javaid F, Cordeiro MF. Glaucoma: the retina and beyond. Acta Neuropathol. 2016; 132: 807–826.
Aboobakar IF, Johnson WM, Stamer WD, Hauser MA, Allingham RR. Major review: exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology. Exp Eye Res. 2017; 154: 88–103.
Quigley HA. The contribution of the sclera and lamina cribrosa to the pathogenesis of glaucoma: diagnostic and treatment implications. Prog Brain Res. 2015; 220: 59–86.
Truong TN, Li H, Hong YK, Chen L. Novel characterization and live imaging of Schlemm's canal expressing Prox-1. PLoS One. 2014; 9: e98245.
Aspelund A, Tammela T, Antila S, et al. The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel. J Clin Invest. 2014; 124: 3975–3986.
Park DY, Lee J, Park I, et al. Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity. J Clin Invest. 2014; 124: 3960–3974.
Sappington RM, Carlson BJ, Crish SD, Calkins DJ. The microbead occlusion model: a paradigm for induced ocular hypertension in rats and mice. Invest Ophthalmol Vis Sci. 2010; 51: 207–216.
Chen H, Wei X, Cho KS, et al. Optic neuropathy due to microbead-induced elevated intraocular pressure in the mouse. Invest Ophthalmol Vis Sci. 2011; 52: 36–44.
Morgan JE, Tribble JR. Microbead models in glaucoma. Exp Eye Res. 2015; 141: 9–14.
Shareef SR, Garcia-Valenzuela E, Salierno A, Walsh J, Sharma SC. Chronic ocular hypertension following episcleral venous occlusion in rats. Exp Eye Res. 1995; 61: 379–382.
Gross RL, Ji J, Chang P, et al. A mouse model of elevated intraocular pressure: retina and optic nerve findings. Trans Am Ophthalmol Soc. 2003; 101: 163–169; discussion 169–171.
Feng L, Chen H, Suyeoka G, Liu X. A laser-induced mouse model of chronic ocular hypertension to characterize visual defects. J Vis Exp. 2013;78:50440.
Yun H, Lathrop KL, Yang E, et al. A laser-induced mouse model with long-term intraocular pressure elevation. PLoS One 2014; 9: e107446.
Grozdanic SD, Betts DM, Sakaguchi DS, Allbaugh RA, Kwon YH, Kardon RH. Laser-induced mouse model of chronic ocular hypertension. Invest Ophthalmol Vis Sci. 2003; 44: 4337–4346.
Fu CT, Sretavan D. Laser-induced ocular hypertension in albino CD-1 mice. Invest Ophthalmol Vis Sci. 2010; 51: 980–990.
Smith RS, Zabaleta A, Savinova OV, John SW. The mouse anterior chamber angle and trabecular meshwork develop without cell death. BMC Dev Biol. 2001; 1: 3.
Downie LE, Stainer MJ, Chinnery HR. Monitoring of strain-dependent responsiveness to TLR activation in the mouse anterior segment using SD-OCT. Invest Ophthalmol Vis Sci. 2014; 55: 8189–8199.
Liu HH, Flanagan JG. A mouse model of chronic ocular hypertension induced by circumlimbal suture. Invest Ophthalmol Vis Sci. 2017; 58: 353–361.
Pepple KL, Choi WJ, Wilson L, Van Gelder RN, Wang RK. Quantitative assessment of anterior segment inflammation in a rat model of uveitis using spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2016; 57: 3567–3575.
Zhang L, Li G, Sessa R, et al. Angiopoietin-2 blockade promotes survival of corneal transplants. Invest Ophthalmol Vis Sci. 2017; 58: 79–86.
Joos KM, Li C, Sappington RM. Morphometric changes in the rat optic nerve following short-term intermittent elevations in intraocular pressure. Invest Ophthalmol Vis Sci. 2010; 51: 6431–6440.
Aihara M, Lindsey JD, Weinreb RN. Experimental mouse ocular hypertension: establishment of the model. Invest Ophthalmol Vis Sci. 2003; 44: 4314–4320.
Manuguerra-Gagne R, Boulos PR, Ammar A, et al. Transplantation of mesenchymal stem cells promotes tissue regeneration in a glaucoma model through laser-induced paracrine factor secretion and progenitor cell recruitment. Stem Cells. 2013; 31: 1136–1148.
Tual-Chalot S, Allinson KR, Fruttiger M, Arthur HM. Whole mount immunofluorescent staining of the neonatal mouse retina to investigate angiogenesis in vivo. J Vis Exp. 2013; e50546.
Chintala SK, Putris N, Geno M. Activation of TLR3 promotes the degeneration of retinal ganglion cells by upregulating the protein levels of JNK3. Invest Ophthalmol Vis Sci. 2015; 56: 505–514.
Nissirios N, Chanis R, Johnson E, et al. Comparison of anterior segment structures in two rat glaucoma models: an ultrasound biomicroscopic study. Invest Ophthalmol Vis Sci. 2008; 49: 2478–2482.
Cone FE, Steinhart MR, Oglesby EN, Kalesnykas G, Pease ME, Quigley HA. The effects of anesthesia, mouse strain and age on intraocular pressure and an improved murine model of experimental glaucoma. Exp Eye Res. 2012; 99: 27–35.
Ruiz-Ederra J, Verkman AS. Mouse model of sustained elevation in intraocular pressure produced by episcleral vein occlusion. Exp Eye Res. 2006; 82: 879–884.
Salinas-Navarro M, Alarcon-Martinez L, Valiente-Soriano FJ, et al. Functional and morphological effects of laser-induced ocular hypertension in retinas of adult albino Swiss mice. Mol Vis. 2009; 15: 2578–2598.
Charles ST, Hamasaki DI. The effect of intraocular pressure on the pupil size. Arch ophthalmol. 1970; 83: 729–733.
Chamot SR, Movaffaghy A, Petrig BL, Riva CE. Iris blood flow response to acute decreases in ocular perfusion pressure: a laser Doppler flowmetry study in humans. Exp Eye Res. 2000; 70: 107–112.
iovs-58-09-29_s01.pdf
Copyright 2017 The Authors
Laser-Induced Ocular Hypertension in Albino CD-1 Mice
Experimental Mouse Ocular Hypertension: Establishment of the Model
Sustained Ocular Hypertension Induces Dendritic Degeneration of Mouse Retinal Ganglion Cells That Depends on Cell Type and Location
Ocular Hypertension in Mice with a Targeted Type I Collagen Mutation
Neuroprotection of Retinal Ganglion Cells by Brimonidine in Rats with Laser-Induced Chronic Ocular Hypertension
From Other Journals
Transcorneal Electrical Stimulation Inhibits Retinal Microglial Activation and Enhances Retinal Ganglion Cell Survival After Acute Ocular Hypertensive Injury
Latrunculin B Reduces Intraocular Pressure in Human Ocular Hypertension and Primary Open-Angle Glaucoma
Thermal Stimulation of the Retina Reduces Bruch's Membrane Thickness in Age Related Macular Degeneration Mouse Models
A Novel Method of Quantitative Anterior Chamber Depth Estimation Using Temporal Perpendicular Digital Photography
A Rayleigh Scatter-Based Ocular Flare Analysis Meter for Flare Photometry of the Anterior Chamber
Eye Anatomy and Disorders
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text:
Pharmacists for Life International (PFLI) is an international pro-life organization advocating the rights of pharmacists who refuse to fill or dispense prescriptions for artificial, hormonal, or emergency contraception to "protect the rights of employees who hold religious beliefs". PFLI holds that no "employee should be forced to choose between their livelihood and their conscience". In the United States, at least six states have such conscience clauses for personnel in medical-related fields.

PFLI President Karen Brauer was fired in 1996 from a Kmart pharmacy in Delphi, Ohio for refusing to fill birth control prescriptions. The American Center for Law and Justice (ACLJ) represented Brauer and filed suit against Kmart in U.S. District Court in Cincinnati in August 1999. In January 2001, the court refused Kmart's request to dismiss the suit, ruling that Brauer's case could go forward under Ohio's conscience law.  On April 16, 2001, in an appearance on Fox News's The O'Reilly Factor, Brauer acknowledged that she did not directly decline or refuse to fill the prescription but, rather, lied to the customer by saying the pharmacy was out of stock of the contraceptive in question (Micronor), which Brauer holds is designed to "terminate a human life that has already begun". When the customer learned the truth she complained to the store's management, which led to the incident which in turn resulted in Brauer's lawsuit.

References

External links
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Anti-abortion organizations


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For the previous round-up posts: Wave 1, Wave 2, Wave 3, Wave 4, Wave 5, Wave 6 and Wave 7!
Crunchyroll returns stealthy with a bunch of simulcasts not necessarily announced themselves. Most turned up without warning though so we had to discover the details ourselves.
Currently this will be the final wave of Spring 2018 seasonal announcements, as there won't be any more turning up over the next couple of weeks aside from To Be Hero Second Season sometime this May. We already covered the details for Isekai Izakaya in the first wave round-up post in case you missed it.
This titles listed below were revealed during the 11th April all the way to 13th April.
Regions: United States, Canada, United Kingdom, Ireland, Australia, New Zealand, South Africa, Denmark, Norway & Sweden.
Kaname's a popular girl at her high school, but it's her popularity off campus that's the problem. Unbeknownst to Kaname, terrorists are plotting her abduction, believing she possesses the abilities of the "Whispered." That's where Sousuke enters the picture. He's a soldier from Mithril, a secret counter-terrorist unit – and he's going undercover at Kaname's school to try and keep her safe.
A war between heaven and hell is raging on Earth – and hormonal fury is raging in Issei's pants. Enter curvy redhead Rias, president of The Occult Research Club: a club that doesn't actually research the occult. They are the occult – and Rias is a Devil!
Regions: United States, Canada, United Kingdom, Ireland, South Africa, Denmark, Norway & Sweden.
One more note to add with regards to High School DxD HERO. The simulcast was delayed due to 'production issues' so the timeslot that Crunchyroll has listed may change each week. In addition due to licensing restrictions (and how AT-X in Japan has timed exclusivity) the simulcast shown will be the censored version and that the uncensored version will be available on the Blu-ray release planned later down the line.
That's all of the remaining titles revealed for Crunchyroll's services. As mentioned in the past there are a couple titles that will be appearing on other platforms, for example Magical Girl Site and Wotakoi: Love is Hard for Otaku will be on Amazon Prime while Dragon Pilot and Piano no Mori are expected to be on Netflix.


text:
1979 Tara 2022
Tara Lynn Halverson
August 18, 1979 — November 8, 2022
Tara Halverson
Our beloved Tara was called home to our heavenly father on November 8th, 2022. She passed away far too soon at the young age of 43. Words cannot describe the grief the family is feeling but they are comforted in knowing that she is now with our Father in heaven, and finally at peace.
Tara was born in Ogden, Utah on August 18th, 1979, to parents Joel Craig Halverson and Tamara Lynn Novosel. Tara was the big sister of the family. She was always there for her sisters as a comforter and protector, both in childhood and adulthood. Her life was centered around her sweet son Jaxxon, and she did anything and everything to make sure her son was without want. Tara was a good mom, above all else, and was always doing everything she could to ensure her son had the best life and was well taken care of. She had a heart of gold and would be there for anyone in a heartbeat. Anyone would tell you that Tara had the biggest heart and was the most kind and caring soul. She always put others before herself and would give anything she had to others in need. Tara had such a big impact on so many people's lives. She was a bright and shining light to all that knew her, and heaven is now a brighter place with her in it.
Tara is survived by her son Jaxxon, mother Tammy, stepmother Debbie, sisters Tanya, Trisha, and Tosha, brothers Kirt, Kyle, and Colten, and 12 nieces and nephews.
Funeral Services will be held November 21, 2022 at Aaron's Mortuary 496 24th St in Ogden, at 1:00 pm, with officiator Pastor Patrick Cross. Burial will take place after funeral services at Lindquist Washington Heights Memorial Park, 4500 S Washington Blvd in Ogden.
The family has been so grateful for receiving donations through GoFundMe. All funds will be used for Jaxxon's care. If you would like to donate, please visit https://gf.me//u/3wc4cs
Nothing can replace the hole we have in our hearts, and the emptiness that is now in the family; our lives and family are now forever changed without our sweet Tara. We want to thank all of the family and friends who have come together to help comfort and support the family during these difficult times.
Psalm 34:17-18 When the righteous cry out for help, the LORD hears and delivers them out of all their troubles. The LORD is near to the brokenhearted and saves the crushed in spirit.
Thank you, Heavenly Father, for saving our sweet Tara, and for comforting our broken hearts.
To order memorial trees or send flowers to the family in memory of Tara Lynn Halverson, please visit our flower store.
Aaron's Mortuary
496 24th St, Ogden, UT 84401


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