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By: PTI | Updated: January 17, 2021 11:13:28 pm Shardul Thakur and teammate Washington Sundar talk during play on … The hosts could declare any moment. For IND vs AUS 4th Test live telecast in India, fans can tune into the Sony Pictures Sports Network (SONY TEN 1, SONY TEN 3 and SONY SIX) at 5:30 AM (IST). Scorecard – https://t.co/bSiJ4wEymL #AUSvIND pic.twitter.com/bPsCBzt9nM. The match will resume on Day 3, at 5:00 AM IST. Starc and Hazlewood along with Cummins are certainly going to come hard at the Indian openers. India finish on 4/0, still need 324 runs to win the fourth and final Test. Brisbane Test on after BCCI-CA talks, crowd capacity capped at 50 percent; Brisbane Test … Complete Scorecard of India vs Australia 4th Test 2018/19, INDIA in AUS only on ESPNcricinfo.com. Maybe the hosts will give the last hour to the Indians. The inevitable has happened. Australia's streaks that have been ended by India: - 16 consecutive Test wins - 2001 in Kolkata & 2008 in Perth - First and only Asian side to win at WACA in 2008 - 19 consecutive ODI wins at home - 2016 in Sydney - 32 years unbeaten at Gabba bw 1989 & 2020. We've been practicing hard after the first Test. Not to forget, debutant T. Natarajan also rose to the occasion in his maiden Test, but what about Mohammad Siraj… He picked up his first five-wicket haul in Tests and bowled with a heart. India vs Australia (IND vs AUS) 4th Test Day 5 Highlights: India chased down 328 in the fourth innings to win the 4th Test vs Australia and claim the series 2-1. Most consecutive Tests unbeaten at a venue 34 Pakistan at National Stadium, Karachi (1955-00) 31 Australia at Gabba (1989-19) * 27 West Indies at Kensington Oval (1948-93) 25 England at Old Trafford (1905-54) 19 West India at Sabina Park (1958-89) Highest successful run chases by India 406 vs WI Port of Spain 1975/76 387 vs Eng Chennai 2008/09 328 vs Aus Brisbane 2020/21 * 276 vs WI Delhi 2011/12 264 vs SL Kandy 2001 Highest successful run chases vs Australia in Australia 414 SA Perth 2008/09 332 Eng Melbourne 1928/29 329 Ind Brisbane 2020/21 India winning a series after losing the first Test 2-1 vs Eng in India 1972/73 2-1 vs Aus in India 2000/01 2-1 vs SL in Sri Lanka 2015 2-1 vs Aus in India 2016/17 2-1 vs Aus in Australia in 2020/21 Most runs scored on Day 5 to win a Test 404 Aus v Eng Leeds 1948 344 WI v Eng Lord's 1984 325 Ind v Aus Brisbane 2020/21 * 317 Aus v Ind Perth 1977/78 317 WI v Eng Leeds 2017. And India rejoice this evening at the Woolloongabba, as the sun smiles on the way down, having narrowly defeated the rains and the shadows. Rohit Sharma looked in good touch during his 44 off 74 balls but was dismissed trying to loft Nathan Lyon over mid-wicket, the kind of shots that has often brought about his dismissal even during earlier Test matches. India vs Australia Test Highlights: Rain stopped play on Day 4 of the fourth and final Test match between Australia and India, at The Gabba in Brisbane. India vs Australia Test Highlights: Day 2 of the ongoing fourth Test match failed to resume after the Tea break at The Gabba, due to heavy rain. Battered, bruised, barely alive. India need 324 runs to win on Day 5 of the 4th Test. Ind vs Aus, 4th Test: Siraj's fiver, Steve Smith's half-century set stage for grand finale at the Gabba Photograph:( AFP ) Follow Us Story highlights. Karen Noronha. IND vs AUS 4th Test: India clinch thrilling series win at The Gabba. How have you won over the most diabolical of nemeses in the cricketing realm: the weather gods, rather like the somewhat lascivious stadium security guard has been tempted by the most testing seductress of them all - Test cricket. Into the shadows went the ball, and disappeared into the boundary at long-off. There are many areas of improvement honestly. Published Date: January 18, 2021 6:56 PM IST, Updated Date: January 18, 2021 6:58 PM IST. India and Australia head to a grand finale of the fourth Test match at the Gabba, Brisbane as visitors need 324 runs to win the game and seal the series. The Indian cricket team suffered a shock in the third Test after three main players - Ravindra Jadeja, Hanuma Vihari and Jasprit Bumrah - suffered injuries. When he doesn't keep well, people criticize him. THE TIMES OF INDIA | Jan 17, 2021, 13:20:01 IST. Sundar batted as if he had already played 20 Tests. Washington Sundar was a net bowler, Natarajan was a net bowler. And India will now take a victory lap, with Rishabh Pant fittingly leading the pack with India's tricolour. Rahane calls Nathan Lyon on to handover a signed Indian jersey to him on the occasion of his 100th Test. Ind vs Aus: Another jolt to India as Jasprit Bumrah ruled out of Brisbane Test While expectations from Siraj and Saini will be high, fans could also see T Natarajan making his Test debut for India. Ind vs Aus: Families of Sundar, Siraj elated with historic Test series win in Australia . Find the complete scorecard of Australia vs India 4th Test Online Virat has been with us despite not being here. I wanted the cracks to do a bit more. The conversation between Pujara and me was that he would bat normal, and I would take it on. The romanticism of Test cricket, the contrast of sheer panache and grit, the coexistence and codependence of the Pujaras and the Pants of the world is what we live for - the euphoria, the heartbreak, the "umpire's call" bruises that hurt more if you lose, but don't hurt if you win. Shardul Thakur celebrates after picking up a wicket. He has been brilliant and that's why we back him. Aditya Desai . Day 1 in a test match India wins with Vijay and Dhawan picking up centuries. Rishabh and Washington were very good at the end. And the scores of wins for the realists is a small price to pay for one moment of magic for the dreamers and the romantics. Now it is over to the batsmen, who have a mountain to climb. India vs Australia Test Highlights: Rishabh Pant slammed a heroic unbeaten knock of 89 runs to steer the visitors to a valiant victory on Day 5 of the fourth Test … DNA Web Team . By FPJ Web Desk. Team India added another feather to their hat with their triumphant Test series victory in Australia to retain the … Australia 369 and 21 for 0 lead India 336 (Thakur 67, Sundar 62, Hazlewood 5-57) by 54 runs. All Rights Reserved. Find the complete scorecard of India vs Australia 4th Test Online It was a fifth day pitch and the ball was turning. I'm really proud of each individual. DNA webdesk. Our bowlers did really well as well, it's just credit to the Indian side for this terrific series. But they have played so well. player of the match. Catch live and fully detailed scorecard of Australia vs India, 4th Test, Jan 15, India tour of Australia, 2020-21 on Cricbuzz Cricket News. Thakur top-scored for India as he made 67 runs while Sundar accumulated 62 runs. Zee Entertainment Enterprises Limited. We have to look back over a lot of things, and we'll go through it as a group, and we have been outplayed by a better side this series. Steven Smith struck 55 off 74 with seven fours as Australia were bowled out 294 in 75.5 overs. The Indians couldn't wait to see Paine (and the rest) at the Gabba. Australia vs India, 4th Test: Nathan Lyon took the wicket of Rohit Sharma on Day 2 in his 100th Test match at The Gabba, and will be eyeing Rishabh Pant's too, when play resumes on Day 3. IND Vs AUS 4th Test: Aussie Fans Called Out For 2019 'No Steve Smith, David Warner' Retort After winning the IND vs AUS 4th Test, Indian cricket fans took to Twitter and smashed Aus fans for their 2019 'no Steve Smith, David Warner' statements. The moment of truth: It was a full-toss, and it was a straight drive that took Rishabh Pant to 89. Ind vs Aus: Another jolt to India as Jasprit Bumrah ruled out of Brisbane Test While expectations from Siraj and Saini will be high, fans could also see T Natarajan making his Test debut for India. 4th Test… Rishabh Pant in action on Day 5 against Australia in Brisbane. Here is a look at the possible Indian … They said no chance after a collapse at the SCG. India vs Australia IND vs AUS 4th Test: Cracks on Gabba strip will play on batsman's mind, feels Mohammed Siraj. They have not only retained the trophy, they've won the series. India finish on 4/0, still need 324 runs to win the fourth and final Test. India vs Australia IND vs AUS 4th Test: No regret, I will keep playing such strokes, says Rohit Sharma. IND vs AUS 4th Test: Rohit Sharma wastes another good start after India's rookie attack restrict hosts at 369 on Day 2 Rohit Sharma once again threw away a good start after India's … AUS vs IND 4th Test: India continue to monitor injuries, to name Playing XI on Friday India's batting coach Vikram Rathour said that the management … Complete Scorecard of Australia vs India 4th Test 2016/17, IND v AUS only on ESPNcricinfo.com. Also Read - Ravichandran Ashwin: Tim Paine Played Perfect Host by Missing Rishabh Pant Stumping Chance at Brisbane, —————————————————————————————————————— Also Read - Rishabh Pant on Preparations Ahead of England Series: Hungry to Cash in on Whatever Opportunities I Get. Didn't think so. Over to Chandigarh as India host Australia in the 3rd of a four test series. A tough character. Share. Australia won a good toss against a depleted India in the fourth and final Test. The tourists punched above their weight nicking out both the Aussie openers quite quickly. Despite being forced into fielding an inexperienced squad for the final Test, India showed incredible desire to go toe-to-toe with the Aussies at their 'Fortress Gabba'. They said no chance without Bumrah, Shami, Jadeja, Ashwin. Playing in his maiden Test series, Mohammed Siraj grabbed 5 for 73 in the Australian second innings on Monday. The character of this team is amazing especially after the 36 all out at Adelaide. With KL Rahul returning home due to a wrist injury and Mayank Agarwal hit on the hand at the nets, India also face a dilemma as they look to bring in someone to replace Hanuma Vihari, who injured his hamstring during the drawn third Test and is unlikely to play as the No. IND Need 328 to Win, Australia still not declaring, this is getting a little strange now. A counter-attack from Shubman Gill (91) set up a thrilling hour of play on either side of the Lunch break, before Ajinkya Rahane joined Cheteshwar Pujara. No one thought about Shubman Gill - the man who replaced his U-19 captain after a horror show, and the composure he's shown on Day 5 of a deciding Test at Australia's fort has been incredible. Australian openers (David Warner and Marcus Harris) gave a strong start to the hosts. Stay updated with Times of India for Live cricket score, ball-by-ball commentary & scorecard of 4th Test match between India and Australia. They complained about the bubble alright, but when they were let out of it, they cut loose and gave it their all, didn't they? For IND vs AUS 4th Test live telecast in India, fans can tune into the Sony Pictures Sports Network (SONY TEN 1, SONY TEN 3 and SONY SIX) at 5:30 AM (IST). Follow Australia vs India, 4th Test, Jan 15, India tour of Australia, 2020-21 with live Cricket score, ball by ball commentary updates on Cricbuzz India finish on 4/0, still needs 324 runs to win the fourth and final Test. AUS vs IND 4th Test Day 1: Inexperienced Indian bowlers hold on despite Labuschagne's ton. But Pujara did what Pujara always does. Watch highlights of AUS vs IND 4th Test Day 3; Test rookies Shardul Thakur and Washington Sundar combined for a rearguard century stand that frustrated Australia… The support the team has given me even when I was not playing has been incredible. Team India added another feather to their hat with their triumphant Test series victory in Australia to retain the … They said no chance of survival on the final day with battered bodies. Rishabh Pant is currently playing on 10 from 23 deliveries. Also Read IND Vs AUS 4th Test: Zomato … The day: It was all set to be a breathtaking finale - and for the chase, history backed Rohit Sharma, whereas recency bias backed Rishabh Pant. The debutant amassed 62 runs studded with six and seven fours. It's pouring in Brisbane and hence the day's play has ended. A salute to the entire Indian contingent for giving us a reason to wake up early, look forward to something with belief and make us smile in these tough times. Natarajan also dismissed Wade just before completing his fifty. India vs Australia IND vs AUS 4th Test: 'To everyone who doubted us after Adelaide' Ajinkya Rahane and co. not only retained the Border-Gavaskar Trophy but also secured an impressive 2-1 series win against Australia on Tuesday. Back then, many believed that the Indian team won the Test series against a weak Australian team as the hosts played without the likes of David Warner and Steve Smith. Australia vs India 4th Test Day 3 Report: Thakur, Sundar help India cut margin in series deciding Test Australia's openers, David Warner (20) and Marcus Harris (1), saw out six overs, and extended the home team's lead to 54 by stumps after India's first innings ended at 336. Some of us were in a lock down for some 6 months where as cricket had started in some other part of the world. For India vs Australia live scores, one can visit the official website and social media pages of the BCCI and Cricket Australia. It's been another enthralling day of Test cricket with Australia upping the ante before India hot back with quick blows. IND vs AUS 4th Test, Day 1 Highlights: Marnus Labuschagne got to his century after Tea but lost his wicket soon. And, I'm going to say it, they've breached Gabbatoir - Australia's pride no longer. With injuries to several key players, either Prithvi Shaw or Mayank Agarwal can make a comeback into the Indian playing XI for the series-decider. Up centuries hug to Pant from a beaming ravi Shaz, safety precautions you … IND vs AUS Test... Well I think we could have picked up wickets pride no longer now it is over.! Good at the Gabba, Brisbane had he stuck around for some in. Would be looking to have some fun and clarity required in the of. Jan 15 - Jan 19, 2021, India in AUS only on.... Australian openers ( David Warner and Marcus Harris ) gave a strong start to the hosts and I... 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Hull MP Emma Hardy says many parents are 'extremely worried' about children going back to school
Children across Hull and East Yorkshire will be returning to school next week
Hull West and Hessle MP Emma Hardy
Hull West and Hessle MP Emma Hardy says many parents are still "extremely worried" about sending their children back to school.
Schools in Hull and the East Riding are due to reopen next week after most pupils were sent home indefinitely in March.
Some are staggering opening dates for different year groups as they attempt to return to normal after lessons were disrupted by the coronavirus lockdown.
Some pupils have not been back to school since then.
Ms Hardy, who is Labour's shadow minister for further and higher education, carried out her own survey in August asking parents how they felt about their children returning to school.
In the survey, parents were asked a variety of questions including what levels of anxiety they had about children going back into the classroom, what their main concerns were and what they thought of the Government's handling of the crisis.
Pupils wash their hands on the first day back to school at Outwood Academy Adwick in Doncaster, as schools in England reopen to pupils following the coronavirus lockdown.
Overall, 41.9 per cent of those who took part said not enough had been done by the Government to prevent the spread of Covid-19 in schools while 45 per cent said track and trace was not effective enough.
In addition, 45.2 per cent said they wanted to see regular testing of students and school staff and 42.1 per cent supported the idea of having smaller class sizes as a way of dealing with social distancing.
Only 18 per cent of respondents scored the Government above five out of 10 in a satisfaction rating on its actions to deal with the pandemic so far.
UK coronavirus infections top 1,700 in biggest daily rise since June
Pupils from North West secondary school self-isolating after student tests positive for coronavirus
Ms Hardy said: "It is clear from the results from this survey that many parents are extremely worried about the Government's handling of the return to school for our children.
"The Government have shown poor leadership and incompetence in their handling of this matter.
"Over 40 per cent of respondents feel that the Government has not done enough to make track and trace effective and that not enough has been done to stop transmission of the virus within schools.
Find the latest coronavirus cases near you
"On top of this they have asked that the Government should provide regular testing for all pupils and staff and reduce class sizes to help combat these issues.
"The Labour Party has clearly stated that getting our children back into schools has been a priority but the Government in its implementation of this has done so poorly, with little or no clarity of procedure to schools and has only heightened parents anxiety in returning our children to school."
Secretary of State for Education Gavin Williamson in Parliament Square in Westminster, London.
Education Secretary Gavin Williamson has said that parents who do not send their children back to school risk putting a "huge dent in their future life chances".
He published an open letter to all parents earlier this week as pupils in other parts of the country returned to school for the first time in months.
"If a child is not in school, they stand to lose far more than just a few months of learning. It could well put a huge dent in their future life chances," Mr Williamson said.
Watch: How to keep school uniforms clean
"Education is a birthright, so let's make sure we get all children back - back to learning, back to playing and back to being kids again."
Mr Williamson said it was "generally accepted" that children's health and wellbeing were more at risk if they did not go to school.
He cited a joint statement by the UK's chief medical officers, which said "very few, if any" children and teenagers would come to long-term harm from coronavirus solely by attending school.
Emma Hardy
Hull City 2-0 Blackburn Rovers highlights as George Honeyman gives Acun Ilicali dream start

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Starting Theatrical
wrathofkublakhan	Profound Living	 March 23, 2018 March 23, 2018 4 Minutes
You got nothing to hit but the heights!"
Like a good book, a piece of theater needs to grab the attention of the audience. Beginnings are so important to pull an audience in and to get receptive with the event. It might begin leisurely like the Grapes of Wrath with a description of a turtle crossing the road or it might be scary on a dark and stormy night.
Call me Ishmael
Ninety-five percent of plays begin straight forward and with a get-down-to-it attitude. The houselights go out, the curtain goes up, the stage lights go on. Someone is "found" on stage, as we say; maybe it is Aunt Eller churning butter setting the scene for Oklahoma! Pardon the exclamation point, it comes with the show title.
Where is Pa going with that Axe?
A variation is making that first entrance. Actors and Directors love an entrance. In this case, the scene is introduced first. The suggested scenery in Our Town needs to be absorbed before the Stage Manager walks on to address the audience and point out the features in the town. Hal Holbrook in his one man show on Mark Twain began by blowing a puff of cigar smoke from the wings to bring him on.
One of my favorites in dance is when the music starts before the curtain goes up. The lights are on behind the curtain and the dancers are already moving. This suggests that our scene has gone on forever, maybe they are sprites or fauns or pixies. This is called a "reveal" when the curtain goes up. Sometimes we bookend it by finishing the same way as the dance continues and we've had a little peek into a magical world.
It was a pleasure to burn
Like opening a book to the first page, the theatrical start is a transition from our real world to a place of imagination. Musicals often have an overture, showcasing the melody of the songs to come. It also showcases the conductor and his orchestra, often finished with a bow.
My favorite, though, is when the transition is built into the music and we are led straight into the show. Guys and Dolls ends it's overture with the curtain rising and we see the cast frozen in mid-stride. This is Runyonland and it pushes the idea of how two-dimensional these cartoonish characters are going to be. With names like Harry the Horse, Nathan Detroit, Scranton Slim and Nicely Nicely Johnson; we are sure to be in for a good time.
All this happened, More or Less
The designer's dream is when there is no curtain at all. With a ballet or opera, we have invested a lot into atmosphere. Getting a half an hour while the audience comes into the theater to feature the scenery and set the mood is a treat. Long ever-shifting light changes are satisfying but probably unnoticed by the layman. Maybe I'll talk to the sound guy to add a bird chirping every two minutes. Let the cast wander into this heavy atmosphere to start the show. This is called "establish and build" because the audience remembers it even as the actor lighting blows it out.
There was a boy called Eustace Clarence Scrubb and he almost deserved it.
Some transitions are famous and have to be done a certain way. One ballet opens with a black scrim down-stage, the lights are on behind the scrim (another reveal) and all we see is fog. The dancers are beneath the fog and then rise up out of it; like magic! Then, we raise the black scrim and all of that cold dry ice fog rolls into the orchestra pit which forces the instruments out of tune. Classic!
You better not never tell nobody but God.
I saw a show once in a small theater. It was by a company from Slovenia. There were three small audience sections with a total capacity of about sixty. A large square rug defined the performance space. A guy walks out and starts to gesture at us. It takes a while but we figure out that he wants us to turn on the lamps placed around the space; not stage lamps but lamps like you have in your house. So, we do and wonder; what is next?
Then a girl comes out with a huge platter of cookies. She walks along and serves us. While this happens, another man gets a woman from the audience to slow dance with him. This is a great way to start theatrical; the audience is paying close attention to the show. It wasn't some crazy carnival clown running up the aisles, thank goodness. Not knowing if you will have to participate will keep your focus through out the play.
Call me Ishmael: Herman Melville, Moby-Dick
Where is Pa going with that Axe?: E. B. White, Charlotte's Web
It was a dark and stormy night: Madeleine L'Engle, A Wrinkle in Time
It was a pleasure to burn: Ray Bradbury, Fahrenheit 451
This all happened, more or less: Kurt Vonnegut, Slaughterhouse-Five
There was a boy called Eustace Clarence Scrubb and he almost deserved it: C. S. Lewis, The Voyage of the Dawn Treader
You better not never tell nobody but God: Alice Walker, The Color Purple
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Third Week in December
On Dec. 22, 1944, future Hall of Famer Steve Carlton was born in Miami, Fla. Carlton would make his Major League debut with the St. Louis Cardinals in 1965, but gained most of his fame as a member of the Philadelphia Phillies, winning four Cy Young awards along the way. "Lefty" enjoyed his finest season in 1972, when he posted a record of 27-10 with an ERA of 1.97 for the last-place Phillies. In 1983, he wore this cap when he collected his 3,521st career strikeout, tying him with Nolan Ryan in the all-time strikeout chase. In May, Carlton had moved past Walter Johnson for the all-time lead in strikeouts.
Hear an excerpt from Steve Carlton's 1994 Hall of Fame Induction speech.
Baseball Hall of Fame>>
This Week in MLB History Archives
Second Week
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Donald Sterling Fined 2.5 Million Dollars And Banned FOR LIFE !!!
After a news conference by NBA Commissioner Adam Silver on the Donald Sterling controversy, punishments for the Clippers owner include a lifetime ban and a $2.5-million fine. Silver also said he would urge NBA owners and the board of governors to force Sterling to sell the team.
I think it is good that the $2.5 million is going towards organizations that fight discrimination. Do you think that this is a fair punishment for a man who is worth way more than $2.5 million? He will make all his money back once he sells the team. You can't teach an old dog new tricks so what can you really do to punish a billionaire. He will always feel the way he feels.
Do You Agree With N.B.A.'s Decision To Ban Donald Sterling For Life ?


text:
Culture & Society News Politics & International Slovakia
Slovakia starts testing marginalized Roma community for coronavirus
Bratislava, Slovakia – A few days after the government's initial announcement, Slovakia started testing its sizable Roma community for coronavirus on Friday.
Slovakia to start large-scale Covid-19 testing in 33 Roma settlements
Prime Minister Igor Matovic announced earlier this week that the testing will be carried out by military doctors until next Thursday, April 9. Authorities will then decide on possible countermeasures to take if the results suggest the virus could be spreading in Roma settlements, including a possible quarantine enforced by the army.
According to the last census, Slovakia's Roma community numbers at more than 100,000 – although real figures are believe to be much higher.
Slovakia's decision to test the Roma community, largely concentrated in the country's eastern half, for coronavirus was also prompted by the discovery that at least 1,500 Roma from 33 different settlements had lately returned from abroad but hadn't self-isolated as legally required. The first results should be known on April 10.
"It is by no means a demonstration of power", assured Matovic on Wednesday. "We just want to make use of doctors in uniform to start fast-testing in the settlements without further overloading the regular health system", the Slovak PM said.
An entire Roma settlement located near the city of Gelnica in eastern Slovakia was already placed under lockdown after one of its members – a young man who eventually tested negative – failed to self-isolate and continued to move around upon his return from the U.K. The settlement should stay in quarantine at least until April 8.
Slovak police arrive in a Roma settlement near Gelnica, in the east of the country. Credit: TASR
A "ticking bomb" to be defused
"If we do not find out quickly how many people in the slums are infected, it will become a ticking bomb", said Peter Marko, a general practitioner from eastern Slovakia, warning that the Roma community might initially be distrustful of the military's involvement and that the possible death of some of its members could lead to an "unpredictable wave of panic".
"It is important that we familiarize them with this and persuade them about what the reasons are to undergo this testing and what the significance of the testing is for them", said Andrea Bučková, the Slovak government's new plenipotentiary for Romani communities. "We are communicating with them in their own languages, in other words, in Romani or in Hungarian".
Accounting for around 2% of Slovakia's total population, the Roma community remains highly marginalized and faces deeply-rooted discrimination in many areas (healthcare, employment, education…). Large parts of the minority continue to live in slum conditions with poor hygienic conditions, making them all the more vulnerable to the Covid-19 disease and their settlements a dangerous breeding ground for the spread of the virus.
Due to the poor sanitary conditions in many Roma settlements in Slovakia, experts believe that coronavirus could lead to 20 additional cases per infected people.
Main photo credit: TASR
TagsCovid-19 pandemic • Discrimination • Ethnic minorities • Healthcare • Igor Matovic • Roma • Slovakia
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Abstract: Today, the traditional classroom model teaching approaches in which learners are not active and teacher control everything is found insufficient by the educators. The effect of change in information and technology is seen in education field, too. In our world in which the only unchanging thing is change, the meaning of concepts such as education, teachers, learner, learning process are changing and as a result the expectation of learners from learning process varies. Consequently, different teaching models which respond the expectations of learners whose expectations differ are needed. One of these models is "Flipped Classroom Model" which started to spread recently. In this model, the effective use of out-of-class time is seen. In such a way that, the teaching in the classroom is presented to learners out of class, it is defined as carrying out the homework and activities, which are expected to be taught out of class because learners need teachers, in the classroom. For this purpose, this study aims to give information about emergence, development process, basis and procedures of Flipped Classroom Model and also reveal unknown aspects of model through discussing effects, advantages and disadvantages in company with literature.


Health Level 7 New Zealand is a national affiliate of HL7 International, dedicated to the goal of achieving interoperable healthcare information. Its primary – but not exclusive - focus is on current and emerging HL7 standards.
The 2018 Annual General Meeting was held at the offices of Sysmex NZ, 386 Manukau Road, Auckland on Wednesday 28th November at 4 pm. Eleven of the previous Board Members were re-elected along with Karen Blake (Health Alliance) who replaces Edwin Ng. At the first meeting of the new Board, held directly afterwards, the following officers were unanimously elected: Peter Jordan (Chairman), Peter Sergent (Vice Chairman), David Moorhouse (Treasurer), Linda McKay (Secretary). Under new Constitutional rules, the Chairman and Secretary will serve two year terms.
Is a highly experienced software architect and developer with a particular interest in healthcare information modelling, exchange and security. Currently, he is contracted as a Solutions Architect to Patients First Ltd, working on standards and architecture in support of the NZ Digital Health Work Programme 2020 – including HL7® FHIR® Terminology Services. Peter also continues to maintain the NZ CDA Toolkit used in GP2GP patient record transfers and the NZ ePrescription Service and his involvement with health information standards dates back to some of New Zealand's earliest HL7 Version 2 messaging solutions in the 1990s. His 3 decades in the IT industry, in the UK and New Zealand, have included spells with vendors of both primary and secondary care applications and various public sector organisations. Peter also represents primary care on the Sector Architects Group Executive and is a Co-Chair of the HL7 International Council and the SNOMED on FHIR Terminology Services Group.
Peter has thirty years' experience in the management of information; initially carrying out complex statistical analysis for research projects but later moving into areas of service provision. Prior to his move to primary health in late 2004, he spent the previous eleven years within a number of District Health Boards. Peter is now an independent consultant. He strongly supports the embracing of international standards such as ISO and HL7 and has been involved in HISO projects covering data dictionaries, information models and data exchange. During time spent within the District Health Boards, completed work on projects in the Middle East and Australia gaining a broader perspective on healthcare provision. He has undertaken numerous and varied roles in working groups advising the Ministry of Health, Accident Compensation Corporation and District Health Boards.
David is an experienced system designer and software developer with over 25 years' experience in NZ and UK. He is currently employed at Pegasus Health as Principal Software Engineer for HealthOne and helped to establish the South Island eReferrals solution. He is a passionate advocate for health interoperability and has hands-on experience implementing HL7 v2.x and FHIR standards. He understands and has developed solutions using modern authentication and Is an experienced system designer and software developer with over 25 years' experience in NZ and UK. He is currently employed at Pegasus Health as Principal Software Engineer for HealthOne and helped to establish the South Island eReferrals solution. He is a passionate advocate for health interoperability and has hands-on experience implementing HL7 v2.x and FHIR standards. He understands and has developed solutions using modern authenticationintegration standards. David considers open and modern standards as the key to driving innovation by making health informatics easier. Along with technical skills David brings in-depth experience of the primary care sector and has held governance roles in non-profit organisations.
Linda has been involved with HL7NZ since shortly after it was formed in 2004 holding the role of administrator and event manager. Linda runs her own event management company and has been involved in running events in Europe, South America and NZ for over 30 years . She has been running health information, health & safety, health management and environmental events here in NZ for over 20 years and is also Practice Manager of a physiotherapy clinic on Auckland's north shore.
David is a Product Strategist at Orion Health and is largely responsible for product innovation, development and prototyping, with particular focus on Orion Health patient facing solutions. He is also the standards expert. Active in the international standards community as the Chair of HL7 New Zealand, David is also a member of the FHIR Management Group, charged with guiding the development of the latest HL7 Standard. David was awarded Chair Emeritus in 2016 as a newly created title honouring the eight years he spent as HL7NZ Chairman and the incredible input and energy he has put into furthering the objectives of HL7NZ.
Is Director of Health Information Standards with the Ministry of Health. Leads the development and implementation of ICT standards supporting the national digital health strategy. Works with the Health Information Standards Organisation (HISO) and represents New Zealand on the SNOMED International Member Forum and advisory groups. Alastair represents the health and disability sector on the Government Enterprise Architecture governance group and enjoys working with the national standards and architecture community.
Is a senior software consultant working in research and development at Sysmex NZ Ltd. His background is Medical Laboratory Science and Health IT, with particular reference to clinical information interoperability and exchange. He has been an HL7 NZ board member since the organisation's inception in 1994 and has played a role encouraging the New Zealand health sector in the adoption of various standards such as HL7 v2 messaging, NZPOCS and LOINC coding and more recently, FHIR.
Is the Chief Architect at Sysmex New Zealand and is responsible for managing the R&D of the Eclair product as well as guiding the direction of other products in the Sysmex portfolio. Graeme holds a BSc and MSc in computer science from Manchester University and certifications in Enterprise Architecture, and has been working in Health IT for 25 years. During this time he has been active building and delivering clinical data repositories across NZ, Australia, Canada & further afield and in promoting and implementing interoperable solutions using HL7 v2, IHE, HL7 CDA and now FHIR.
Is Chief Technology Officer at Healthlink, where he oversees development and deployment of products using HL7 technologies from version 2.1 to CDA and now FHIR. Before moving to Auckland from the USA in 2017, he was Vice President of Apelon, Inc., a professional services and software company focused on semantic interoperability. He has also been Product Manager at GE Healthcare (in partnership with Intermountain Health Care) and worked as a Health Data Analyst at the Missouri Hospital Association. John has been a member of HL7 International since 1998, primarily active in the Vocabulary Work Group. He holds a Master of Business Administration (finance) and studied medical informatics at the University of Utah.
Is Regional Manager Health Information, Office of the CCIO, healthAlliance. Karen has worked in midwifery clinical practice for over 20 years, in both NZ and Australia. Five years ago she transitioned into health informatics, becoming the first Chief Nursing and Midwifery Information Officer in Australia, implementing a large enterprise EMR. She returned home to NZ two years ago, and now works across the northern region at healthAlliance providing clinical leadership to the ISSP. Karen is a member of HISO, and sits on a range of clinical and IT regional and national governance and advisory groups. Her clinical informatics credentials include CHIA which she completed in 2017, and she is currently studying a Post Grad Diploma in Health Informatics at Auckland University. When not at work Karen volunteers as a rural operational fire fighter, and maintains her clinical practice as a first responder attending medical emergencies and MVAs, as well as structural and vegetation fires.
Is Executive Director, Personalized Healthcare Programs, at Sutter Health. From 1996-2008, Martin was founder and CEO of Enigma CKM Inc., a New Zealand owned vendor that created a patented clinical decision support system. In 2008 the technology was acquired by the prestigious California healthcare provider, Palo Alto Medical Foundation and has been developed into the Mpower™ system for personalized care. Since joining PAMF, he served as Executive Director in the David Drucker Center for Health Systems Innovation, and is now leading the migration of the Mpower system from the Innovation Center to an operationalized, enterprise application, deployed across Sutter Health, a not-for-profit healthcare provider serving 2 million patients in Northern California. Martin qualified as a physician (MB ChB) from Birmingham University, UK, specialized in trauma orthopedic surgery (FRCSEd), and studied for an MBA from Cranfield University, UK, before moving into the area of applied clinical informatics. He is the past chairman of HL7NZ.
Defines himself as an e-Health Cybernetician, with the certificates for SNOMED CT Implementation and Contents Development, dealing with quality and safety information for the Auckland District Health Board. Ray received PGDip HSci Health Informatics from the University of Auckland after studying papers focussed on population health. Ray's original background is multimedia, hypermedia and massive parallel processing in which he received BEng in Information Science from the Kyoto University. Ray designed and implemented various clinical information systems in a Japanese health IT vendor, advocated health interoperability standards in the HL7 Japan and was certified as a health information manager / clinical coder (ICD 10 and ICD 9 CM) by the Japan Hospital Association before coming to New Zealand in 2007. Ray wrote a paper which was accepted at the HINZ 2013 Conference about the roles which the social media played in the general public's responses to the Fukushima Nuclear Accident.
"To provide a comprehensive framework and related standards for the exchange, integration, sharing, and retrieval of electronic health information that supports clinical practice and the management, delivery and evaluation of health services. Specifically, to create flexible, cost effective standards, guidelines, and methodologies to enable healthcare information system interoperability and sharing of electronic health records.
These efforts enable effective, efficient communication between the constituents of the healthcare community as represented by our membership, which consists of an international community of healthcare organizations, vendors, healthcare information systems developers, consultants, systems integrators, and related public and private health services agencies.
The mission of HL7 encompasses the complete 'life cycle' of a standards specification - development, adoption, market recognition, utilization and adherence. The HL7 specifications are unified by shared reference models of the healthcare and technical domains."
Democratic election of the Board and technical leaders.
Acting as a forum for HL7® related standards activity in New Zealand.
Maintaining the capability to give advice on the use of HL7® standards in New Zealand.
Providing standards-related education and promoting HL7® certification.
Hosting periodic HL7® and related standards workshops and seminars in New Zealand.
Acting as point of contact between the Ministry of Health and HL7® International.
Participating in the work of HL7® International.
Developing relationships with other HL7® Affiliates.


text:
#include "poi.h"

/**
 * @brief POI::POI
 */
POI::POI(){
}

/**
 * @brief POI::add_detections
 * Adds OOIs for a specific frame in a POI.
 * @param frame_num
 * @param detections
 */
void POI::add_detections(int frame_num, std::vector<DetectionBox> detections) {
    if (m_start == -1)
        m_start = frame_num;
    OOIs[frame_num] = detections;
}

/**
 * @brief AnalysisInterval::set_end_frame
 * Sets the end frame of the POI.
 * @param frame_num
 */
void POI::set_end_frame(int frame_num) {
    m_end = frame_num;
}

/**
 * @brief Analysis::get_detections_on_frame
 * Returns all detections on a specified frame in the analysed video.
 * @param frame_num
 * @return
 */
std::vector<cv::Rect> POI::get_detections_on_frame(int frame_num) {
    std::vector<cv::Rect> rects = {};
    if(in_interval((frame_num))){
        for(DetectionBox ooi: OOIs[frame_num]){
            rects.push_back(ooi.get_rect());
        }
    }
    return rects;
}

/**
 * @brief POI::read
 * Reads POI from json format.
 * @param json
 */
void POI::read(const QJsonObject& json) {
    this->m_start = json["start"].toInt();
    this->m_end = json["end"].toInt();
    for(int i = m_start; i != m_end; i++){
        QJsonArray json_frame_OOIs = json[QString::number(i)].toArray();
        std::vector<DetectionBox> oois;
        for(int j = 0; j != json_frame_OOIs.size(); j++){
            DetectionBox ooi;
            ooi.read(json_frame_OOIs[j].toObject());
            oois.push_back(ooi);
        }
        this->OOIs.insert(std::make_pair(i, oois));
    }
}

/**
 * @brief POI::write
 * Writes POI to json format.
 * @param json
 */
void POI::write(QJsonObject& json) {
    json["start"] = m_start;
    json["end"] = m_end;
    for(const auto& ooi_pair : OOIs){
        QJsonArray json_frame_OOIs;
        int frame = ooi_pair.first;
        std::vector<DetectionBox> oois = ooi_pair.second;
        for (DetectionBox o : oois) {
            QJsonObject json_ooi;
            o.write(json_ooi);
            json_frame_OOIs.append(json_ooi);
        }
        json[QString::number(frame)] = json_frame_OOIs;
    }
}

redpajama_set_name: RedPajamaGithub


The earthy, complex flavour profiles of mushrooms make them an incredibly versatile ingredient this time of year. From woody base notes, to forest fragrance, the diversity of this family are as wild as they are exotic.
Even at its most basic, the field mushroom has been the unsung champion of the full English. Slow cooked in butter with a hit of black pepper, salt and even a small dose of garlic, and these dark little things provide one of the most powerful cornerstones to what is arguably our nations favourite breakfast. Anyone having worked the breakfast line will know the inherent value of these things, a cheap staple that delivers big on flavour.
Of course the Portobello mushroom, with it's added heft makes for meaty additions to burgers, or even a ground beef replacement in its own right. The rise in vegan and vegetarianism has led to a spike in mushroom heavy dishes thanks to their natural ability to hit a strong savoury profile. Naturally high in protein, they really do tick some boxes in vegetarian dishes and offer a broad spectrum of textures.
Those savoury notes are perhaps never more celebrated than in shiitake mushrooms. Used throughout Chinese and Japanese cuisine, the intense depth they harness is often infused to create umami rich broths to carry chewy noodles. Oyster and wood ear mushrooms also work in this realm, but when adding them to a broth attention needs to be given to the resulting texture. Too chewy and you could sacrifice the overall dish.
In recent years there's been a lot of attention given to foraging and while dedicating time for kitchen staff to go out into the woods for the morning, the impact on production levels can suffer. Good supply of seasonal ingredients is imperative to all kitchens, but the hunt for chantrelles and porcini can sometimes come up empty. These two woodland favourites grow well in the UK and work in a wide range of dishes. The chantrelle lending itself splendidly to venison and mild game dishes, while the porcini, or cep brings gusto and might to everything from taglietelle to hearty casseroles.
The characteristically deep notes of porcini can also be exploited by using the dried variety. On hydration they release intense, concentrated flavour, which can be a handy option during autumn when diners seek comfort, warmth and heavier flavours.
Mushrooms occupy a unique area of produce and require incredibly select sourcing. While your average field mushroom can afford to not be too attractive, chantrelles and oyster mushrooms that often play a visual role in plating need to be harvested, handled and delivered with care. As serious purveyors of good mushrooms, Fresh Direct can give you reliable access to some of the finest available and keep your kitchen armed with some of the seasons finest fungi.


text:
"""
Helper class to writing deterministic time-based unit tests.

Do not use this module.  It is a lie.  See L{twisted.test.test_task.Clock}
instead, but don't use that either because it might also be a lie.
"""

class Clock(object):
    rightNow = 0.0

    def __call__(self):
        return self.rightNow

    def install(self):
        # Violation is fun.
        from twisted.internet import base, task
        from twisted.python import runtime
        self.base_original = base.seconds
        self.task_original = task.seconds
        self.runtime_original = runtime.seconds
        base.seconds = self
        task.seconds = self
        runtime.seconds = self

    def uninstall(self):
        from twisted.internet import base, task
        from twisted.python import runtime
        base.seconds = self.base_original
        runtime.seconds = self.runtime_original
        task.seconds = self.task_original

    def adjust(self, amount):
        self.rightNow += amount

    def pump(self, reactor, timings):
        timings = list(timings)
        timings.reverse()
        self.adjust(timings.pop())
        while timings:
            self.adjust(timings.pop())
            reactor.iterate()
            reactor.iterate()


text:
FCPS Names Finalists for the Student Member of the Board of Education of Frederick County
Five talented and accomplished Frederick County Public Schools (FCPS) students are in the running to become the next Student Member of the Board of Education of Frederick County. These students have been chosen through a vetting process by the Frederick County Association of Student Councils (FCASC) and advisors of the local Student Government Association.
The five candidates, listed alphabetically by last name, are:
Bella Amell, a junior at Brunswick High School. She serves as Junior Class President, President of the Model UN Club, and Vice-President of the Student Council.
Hannah Morin, a junior at Linganore High School. She is President of the Class of 2023, Historian for the Environmental Club and is a Hugh O'Brian Youth Leadership Ambassador.
Michael Olson, attends Middletown High School and is a sophomore. He is the Evaluations Coordinator for the Maryland Association of Student Councils (MASC), serving on the Executive Board, is the MASC Liaison to the FCASC, and is the Vice President of the Student Government Association.
Lucas Tessarollo, a junior at Gov. Thomas Johnson High School. He serves as President of the SGA and is a member of the Model UN, Key and FBLA Clubs.
Brady Vlha, a junior at LInganore High School, is Junior Class Historian, a member of the Lancer Leaders Team and has served in several class councils and offices, as well as student government.
A virtual candidates' forum was held on January 6, 2022; candidates shared their vision for the position and discussed how they would represent students in FCPS. Online voting has begun and is open to FCPS middle and high school students. The popular vote at each school will determine who the school's electors will cast their ballots for in the Electoral College during the February 3, 2022, Frederick County Association of Student Councils' General Assembly. The ballot can be accessed through this link:
https://tinyurl.com/2022smob.
Sam Starrs, an Oakdale High School senior, is the current Student Member of the Board of Education. His term runs through June 30.
FY2023 Operating Budget
Budget FAQ
FCPS Calendar
Support Recruitment
Teacher Job Fair
FCPS Proud


text:
A 36-Year-Old Man With Paresthesias and a Headache
Download "A 36-Year-Old Man With Paresthesias and a Headache"
Buck Elliott
1 Arthritis & Rheumatism (Arthritis Care & Research) Vol. 59, No. 9, September 15, 2008, pp DOI /art , American College of Rheumatology CLINICOPATHOLOGIC CONFERENCE A 36-Year-Old Man With Paresthesias and a Headache FLAVIA V. CASTELINO, JASON H. WASFY, AND DEBORAH COLLIER CASE PRESENTATION History of the present illness A 36-year-old man with a history of non-hodgkin s lymphoma was admitted to the hospital with paresthesias and a headache. His paresthesias began 5 months prior to admission, when he developed left leg numbness and pain, accompanied by an erythematous rash that he described as splotchy. The rash appeared initially on the patient s left leg, but then expanded to include his torso and upper extremities. The rash, numbness, and pain all resolved without intervention after 1 week. Three months prior to admission, he experienced recurrent numbness in the left leg that again resolved spontaneously after several days. Two months prior to admission, the patient s symptoms intensified. He developed bilateral numbness and tingling, first in both feet and then in both hands. He noted that grasping objects with his hands caused a burning sensation in his palms, and he experienced pain and swelling in his left foot and ankle. After these symptoms had been present for several weeks, the patient established care with a primary care physician. At his first appointment his erythrocyte sedimentation rate (ESR) was 42 mm/hour (normal range 1 20). An assay for antinuclear antibodies (ANA) was positive at a titer of 1:160 (speckled), but antibodies to double-stranded DNA and to extractable nuclear antigens (Ro, La, Sm, and RNP) were negative. The laboratory results are shown in Table 1. One month before admission, the patient developed unbearable pain in his feet and noted that his socks felt too tight. He reported tingling in his hands, nausea, and daily emesis. The patient was referred for nerve conduction velocity and electromyography of the lower and upper extremities. These investigations revealed a symmetric sensory polyneuropathy that predominantly involved the lower extremities. The patient was prescribed gabapentin Flavia V. Castelino, MD, Jason H. Wasfy, MD, Deborah Collier, MD: Massachusetts General Hospital, Boston. Address correspondence to Flavia V. Castelino, MD, Massachusetts General Hospital, Yawkey Center, Suite 2C-2100, 55 Fruit Street, Boston, MA partners.org. Submitted for publication January 25, 2008; accepted in revised form May 2, (200 mg 3 times daily), but his symptoms persisted. Three days prior to admission, the patient developed a severe occipital headache that did not remit despite use of ibuprofen (600 mg 3 times daily). On the morning of admission, the patient presented to his primary care doctor reporting a severe headache (rated as 10/10), profound fatigue, and numbness, pain, and weakness in both feet. His blood pressure was 168/119 mm Hg in the right arm and 175/123 mm Hg in the left arm. He was referred to the emergency department for hypertensive urgency. Past medical history The patient s non-hodgkin s lymphoma was diagnosed at age 16 years. He had been treated with a standard chemotherapy regimen for 6 cycles (CHOP: cyclophosphamide, hydroxydaunomycin [doxorubicin], vincristine, and prednisone). This treatment was presumed to have resulted in a cure. The patient was also diagnosed with iron deficiency anemia several years before admission. An esophagogastroduodenoscopy at that time was normal. Family and social history The patient s family history was remarkable for the fact that his father had multiple strokes before the age of 40 years. In addition, the patient reported many relatives on both parents sides with hypertension. The age of those individuals at the time of their hypertension onset was not known. The patient worked as a bartender and drank approximately 40 alcoholic beverages/week. He also smoked 1 pack of cigarettes/day and reported active cocaine use by nasal insufflation and occasionally by intravenous use. His most recent cocaine use had occurred 1 day prior to admission. Review of systems The patient reported a 20-pound weight loss over the 5 months prior to admission. He denied alopecia, oral ulcers, dry mouth, dry eyes, photosensitivity, pleuritic chest pain, and Raynaud s phenomenon. He also denied fevers, sweats, auditory or visual changes, and lower back pain. 1358
2 Clinicopathologic Conference 1359 Table 1. Laboratory results* Variable Normal value 6 weeks before admission Admission 3 months after admission White blood cell count, cells/mm 3 4,500 11,000 7,300 11,600 7,800 Differential cell count, % Neutrophils Lymphocytes Monocytes Eosinophils Hematocrit, % Platelets, cells/mm 3 150, , , , ,000 Mean corpuscular volume, fl Red blood cell distribution width, % International normalized ratio N/A 1.1 Partial thromboplastin time, seconds Prothrombin time, seconds Glucose, mg/dl Sodium, mmoles/liter Potassium, mmoles/liter Chloride, mmoles/liter Bicarbonate, mmoles/liter Urea nitrogen, mg/dl Creatinine, mg/dl Total bilirubin, mg/dl Direct bilirubin, mg/dl Albumin, gm/dl Calcium, mg/dl Alkaline phosphatase, units/liter Aspartate aminotransferase (SGOT), units/ liter Alanine aminotransferase (SGPT), units/liter Urinalysis Blood Negative Negative 1 Negative Protein Negative Negative 2 Trace Red blood cells, per hpf White blood cells, per hpf Bacteria Negative Negative Negative Rheumatoid factor, IU/ml ANA Negative at 1:40 and 1:160 Positive at 1:160 Positive at 1:40 and 1:160 C3, mg/dl C4, mg/dl ESR, mm/hour C-reactive protein, mg/dl ANCA Negative Cryoprotein None None None * N/A not applicable; SGOT serum glutamic oxaloacetic transaminase; SGPT serum glutamic pyruvic transaminase; hpf high-power field; ANA antinuclear antibodies; ESR erythrocyte sedimentation rate; ANCA antineutrophil cytoplasmic antibody. Physical examination In the emergency department, the patient s temperature was 97.9 F; his pulse and respiratory rate were 126 beats/minute and 18 breaths/minute, respectively; his blood pressure was 174/113 mm Hg in the left arm and 180/110 mm Hg in the right arm; and his oxygen saturation was 98% on room air. Examination of his head, eyes, ears, nose, and throat revealed no abnormalities. There was no cervical, supraclavicular, axillary, or femoral adenopathy. His skin was clear, with no signs of the previous rash. Cardiac auscultation revealed a tachycardia with regular rhythm and normal S 1 and S 2 without murmurs. The lung examination revealed normal breath sounds bilaterally, and his abdomen was benign. The patient s extremities had no clubbing, cyanosis, or edema, but there was tenderness along the anterior joint line of the left ankle. The neurologic examination was significant for decreased sensation bilaterally to light touch and pinprick to the mid-shins. The same sensory modalities were also decreased in the left arm, in the distribution of the superficial radial nerve. Motor strength was intact in both the upper and lower extremities. The deep tendon reflexes were 2 and symmetric, and the plantar responses were flexor.
3 1360 Castelino et al The patient was admitted for management of his hypertension and further evaluation. Figure 1. Computed tomography angiogram showing multiple hypoperfused areas of the kidneys bilaterally suggestive of multiple infarctions (original magnification mm, DPI). Laboratory and radiologic evaluation The complete blood count and serum chemistries on admission are shown in Table 1. The serum creatinine was 1.3 mg/dl (baseline 0.7 mg/dl, normal range ) and the blood urea nitrogen was 10 mg/dl (normal range 8 25). A urinalysis with microscopic examination of the sediment was notable for 2 protein on dipstick, but no white or red blood cells and no casts. A urine microalbumin: creatinine ratio was 93.5 mg per gram of creatinine (normal value 30). A chest radiograph revealed a normal cardiac:chest ratio and no infiltrates. A computed tomography (CT) scan of the head without intravenous contrast showed no evidence of midline shift or acute bleeding. Initial hospital course The patient s hypertensive urgency was treated with intravenous labetalol (20 mg once), followed by oral metoprolol (37.5 mg 4 times daily). By hospital day 2, his blood pressure had improved to 140/80 mm Hg and his headache had resolved. A CT angiogram of the chest, abdomen, and pelvis revealed multiple, bilateral areas of hypoperfusion in the kidneys (Figure 1). These findings suggested parenchymal infarctions or medium-vessel occlusive disease. There were no pulmonary infiltrates and no lymphadenopathy. A mesenteric and renal angiogram showed smallvessel occlusions of the arcuate and interlobular arteries of the kidneys bilaterally, but no microaneurysms, beading, or vascular malformations (Figure 2). Additional serologic evaluations were performed. The patient s ESR was 42 mm/hour (normal range 0 17 mm/ hour) and his C-reactive protein (CRP) level was 37.4 mg/dl (normal value 8). His plasma renin level was 5.1 ng/ml/hour (reference range 1.5), consistent with renovascular hypertension. An assay for ANA was positive at a titer of 1:40 and 1:60 in a speckled pattern, but antibodies to extractable nuclear antigens and to doublestranded DNA were again negative, as were assays for rheumatoid factor and antineutrophil cytoplasmic antibodies (ANCAs). The serum C3 and C4 levels were 94 mg/dl (normal range ) and 17 mg/dl (normal range 20 58), respectively. The CH50 was 144 units/ml (normal range ). A diagnostic procedure was performed. Figure 2. A, Renal angiogram showing diffuse nonspecific small-vessel occlusions involving the bilateral arcuate and interlobular renal arteries (original magnification mm, DPI). B, Mesenteric angiogram did not demonstrate any evidence of wall irregularity or aneurysm (original magnification mm, DPI).
4 Clinicopathologic Conference 1361 CASE SUMMARY Table 2. Differential diagnosis Recurrent lymphoma Effects of cocaine abuse Cocaine-associated vasculitis Effects of intravenous drug abuse Hepatitis B virus associated polyarteritis nodosa Hepatitis C virus associated cryoglobulinemia Human immunodeficiency virus neuropathy Primary systemic vasculitides Classic polyarteritis nodosa Antineutrophil cytoplasmic antibody associated Wegener s granulomatosis Microscopic polyangiitis Churg-Strauss vasculitis A 36-year-old man with a history of non-hodgkin s lymphoma and cocaine use presented with a stuttering but increasingly severe peripheral neuropathy, arthralgias, and new-onset hypertensive urgency associated with bilateral renal infarctions. DIFFERENTIAL DIAGNOSIS The principal components of the differential diagnosis in this case are a recurrence of the patient s remote lymphoma, the effects of active cocaine use, potential infectious complications of intravenous drug use, and systemic vasculitis (Table 2). Recurrent lymphoma Recurrence of the patient s malignant disease must be considered. Lymphoma can be associated with symptoms and signs that mimic systemic vasculitis, such as a multifocal neuropathy (1). In patients with non-hodgkin s lymphoma, malignant cells occasionally infiltrate nerves and cause axonal damage, which can resemble an asymmetric mononeuritis multiplex or a more diffuse peripheral neuropathy (2). Non-Hodgkin s lymphoma can also cause cutaneous vasculitis with palpable purpura and necrotizing leukocytoclastic vasculitis (3), and is sometimes associated with a positive ANA (4). However, in our patient, the absence of lymphadenopathy on both physical examination and radiographic studies suggested that a lymphoma recurrence was not likely. Cocaine abuse The patient s active substance abuse may have also contributed to his presentation. Cocaine can cause a number of clinical vascular events, many of which are mediated by vasoconstriction leading to ischemia and acute hypertension (5). Vascular events related to cocaine use include myocardial infarction, cerebral vasoconstriction syndromes, mesenteric ischemia, and (rarely) renal infarction (6). Cocaine-associated vasculitis is uncommon. Two case reports described in the literature are potentially relevant to our patient. In one report, a 35-year-old woman with a history of asthma and cocaine use presented with fatigue, palpable purpura of her lower and upper extremities, and arthritis of her knees and ankles. Her acute-phase reactants (ESR and CRP) were normal, and assays for autoantibodies, cryoglobulins, and complement levels were negative or normal. Skin biopsy samples revealed fibrin thrombi and mild leukocytoclasis, findings that were attributed to a cocaine-induced vasculopathy (7). In a second report, a 27-year-old cocaine addict presented with progressive pharyngitis, fatigue, and cutaneous lesions on her face, arms, legs, and back. She had an ANA at a titer of 1:640, an ESR of 150 mm/hour, and a positive assay for ANCAs by immunofluorescence (8). Serial skin biopsy samples were notable for extensive neutrophilic infiltrates and a few small blood vessels with inflammatory infiltrates. The final diagnosis was cocaineinduced vasculitis. Cocaine is known to have toxic effects on the kidneys, affecting vascular reactivity and renal hemodynamics (6). Therefore, it is conceivable that our patient s cocaine abuse led to his renal infarctions and hypertension. However, a peripheral neuropathy such as the one developed by our patient, a sensory mononeuritis multiplex, is unusual in the setting of cocaine use. In addition, despite being floridly abnormal, the vascular imaging studies in our patient were not specific for cocaine-induced vasculopathy or any other single form of vascular disease. Infectious complications of intravenous drug abuse Given the patient s history of intravenous drug use, certain parenteral infections must be considered. In particular, hepatitis C virus (HCV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV) infections must be excluded. HCV-related cryoglobulinemia, a vasculitis of both small- and medium-sized blood vessels, often involves the skin, peripheral nerves, kidneys, and other organs. Complications of medium-vessel disease (such as those apparent on our patient s angiogram) are unusual in HCV-related cryoglobulinemia in the absence of smallvessel vasculitis, particularly palpable purpura (9). The absence of clinical signs of a small-vessel vasculitis at presentation and the patient s negative rheumatoid factor argue against HCV-related cryoglobulinemia. HBV-associated polyarteritis nodosa (PAN) is a form of medium-vessel vasculitis that is also mediated by immune complex deposition. HBV-associated PAN occurs in the setting of active HBV infection, typically within 6 8 months of the acquisition of HBV. This disorder is characterized by fever, weight loss, and multisystem dysfunction, including but not limited to peripheral neuropathy, an array of cutaneous findings, renal insufficiency, and hypertension (10). Vasculitic neuropathy, often leading to a crippling motor mononeuritis multiplex or a painful sensory neuropathy, is common in PAN. The patient in this case developed a symmetric sensory polyneuropathy. Although the classic syndrome of vasculitis neuropathy is a mononeuritis multiplex, symmetric sensory polyneuropathy is also well described (11).
5 1362 Castelino et al Figure 3. A, Left sural nerve biopsy specimen demonstrates chronic inflammatory changes in a section of a longitudinal vessel supplying the epineurium (hematoxylin and eosin stained; original magnification mm, DPI). B, Cross-section of an arteriole from sural nerve biopsy sample demonstrating inflammatory change in the vessel wall (hematoxylin and eosin stained; original magnification mm, DPI). C, Section from sural nerve biopsy sample demonstrating fibrinoid necrosis with pleomorphic cell infiltration (hematoxylin and eosin stained; original magnification mm, DPI). D, Section from left quadriceps muscle biopsy sample demonstrating arteritis involving a muscular artery of the interfascicular fibrous septa (original magnification mm, DPI). HIV infection has been associated with a number of vasculitis syndromes, including disorders that bear a strong resemblance to PAN with involvement of the skin, peripheral nerves, and skeletal muscles (12). Peripheral neuropathy with distal, symmetric disease is the most common neurologic manifestation of HIV (13). Mononeuritis multiplex is a rare manifestation of HIV and usually indicates the presence of an underlying vasculitis (14). Primary systemic vasculitides This patient s multi-organ system presentation of peripheral neuropathy, renal infarctions, and joint inflammation occurring in the absence of pulmonary involvement are highly consistent with classic PAN, a necrotizing form of systemic vasculitis that involves medium-sized muscular arteries and arterioles. The other types of systemic vasculitis that are often associated with vasculitic neuropathy are those that are commonly associated with ANCAs: Wegener s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome (15). Among these 3 disorders, peripheral nerve involvement is more common in both Churg-Strauss syndrome and microscopic polyangiitis, but devastating peripheral neuropathy can occur in Wegener s granulomatosis as well. Our patient did not have ANCAs in his serum and had no indication of pulmonary disease, significantly reducing the likelihood of an ANCA-associated vasculitis. In summary, both classic (idiopathic) and HBV-related PAN appeared to be strong possibilities as the explanation for this patient s problems. A cocaine-associated vasculopathy could also have explained many of his clinical manifestations.
6 Clinicopathologic Conference 1363 ADDITIONAL EVALUATION Additional serologic evaluations after admission revealed that the patient was negative for antibodies to HCV and HIV. An assay for cryoglobulins was also negative. However, HBV serology revealed that the patient was positive for both the HBV surface antigen and e antigen and the IgM core antibody, but negative for antibodies to this virus. These findings were consistent with an acute HBV infection. The patient s HBV viral load was 121 million IU/ml. The patient s positive HBV serology offered a strong possible explanation for his presentation. However, the renal and mesenteric angiographic findings were not diagnostic of vascular injury associated with HBV-related PAN. Angiographic findings, including microaneurysms and occlusive disease, are present in a range of 40 90% of patients with PAN at the time of clinical presentation; however, the frequency of specific findings is limited by non-specificity and sampling bias (16). Since the patient did not have classic PAN findings, he underwent both a peripheral nerve and muscle biopsy. Biopsy findings of the left sural nerve showed chronic granulomatous inflammation in the vessels supplying the epineurium of the sural nerve (Figure 3A). A trichrome stain revealed moderate secondary loss of myelinated axons. The chronicity of the inflammation was consistent with PAN, as opposed to an acute vasculopathy or arteritis caused by cocaine. Left quadriceps muscle biopsy findings showed arteritis involving a muscular artery of the interfascicular fibrous septa (Figure 3D). As with the sural nerve biopsy results, the chronicity of the inflammation supported the diagnosis of PAN. In the setting of active HBV infection, these histopathologic findings confirmed the diagnosis of HBV-related PAN. DISCUSSION Active hepatitis B infection is strongly associated with PAN, and has been reported to occur in up to 36% of patients with PAN in France before 1995 (10). Although it is difficult to pinpoint the timing of the patient s infection precisely, we believe that he probably acquired his HBV infection approximately 5 months prior to admission through the intravenous use of cocaine. In this context, it is notable that the patient also had a positive IgM anti hepatitis B core antibody, which typically persists for at least 6 months following infection. Approximately 70% of patients with acute HBV infections have subclinical (anicteric) hepatitis, which is the likely explanation for his only mildly elevated serum aminotransferase levels at the time of presentation (17). His splotchy rash was consistent with a viral exanthem that is typical of acute HBV infections (18). Kussmaul and Maier first described PAN in 1866 (19). The disease typically occurs in middle-aged adults and is usually a multisystem disease process characterized by fatigue, weakness, hypertension, renal insufficiency, rash, and neuropathy. The American College of Rheumatology (ACR) has devised classification criteria for the inclusion of patients in studies of PAN (20). The presence of 3 or more ACR criteria is associated with a sensitivity of 82.2% and a specificity of 86.6%. Gocke et al (21) and Trepo and Thivolet (22) described the association between PAN and HBV in HBVassociated PAN is attributed to high viral replication leading to antigen excess and the formation of soluble immune complexes, which deposit in the arterial walls (23). ANCA serology is negative in these patients. The declining incidence of HBV-associated PAN since the late 1980s has been attributed to the introduction of the HBV vaccine and the consequent safety of blood products. The approach to treating HBV-associated PAN has evolved over the past decades and is changing more quickly now with the availability of effective antiviral therapies. The major components of treatment are now glucocorticoids, antiviral agents, and often plasma exchange. In contrast, from the 1950s through the 1970s, prolonged glucocorticoid use was deemed essential for the suppression of inflammation. Unfortunately, this led to further replication of the virus and frequent relapses (30% at 1 year and 42% at 5 years) (10). In 1988, Trepo et al reported a retrospective analysis of 7 patients with HBV-associated PAN treated between 1979 and 1985 with a therapeutic protocol of glucocorticoids for 2 weeks, followed by initiation of antiviral therapy with vidarabine, and plasma exchange (initially performed 3 times per week for the first 3 weeks, followed by 1 time per week, then weekly for 3 6 weeks) (24). The rationale for this therapeutic approach included glucocorticoids to control inflammation, plasma exchange to remove immune complexes and improve the capacity of the reticuloendothelial system to clear these complexes, and antiviral therapy to suppress HBV replication and facilitate immune complex clearance by decreasing viral load. Six of the 7 patients treated were clinically and virologically cured and did not relapse during a range of up to 7 years in followup. Guillevin et al performed a retrospective analysis of 115 patients with HBV-associated PAN (either biopsy proven or positive angiogram with clinical symptoms) (25). These investigators evaluated the frequency, clinical characteristics, and long-term outcome based on various treatment protocols from Most treatment protocols utilized an antiviral agent (more recent trials used lamivudine), glucocorticoids, and plasmapheresis. Seroconversion from hepatitis B e antigen to hepatitis B e antibody was the strongest indicator of survival, and all patients who seroconverted achieved clinical remission without relapse. Among those patients treated without an antiviral agent, the seroconversion rate of HBV was 15% compared with 49% among patients treated with the antiviral strategy. The role of plasma exchange in HBV-associated PAN has not been studied in randomized controlled trials. Guidelines published by the American Society for Apheresis classify vasculitis as a category III indication for plasmapheresis; i.e., the procedure is not clearly indicated based on insufficient evidence, conflicting results, or inability to document a favorable risk-to-benefit ratio (26,27). Guillevin et al showed that the combination of glucocorticoids and plasma exchange was of no further benefit in prevent-
7 1364 Castelino et al ing relapse and offered no survival benefit when compared with glucocorticoids alone in patients with systemic PAN (without HBV) or Churg-Strauss syndrome (28). Based on the absence of proof that plasma exchange is required to treat HBV-associated PAN effectively (29), we opted to treat our patient initially with glucocorticoids and antiviral therapy alone. THE PATIENT S COURSE Our patient s headache and hypertension resolved quickly with the addition of labetalol and amlodipine. His serum creatinine level normalized and he did not have any further evidence of organ-threatening disease. During his hospitalization, he was started on entecavir 5 mg by mouth daily and prednisone 60 mg daily. The prednisone was tapered off over 2 weeks. Although lamivudine and other earlier antiviral agents have proven effective for HBVassociated PAN, entecavir was used in this patient because it has exhibited antiviral efficacy superior to that of lamivudine in dose-finding studies (30). Entecavir can also be used with impaired renal function and is currently considered a standard treatment for hepatitis B infection (31). Three months after discharge, the patient s HBV viral load was below the detectable range and he had seroconverted from HBV e antigen positive to HBV e antibody positive. His neurologic condition had improved, with decreased pain in his feet. Some pain and numbness persisted in his left arm. The patient continued to drink alcohol daily but abstained from cocaine. FINAL DIAGNOSIS Hepatitis B virus associated polyarteritis nodosa. ACKNOWLEDGMENT We appreciate the thoughtful review of the manuscript by John Stone, MD. 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