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Reply to Introduce Yourself / Say Hello! here!

petrapetruta posted a reply:

jacquesjacobs:


Hello there and welcome!We hope to see some catchy contribution from you too! :-)




epl

Reply to The Rainbow Round Game

PelicanPete posted a reply:

Red




epl

Reply to Introduce Yourself / Say Hello! here!

Rémi de Valenciennes posted a reply:

Hello,
I'm Rémi from Lille (North of France). I think we need color nowadays !




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Reply to The Rainbow Round Game

paul_appleyard posted a reply:

Green




epl

Reply to Introduce Yourself / Say Hello! here!

petrapetruta posted a reply:

Rémi de Valenciennes:


I absolutely agree with you!
And welcome! :-)




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Reply to Introduce Yourself / Say Hello! here!

Cigaleto posted a reply:

Hello, je suis Agnès de France. J habite en Provence, le pays des cigales et de la lavande. Un région pleine de couleurs.




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Reply to Alphabet Game

Jeniverse Photography posted a reply:

Q is for Queerlesque




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Reply to Introduce Yourself / Say Hello! here!

Alex Borbely posted a reply:

Alex Borbely from the north shore of Lake Ontario, Canada! I have been doing mostly nature photography for just over a decade. Self taught and focus mainly on freezing movement! Be well and safe!
Alex




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ID card replacement to resume

The Immigration Department announced today that the operation of all nine Smart Identity Card Replacement Centres will be fully resumed on May 11 in light of the more stabilised epidemic situation.

 

The department earlier suspended the replacement of Hong Kong identity cards at the centres to avoid the increased risk of spreading COVID-19.

 

To arrange for people affected by the service suspension to replace their identity cards in an orderly manner, the Secretary for Security has made an amendment order to revise the replacement period for people born in 1957 to 1963 and 1970 to 1976 and the arrangement for members of the sixth term of District Councils.

 

Click here for the arrangements.

 

If the replacement of identity cards needs to be suspended again in the future to cope with a sudden turn of the epidemic situation, the amendment order also provides that if all the centres are not in service for a period of 21 working days or more from May 11 to July 27 for public health reasons, the specified period for the above people will be further extended or amended.

 

The amendment order will be tabled at the Legislative Council on May 13 for negative vetting.

 

To reduce crowd gatherings, applicants who have not made appointments previously should do so via the Internet, the department’s mobile application or the 24-hour hotline at 2121 1234.

 

The department also appealed to applicants to pre-fill the application form when making appointments through the Internet or mobile application.

 

For details click here or call 2824 6111.




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Atomic force microscopy-based characterization of the interaction of PriA helicase with stalled DNA replication forks [DNA and Chromosomes]

In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.




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Episode 57 - The Internet of Apple press releases (IoAPR) iPads, red iPhones, black OnePlus phones and Android O

Gather round as three men spend 30 minutes talking about tech. Wait, what do you mean 'no thanks'?! Matt Egan shares the mic with David Price and Henry Burrell to thrash out why Apple deemed a press release adequate to announce the successor to 2014's iPad Air 2. There's also a slick new red iPhone, and a black OnePlus 3T. What's with the limited editions, eh? Or are they even limited? The gang also chat about the developer preview of Android O, out now while Android N is barely months old. Is it too early to say if it'll kick ass, and why do Google and Apple need such long public lead time with new OS builds?  


See acast.com/privacy for privacy and opt-out information.




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Glucose-Induced Reactive Oxygen Species Cause Apoptosis of Podocytes and Podocyte Depletion at the Onset of Diabetic Nephropathy

Katalin Susztak
Jan 1, 2006; 55:225-233
Complications




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Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats

G Xu
Dec 1, 1999; 48:2270-2276
Articles




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Reply: Clarifying the Utility of Myocardial Blood Flow and Myocardial Flow Reserve After Cardiac Transplantation




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Atomic force microscopy-based characterization of the interaction of PriA helicase with stalled DNA replication forks [DNA and Chromosomes]

In bacteria, the restart of stalled DNA replication forks requires the DNA helicase PriA. PriA can recognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilitate the loading of the helicase DnaB onto the DNA to restart replication. Single-stranded DNA–binding protein (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, although it has been shown that the two proteins interact both physically and functionally. Here, we used atomic force microscopy to visualize the interaction of PriA with DNA substrates with or without SSB. These experiments were done in the absence of ATP to delineate the substrate recognition pattern of PriA before its ATP-catalyzed DNA-unwinding reaction. These analyses revealed that in the absence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand. Such a preference has not been observed for 5'- and 3'-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's selection of DNA substrates. Furthermore, we found that in the absence of SSB, PriA binds exclusively to the fork regions of the DNA substrates. In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB. We also demonstrate that the remodeling of PriA requires a functional C-terminal domain of SSB. In summary, our atomic force microscopy analyses reveal key details in the interactions between PriA and stalled DNA replication forks with or without SSB.




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Superior Long-term Survival for Simultaneous Pancreas-Kidney Transplantation as Renal Replacement Therapy: 30-Year Follow-up of a Nationwide Cohort

OBJECTIVE

In patients with type 1 diabetes and end-stage renal disease, it is controversial whether a simultaneous pancreas-kidney (SPK) transplantation improves survival compared with kidney transplantation alone. We compared long-term survival in SPK and living- or deceased-donor kidney transplant recipients.

RESEARCH DESIGN AND METHODS

We included all 2,796 patients with type 1 diabetes in the Netherlands who started renal replacement therapy between 1986 and 2016. We used multivariable Cox regression analyses adjusted for recipient age and sex, dialysis modality and vintage, transplantation era, and donor age to compare all-cause mortality between deceased- or living-donor kidney and SPK transplant recipients. Separately, we analyzed mortality between regions where SPK transplant was the preferred intervention (80% SPK) versus regions where a kidney transplant alone was favored (30% SPK).

RESULTS

Of 996 transplanted patients, 42%, 16%, and 42% received a deceased- or living-donor kidney or SPK transplant, respectively. Mean (SD) age at transplantation was 50 (11), 48 (11), and 42 (8) years, respectively. Median (95% CI) survival time was 7.3 (6.2; 8.3), 10.5 (7.2; 13.7), and 16.5 (15.1; 17.9) years, respectively. SPK recipients with a functioning pancreas graft at 1 year (91%) had the highest survival (median 17.4 years). Compared with deceased-donor kidney transplant recipients, adjusted hazard ratios (95% CI) for 10- and 20-year all-cause mortality were 0.79 (0.49; 1.29) and 0.98 (0.69; 1.39) for living-donor kidney and 0.67 (0.46; 0.98) and 0.79 (0.60; 1.05) for SPK recipients, respectively. A treatment strategy favoring SPK over kidney transplantation alone showed 10- and 20-year mortality hazard ratios of 0.56 (0.40; 0.78) and 0.69 (0.52; 0.90), respectively.

CONCLUSIONS

Compared with living- or deceased-donor kidney transplantation, SPK transplant was associated with improved patient survival, especially in recipients with a long-term functioning pancreatic graft, and resulted in an almost twofold lower 10-year mortality rate.




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B1-B bombers deployed to Guam

Four B1-B Lancer bombers and 200 airmen were deployed to Andersen Air Force Base, Guam, from Texas for training operations, the U.S. Air Force announced on Monday.




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Amylin Replacement With Pramlintide in Type 1 and Type 2 Diabetes: A Physiological Approach to Overcome Barriers With Insulin Therapy

John B. Buse
Jul 1, 2002; 20:
Feature Articles




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Can We Replay History?


After the kids' party games and the birthday cake came the action-packed Steve McQueen movie. My friend's parents had rented a movie projector. They hooked up the reel and let it roll. But the high point came later when they ran the movie backwards. Bullets streamed back into guns, blows were retracted and fallen protagonists recoiled into action. The mechanism that pulls the celluloid film forward for normal showing, can pull the film in the reverse direction, rolling it back onto the feeder reel and showing the movie in reverse.

If you chuck a round pebble off a cliff it will fall in a graceful parabolic arch, gradually increasing its speed until it hits the ground. The same pebble, if shot from the point of impact, at the terminating angle and speed, will gracefully and obligingly retrace its path. (I'm ignoring wind and air friction that make things a bit more complicated.)

Deterministic mechanisms, like the movie reel mechanism or the law of gravity, are reversible.

History is different. Peoples' behavior is influenced by what they know. You pack an umbrella on a trip to the UK. Google develops search algorithms not search parties because their knowledge base is information technology not mountain trekking. Knowledge is powerful because it enables rational behavior: matching actions to goals. Knowledge transforms futile fumbling into intelligent behavior.

Knowledge underlies intelligent behavior, but knowledge is continually expanding. We discover new facts and relationships. We discover that things have changed. Therefore tomorrow's knowledge-based behavior will, to some extent, be unpredictable today because tomorrow's discoveries cannot be known today. Human behavior has an inherent element of indeterminism. Intelligent learning behavior cannot be completely predicted.

Personal and collective history does not unfold like a pre-woven rug. Human history is fundamentally different from the trajectory of a pebble tossed from a cliff. History is the process of uncovering the unknown and responding to this new knowledge. The existence of the unknown creates the possibility of free will. The discovery of new knowledge introduces indeterminism and irreversibility into history, as explained by the philosophers G.L.S. Shackle and Karl Popper.

Nonetheless history is not erratic because each increment of new knowledge adds to the store of what was learned before. Memory is not perfect, either of individuals or groups, but it is powerful. History happens in historical context. For instance, one cannot understand the recent revolutions and upheavals in the Arab world from the perspective of 18th century European revolutions; the historical backgrounds are too different, and the outcomes in the Middle East will be different as well. Innovation, even revolution, is spurred by new knowledge laid over the old. A female municipal official slapped a Tunisian street vendor, Mohamed Bouazizi. That slap crystalized Mr Bouazizi's knowledge of his helpless social impotence and lit the match with which he immolated himself and initiated conflagrations around the Mideast. New knowledge acts like thruster engines on the inertial body of memory. What is emerging in the Mideast is Middle Eastern, not European. What is emerging is the result of new knowledge: of the power of networking, of the mortality of dictators, of the limits of coercion, of the power of new knowledge itself and the possibilities embedded in tomorrow's unknowns.

Mistakes are made, even with the best intentions and the best possible knowledge. Even if analysts knew and understood all the actions of all actors on the stage of history, they still cannot know what those people will learn tomorrow and how that new knowledge will alter their behavior. Mistakes are made because history does not unwind like a celluloid reel.

That's not to say that analysts are never ignorant, negligent, stupid or malicious. It's to say that all actions are, in a sense, mistakes. Or, the biggest mistake of all is to think that we can know the full import of our actions. We cannot, because actions are tossed, like pebbles, into the dark pit of unknown possible futures. One cannot know all possible echoes, or whether some echo might be glass-shatteringly cataclysmic.

Mistakes can sometimes be corrected, but never undone. History cannot be run backwards, and you never get a second chance. Conversely, every instant is a new opportunity because the future is always uncertain. Uncertainty is the freedom to err, and the opportunity to create and discover. 




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Alabama School Board Members Weigh In on Plan to Replace Them

State Board of Education members weighed in today about a proposal to eliminate their elected positions and replace the board with an appointed commission.




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Rapid Deployment of Remote Learning: Lessons From 4 Districts

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.




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N.J. Supreme Court Rejects Gov. Christie's Motion to Replace Funding Formula

Gov. Christie has pushed to flatten the state's funding formula so that the state's impoverished urban districts would get the same amount of money wealthy suburban districts get.




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Rapid Deployment of Remote Learning: Lessons From 4 Districts

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.




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Rapid Deployment of Remote Learning: Lessons From 4 Districts

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.




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Ancestral Gumbel-Top-k Sampling for Sampling Without Replacement

We develop ancestral Gumbel-Top-$k$ sampling: a generic and efficient method for sampling without replacement from discrete-valued Bayesian networks, which includes multivariate discrete distributions, Markov chains and sequence models. The method uses an extension of the Gumbel-Max trick to sample without replacement by finding the top $k$ of perturbed log-probabilities among all possible configurations of a Bayesian network. Despite the exponentially large domain, the algorithm has a complexity linear in the number of variables and sample size $k$. Our algorithm allows to set the number of parallel processors $m$, to trade off the number of iterations versus the total cost (iterations times $m$) of running the algorithm. For $m = 1$ the algorithm has minimum total cost, whereas for $m = k$ the number of iterations is minimized, and the resulting algorithm is known as Stochastic Beam Search. We provide extensions of the algorithm and discuss a number of related algorithms. We analyze the properties of ancestral Gumbel-Top-$k$ sampling and compare against alternatives on randomly generated Bayesian networks with different levels of connectivity. In the context of (deep) sequence models, we show its use as a method to generate diverse but high-quality translations and statistical estimates of translation quality and entropy.




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Generative Feature Replay with Orthogonal Weight Modification for Continual Learning. (arXiv:2005.03490v1 [cs.LG])

The ability of intelligent agents to learn and remember multiple tasks sequentially is crucial to achieving artificial general intelligence. Many continual learning (CL) methods have been proposed to overcome catastrophic forgetting. Catastrophic forgetting notoriously impedes the sequential learning of neural networks as the data of previous tasks are unavailable. In this paper we focus on class incremental learning, a challenging CL scenario, in which classes of each task are disjoint and task identity is unknown during test. For this scenario, generative replay is an effective strategy which generates and replays pseudo data for previous tasks to alleviate catastrophic forgetting. However, it is not trivial to learn a generative model continually for relatively complex data. Based on recently proposed orthogonal weight modification (OWM) algorithm which can keep previously learned input-output mappings invariant approximately when learning new tasks, we propose to directly generate and replay feature. Empirical results on image and text datasets show our method can improve OWM consistently by a significant margin while conventional generative replay always results in a negative effect. Our method also beats a state-of-the-art generative replay method and is competitive with a strong baseline based on real data storage.




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Cellular internet of things : from massive deployments to critical 5G applications

Liberg, Olof, 1943- author.
9780081029039 (electronic bk.)




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Fitting a deeply nested hierarchical model to a large book review dataset using a moment-based estimator

Ningshan Zhang, Kyle Schmaus, Patrick O. Perry.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2260--2288.

Abstract:
We consider a particular instance of a common problem in recommender systems, using a database of book reviews to inform user-targeted recommendations. In our dataset, books are categorized into genres and subgenres. To exploit this nested taxonomy, we use a hierarchical model that enables information pooling across across similar items at many levels within the genre hierarchy. The main challenge in deploying this model is computational. The data sizes are large and fitting the model at scale using off-the-shelf maximum likelihood procedures is prohibitive. To get around this computational bottleneck, we extend a moment-based fitting procedure proposed for fitting single-level hierarchical models to the general case of arbitrarily deep hierarchies. This extension is an order of magnitude faster than standard maximum likelihood procedures. The fitting method can be deployed beyond recommender systems to general contexts with deeply nested hierarchical generalized linear mixed models.




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Scaling limits for super-replication with transient price impact

Peter Bank, Yan Dolinsky.

Source: Bernoulli, Volume 26, Number 3, 2176--2201.

Abstract:
We prove a scaling limit theorem for the super-replication cost of options in a Cox–Ross–Rubinstein binomial model with transient price impact. The correct scaling turns out to keep the market depth parameter constant while resilience over fixed periods of time grows in inverse proportion with the duration between trading times. For vanilla options, the scaling limit is found to coincide with the one obtained by PDE-methods in ( Math. Finance 22 (2012) 250–276) for models with purely temporary price impact. These models are a special case of our framework and so our probabilistic scaling limit argument allows one to expand the scope of the scaling limit result to path-dependent options.




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Brazil's Amazon: Surge in deforestation as military prepares to deploy

The military is preparing to deploy to the region to try to stop illegal logging and mining.





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Le Rapport trimestriel de la BRI analyse le repli et le rebond des marchés

French translation of the BIS press release about the BIS Quarterly Review, March 2019




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http://digg.com/submit?url=http://www.edge.org/conversation/a-universe-of-self-replicating-code




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Why Scottish Archaeologists Are Building a Replica of an Iron Age Stone Tower

By building a new broch, the project aims to better understand how and why the original structures were constructed




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Olympic Games Replay: Fantastic figure skating from Pyeongchang 2018

As the planet deals with the pandemic and the crisis involving the spread of COVID-19, the world of sport watches and waits alongside the global population. This Saturday, March 21, will be the first of five weeks of programming at CBC Sports which will showcase some of the memorable moments from the most recent editions of the Olympics.



  • Sports/Olympics/Winter Sports/Figure Skating

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Watch Olympic Games Replay: Pyeongchang 2018 Figure Skating

Watch Olympic Games Replay, a look back at some of the most exciting moments in past Games. On this week's edition of the program, watch action from the Pyeongchang 2018 figure skating competitions.



  • Sports/Olympics/Winter Sports/Figure Skating

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‘Army won’t be deployed in Mumbai, will fight Covid-19 together’: Uddhav Thackeray – Hindustan Times

  1. ‘Army won’t be deployed in Mumbai, will fight Covid-19 together’: Uddhav Thackeray  Hindustan Times
  2. Maharashtra may extend lockdown to end of May, hints CM Uddhav Thackeray  Times of India
  3. Maharashtra CM Uddhav Thackeray announces compensation for kin of deceased  TIMES NOW
  4. Restrict entry-exit of migrants in Maharashtra: Raj Thackeray  Deccan Chronicle
  5. Uddhav Thackeray: You are the soldiers, no need for the Army  Mumbai Mirror
  6. View Full coverage on Google News



  • IMC News Feed

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Olympic Games Replay: Rio 2016 Women's Soccer

Watch the Canadian women's soccer team compete at the Summer Games in Brazil.




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Olympic Games Replay: Rugby 7s run wild at Rio 2016




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Brazil prepares to deploy troops into the Amazon to fight rising deforestation

Deforestation in Brazil's Amazon rainforest rose sharply in April, government data showed on Friday, as the coronavirus outbreak keeps many environmental enforcers out of the field and the country prepares to deploy troops to fight illegal logging.




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Richard Cockerill looks for homegrown heroes as Edinburgh replenish ranks

Edinburgh Rugby have announced the signing of three Scottish qualified youngsters in Nathan Chamberlain, Ben Muncaster and Dan Gamble on academy deals which will turn into full-time contracts next summer, and head coach Richard Cockerill has promised that three current academy prospects in Rory Darge, Connor Boyle and Sam Grahamslaw will soon be elevated to the senior squad ahead of next season.




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Jim Sillars says SNP may have to be replaced by new independence party

THE SNP is so rotten it may have to be replaced by a new independence party, its former deputy leader has said.




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Plan to replace busy Scottish ferry with bridge

It crosses one of the most scenic waterways in Scotland and is the second busiest by volume of passengers in the country.




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Rapid Deployment of Remote Learning: Lessons From 4 Districts

Chief technology officers are facing an unprecedented test of digital preparedness due to the coronavirus pandemic, struggling with shortfalls of available learning devices and huge Wi-Fi access challenges.




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Nicotine Replacement Therapy During Pregnancy and Infantile Colic in the Offspring

Infantile colic affects almost 10% of all infants and is characterized by crying and fussing in an otherwise healthy and well-fed infant. Prenatal exposure to tobacco smoking is a risk factor, but it is unclear whether nicotine causes the association.

Infants exposed to nicotine replacement therapy during pregnancy had elevated infantile colic risk of the same magnitude as infants exposed to tobacco smoking. Intrauterine exposure to nicotine may play a causal role in the pathogenesis of infantile colic. (Read the full article)




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Nicotine Replacement Therapy in Pregnancy and Major Congenital Anomalies in Offspring

Smoking has been found to increase the risk of some specific congenital anomalies; however, results remain inconsistent. Nicotine replacement therapy (NRT) is increasingly being used as for smoking cessation in pregnancy although little is known about its association with congenital anomalies.

Being prescribed NRT while pregnant was not associated with major congenital anomalies (MCA), except a small increase in respiratory anomalies (3/1000 births). This must be considered in context of the rarity of MCAs and higher morbidities in the NRT group. (Read the full article)




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Enter for Your Chance to Win a OnePlus 2

Is $349 still too pricey for a OnePlus 2? Enter our contest and you could get one for free.




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MK-571, a cysteinyl leukotriene receptor-1 antagonist, inhibits hepatitis C virus (HCV) replication [Antiviral Agents]

The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct acting-antivirals (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7.5 cells stably harboring a subgenomic genotype 1b replicon. A dose-dependent decrease of HCV RNA levels was observed upon MK-571 administration, with an EC50 of 9±0.3 μM and a maximum HCV RNA level reduction of approximatively 1 Log10. MK-571 also reduced the replication of the HCV full-length J6/JFH1 model in a dose-dependent manner. However, probenecid and apigenin homodimer (APN), two specific inhibitors of MRP-1, had no effect on HCV replication. In contrast, the CysLTR1 antagonists SR2640 increased HCV-SGR RNA levels in a dose-dependent manner, with a maximum increase of 10-fold. In addition, a combination of natural CysLTR1 agonist (LTD4) or antagonists (zafirlukast, cinalukast, and SR2640) with MK-571 completely reversed its antiviral effect, suggesting its anti-HCV activity is related to CysLTR1 rather to MRP-1 inhibition. In conclusion, we showed that MK-571 inhibits HCV replication in hepatoma cell cultures by acting as a CysLTR1 receptor antagonist, thus unraveling a new host-virus interaction in the HCV life cycle.




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Reply to Kim et al., "Optimal Dose or Optimal Exposure? Consideration for Linezolid in Tuberculosis Treatment" [Author Reply]

We thank Kim and colleagues for their interest in our study....




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Comparative plasma pharmacokinetics of ceftriaxone and ertapenem between normoalbuminemia, hypoalbuminemia and with albumin replacement in a sheep model. [Pharmacology]

Background

Optimal concentrations of unbound antimicrobials are essential for maximum microbiological effect. Although hypoalbuminemia and albumin fluid resuscitation are common in critical care, the effects of different albumin concentrations on the unbound concentrations of highly protein-bound antimicrobials are not known. The aim of this study was to compare effects of different albumin states on total and unbound concentrations of ertapenem and ceftriaxone using an ovine model.

Methods

Design

Prospective, three phase intervention observational study.

Subjects

Healthy Merino sheep.

Interventions

Eight sheep were subject to three experimental phases; normoalbuminemia, hypoalbuminemia using plasmapheresis and albumin replacement using a 25% albumin solution. In each phase, ceftriaxone 40 mg/kg and ertapenem 15 mg/kg were given intravenously. Blood samples were collected at pre-defined intervals and analyzed using an ultra-high-performance liquid chromatography tandem mass spectrometry method. Pharmacokinetic parameters such as area under the curve (AUC0-24), plasma clearance (CL) and apparent volume of distribution in the terminal phase (Vd) were estimated and compared between the phases.

Results

The protein and albumin concentrations were significantly different between phases. Hypoalbuminemia resulted in a significantly lower AUC0-24 and higher CL of total and unbound concentrations of ceftriaxone compared to the other phases. Whereas albumin replacement led to higher AUC0-24 and lower CL compared to other phases for both drugs. The Vd for total drug concentrations for both drugs were significantly lower with albumin replacement.

Conclusions

For highly protein-bound drugs such as ceftriaxone and ertapenem, both hypoalbuminemia and albumin replacement may affect unbound drug exposure.




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Technology 'Doesn't Replace Good Teaching'

Anne Jenks, Michelle Shory, Ed.S, Irina V. McGrath, Ph.D, Kim Jaxon, Dr. Beth Gotcher, Elizabeth Stringer Keefe, Ph.D., and Keisha Rembert share their suggestions for using tech effectively in class.