This winter was exactly what I wanted and needed it to be for my training. I was signed up for a lot of events due to the Freezeroo series, on top of Lake Effect being tradition with the girls now. I knew that I shouldn't race all of them, and it made the most sense to pick and choose which ones would be more important. I really wanted a 10k PR(the weekend following this race), which meant this half marathon would be best suited to be a long workout. Ya know, just finally catching up on these posts here. Not that it matters- but will be fun to look back years from now and be able to read these (for me).
I picked up my friend Dawn that morning on the way out to Syracuse and we had a really easy ride which was a good start to the day. We both had to extend warm-up and cool-downs for the race to hit mileage for the day, so we grabbed our bibs and then started getting going.
Having done the race twice before(2014, 2015), I pretty much knew what to expect. At least this year there wasn't any fresh snow, so we wouldn't be encountering a trashed back half of the course(last year). Warm-up felt decent, followed by some strides. It wasn't too cold out so I was comfortable enough in my Zensah Tech+ socks, Saucony Ignite shorts, with arm warmers and the ultimitt gloves. Since I wasn't racing all out, I didn't run in the Type A6. The fast twitch are my go to for workouts and I also raced Erie in them so it made sense to use those this time around.
The plan was to run the first 10 miles around goal marathon pace (6:40ish), and then pick it up for the last 3.1 miles after that. I knew it was going to be tough to hold back, but I also kept in mind the purpose of the workout which really helped. Shortly after the start I found myself tucked in with a group of guys, something made us chuckle (I think some random guy on the course) and we found ourselves chatting after that.We talked goals non-chalantly and kind of came to an agreement to help each other and try to run together. I told them my plan for the first 10, and we went on our way.
We ran almost the entire race together!
We clicked the miles off near perfectly with pace, and chatted about upcoming goals and races as we did so. The pace felt good and I remember feeling like this pace wasn't a complete pipe dream for Boston this year. I kind of figured out mid-race that it was going to be a PR for the guys I was running with, which only motivated me more to hang on and I encouraged them as we ran. I tried not to count women as we started seeing leaders come back at us(double out and back course), because I didn't want to get caught up in racing mentality. I saw Dawn which was a good boost, and then we hit the turnaround and my personal favorite part. Seeing everyone coming at you as you're running back. I love how encouraging everyone is and really lets the running community shine. The guys that I was running with know a LOT of people (they run with a Syracuse group), so we got lots of extra cheers. Then we saw Britt and she joked about me always being with groups of guys, we all chuckled.
I saw my friend Megan and was making funny faces and arm movements, I'm really glad the photographer caught it. Shows I really was having fun and enjoying the workout/race!
When we started the second out and back, the wind was far more significant than the first trip out. My quads got a bit cold and I did some random surges occasionally just to change things up. At this point we were talking less, but still running on pace and helping each other. I kept saying "just get to the turnaround and no more headwind". Finally we hit the turnaround and as it happens, we got the reprieve from the wind. I felt a little sluggish for about a mile after we turned, and worried I wouldn't be able to pick up the pace soon. But, I surged forward before 10 and one of the guys went with me. About a mile later I was solo, but running strong and I knew I was picking it up. I could see the next girl in the distance, and wanted to see how much I could reel her in.
The last few miles were good, and certainly reassuring being able to finish a solid workout. I closed the gap a lot on 3rd place female, but couldn't quite catch her in time before we reached the finish. It was a close one though.
I finished in 1:26:41 which is 6:37 pace, and good enough for 4th place for a workout. I am really pleased with that, and technically it's my second fastest half behind my 1:24:51 at Philly in November. Definitely confidence boosting to run strong longer workout with still a good amount of training to be done before Boston. I used this as a good training day but also nutrition practice. I drank Gen UCAN prior to the race, which has worked really well for me the last few years. I actually didn't end up taking anything besides water during the race (stomach wasn't feeling a gel), but still good practice at water stops and holding pace.
Dawn, Britt and I after Blues Boozy Brunch!
Afterwards was the best part, as always. Boozey Blues Brunch at Empire Brewing Company. Good beer while we waited for a table, followed by sitting right behind the jazz band and demolishing huge plates of the best food while chatting. We missed our partner in crime Heather as she was stuck in Hawaii (I don't feel too bad for her on that one, but we did miss her).
All in all it was a successful and fun day with friends, just what running should be!
Great job!! I love when you run a race as a workout and have a good experience with it.
Thanks! Definitely a plus to have it go well, not that we ever want bad workouts- but of course it happens.
I think my jaw is still on the floor that 6:40's is a possible Boston goal pace... you are incredible, my friend!! And that is one incredibly speedy half! Way to go!!
Thank you Laura! I think I'm still wrapping my own head around 6:40's LOL!


text:
General (Ret.) Charles R. Holland
Board Director
General (Ret.) Holland was born in West Virginia. He entered the U.S. Air Force Academy and graduated in 1968 with a BS in Aeronautical Engineering. He received Masters Degrees in Business Management from Troy State University in 1976 and in Astronautical Engineering from the Air Force Institute of Technology in 1978. He completed several professional military education schools to include the Industrial College of the Armed Forces in 1986. In addition, he completed the Program for Senior Officials in National Security in 1990 and the National and International Security Management Program in 1998, both at Harvard University.
During that assignment he was responsible for all special operations forces of the Army, Navy and Air Force, both active duty and reserve. Prior to the culmination of his active duty military career, he commanded a squadron in the Philippines, two Air Force Wings, served as Deputy Commanding General of the Joint Special Operations Command, and was Commander of the Special Operations Command, Pacific. Prior to commanding USSOCOM, he commanded the Air Force Special Operations Command and was the Vice Commander of U.S. Air Forces in Europe. He was a Command Pilot with over 5000 flying hours which included over 100 combat missions in multiple C-130 and SOF aircraft to include a combat tour in the AC-130 Gunship at Ubon RTAFB, Thailand during the war in Southeast Asia.
Upon retirement, he now serves as a Director or Advisor on multiple corporate boards and acts as an independent consultant for several companies to include the USAF and the Lawrence Livermore National Laboratory (LLNL). For the past fourteen years, he has provided executive level counsel for Air Force wargame design in a joint, combined, interagency and multi-level security construct while over the last seven years serving as a Strategic Advisor for LLNL. Beyond these duties, he is a volunteer Director Emeritus on the Special Operations Warrior Foundation Board which provides college educations to the children of fallen special operations personnel and if severely wounded, the foundation ensures that loved ones have immediate funds available to travel to be bedside when they are needed most.

redpajama_set_name: RedPajamaCommonCrawl


text:
The Northeast School (or District No. 1 School) is a historic school building at 981 Summit Road in Richmond, Massachusetts.  Possibly built as early as 1791, it is one of the oldest surviving district school buildings in the state.  Now maintained by the local historical society, it was listed on the National Register of Historic Places in 2002.

Description and history
The Northeast School is located in a rural setting of northern Richmond, on the west side of Summit Road just west of its junction with Swamp Road.  It is a single-story wood-frame structure with a gabled roof.  The main portion of the building measures , and there is an extension on the north end that measures .  The basic construction is post and beam, and the building received significant restorative work in the late 19th century.

The exact construction date of the school is unclear, but is probably 1791.  Town records indicate that a school building was standing near this road junction (known as Stevens Corners) in 1791, with no mention of earlier schools.  No substantive repairs or reconstructions are recorded until 1802, when a stove was installed, and 1808, when additional repairs were ordered.  The schoolhouse remained in use until 1937, when a new townwide school was opened.  It was sold and used by farmer for storage and as a pighouse.  In 1993 the Richmond Historical Society acquired the building, restored it, and moved it across the street to its present location.  Of the town's six district schools built, it is the best preserved, and the only surviving one that has not been readapted for residential use.

See also
National Register of Historic Places listings in Berkshire County, Massachusetts

References

School buildings on the National Register of Historic Places in Massachusetts
National Register of Historic Places in Berkshire County, Massachusetts
Richmond, Massachusetts

redpajama_set_name: RedPajamaWikipedia


GK News Show Pro is a complex and powerful widget used for displaying posts with thumbnails and additional content like title, text and additional information. It creates most of the demo content on the homepage in this theme.
Please remember that you can use a lot of additional styles in this widget – more details you can find on the Widget Styles page.


The City of Boise Human Resources Department seeks to ensure that the Best Employees Work for the Best Employer to make Boise the most livable city in the country.
Our Team is here to support an engaged and productive workforce. We are always seeking talented employees who want to join our mission, share our vision, and believe in our values.
The City of Boise has a workforce of approximately 1600 in 13 departments that offer a range of services. These services are achieved through teamwork and aspire to positively affect the lives of our citizens and to make a difference in our community. We consciously use our vision, mission, and values to drive our day-to-day and long-term decision making.
The City of Boise is committed to providing equal employment opportunity for all persons without regard to race, color, religion, gender, age, national origin, sexual orientation, gender identity, disability, veteran status, or any other applicable legally protected status. Applicants may request accommodation by calling (208) 972-8090 or TTY (800) 377-3529. Qualified veterans will receive preferential treatment in accordance with Idaho State Law.


There's no going back. Retail will never be the same again as online shopping has created a global network of competition for nearly every type of product. E-commerce has created higher expectations for consumer convenience and competitive prices, but it has also given brick and mortar retailers new opportunities to shine in relation to their virtual counterpart. In a recent Forbes interview, Perry Kramer of Boston Retail Partners noted the trick to enduring this new convenience economy is competing with a quality customer experience.
For brick and mortar retailers, the game is changing and new rules are being written by the moment. Still, recent Pew Research Center research revealed 63% of Americans prefer brick and mortar over online retail. And the U.S. Department of Commerce Census Bureau reports that 92 percent of retail dollars are still spent in brick and mortar stores.
With the awareness of an impending evolution, the question turns not toward what (evolve) or when (now), but toward the question of how? Creating a great customer experience begins with understanding the customer's experience. Tracking and analyzing customer traffic patterns can inform not only the volume of customers but also the subtleties of where and how customers spend their time in the store, and how travel or queue patterns relate to sales. Data such as footfall analytics and wait times can help retailers understand in-store dynamics to better design a fresh customer experience as well as evolve customer service strategies and priorities.
Today's queue management technology automates the collection and delivery of real-time and historical data pertaining to service efficiency and customer experience in the queue. Offering real-time insights typically associated with online shopping, in-store queue management technology provides easy-to-implement monitoring that eliminates the guesswork for managers, guiding their decisions on and off the floor.
Through in-store monitoring, performance metrics are delivered in real-time through dashboards or alerts to store managers and employees. With these metrics in hand it becomes possible to predict and respond to the lulls and rushes of waiting customers, reallocating employee resources to deal with the demand.
Real-time data allows front-line employees to be proactive and take immediate action to immediately improve service efficiency and quality, minimize wait times, and improve the morale of those waiting. The end result? A streamlined customer experience that increases conversion rates, basket size, and customer loyalty.
Using state-of-the art sensors, advanced algorithms, and real-time reporting and alerts, Qtrac technology solutions help optimize service delivery while dramatically improving the customer experience.
as well as when they spend time in a targeted store zone.
as well as open or available service points.
Qtrac's holistic approach leverages technology to boost service efficiency, operational effectiveness, and the customer experience.


The DRPS has released surveillance images of two men who allegedly used bank cards stolen from a senior in Port Perry.
Shortly after 3 p.m. on Thursday (July 5), officers were called to Vos Your Independent Grocer in Port Perry after a 83-year-old man reported having his wallet and car keys stolen.
The elderly victim was putting groceries away into his vehicle when an unknown suspect approached the senior and started placing his groceries in his vehicle. The victim told the suspect that he didn't need help but the man insisted. When the victim's daughter exited the store, the suspect fled on foot.
Investigators were able to get video surveillance of two suspects utilizing the stolen bank cards at a nearby ATM in Port Perry within minutes of the cards being stolen.
Suspect #1 is described as male, white, medium build, 30 to 40's, dark hair, beard wearing short-sleeved white/blue plaid button-up shirt, navy blue shorts and a dark Tilly hat.
Suspect #2 is described as male, white, 30 to 40's, thin build, brown hair, clean shaven wearing blue/white shirt with a polo emblem, Puma baseball hat and dark shorts.
Anyone with information that could help investigators is asked to contact D/Cst. Burns of the North Division Criminal Investigation Bureau at 1-888-579-1520 ext. 2676.


Is therapy right for me? Do I really need therapy? How can therapy help me? What is therapy like?
Yes. Learning about yourself and acquiring communication skills can create change in your relationship.
How old should children be to start therapy?
Children can enter therapy once a behavioral or emotional concern has been identified.
Will a diagnosis be required by insurance company?


A federal jury in Washington convicted four Blackwater Worldwide guards Wednesday in the fatal shooting of 14 unarmed Iraqis, seven years after the American security contractors fired machine guns and grenades into a Baghdad traffic circle in one of the most ignominious chapters of the Iraq war.
The guilty verdicts on murder, manslaughter and gun charges marked a sweeping victory for prosecutors, who argued in an 11-week trial that the defendants fired recklessly and out of control in a botched security operation after one of them falsely claimed to believe the driver of an approaching vehicle was a car bomber. Jurors rejected the guards' claims that they were acting in self-defense and were the target of incoming AK-47 gunfire.
Overall, defendants were charged with the deaths of 14 Iraqis and the wounding of 17 others at Baghdad's Nisour Square shortly after noon Sept. 16, 2007. None of the victims was an insurgent.
The jury of eight women and four men deliberated 28 days before convicting Nicholas A. Slatten, 30, of Sparta, Tenn., of murder. Also convicted were Paul A. Slough, 35, of Keller, Tex., of 13 counts of manslaughter and 17 counts of attempted manslaughter; Evan S. Liberty, 32, of Rochester, N.H., of eight counts of manslaughter and 12 counts of attempted manslaughter; and Heard, 33, of Knoxville, Tenn., of six counts of manslaughter and 11 counts of attempted manslaughter.
Jurors also convicted Slough, Liberty and Heard of using military firearms while committing a felony. Prosecutors dropped three counts against Heard after jurors deadlocked on them.
Slatten faces a mandatory sentence of life in prison for murder. The others — who, like Slatten, are military veterans — face a mandatory minimum sentence of 30 years in prison.
U.S. District Judge Royce C. Lamberth ordered the men held pending sentencing. Jurors declined to comment.
The outcome capped a difficult, years-long quest by prosecutors to bring the case to trial and a milestone in the government's efforts to monitor security contractors' conduct on the battlefield.
The contractor shootings and the U.S. government's refusal to allow the men to be tried in Iraq sent relations between the two countries into a crisis, and the Blackwater name became shorthand for unaccountable U.S. power.
Seven years after American security contractors killed 14 unarmed Iraqis by firing machine guns and grenades into a Baghdad traffic circle, a jury in Washington convicted all four Blackwater Worldwide guards charged in the incident, one of the most ignominious chapters of the Iraq war.
American security contractors killed 14 unarmed Iraqis by firing machine guns and grenades into a Baghdad traffic circle.
The security firm's founder, Erik Prince, eventually left the company, which was renamed Xe Services, then later sold and renamed Academi.
"We at ACADEMI are relieved that the justice system has completed its investigation" into the tragedy and that any wrongdoing "has been addressed by our courts," company spokeswoman Callie Wang said in a statement.
In Congress, lawmakers denounced the Blackwater shootings as recently as this summer, but legislation that would provide clearer jurisdiction to prosecute criminal wrongdoing overseas by private contractors has languished for years.
Prosecutors called 71 witnesses to four for the defense. The witnesses included victims, surviving relatives and nine fellow Blackwater guards. The 30 Iraqis who testified represented the largest number of foreign witnesses to travel to the United States for a criminal trial, prosecutors said.
At the time of the incident, the defendants were among 19 Blackwater guards providing security for State Department officials in Iraq. Their convoy, called Raven 23, was clearing a path back to the nearby Green Zone for another Blackwater team evacuating a U.S. official from a nearby car bombing.
Assistant U.S. Attorney Anthony Asuncion told jurors that Slatten "lit the match that ignited the firestorm," firing his sniper rifle at the driver of a stopped white Kia sedan, killing him.
Slough, the convoy command vehicle's turret gunner, joined in as other Raven 23 members fired into stopped traffic and then turned more firepower onto a panicked, fleeing crowd, prosecutors said.
The only damage caused to the convoy's command vehicle came from shrapnel by an American grenade fired at short range, the government said.
To buttress their case, prosecutors contended that Slatten and Liberty held hostile views about Iraqi civilians and that Slough on occasion fired weapons at Iraqi targets without provocation.
The defendants' attorneys said their clients acted reasonably at a time when the Iraqi capital was the scene of "horrific threats" from car bombs, ambushes and follow-on attacks, sometimes aided by Iraqi security forces infiltrated by guerrillas.
At trial, under cross-examination, some former Blackwater employees differed over whether Slatten or others fired the first shots, and some agreed that they heard incoming AK-47 fire.
Charges in the shooting were first brought against six Blackwater employees in 2008, one of whom, Jeremy Ridgeway, pleaded guilty to manslaughter and testified for the government in the current trial. Charges against another man, Donald Ball, were dropped.
A federal judge, however, threw out the other indictments in 2009, saying that prosecutors improperly relied on statements that the guards gave the State Department immediately after the shooting, believing that they would not be used in court. An appeals court reversed that ruling in 2011, enabling prosecutors to obtain fresh indictments.
The remaining four defendants claimed the violence was triggered by Ridgeway, who a prosecutor conceded suffered from post-traumatic stress disorder and "lost it" in Iraq, and by the convoy's team leader, Jimmy Watson.
Watson and two other members of the Blackwater team were granted limited immunity by the government to testify against their former colleagues.
Wednesday's verdict by a civilian jury against the contractors marked a striking departure from how the military justice system dealt with U.S. service members accused of killing 25 unarmed Iraqi in a 2005 raid on their home in Anbar province.
Eight U.S. Marines were initially charged in the Haditha incident, but one was acquitted and six others had charges ranging from involuntary manslaughter to assault against them dropped. Ultimately, only one, Staff Sgt. Frank Wuterich, was convicted of negligent dereliction of duty in connection with the incident, receiving a reduction in rank and no jail time.
Julie Tate and Christian Davenport contributed to this report.


But there's more to building a solid retirement plan, or what I call a "Retirement Masterpiece," than accumulating money. Eventually, you'll want to shift gears and preserve what you've built.
The answer is to start by figuring out how much money you'll need to cover your expenses, including fixed expenses (mortgage or rent payments, insurance premiums, etc.), variable expenses (clothing, car maintenance), debt (outstanding student loans for yourself or your children, credit cards) and any one-offs (a new roof, for example, or a big vacation you plan to take).
Your guaranteed sources of income, such as Social Security or a pension, will be used to pay those expenses. If they aren't enough, your adviser can help you find others.
You probably wouldn't consider going without fire insurance for your home, even though the odds of your house burning down are low—about 3%.
Similarly, it's important to hedge against risks that can "burn down" your income plan. For one example, the chances are much higher than in the past that you'll have some kind of long-term care need that is expensive and ongoing, especially considering we are all living longer. As a result, you'll want to be prepared for this very real risk.
Some estate planning also is in order to protect yourself from taxes—particularly in states that have an estate tax, as the exemptions levels are usually much lower than the federal level. And you'll want to make sure that if one spouse passes away, the other will have enough income to last the rest of his or her life.
Now that those first two pillars of your retirement plan are taken care of, it's time to talk about how to continue to grow your money.
Whether it's conservative or aggressive risk, it's up to you, because these are the dollars you will have left after you've built your income and protection plans.
Smart strategizing also can help reduce estate taxes, so if you didn't address this in your protection plan, get to it during estate planning.


GMPH is 21 years old, and resides just north of Calgary, Alberta. When not loathing in the kingdom, or keeping things tidy, he enjoys video games. Known to throw down on some 360, he is actually a Nintendo-nerd from old school to present. Which is an obvious inspiration of the chiptunes played in his show.
GMPH plays mostly soundtracks, and has a fairly good collection of not only movie OSTs but also video game soundtracks, ranging fron 8-bit to fully orchestrated styles. The main "name bands" you'll hear will be either Machinae Supremacy or the Gorillaz, but they're by no means the only vocal tracks present on the show. The show will play nearly any style of music or artist upon request, the only real limitation being how quickly GMPH is able to find songs to play.
Requests are both welcomed and appreciated. Donations will be put towards radio games, just try to warn GMPH before sending.


text:
Q: Magento Dashboard Graph I'm wondering if anyone knows what I would need to do to adjust the dashboard to show the last day (since midnight) instead of the last 24 hours.

A: You have to rewrite the block Mage_Reports_Model_Resource_Order_Collection and override the method getDateRange as follows:
public function getDateRange($range, $customStart, $customEnd, $returnObjects = false)
{
    $dateEnd   = Mage::app()->getLocale()->date();
    $dateStart = clone $dateEnd;

    // go to the end of a day
    $dateEnd->setHour(23);
    $dateEnd->setMinute(59);
    $dateEnd->setSecond(59);

    $dateStart->setHour(0);
    $dateStart->setMinute(0);
    $dateStart->setSecond(0);

    switch ($range)
    {
        case '24h':
            $dateEnd = Mage::app()->getLocale()->date();
            $dateEnd->addHour(1);
            $dateStart = clone $dateEnd;
            // OLD: use the last 24 hours
            // $dateStart->subDay(1);
            // NEW: use the current day since midnight
            $dateStart->setMilliSecond(0);
            $dateStart->setSecond(0);
            $dateStart->setMinute(0);
            $dateStart->setHour(0);
            break;

        case '7d':
            // substract 6 days we need to include
            // only today and not hte last one from range
            $dateStart->subDay(6);
            break;

        case '1m':
            $dateStart->setDay(Mage::getStoreConfig('reports/dashboard/mtd_start'));
            break;

        case 'custom':
            $dateStart = $customStart ? $customStart : $dateEnd;
            $dateEnd   = $customEnd ? $customEnd : $dateEnd;
            break;

        case '1y':
        case '2y':
            $startMonthDay = explode(',', Mage::getStoreConfig('reports/dashboard/ytd_start'));
            $startMonth = isset($startMonthDay[0]) ? (int)$startMonthDay[0] : 1;
            $startDay = isset($startMonthDay[1]) ? (int)$startMonthDay[1] : 1;
            $dateStart->setMonth($startMonth);
            $dateStart->setDay($startDay);
            if ($range == '2y') {
                $dateStart->subYear(1);
            }
            break;
    }

    $dateStart->setTimezone('Etc/UTC');
    $dateEnd->setTimezone('Etc/UTC');

    if ($returnObjects) {
        return array($dateStart, $dateEnd);
    } else {
        return array('from' => $dateStart, 'to' => $dateEnd, 'datetime' => true);
    }
}

The code in the case '24h' block has been changed. This should be enough.
Hint: Grep for 24h under app/code/core/Mage to find all the places which are relevant for this functionality.

redpajama_set_name: RedPajamaStackExchange


Arena Experience: 2300 is the highest i got on my warrior in WotLk i then rolled a paladin my exp on him is 2214 atm as holy with the setup feral unholy dk hpala and as ret its 2206 ret rogue dk.
Season 9: 2206 Season 10: 2214 in arena 2297 in RBG.
/Played: 163 days and 9 hours.
How long have you been playing?: I think i played the game for about 4 years now and i have always been interested in PvP i never liked Pve.
How did you find this guild?: I changed from horde to Alliance not long ago and i had no guild i saw Fullflush in Stormwind and i asked him some questions and he told me to apply.
couple things. we will expect you to be vocal, talk with the FC. Know how to use cooldowns and communicate the ones you have. Youll be primarily a defence healer, and must also know how to do that effectively. When to place banner, when to be close for smoke bomb etc.


text:
Jan Klíma (* 8. prosince 1943 Vysoké Mýto) je český odborník na dějiny Portugalska, dějiny portugalsky mluvících zemí, dějiny Afriky a Latinské Ameriky.

Po maturitě absolvoval Pedagogický institut v Pardubicích (1960–1964, český jazyk – hudební výchova) a Filozofickou fakultu Univerzity Karlovy v Praze (1967-1972, historie – český jazyk a literatura). Na FF UK v Praze složil rigorózní zkoušku (1973, PhDr.), tamtéž se roku 2000 habilitoval v oboru obecných a světových dějin. Hovoří německy, anglicky, španělsky a portugalsky.

Biografie
Učil na základních školách v Tatenicích a Luži, od roku 1972 v gymnáziu Vysoké Mýto. Jako expert PZO Polytechna pracoval dva roky (1985–1986, 1987–1988) v Mosambiku ve funkci koordinátora vzdělávání a kvalifikace. Roku 1992 působil na velvyslanectví České a Slovenské federativní republiky v Luandě (Angola) na pozici prvního tajemníka a chargé d'affaires až do nucené evakuace úřadu.

Od roku 1993 vyučoval na Vysoké škole pedagogické v Hradci Králové poté transformované na Univerzitu Hradec Králové jako odborný asistent a docent světových dějin v Historickém ústavu a naposledy na Katedře politologie Filozofické fakulty UHK. Přednášel na univerzitách v Portugalsku a Španělsku, spolupracoval s Kapverdskou univerzitou Jeana Piageta.

Publikoval dlouhou řadu odborných i popularizačních článků v odborných časopisech i ve sbornících v češtině, angličtině, španělštině a portugalštině, zpracoval vysokoškolské učební texty. Tématům své specializace věnoval řadu knižních titulů.

Výběr z bibliografie
Knižní publikace k dějinám Portugalska:

Dějiny Portugalska. Praha: Nakladatelství Lidové noviny (ediční řada Dějiny států), 1. vyd. 1996, 2. rozšířené vyd. 2007, ISBN 978-80-7106-903-4

Dějiny Portugalska v datech. Praha: Libri, 2007, ISBN 978-80-7277-166-0

Madeira. Praha: Libri (ediční řada Stručná historie států), 2011, ISBN 978-80-7277-497-5

Dějiny Azorských ostrovů a Madeiry. Praha: Nakladatelství Lidové noviny (Dějiny států), 2020, ISBN 978-80-7422-756-1

Salazar, tichý diktátor. Praha: Aleš Skřivan ml., 2005, ISBN 80-86493-15-6

Dekolonizace portugalské koloniální říše. Historická motivace – Specifika – Průběh. Hradec Králové: Gaudeamus, 2000, ISBN 80-7041-256-9

Zámořské objevy. Vasco da Gama a jeho svět. Praha: Libri, 2006, ISBN 80-7277-326-7 (cena Klubu autorů literatury faktu)

Poslední koloniální válka. Praha: Libri, 2001, ISBN 80-7277-033-0

Knižní publikace k dějinám lusofonních zemí:

Angola. Praha: Libri (ediční řada Stručná historie států), 2003, ISBN 80-7277-155-8

Dějiny Angoly. Praha: Nakladatelství Lidové noviny (Dějiny států), 1. vyd. 2008, 2. rozšířené vyd. 2019, ISBN 978-80-7422-721-9

Mosambik. Praha : Libri (Stručná historie států), 2007, ISBN 978-80-7277-343-5

Dějiny Mosambiku. Praha: Nakladatelství Lidové noviny (Dějiny států), 2010, ISBN 978-80-7422-040-1

Guinea-Bissau. Praha: Libri (Stručná historie států), 2006, ISBN 80-7277-329-1

Dějiny Guineje-Bissau. Praha: Nakladatelství Lidové noviny (Dějiny států), 2015, ISBN 978-80-7422-376-1

Kapverdské ostrovy. Svatý Tomáš a Princův ostrov. Praha: Libri (Stručná historie států), 2008, ISBN 978-80-7277-380-0

Dějiny Kapverdských ostrovů, Svatého Tomáše a Princova ostrova. Praha: Nakladatelství Lidové noviny (Dějiny států), 1. vyd. 2014, 2. rozšířené vyd. 2017, ISBN 978-80-7422-558-1

Kapverdští sokolové. Česká inspirace v dějinách atlantského souostroví. Sokols de Cabo Verde. A inspiração checa na história do arquipélago atlântico (dvojjazyčně). Hradec Králové-Ústí nad Orlicí: Oftis, 2016, ISBN 978-80-7405-399-3

Květy ostrovní Sahary. Kapverdská literatura. Praha: Scriptorium, 2019, ISBN 978-80-88013-91-4

Východní Timor. Praha: Libri (Stručná historie států), 2003, ISBN 80-7277-203-1

Macao. Praha: Libri (Stručná historie států), 2012, ISBN 978-80-7277-466-1

Portugalská Indie. Praha: Libri (Stručná historie států), 2010, ISBN 978-80-7277-475-3

Knižní publikace k dějinám Afriky a kolonialismu:

Dějiny Afriky. Vývoj kontinentu, regionů a států. Praha: Nakladatelství Lidové noviny, 2012, ISBN 978-80-7422-189-7

Namibie. Praha: Libri (Stručná historie států), 2009, ISBN 978-80-7277-439-5

Dějiny Namibie. Praha: Nakladatelství Lidové noviny (Dějiny států), 2015, ISBN 978-80-7422-375-4

Dějiny španělské Afriky a Rovníkové Guineje. Praha: Nakladatelství Lidové noviny, 2017, ISBN 978-80-7422-616-8

Pod německou vlajkou. Příběh jedné koloniální říše. Praha: Libri, 2005, ISBN 80-7277-282-1

Afrika ve vichru svobody. Praha: Nakladatelství Lidové noviny, 2021, ISBN 978-80-7422-796-7

Nad Angolou zataženo. Praha: Nakladatelství Lidové noviny, 2022, ISBN 978-80-7422-867-4

Knižní publikace k dějinám Latinské Ameriky:

Dějiny Latinské Ameriky. Vývoj oblasti, regionů a států. Praha: Nakladatelství Lidové noviny, 2015, ISBN 978-80-7422-368-6

Dějiny Brazílie. Praha: Nakladatelství Lidové noviny (Dějiny států), 1. vyd. 1998, 2. rozšířené vyd. 2011, ISBN 978-80-7422-107-1

Brazílie. Praha: Libri (Stručná historie států), 2003, ISBN 80-7277-176-0

Simón Bolívar. Praha: Panorama, 1983, 11-097-83 (překlad do polštiny - Śląsk, Katowice 1988)

Zrození Latinské Ameriky. Simón Bolívar a jeho doba. Praha: Libri, 2007, ISBN 978-80-7277-270-4

Předchůdci latinskoamerické svobody. Tiradentes, Hidalgo, Artigas. Praha: Scriptorium, 2016, ISBN 978-80-88013-34-1

Cestopisy:

Kam dohlédnu z Vumby. Praha: Panorama, 1990, ISBN 80-7038-090-X

Kapverdy znovu objevené (s Janem Vítkem). Hradec Králové: Paradise Studio, 2002, ISBN 80-238-9364-5

Zajímavosti
 V roce 1998 byl docent Jan Klíma členem týmu expedice Monoxylon II, kdy byly testovány za pomoci metod a technik experimentální archeologie možnosti pravěkého námořnictví. Účastníci expedice pod vedením docenta Radka Tichého z Univerzity Hradec Králové nejprve vytvořili člun monoxyl – za pomoci primitivních nástrojů, jejichž znalost je z neolitu doložena. Na něm obepluli část pobřeží jižní Evropy a celá expedice po stopách neolitických námořníků byla zakončena v Lisabonu. Tato výprava byla jediným českým zástupcem na zde právě probíhajícím Expu 1998.
 Expedice Kapverdy v roce 2002, kterou podnikl docent Jan Klíma s geologem, docentem Janem Vítkem, vedla ke získání geologického materiálu i cenných historických dokumentů o kapverdských Sokolech. Úsilí započaté touto expedicí bylo završeno v roce 2015 odhalením pamětní desky ve městě Mindelu na ostrově São Vicente, připomínající činnost kapverdské sokolské organizace, která byla založena koncem roku 1932 po vzoru českého Sokola.

Externí odkazy

 Rozsáhlý seznam odborných publikací, textů a popularizačních článků, jejichž autorem nebo tématem je historik Jan Klíma, v databázi Historického ústavu AV ČR.

 Zpráva o odhalení slavnostní desky Kapverským Sokolům
 V africkém žáru pod sokolskou perutí
 Tichý, Radek: Monoxylon II: Plavba po 8000 letech. Dobrodružství experimentální archeologie, Náchod, JB production, 1999.
 Bibliografie dějin českých zemí
 Tři dny a dvě noci. Bývalý diplomat Jan Klíma vzpomíná na masakr v Angole

Čeští historikové
Čeští spisovatelé vědecké literatury
Čeští překladatelé
Absolventi Filozofické fakulty Univerzity Karlovy
Vyučující na Univerzitě Hradec Králové
Narození v roce 1943
Narození 8. prosince
Narození ve Vysokém Mýtě
Žijící lidé
Muži
Historikové 20. století
Historikové 21. století


text:
Q: Постфиксный декремент большая просьба помочь разобраться со следующим примером:
int a = -1;
a = a-- *a;

Почему консоль выводит ответ "2"?

A: В реальном коде крайне не рекомендуется в одном и том же выражении повторно использовать переменную, над которой выполняется операция инкремента или декремента.
Объяснение
Постфиксная операция работает так:

*

*Запоминаем значение операнда

*Изменяем операнд

*Подставляем в выражение запомненное значение

Расставим скобки согласно приоритету операторов и начнем вычислять:
a = (a--) * a  // a: -1
a = -1 * a     // a: -2
a = -1 * -2    // a: -2
a = 2          // a: -2 (все еще, потому что присвоение не отработало)

В итоге a стало равно 2.
Почему это плохо?
А чтобы понимать, почему написание такого кода сравнимо с использованием goto (а по-моему, даже хуже), рассмотрим такой пример:
a = a * (a--)  // a: -1

Думаете, операция в скобках выполнится первой? Нет, операции в C# выполняются слева направо, приоритеты и скобки только устанавливают ассоциативность. Так что сначала в выражение подставится результат "вычисления" первого операнда. А в C++, если я правильно помню, это вообще undefined behavior.
a = -1 * (a--) // a: -1
a = -1 * -1    // a: -2
a = 1          // a: -2

После того, как присвоение отработает, в a будет 1.
Для тренировки предлагаю решить вручную классическую задачу
int i = 5;
i = ++i + ++i;

Должно получиться 13.
А когда использование этих операций допустимо?
Когда вы не используете эту переменную в том же выражении, вы не будете думать, как второе ее вхождение подставится в это выражение. Пример:
while (--i > 0) ...

A: Постфиксный декремент возвращает значение переменной, данной на вход, а уже потом производит вычитание единицы из неё.
Ход действий в данном случае:
1) a = -1;
2) a = a-- * a;
3) a = -1 * a;
4) Выполняется декремент, a = -2;
5) a = -1 * -2;
6) a = 2;


text:
Towards enhanced understanding of idiopathic ketotic hypoglycemia: a literature review and introduction of the patient organization, Ketotic Hypoglycemia International
Danielle Drachmann1,
Erica Hoffmann1,
Austin Carrigg1,
Beccie Davis-Yates1,2,
Valerie Weaver1,
Paul Thornton3,
David A. Weinstein4,
Jacob S. Petersen5,
Pratik Shah6 &
Henrik Thybo Christesen ORCID: orcid.org/0000-0001-5330-68537,8
Orphanet Journal of Rare Diseases volume 16, Article number: 173 (2021) Cite this article
Idiopathic Ketotic hypoglycemia (IKH) is a diagnosis of exclusion. Although considered as the most frequent cause of hypoglycemia in childhood, little progress has been made to advance the understanding of IKH since the medical term was coined in 1964. We aimed to review the literature on ketotic hypoglycemia (KH) and introduce a novel patient organization, Ketotic Hypoglycemia International (KHI).
IKH may be diagnosed after the exclusion of various metabolic and hormonal diseases with KH. Although often mild and self-limiting, more severe and long-lasting IKH occurs. We therefore divide IKH in physiological KH and pathological KH, the latter defined as recurrent symptomatic, or occasionally symptomatic, episodes with beta-hydroxybutyrate ≥ 1.0 mmol/L and blood glucose < 70 mg/dL (3.9 mol/L), in the absence of prolonged fasting, acute infections and chronic diseases known to cause KH. Pathological KH may represent undiscovered diseases, e.g. glycogen storage disease IXa, Silver–Russel syndrome, and ketone transporter defects, or suggested novel disease entities identified by exome sequencing. The management of KH aims to prevent hypoglycemia, fatty acid oxidation and protein deficiency by supplying adequate amounts of carbohydrates and protein, including nutritional therapy, uncooked cornstarch, and sometimes continuous tube feeding by night. Still, intravenous dextrose may be needed in acute KH episodes. Failure to acknowledge that IKH can be more than normal variation may lead to under-treatment. KHI is a non-profit, patient-centric, global organization established in 2020. The organization was created by adult IKH patients, patient family members, and volunteers. The mission of KHI is to enhance the understanding of IKH while advocating for patients, their families and the continued research into KH.
IKH is a heterogeneous disorder including physiological KH and pathological KH. IKH may represent missed diagnoses or novel disease entities, but shares common management principles to prevent fatty acid oxygenation. KHI, a novel patient organization, aims to enhance the understanding of IKH by supporting IKH families and research into IKH.
Due to the lack of cerebral energy stores the brain depends on a continuous supply of glucose as a primary energy substrate. The brain is also capable of utilizing ketones, which occurs with fasting or chronic feeding of a high fat/low carbohydrate diet. The integration of metabolic pathways (glycogenolysis, gluconeogenesis, and fatty acid oxidation) and multiple counter-regulatory hormones (glucagon, epinephrine, growth hormone, and cortisol) combine to maintain normoglycemia. Hypoglycemia in children older than one month is uncommon, even in the setting of fasting. Ketosis during hypoglycemia, here referred to as ketotic hypoglycemia (KH), simply describes the physiologic changes (increased ketogenesis) which should occur in the setting of counter-regulation [1]. Despite more recent advances, only a minority of children with KH receive an endocrine or metabolic disorder diagnosis. The majority of KH patients are classically diagnosed as having "idiopathic" ketotic hypoglycemia (IKH), also known as accelerated starvation. IKH is considered the most frequent cause of hypoglycemia in childhood [2,3,4]. Data about the incidence and prevalence of KH and IKH are missing, but KH is the most common diagnosis applied to episodes of hypoglycemia in children in emergency departments in the US [2, 3]. While IKH is currently defined as a collective set of symptoms not related to an underlying pathology, severe IKH might still be considered as a rare disease entity in and of itself. A search of Orphanet for "idiopathic ketotic hypoglycemia" and "ketotic hypoglycemia" yielded neither an Orpha number, an Online Mendelian Inheritance in Man (OMIM) geno- or phenotype reference number, or an ICD-10 number. KH is referenced in the Human Phenotype Ontology (HPO) as HP:0012734, a sign of other known rare diseases [5, 6].
Little progress has been made to advance the understanding of IKH since 1964, where unexplained KH was reported in eight children after exclusion of hormonal and metabolic diseases [7]. IKH has been considered by some as a non-pathological condition in infants, representing the lower tail of the Gaussian normal distribution for fasting tolerance [8]. However, some children with unexplained KH, or IKH, are more severely affected and do not go into remission before school age and may even have IKH in adulthood. Such individuals had not had a patient organization with which to gain support, scientific information or research data, and currently do not have any standardized clinical management guidelines to follow. The aim of this paper is to review the literature on KH and introduce a novel patient organization, Ketotic Hypoglycemia International (KHI). Because much of the research available is centered on the pediatric population, this paper focuses solely on IKH in children.
Metabolism of glucose, fats and ketones
In healthy individuals maintenance of stable plasma glucose (PG) concentration is easily performed by the body's neuroendocrine and metabolic defenses, and potential consequences from prolonged fasting are low. However, a disproportionate balance between cellular glucose entry and glucose outflow secondary to deficient delivery of glucose into circulation, excessive glucose removal from circulation, or both, will place the body in a state of hypoglycemia [9, 10]. While glucose entry from the blood to the brain neurons and to liver cells is dependent on glucose concentration gradients, most other tissues (primarily muscle tissue) are dependent on insulin for glucose entry to the cells. As PG begins to fall, the pancreas stops producing insulin and decreases the amount of glucose available to most tissues, with the exception of the brain.
If the PG continues to fall, the counter-regulatory hormones glucagon, cortisol, growth hormone, epinephrine (adrenaline) and norepinephrine (noradrenaline) are released into circulation, and the breakdown of triglycerides to glycerol and fatty acids in the adipocytes (lipolysis) occurs, Fig. 1 [10,11,12]. The glycerol is then converted to glucose in the liver (gluconeogenesis). Both glycerol and amino acids serve as substrates for glucose production in the hormonally controlled gluconeogenesis. The free fatty acids from lipolysis are processed by liver cell mitochondria into acetoacetate (AcAc), beta-hydroxybutyrate (BOHB), and, to a lesser degree, acetone, which together are named ketone bodies. These ketone bodies are an alternative source of energy for the brain and muscles when glucose is unavailable [13, 14].
Selected details on the glucose and ketone body metabolism. Representation of selected details of the metabolism at the low insulin—high insulin counter-acting hormones state. Only cells of the liver, fat tissue and major fuel consuming organs are shown. Gluconeogenesis from amino acids, lactate/Cori cycle, and pathway details are omitted. Green line: Mitochondrial membrane. Blue circle: Citric acid cycle. Key enzymes in ketogenesis (arrows): (1) triglycerate lipase; (2) acetyl CoA carboxylase; (3) HMG CoA synthase. Key enzymes in ketolysis: (4) CoA-oxoacid transferase (SCOT); (5) michochondrial acetoacetyl CoA thiolase (MAT; beta-ketothiolase). Ac acetone, AcAc acetoacetate, ATP adenosine triphosphate, BOHB beta-hydroxybutyrate, FA fatty acids, OA oxaloacetate, TG triglyceride
Fuel production in infants and children is similar to that of adults; however, due to their larger brain size in proportion to their body weight, PG concentrations in infants and children drop more rapidly and elevated ketone body levels (hyperketonemia) develop sooner [10, 13]. The brain has back-up stores of fuel in the form of glycogen to compensate for low PG levels [14,15,16]. These glycogen stores only last a few minutes, so individuals that cannot regulate their PG levels are at risk for interruption of glucose delivery to the brain, putting them in danger of devastating consequences. Recovery is usually complete from short-lived episodes of hypoglycemia, though prolonged and severe hypoglycemia can cause permanent brain damage [14, 17,18,19].
Ketone bodies can protect the brain from damage by providing an alternate fuel source. Ketones provide 2–6% of the body's energy requirements after an overnight fast and up to two-thirds of the brain's energy needs after a prolonged fast or during starvation [13, 14]. Normal infants and children can also develop hyperketonemia during illness, after bouts of vomiting or diarrhea, or after prolonged fast with an inverse relation to age [20,21,22,23,24].
The normal serum concentration of ketones measured as 3-BOHB is assay-dependent, but invariably given as < 0.6 mmol/L [25, 26]. Hyperketonemia is most often defined as BOHB concentrations between 1.0 and 3.0 mmol/L [25]. This definition reflects to the authors' clinical experience the threshold of symptomatic ketosis, which begins around 1.0 mmol/L.
Ketoacidosis is defined as BOHB > 3.0 mmol/L with resultant metabolic acidosis [25, 26]. The metabolic acidosis occurs as the rapid rise in ketone bodies and subsequent saturation of skeletal muscle uptake mechanisms causes an increase in serum hydrogen ion concentration that overwhelms the body's natural buffering system [25]. In studies with prolonged fasting in healthy controls, the 90th percentile of BOHB reached 1.0 mmol/L after 15 h fast in 1–12 months old infants; 0.9 mmol/L at age 1–7 year; and 0.3 mmol/L at age 7–15 years [22]. The 97.5th percentile of BOHB after 14 h fast was 1.5 mmol/L in 3-y-olds; 0.7 mmol/L at age 9 years; and after 40 h fast 8.9 mmol/L at age 6–11 years [23, 24].
In the acute phase, high ketones can cause nausea, vomiting, abdominal pain, muscle cramps, headache, lethargy, and at its most severe, coma and polypnea (Kussmaul breathing) [3, 26]. Acetone excretion by the lungs results in a characteristic aromatic smell on the breath. If measures are not taken to arrest ketogenesis and flush out excess ketones from the body, ketoacidosis can develop, constituting a need for emergent intervention [25]. Chronic ketosis can result in poor growth, hepatic transaminase elevation, and osteoporosis [27].
Diagnosis of ketotic hypoglycemia
Definition of KH and IKH
IKH has long been considered the lower end of normal variation for fasting tolerance in infants [8] However, IKH seems to represent a broad clinical spectrum from occasional mild KH in infancy to severe and more long-lasting KH, sometimes with other clinical or biochemical manifestations. We propose that IKH be split into physiological KH and pathological KH. We define pathological KH as recurrent symptomatic, or occasionally symptomatic, episodes with BOHB ≥ 1.0 mmol/L and blood glucose < 70 mg/dL (3.9 mmol/L), in the absence of prolonged fasting, acute infections and chronic diseases known to cause KH. This definition allows for episodes with euglycemic hyperketosis.
Physiological KH is most commonly seen in normal children with intercurrent acute illness causing prolonged starvation and increased metabolism due to fever. Moreover, KH may be frequent in conditions with excess starving or malnutrition. In a few studies, KH was reportedly common in African children with chronic malnutrition or severe malaria [28, 29].
Pathological forms of KH are seen in children with deficiencies in the counter regulatory hormones such as cortisol or growth hormone, or in metabolic conditions such as glycogen storage disease (GSD, specifically GSD 0, III, VI, and IX), disorders of ketone transport and ketone utilization, and defects in protein metabolism, Table 1 [30, 31]. Specific syndromes with KH should be identified, e.g. Silver–Russell syndrome where more than one in four have KH after a simple overnight fast [32, 33].
Table 1 Causes to ketotic hypoglycemia in children
IKH may be diagnosed when all the above causes have been excluded. Because there may be many yet undiscovered specific etiologies for IKH, it can be considered as a condition with disturbed glucose homeostasis, the cause being failure of meaningful hepatic gluconeogenesis rather than an accelerated glucose oxidation rate [9, 31, 34]. In keeping, hypoalaninemia has been found in children with KH compared to age-matched controls [35]. The body's inability for self-regulation results in a state of low PG levels with elevated ketones and various outward signs and symptoms shown by the child.
No uniform diagnostic criteria for PG or ketone body concentrations have been established for the diagnosis of KH. Hypoglycemia in adults and children cannot be defined by a single PG cut-off [13, 36]. van Veen et al. found that children below 2 years had physiological KH with PG below 70 mg/dL (3.9 mmol/L) and hyperketonemia after fasting for 15 h or shorter [21]. This study, however, included children with potential pathological KH.
In children with the diagnosis of IKH, hyperketonemia with euglycemia appears to occur more frequent than hyperketonemia with hypoglycemia [26]. In the author's experience (HTC), this may, however, be the result of non-recorded nocturnal hypoglycemia as demonstrated with continuous glucose monitoring (CGM).
The demonstration of Whipple's triad for hypoglycemia (symptoms and signs, low PG and relief of symptoms and signs after normalization of PG) is often used to support the diagnosis of hypoglycemia, but is not straight forward in KH. Symptoms are difficult to read in infants and recurrent hypoglycemia leads to hypoglycemia-associated autonomic failure with blunting of the autonomic symptoms of hypoglycemia, which results in hypoglycemia unawareness, irrespective of age [37, 38]. The clinical picture of IKH is described below.
Clinical picture of IKH
Episodes of KH are usually seen from around 6 months' age, with the hypoglycemia attributed to poor oral intake or illness [3, 9, 39]. In a series of 62 children with KH, 29% had, however, no history of a precipitating event that could explain the hypoglycemia [40]. To the authors' experience, increased physical activity and poor food intake the day before can be identified in a higher number of patients after detailed evaluation at the time of a KH event.
Remission of IKH is classically thought to occur between 6–7 years of age when children have increased their muscle mass and decreased their glucose requirement per unit of body mass [40, 41]. In some patients, episodes of KH may persist past puberty into adulthood, and family investigations may reveal parents with a history of KH [42]. This should prompt further diagnostic investigations and be regarded as pathological KH.
Children with KH may exhibit a wide range of symptoms and signs. Younger children cannot be relied upon to accurately recognize and communicate symptoms of hypoglycemia [13, 37, 38, 43,44,45]. It is often up to the primary caregiver(s) to interpret whether the child is experiencing a hypoglycemic event and if intervention is warranted. Episodes frequently occur in the morning after an overnight fast (10–12 h). In response to the hypoglycemic state overnight, ketone development has already begun, making management of symptoms a challenge for caregivers [40].
Symptoms and signs of the combination of hyperketosis and hypoglycemia in KH include nausea, abdominal pain, vomiting, headache, lethargy, pallor, sweating, tremors, muscle cramps, visual/sensory disturbances, speech difficulty, mental confusion, bizarre behavior (such as crying for no reason), temper tantrums, restlessness, personality changes, seizures and coma [3, 7, 14, 26, 40, 41]. The presence of neuroglycopenic symptoms despite the brain-protective hyperketonemia may suggest a ketone utilization or ketone transport defect in these patients. What makes KH particularly complex is that some of the symptoms, such as muscle cramps, headache and abdominal pain, may result from either hypoglycemia or hyperketonemia.
Some children with IKH are small and thin for their age, with minimal fat deposits or muscle development [41]. Such children have little to no tolerance for fasting and often display poor eating habits. The poor appetite may be caused by hyperketonemia, inducing a vicious cycle provoking further KH.
Diagnostic procedures in IKH
If the KH is not investigated during a spontaneous acute episode with severe symptoms and signs, a controlled fasting test in the hospital setting can help to establish the KH diagnosis and to give an impression of its severity. Dependent on age, an overnight fasting study can be performed until the glucose is either < 50 mg/dl (2.8 mmol/L) or the BOHB is > 2 mmol/L. At the end of the fasting study, a diagnostic critical sample is obtained. A controlled fasting study with frequent monitoring of both glucose and BOHB allows the physician to identify when the BOHB rises above 1 mmol/L and thus gives the family an understanding of the child's fasting tolerance. Permanent or excessive ketosis should lead to investigations for ketone transporter or utilization defects.
Once the diagnosis of IKH is established, the frequency and severity of KH should be determined as part of the initial work up. Home monitoring with point of care (POC) meters with testing for glucose and ketones should be performed, particularly on waking in the morning or with symptoms until a true pattern emerges. CGM may be helpful, but are not rigorously studied in IKH and cannot stand alone due to inaccuracy at lower glucose levels. The episodical nature of KH may call for prolonged home monitoring in pathological KH (see also the Management section below).
Patients with pathological KH represent a diagnostic challenge to physicians and caretakers. Pathological KH with or without atypical manifestations should lead to expanded diagnostic procedures. A clinical example is given in Table 2.
Table 2 A child with idiopathic ketotic hypoglycemia
Search of new causes to KH
A predominance of IKH in males has been reported [3, 40]. This may suggest an unrecognized disease on the X-chromosome such as GSD IXa in these children. Indeed, several patients diagnosed with KH or IKH have been found to have mutations in PHKA2 [30, 40, 46]. By use of trio exome sequencing, research has identified mutations not only in PHKA2, but also in SLC16A1 (MCT1), NCOR1, IGF2BP1, SGLT2 and NEK11 as (potential) novel causes of more atypical children with otherwise unexplained KH [42, 47].
SLC16A1 codes for monocarboxylase transporter 1 (MCT1), which mediates transport of pyruvate, lactate and ketone bodies across cell membranes. Patients with heterozygous or homozygous inhibiting mutations in SLC16A1 presented with moderate or profound ketosis and sometimes hypoglycemia at fasting or during infections, with onset in the first years of life [40, 47, 48]. In some of the patients, migraine, exercise intolerance, developmental delay, microcephaly and abnormal MRI of the brain were noted.
The study of Alhaidan et al. identified predicted disease-causing heterozygous DNA variants in NCOR1, IGF2BP1, SLC5A2 (SGLT2) and NEK11, respectively, in four children with otherwise unexplained KH [42]. The NCOR1/HDAC3 complex is involved in the regulation of liver phosphoenolpyruvate carboxykinase 1 (PCK1), glucose 6-phosphatase catalytic (G6PC) and hepcidin. The KH patient with an NCOR1 mutation had loose stools and iron deficiency anemia as additional features, the latter possibly caused by hepcidin overexpression. Of note, G6PC homozygous mutations leads to GSD Ia with non-ketotic hypoglycemia, hepatomegaly and iron deficiency [49].
IGF2BP1 (not to be confused with IGFBP1) is a sparsely described translational regulator of several proteins, including IGF2, which is involved in cell growth and differentiation and activates the insulin receptor. Patients with IGF2-producing tumors have impaired glycogenolysis and gluconeogenesis with hypoglycemia and suppressed insulin secretion [50,51,52]. The KH patient with a heterozygous IGFBP1 mutation had short stature and retarded bone age without identifiable defects in the growth hormone axis as additional features.
Heterozygous mutations in SLC5A2, which encodes the sodium glucose co-transporter 2 (SGLT2), cause familial renal glucosuria (FRG) [53]. The KH patient with a heterozygous SLC5A2 mutation had intermittent glucosuria, rapid clearance of glucose and drastically increased fasting p-GLP1 as additional features, suggesting KH in infancy as a novel manifestation of FRG.
The mitosis gene A-related kinase 11 gene NEK2 has not been linked to other diseases in humans than KH. In a heterozygous NEK11 mutation mouse model, a significant reduction in glucose levels was the only reported feature [54]. The KH patient with a heterozygous NEK11 mutation had recurrent migraine, cognitive and motor deficits, mild liver affection, absent glucose response to i.m. glucagon and decreased p-IGFBP3 as additional features.
A number of children with pathological KH remains unexplained despite trio exome sequencing [42]. Pathological KH may well represent a disease entity with several different unidentified monogenetic, digenic, polygenetic, or epigenetic causes [12, 30]. A case report with KH in one, but not the other homozygotic twin illustrates the complexity of KH [55].
Management of idiopathic ketotic hypoglycemia
The monitoring and treatment of children with IKH should be individualized according to severity, frequency and response. While physiological KH only will need attention in case of acute illness or prolonged fasting, pathological KH may need everyday monitoring and treatment. Common management principles for pathological KH are presented in Table 3. POC glucometers have different diagnostic performances and are less reliable in the lower range [56,57,58]. Moreover, finger prick capillary PG concentrations derive from the optimal venous PG concentration, and the automatic 1.1 conversion factor from whole blood POC glucometers to report PG concentrations may not reflect the actual erythrocyte volume fraction of an infant. Despite these limitations, home monitoring with POC testing for PG and ketones should be used in monitoring KH in its severe forms. POCT for blood BOHB should be preferred from the less precise urine stix AcAc [59].
Table 3 Management of pathological KH in children
As the frequency and severity of KH episodes vary, the need for home monitoring must be individualized for each patient. Severely affected children may benefit from CGM, although low glucose values or decreasing trend alarms should be controlled with a glucometer to improve precision.. As hyperketonemia may be of clinical significance without simultaneous hypoglycemia, blood ketone monitoring may be recommended for normoglycemic patients exhibiting signs and symptoms of illness.
POC monitoring may be an economic burden on the family, as well as a logistical challenge for custodial daycare and school personnel. On the other hand, POC testing may facilitate the correct identification of episodic behavioral changes as symptoms of KH instead of general "bad behavior", psychosocial reactions, or ADHD, which had occurred according to the anecdotal experience in the new patient organization, KHI. Still, the need of monitoring should be evaluated regularly to avoid both "over"- and "under"-monitoring.
The Pediatric Endocrine Society recommends maintaining a PG concentration of > 70 mg/dL (3.9 mmol/L) as goal of treatment for hypoglycemia in infants and children, however allowing for an individualized, tailored approach to management [13]. To the authors´ experience, children with pathological KH benefit from an individualized PG goal to keep BOHB < 1.0 mmol/L. This may fit with a PG kept > 70 mg/dL (3.9 mmol/L), but an individual PG goal for each child to avoid hyperketosis should be determined in the diagnostic process.
Nutritional therapy, avoidance of prolonged fasting, increased frequency of feedings, and close monitoring of oral intake, especially in times of stress or high activity, are suggested to mitigate episodes of hypoglycemia [12, 13]. Uncooked cornstarch has been used to extend the times between feedings by delaying onset of hypoglycemia. Traditional cornstarch has been used for 40 years to prevent nocturnal hypoglycemia, with the measured length of time for digestion being 3–4 h [27, 60].
For some children with pathological KH, as in those with KH due to GSD I, an overnight administration of cornstarch is necessary. In addition to cornstarch therapy, children with pathological KH that are unable to maintain fasting for any significant length of time may be evaluated for gastrostomy tubes for bolus or continuous tube feedings [27, 60]. Protein-rich diet or dietary products should be considered if low protein or prealbumin concentrations are documented. Proteins provide substrate for gluconeogenesis and may reduce muscle cramps associated to KH.
Nausea and vomiting caused by ketones may lead to further decline in PG if hyperketosis is not recognized and treated. The acute treatment principle includes administration of high glycemic index (i.e. dextrose-rich) foods or drinks to provide energy from glucose metabolism instead of fatty acid metabolism which leads to further ketone body formation.
If hypoglycemia is unable to be corrected or the child becomes increasingly unresponsive, emergency intervention should be sought. Buccal carbohydrate gel administration, intravenous (IV) dextrose or intramuscular glucagon (if proven effective and safe by formal testing) may be administered to raise PG concentrations to ≥ 70 mg/dL (3.9 mmol/L). Of note, some patients with IKH have a normal i.m. glucagon response without provoking lactate acidosis, unlike the response in those with GSD I [3, 35, 39].
Elimination of ketones can take hours, and if the child is in an acidotic state, IV fluid therapy may be needed to return the patient to homeostasis. Intravenous dextrose can help to stop ketogenesis and lipolysis, and rehydration assists in renal excretion of ketones [12, 25, 41]. A better understanding of KH through identification of novel genetic causes may help physicians to target the treatment of children with pathological KH.
Ketotic Hypoglycemia International
Established in January, 2020, Ketotic Hypoglycemia International (KHI) is a new, worldwide patient organization for families affected by idiopathic ketotic hypoglycemia (IKH). Our scientific advisory board and organization board of directors are volunteers. The mission of KHI is to enhance the understanding of IKH for the benefit of children, parents, and families who have been affected by IKH. KHI aims to support patients and their families by sharing knowledge about IKH, and to support the continued research into etiology, monitoring, and treatment.
We define our patient target group as patients with KH without a known clinical metabolic or hormonal etiology. This is to differentiate KHI from patient organizations for GSD, growth hormone deficiency and adrenal insufficiency, even though members of these groups may also experience KH symptoms. KHI welcomes all patients who suffer from KH in our support group, where we will assist them in connecting with other disease specific support organizations.
Which challenges are we facing?
Current literature provides a broad, unclear etiology and pathophysiology of IKH, thereby limiting the scope of understanding especially the more severely affected patients. The KHI support group has the impression that pathological KH may often be underdiagnosed and inappropriately treated. For those with pathological KH there is the lack of support for both the patients and their primary caregivers. Rare diseases often come with additional stress to the family unit, as advocacy, research, and support falls on the patient and family members. It has been shown that in the case of a rare disease diagnosis, oftentimes the parent or caregiver will have a better understanding of the disease process than the healthcare team providing care for the patient. Limited access to services and government support, fragmented communication, and minimal experts in the field result in the need for family to step in as a patient medical navigator and advocate [61].
Advocating for a child without a diagnosis can become overwhelming to the family as social support dwindles and health care management becomes convoluted. The initial screening for KH is not standardized in many institutions, and when a diagnosis of IKH is made, parents have reported feelings that providers had offered minimal education and instruction on management. This results in families navigating uncharted territory with episodes of KH, hospitalizations, pushback from schools regarding symptom management and prevention plans, etc., while being explained that KH does not meet the definitions of a rare disease and therefore may not qualify for extra services.
KHI recognizes that pathological KH, as with many health conditions, is not only affecting the child, but creating daily challenges for the families and caregivers. The most significant of these challenges is the fear of hypoglycemic episodes that can lead to a range of complications and can have devastating consequences.
KHI aims to globally unite leading hypoglycemia experts with patients, caregivers, and healthcare providers, and to establish a greater understanding of IKH in the hopes to facilitate improved treatment options and greater quality of life for individuals suffering from KH.
KHI was launched on a variety of social media platforms in January 2020 in an effort to connect with families from across the globe. The interest from families affected by KH was significant. We found that the majority of the families were affected by IKH and had been left in limbo with no recognized specialists to reach and no patient organization. The Facebook page for KHI, https://www.facebook.com/ketotichypoglycemiainternational/, has been exceptionally successful, leading to the formation of a Facebook group with more than 900 families thus far.
This is the first time these families have been able to enter into a support network of like-minded peers to share the daily difficulties presented with this condition, as well as offer and receive empathy and advice. We are committed to support and advocate for those in the KH community through our international KHI Parents Support Group by utilizing the contributions of general medical guidance made by our scientific advisory board, supporting research in the general well-being of KH-families, and furthering research into KH etiology, diagnosis, and management.
The organization aims to challenge current perceptions and attitudes to expand the recognition that IKH is more than a normal variation, and establish an international platform for future research collaboration. KHI strives to prevent IKH families from feeling silenced and underserved, as seen in other rare disease families [62]. KHI continues to bridge the gaps between doctors, families, providers, research, and awareness.
KHI strives to be recognized not only as a symptom-union, but as a rare disease partner, supporting research towards better understanding of the multifactorial causes of IKH and the genetic complexities of the numerous rare diseases it is associated with. All patients with KH share many of the same challenges, which is why collaboration with other rare disease patient organizations is of high priority.
IKH is a clinically heterogeneous disorder including physiological KH and pathological KH. Pathological KH affects the health and well-being of its patients and their families. IKH patients currently do not have known causative genetic mutations or metabolic disorders, but novel causes may emerge in future studies. In addition to unknown etiology, patients with pathological KH have limited access to support, family resources, and medical management recommendations. KHI was formed as a novel patient organization to enhance the understanding of IKH, attempting to bridge the gap between patients, families, providers, researchers, and support, ultimately to improve the management of IKH and thereby to increase the quality of life for patients living with KH.
Owen OE, Reichard GA Jr, Patel MS, Boden G. Energy metabolism in feasting and fasting. Adv Exp Med Biol. 1979;111:169–88.
White K, Truong L, Aaron K, Mushtaq N, Thornton PS. The incidence and etiology of previously undiagnosed hypoglycemic disorders in the emergency department. Pediatr Emerg Care. 2020;36(7):322–6.
Daly LP, Osterhoudt KC, Weinzimer SA. Presenting features of idiopathic ketotic hypoglycemia. J Emerg Med. 2003;25(1):39–43.
Pershad J, Monroe K, Atchison J. Childhood hypoglycemia in an urban emergency department: epidemiology and a diagnostic approach to the problem. Pediatr Emerg Care. 1998;14(4):268–71.
Köhler S, Carmody L, Vasilevsky N, Jacobsen JOB, Danis D, Gourdine JP, et al. Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources. Nucleic Acids Res. 2019;47(D1):D1018–27.
Shefchek KA, Harris NL, Gargano M, Matentzoglu N, Unni D, Brush M, et al. The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species. Nucleic Acids Res. 2020;48(D1):D704–15.
Colle E, Ulstrom RA. Ketotic hypoglycemia. J Pediatr. 1964;64:632–51.
Senior B. Ketotic hypoglycemia. A tale (tail) of Gauss? J Pediatr. 1973;82(3):555–6.
Bodamer OA, Hussein K, Morris AA, Langhans CD, Rating D, Mayatepek E, et al. Glucose and leucine kinetics in idiopathic ketotic hypoglycaemia. Arch Dis Child. 2006;91(6):483–6.
Sprague JE, Arbeláez AM. Glucose counterregulatory responses to hypoglycemia. Pediatr Endocrinol Rev. 2011;9(1):463–73.
Gandhi K. Approach to hypoglycemia in infants and children. Transl Pediatr. 2017;6(4):408–20.
Ghosh A, Banerjee I, Morris AAM. Recognition, assessment and management of hypoglycaemia in childhood. Arch Dis Child. 2016;101(6):575–80.
Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussain K, et al. Recommendations from the pediatric endocrine society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J Pediatr. 2015;167(2):238–45.
Langdon DR, Stanley CA, Sperling MA. Hypoglycemia in the toddler and child. In: Sperling MA, editor. Pediatric endocrinology. 4th ed. Philadelphia: Elsevier; 2014. p. 920–55.
Brown AM, Ransom BR. Astrocyte glycogen and brain energy metabolism. Glia. 2007;55(12):1263–71.
Rich LR, Harris W, Brown AM. The role of brain glycogen in supporting physiological function. Front Neurosci. 2019;13:1176.
Lucas A, Morley R, Cole TJ. Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia. BMJ. 1988;297(6659):1304–8.
Menni F, de Lonlay P, Sevin C, Touati G, Peigné C, Barbier V, et al. Neurologic outcomes of 90 neonates and infants with persistent hyperinsulinemic hypoglycemia. Pediatrics. 2001;107(3):476–9.
Helleskov A, Melikyan M, Globa E, Shcherderkina I, Poertner F, Larsen AM, et al. Both low blood glucose and insufficient treatment confer risk of neurodevelopmental impairment in congenital hyperinsulinism: a multinational cohort study. Front Endocrinol. 2017;8:156.
Saudubray JM, Marsac C, Limal JM, Dumurgier E, Charpentier C, Ogier H, et al. Variation in plasma ketone bodies during a 24-hour fast in normal and in hypoglycemic children: relationship to age. J Pediatr. 1981;98(6):904–8.
van Veen MR, van Hasselt PM, de Sain-van der Velden MG, Verhoeven N, Hofstede FC, de Koning TJ, et al. Metabolic profiles in children during fasting. Pediatrics. 2011;127(4):1021.
Bonnefont JP, Specola NB, Vassault A, Lombes A, Ogier H, de Klerk JB, et al. The fasting test in paediatrics: application to the diagnosis of pathological hypo- and hyperketotic states. Eur J Pediatr. 1990;150(2):80–5.
Lamers KJ, Doesburg WH, Gabreëls FJ, Romsom AC, Renier WO, Wevers RA, et al. Reference values of blood components related to fuel metabolism in children after an overnight fast. Clin Chim Acta. 1985;145(1):17–26.
Lamers KJ, Doesburg WH, Gabreëls FJ, Lemmens WA, Romsom AC, Wevers RA, et al. The concentration of blood components related to fuel metabolism during prolonged fasting in children. Clin Chim Acta. 1985;152(1–2):155–63.
Laffel L. Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes. Diabetes Metab Res Rev. 1999;15(6):412–26.
Millar R, Harding A. Review article: accelerated starvation of childhood: have i judged ketones? Emerg Med Australas. 2019;31(3):314–20.
Weinstein DA, Steuerwald U, De Souza CFM, Derks TGJ. Inborn errors of metabolism with hypoglycemia: glycogen storage diseases and inherited disorders of gluconeogenesis. Pediatr Clin N Am. 2018;65(2):247–65.
Monde AA, Djessou SP, Camara CM, Tiahou GG, Koffi G, Djohan F, et al. Prevalence of ketotic hypoglycaemia among schoolchildren in the village of Ahoué in Côte-d'Ivoire. Bull Soc Pathol Exot. 2010;103(2):96–9.
White NJ, Miller KD, Marsh K, Berry CD, Turner RC, Williamson DH, et al. Hypoglycaemia in African children with severe malaria. Lancet. 1987;1(8535):708–11.
Brown LM, Corrado MM, van der Ende RM, Derks TG, Chen MA, Siegel S, et al. Evaluation of glycogen storage disease as a cause of ketotic hypoglycemia in children. J Inherit Metab Dis. 2015;38(3):489–93.
Dahlquist G, Gentz J, Hagenfeldt L, Larsson A, Löw H, Persson B, et al. Ketotic hypoglycemia of childhood—a clinical trial of several unifying etiological hypotheses. Acta Paediatr Scand. 1979;68(5):649–56.
Wakeling EL, Brioude F, Lokulo-Sodipe O, O'Connell SM, Salem J, Bliek J, et al. Diagnosis and management of Silver–Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017;13(2):105–24.
Azcona C, Stanhope R. Hypoglycaemia and Russell-Silver syndrome. J Pediatr Endocrinol Metab. 2005;18(7):663–70.
Huidekoper HH, Duran M, Turkenburg M, Ackermans MT, Sauerwein HP, Wijburg FA. Fasting adaptation in idiopathic ketotic hypoglycemia: a mismatch between glucose production and demand. Eur J Pediatr. 2008;167(8):859–65.
Pagliara AS, Kari IE, De Vivo DC, Feigin RD, Kipnis DM. Hypoalaninemia: a concomitant of ketotic hypoglycemia. J Clin Investig. 1972;51(6):1440–9.
Cryer PE, Axelrod L, Grossman AB, Heller SR, Montori VM, Seaquist ER, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94(3):709–28.
Cryer PE. Symptoms of hypoglycemia, thresholds for their occurrence, and hypoglycemia unawareness. Endocrinol Metab Clin North Am. 1999;28(3):495–500.
Hussain K, Bryan J, Christesen HT, Brusgaard K, Aguilar-Bryan L. Serum glucagon counterregulatory hormonal response to hypoglycemia is blunted in congenital hyperinsulinism. Diabetes. 2005;54(10):2946–51.
Haymond MW, Pagliara AS. Ketotic hypoglycaemia. Clin Endocrinol Metab. 1983;12(2):447–62.
Kaplowitz P, Sekizkardes H. Clinical and laboratory characteristics and follow up of 62 cases of ketotic hypoglycemia: a retrospective study. Int J Pediatr Endocrinol. 2019;2019:3.
Mridha A, Martin A. Ketotic hypoglycemia in children: a review. Bangladesh J Child Health. 2019;43(2):113–6.
Alhaidan Y, Larsen MJ, Schou AJ, Stenlid MH, Al Balwi MA, Christesen HT, et al. Exome sequencing revealed DNA variants in NCOR1, IGF2BP1, SGLT2 and NEK11 as potential novel causes of ketotic hypoglycemia in children. Sci Rep. 2020;10(1):2114.
Cryer PE. Hypoglycemia-associated autonomic failure in diabetes. Handb Clin Neurol. 2013;117:295–307.
Christesen HB, Brusgaard K, Beck Nielsen H, Brock JB. Non-insulinoma persistent hyperinsulinaemic hypoglycaemia caused by an activating glucokinase mutation: hypoglycaemia unawareness and attacks. Clin Endocrinol. 2008;68(5):747–55.
Christesen HT, Brusgaard K, Hussain K. Recurrent spontaneous hypoglycaemia causes loss of neurogenic and neuroglycopaenic signs in infants with congenital hyperinsulinism. Clin Endocrinol. 2012;76(4):548–54.
Ago Y, Sugie H, Fukuda T, Otsuka H, Sasai H, Nakama M, et al. A rare PHKA2 variant (p.G991A) identified in a patient with ketotic hypoglycemia. JIMD Rep. 2019;48(1):15–8.
van Hasselt PM, Ferdinandusse S, Monroe GR, Ruiter JP, Turkenburg M, Geerlings MJ, et al. Monocarboxylate transporter 1 deficiency and ketone utilization. N Engl J Med. 2014;371(20):1900–7.
Al-Khawaga S, AlRayahi J, Khan F, Saraswathi S, Hasnah R, Haris B, et al. A SLC16A1 Mutation in an infant with ketoacidosis and neuroimaging assessment: expanding the clinical spectrum of MCT1 deficiency. Front Pediatr. 2019;7:299.
Kishnani PS, Austin SL, Abdenur JE, Arn P, Bali DS, Boney A, et al. Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. Genet Med. 2014;16(11):e1.
Eastman RC, Carson RE, Orloff DG, Cochran CS, Perdue JF, Rechler MM, et al. Glucose utilization in a patient with hepatoma and hypoglycemia: assessment by a positron emission tomography. J Clin Investig. 1992;89(6):1958–63.
Møller N, Schmitz O, Jørgensen JO, Astrup J, Bak JF, Christensen SE, et al. Basal- and insulin-stimulated substrate metabolism in patients with active acromegaly before and after adenomectomy. J Clin Endocrinol Metab. 1992;74(5):1012–9.
Shapiro ET, Bell GI, Polonsky KS, Rubenstein AH, Kew MC, Tager HS. Tumor hypoglycemia: relationship to high molecular weight insulin-like growth factor-II. J Clin Investig. 1990;85(5):1672–9.
Santer R, Kinner M, Lassen CL, Schneppenheim R, Eggert P, Bald M, et al. Molecular analysis of the SGLT2 gene in patients with renal glucosuria. J Am Soc Nephrol. 2003;14(11):2873–82.
Koscielny G, Yaikhom G, Iyer V, Meehan TF, Morgan H, Atienza-Herrero J, et al. The International Mouse Phenotyping Consortium Web Portal, a unified point of access for knockout mice and related phenotyping data. Nucleic Acids Res. 2014;42:D802–9.
Marcus C, Alkén J, Eriksson J, Blom L, Gustafsson J. Insufficient ketone body use is the cause of ketotic hypoglycemia in one of a pair of homozygotic twins. J Clin Endocrinol Metab. 2007;92(11):4080–4.
Beardsall K. Measurement of glucose levels in the newborn. Early Hum Dev. 2010;86(5):263–7.
Woo HC, Tolosa L, El-Metwally D, Viscardi RM. Glucose monitoring in neonates: need for accurate and non-invasive methods. Arch Dis Child Fetal Neonatal Ed. 2014;99(2):F153–7.
Adamkin DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics. 2011;127(3):575–9.
Vanelli M, Mastrorilli C, Fainardi V, Iovane B, Scarabello C, Veronese P, et al. Clinical utility of beta-hydroxybutyrate measurement in the management of physiological ketosis at home in children under 5. Acta Biomed. 2019;90(2):215–20.
Ross KM, Brown LM, Corrado MM, Chengsupanimit T, Curry LM, Ferrecchia IA, et al. Safety and efficacy of chronic extended release cornstarch therapy for glycogen storage disease type I. JIMD Rep. 2016;26:85–90.
Currie G, Szabo J. "It is like a jungle gym, and everything is under construction": the parent's perspective of caring for a child with a rare disease. Child Care Health Dev. 2019;45(1):96–103.
Lopes MT, Koch VH, Sarrubbi-Junior V, Gallo PR, Carneiro-Sampaio M. Difficulties in the diagnosis and treatment of rare diseases according to the perceptions of patients, relatives and health care professionals. Clinics (Sao Paulo). 2018;73:e68.
All work for this manuscript contributed voluntarily, without monetary compensation.
Ketotic Hypoglycemia International (KHI), Skanderborg, Denmark
Danielle Drachmann, Erica Hoffmann, Austin Carrigg, Beccie Davis-Yates & Valerie Weaver
School of Social Science, Nottingham Institute of Education, Nottingham, UK
Beccie Davis-Yates
Cook Children's Medical Center, Fort Worth, TX, USA
Paul Thornton
Glycogen Storage Disease Program, University of Connecticut, Farmington, CT, USA
David A. Weinstein
Novo Nordisk A/S, Bagsværd, Denmark
Jacob S. Petersen
Endocrinology Department, The Royal London Children's Hospital, Barts Health NHS Trust and Queen Mary University London, London, UK
Pratik Shah
Department of Clinical Research, University of Southern Denmark, Odense, Denmark
Henrik Thybo Christesen
Hans Christian Andersen Children's Hospital and Steno Diabetes Centre Odense, Odense University Hospital, JB Windsloews Vej 4, 5000, Odense C, Denmark
Danielle Drachmann
Erica Hoffmann
Austin Carrigg
Valerie Weaver
DD and HTC conceived the article idea. All authors read and approved the final manuscript..
Correspondence to Henrik Thybo Christesen.
Consent for publication of data in Table 2 was obtained from the parents.
Drachmann, D., Hoffmann, E., Carrigg, A. et al. Towards enhanced understanding of idiopathic ketotic hypoglycemia: a literature review and introduction of the patient organization, Ketotic Hypoglycemia International. Orphanet J Rare Dis 16, 173 (2021). https://doi.org/10.1186/s13023-021-01797-2
Idiopathic ketotic hypoglycemia
Glycogen storage disease
Ketone bodies
Rare endocrinological diseases


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Cinderella has been invited to a dance that the prince has organized. She is very excited and did not know what to wear. Help choose the costume. To do this, click on a garment and dragging the body of Cinderella. Cinderella is a cartoon character from the Walt Disney name. Have all items of clothing that need to go to a dance. Have many dresses of many colors, you have all the accessories and jewelry.
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Games of the Generation: Horizon Zero Dawn gave us an instant fan-favorite in Aloy
By Matt Phillips published 12 September 20
Aloy, is it me you're looking for?
(Image credit: Guerrilla Games)
Games of the Generation
As we approach the launch of the PS5 and Xbox Series X, TechRadar is looking back at the games that made this generation great. This week's entry? Horizon Zero Dawn.
Dutch studio Guerrilla Games made a name for itself as the developer of the Killzone series, an iconic PlayStation franchise that spanned five installments over four PlayStation generations.
So, it was somewhat of a surprise when the developer announced at E3 2015 that its new IP wasn't an FPS at all, but rather Horizon Zero Dawn - a singleplayer, narrative, character-focused open-world RPG… with robot dinosaurs.
It may seem like an odd premise, but Horizon Zero Dawn released in 2017 to critical acclaim and cemented Aloy's place as a PlayStation icon - and Horizon Zero Dawn's place as one of the greatest games of this generation.
An epic journey
Horizon Zero Dawn starts by introducing the player to Rost and a young Aloy, as they journey across the hostile world of Horizon to perform a ritual with the Nora Tribe, who have declared the pair outcasts - but we won't spoil why.
As we journey, Rost explains the mysterious world of Horizon, from the Old Ones who betrayed the Goddess to the gigantic machines that roam the wilderness. The awe that this opening cinematic inspires is captivating and immediately you're drawn into the rich lore of the world - which only gets more intriguing as you progress.
A large part of what makes Horizon Zero Dawn so captivating lies in its intricacies. If Guerrilla Games had released a simple game, with an intriguing protagonist and robot dinosaurs, that would have been enough to spark interest. But instead, the developer goes above and beyond to immerse the player through the game's mechanics.
One example of this is in the dialogue options, which allow you to further question aspects of the narrative, helping you understand Aloy's anger towards the Nora Tribe and her curiosity about the world around her - and therefore, understand Aloy more as a character in her own right.
Horizon Zero Dawn's world also has incredibly detailed lore attached to it, including several tribes all with their own unique beliefs, styles and political systems that can be investigated through conversations and side quests. This helps to flesh out the world, with all its moving parts, and encourages you to continue unearthing its secrets even after the credits have rolled.
Truly fun gameplay
A game about uncovering the mystery of a long-forgotten civilization and the social laws of primitive tribes could be forgiven for dipping into the bleak and depressing. But Horizon Zero Dawn always has fun at its core. Through its bevy of weapons to its in-depth skill tree, there is always something new and entertaining to be testing when it comes to Horizon's combat.
And that's not even covering the incredible variety and detailed enemy design. The mechanical dinosaurs that rule the expansive open-world really are the star of the show and each poses a unique and exciting challenge to Aloy. From the mountable Striders to the terrifying Thunderjaws each type of creature you encounter will require a different strategy to take down. Luckily, they all also have big glowing weak points for you to target, but that doesn't mean surviving a Bellowback encounter will be easy.
Combat in Horizon is complemented by the crafting and economic systems. Collecting plants and resources on the roadsides will allow you to craft ammo for your various weapons or sell resources to buy new items for your arsenal. It's all simple enough and in no way groundbreaking but it effectively discourages fast travel in the early game. Instead, you'll reap better rewards by exploring on foot and always considering the risk in navigating a new area.
PlayStation all-star
The opening of the Horizon Zero Dawn has you playing as Aloy as she grows up, raised by her adoptive father Rost, living as an outcast of the Nora Tribe. Allowing the player to experience Aloy's vulnerability in her youth helps us to empathize with her struggles, confusion and anger toward the tribe that cast her out as an infant.
It's this opening section of the game that sets Aloy apart from other typical game protagonists. Horizon Zero Dawn's story is one of a young woman's strive to discover who she is and where she is from. This relatable struggle leads to the player also finding out about the world and its people, but it is all secondary to Aloy. It's refreshing to have a game protagonist that isn't just a bloodthirsty killer on a mission, but instead an young woman unraveling a personal mystery.
From the beautiful landscapes to the engaging combat Horizon Zero Dawn has a little something for everyone. It's not perfect, sometimes the open world can feel a little empty, the side quests aren't up to the quality of something like the Witcher series, and conversations can sometimes feel a little lifeless; but Horizon Zero Dawn still manages to tell a unique story that we can't wait to explore more in Horizon Forbidden West.
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This is a discussion on overview map scale within the MapPoint Desktop Discussion forums, part of the Map Forums category; My application opens a form containing a map that does not include the legend and overview map by default. I ...
Senior Member Black Belt
My application opens a form containing a map that does not include the legend and overview map by default. I have a custom toolbar with a legend icon that opens the legend and overview map pane, but when it is first opened, the overview map shows all of North America, not the overview area of the map. If the user pans or zooms, the overview map displays correctly.
Is there a way to force the overview map to generate a proper map when the pane is first opened?
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Member Yellow Belt
how about once the map has opened, and the panes displayed, move your position slightly? or open the panes after the map?
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S & P 500
US economy adds far fewer jobs than expected in May
Gina Heeb
Jun. 7, 2019, 08:39 AM
REUTERS / Brian Snyder
The official US employment report out Friday showed that hiring slowed sharply last month and that wage growth cooled.
The report could add to concerns that the US's economic expansion is running out of steam.
It could also bolster expectations for the Federal Reserve to lower interest rates.
In the latest snapshot of the American economy, the official US employment report out Friday showed that hiring slowed sharply in May and that wage growth cooled.
The Bureau of Labor Statistics said the US economy added 75,000 nonfarm payrolls in May, compared with economist expectations for an increase of 180,000 jobs. The unemployment rate held steady at 3.6%.
Average hourly earnings rose by 0.2% in May, the same as in the previous month. That brought wage growth from a year earlier to 3.1%, missing economist expectations.
The labor market was slow to pull Americans from the sidelines in May. The labor-force participation rate remained at 62.8%, which is low by historical standards and compared with other countries.
The latest employment report could add to concerns that the US's economic expansion is running out of steam. Escalating trade tensions have put businesses and investors on edge in recent weeks, with growth in the US and elsewhere already expected to slow over the next year.
"Not good," Austan Goolsbee, the chairman of the Council of Economic Advisers in the Obama White House, said of the May jobs report. "Let's hope it is a blip and not an indication of a substantial slowdown. But the other indicators are also pointing to substantial GDP growth problems and so it's moving into yellow light territory."
President Donald Trump increased tariffs on China last month and threatened to expand them to a broader range of products. He has separately vowed to slap duties on all imports from Mexico, the US's largest trading partner.
"In our estimation the trade wars the United States finds itself ensnared in are going to cause hiring to slow as business sentiment eases, productivity-enhancing capital expenditures fall off, and the damage eventually spills over into the consumer sector," said Joseph Brusuelas, the chief economist at RSM.
On average, the US has added 151,000 jobs each month since March.
Friday's results are likely to bolster expectations for lower borrowing costs. Federal Reserve Chairman Jerome Powell signaled last week he was open to cutting interest rates if trade conditions worsened.
"This is the type of read the doves will really take to, as it supports the argument for cutting rates beyond politics or trade issues, which were never part of the Fed's mandate to begin with," said Mike Loewengart, the vice president of investment strategy at E-Trade.
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