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Low molecular weight heparin does not prevent VTE after knee arthroscopy, studies show




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How to write an operation note




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GLP-1 shortages will not resolve this year, EMA warns, amid concern over off-label use




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Helen Salisbury: Weight loss treatment—available in theory but not in practice




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Russia and 9/11: Roads not taken

Russia and 9/11: Roads not taken Expert comment NCapeling 9 September 2021

Many Russia watchers recall the fleeting moment 20 years ago when the country could have moved away from a path of confrontation with the US.

On 12 September 2001, Russian president Vladimir Putin was the first foreign leader to call George W. Bush to express his condolences – and to offer him support.

Just the previous year, Putin had said Russia joining NATO was a possibility and it suited Russia to draw parallels between the terrorist attacks on the US and its own ‘anti-terrorist’ campaign in Chechnya at the time.

Even though much of the Russian commentary about 9/11 professed empathy rather than sympathy, in their eyes the US was both a victim – as Russia likes to see itself – and ‘had it coming’ while Russia was blameless.

At that time, many in the West were still tempted by the idea Putin’s Russia might develop in a liberal direction, and Putin himself wanted to be seen as constructive especially after Chechnya. He may also have also assumed that, if Russia joined the international alliance, it would be as a co-leader with the US.

An offer which was never stated

Whether he was sincere in his condolences or not, Putin was of course not offering something for nothing – but then few countries ever do. Although less than one-tenth into his time in control of Russia (so far), Putin was still feeling his way but was not a naive president having already been through the controversial sinking of the Kursk submarine.

The quid pro quo, unstated and only dawning on Washington much later, was for the US to keep out of what Russia saw – and still sees – as its backyard

His first move was to facilitate access to bases in Central Asia for the US campaign in Afghanistan – vital initially but less so later. Apparently, this offer was against the wishes of many of his senior military commanders – although the extent to which it was in his gift to grant such access is questionable.

The quid pro quo, unstated and only dawning on Washington much later, was for the US to keep out of what Russia saw – and still sees – as its backyard. Putin probably misjudged that the US would have neither the inclination nor the capacity to be in that region for anything other than supply chain purposes. And he hoped America now needed Russia after the humiliations of the 1990s.

Common interests could once have been the basis of a partnership with Russia; but to Moscow that meant a partnership of equals which recognized the Kremlin’s self-declared right to conduct out-of-area operations. But the US took a different view and, with nothing written down and no memorandum ever signed, the ensuing disappointment for Russia was gradual but inexorable.

A purely practical reason for declining the ‘offer’ was that, despite its own illusions, Russia had little to bring to the table which was useful and could be offered on acceptable terms. Subsequent initiatives – from specific joint terrorism initiatives to a ‘grand reset’ – could not narrow differences to the point where the character of the relationship changed.

The Northern Distribution Network for supplying US forces in Afghanistan – Russia’s most practical contribution to the notional common cause – took almost a decade to be established and was plagued by problems which often come with a dependence on Russian goodwill.

The Kremlin also had the pleasure of watching US hubris lead to failure in Iraq. And, although knowing the US intervention in Afghanistan would never end well, even Russia could not have foreseen the scale of the defeat and humiliation of chaotic withdrawal.

US achievements with Russia’s neighbours

When it comes to Russia’s post 9/11 ‘offer’ and subsequent expectations, many of the other newly independent countries might never have achieved what they have over the past 20 years if the US had agreed – tacitly or otherwise – to sit back and accept Moscow’s droit de regard over them.

Although knowing the US intervention in Afghanistan would never end well, even Russia could not have foreseen the scale of the defeat and humiliation of chaotic withdrawal

From the Kremlin’s perspective, these states were Russia’s ‘kith and kin’ but it underestimated US willingness to support smaller states over a ‘great power’ – especially as George H.W. Bush pleaded to those states not to go too far too fast. Albeit uneven, most have benefitted from US support for their own independence as well as practical assistance to strengthen their institutions and diversify external relationships.

The three Baltic states consolidated their democracies while their economies, which severed many ties with Russia early, are flourishing and prosperous in contrast to those still in the Russian orbit. They are not only members of NATO and the European Union (EU) but have on occasion been moral leaders as in the case of Lithuania facing down both Belarus and China.

Ukraine has undergone two revolutions in attempting to follow the paths of the Baltic states that continues today. After many false starts Moldova has undergone a similar change recently but at the ballot box not on the streets, to give itself another shot at the prize of true democracy and international acceptance.

Georgia conducted the most radical governance reforms seen in the region after its own revolution although it has taken a few steps backwards of late. Kazakhstan and Uzbekistan have strengthened their independence since then and adjusted their modus vivendi with Russia to their advantage. Putin would hardly be able to give the same assurances about use of bases there today – and indeed reportedly brushed off a request by Biden to use them in the current withdrawal.

Only a minority of formerly Soviet republics have made no progress whatsoever at the governmental level – Belarus and Turkmenistan for sure, perhaps Azerbaijan and Tajikistan too depending on the criteria.

The roads not taken

America’s failure was not so much rejecting Russia’s offer of partnership but failing to pay sufficient attention to it because Russia was still regarded as weak despite being relatively strong in its immediate neighbourhood.

The question of whether it was worth alienating Russia is a moral one. Refusing to sign the Paris Charter – which recognizes the right of independent states to form their own alliances – would have been a further betrayal of people who have long been subjected to their future being decided by stronger powers around them. But Russia may have chosen a path of confrontation anyway as, for the Kremlin, suzerainty over its former republics is considered an entitlement which comes with being a great power.

Although impossible to conclusively prove, all previous frameworks of Russian assumptions and habits of Russian behaviour indicate Moscow would have pocketed the deal and simply moved on anyway. It certainly seems likely that Russia’s other outrages and offenses over the years – from the murders of Litvinenko and Skripal in the UK to the manipulation of information and elections – would still have occurred even if a shabby deal had been made over the heads of the new states on Russia’s borders.

The atrocity of 9/11 was really an opportunity for Russia, a genuine potential turning point and a chance to create a new relationship with the outside world – but its expectations were unrealistic. Russia blew it with demands at the time that could not be met – and rightly were not met. The US rarely receives credit for withstanding Russian blandishments at a moment when its own aura of strength had been so cruelly and effectively punctured by the most brazen of attacks.




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Culture notes: Populists of the world unite

Culture notes: Populists of the world unite The World Today rsoppelsa.drupal 25 May 2022

America’s hard-right has successfully played a long game at home, and now it’s schmoozing Europe. We should be worried, says Catherine Fieschi

The politics of advanced democracies is a rather Janus-faced affair these days. No sooner have we breathed a sigh of relief at the results of the French presidential election than a leaked United States Supreme Court document on Roe v Wade signals American abortion rights are under threat. 

Yes, Europe seems to be maintaining political unity in its support of Ukraine, and the US is lavishing eye-watering sums on it both in military and humanitarian aid. Yet one cannot help but feel that these might be short-lived spells of relief in the face of mounting storm clouds on the political horizon. Both at the domestic and international level, populist politics looks to be gathering pace still. 

On the domestic front, we should be cautious in our relief. In the French elections Emmanuel Macron was indeed re-elected, and comfortably so, but there is no denying the space occupied by populist politicians on the left and the right. In the first round, Marine Le Pen gained 23 per cent of the vote, left populist candidate Jean-Luc Mélenchon 22 per cent, and far-right candidate Éric Zemmour 7 per cent. Add to this a record low turnout, and the picture is one of a system in which mainstream politics has overall been rejected in favour of various populist options. 

The Hungarians weren’t so lucky, and Viktor Orbán’s capture of the media and quashing of the opposition over his years in power delivered solid victory. 

What should be cause for further concern is what is happening in the United States, as well as its potential impact on European politics. A quick flick through American politics today suggests dysfunctionalities of staggering magnitude and depth, and the full extent of the success of the right-wing Republican project, as confirmed by the intention to reverse Roe v Wade. 

Any reversal of Roe v Wade is a further step towards a drastic re-territorialization of American politics: into red states and blue states, into urban v rural, into places where taxes fund public education and public goods and where they won’t. It is also about a re-territorialization of institutional power away from the federal and into state institutions. 

The words of JD Vance, the Ohio Republican senatorial candidate – author of the rather good memoir Hillbilly Elegy – pander to an ‘American heartlands’ view of the United States’ role in the world. Asked about the fate of Ukraine, Vance simply replied that he ‘didn’t really care what happens to Ukraine one way or another’. 

On an even more basic level, we would do well to keep in mind that there were 440 anti-voter bills in 49 states at the end of 2021 and rising, calling into question citizens’ basic rights to vote. Republicans have pursued this agenda relentlessly. They have played a long game and invested in media, education and minor and not so minor projects – all of which have secured them a social and political base that is well-disposed towards the deep reversal of the American liberal global project and that of its allies across the world.

The arrival of the Fox News-driven Conservative Political Action Conference in Hungary in May is deeply worrying

And it is perhaps on this last point that we should be most alarmed. Between May 18-20, the Conservative Political Action Conference, an American conclave of the right, was held in Europe. Viktor Orbán gave the keynote speech, and other speakers included the Brazilian President Jair Bolsonaro’s son, Eduardo, and the president of Spain’s far-right party Vox, Santiago Abascal, as well as some well-known American Trumpian voices, including Trump himself. Marine Le Pen, whose earlier appearance at the conference had met with rapturous applause, chose not to cosy-up too closely to Orbán in the run-up to the French parliamentary elections in June but she sent her deputy. 

The export of the Fox News-driven conference from across the Atlantic is deeply worrying. Up until now populists have failed in their attempts at international alliances. At the European Union level their nationalism has always been in the way of their working together, and their groups tend to be short-lived or ineffective as a result. As for American attempts in Europe, the one led by Steve Bannon, the former White House adviser, in 2020 that aimed to create an Academy for the Judeo-Christian West ended as a damp squib – possibly not helped by his dismissal from the White House amid charges of defrauding donors.

But something may be changing: the conference’s embrace of Orbán and an international smattering of ‘strongmen’ hailing from the hard-right, aligned with Putin and sup-ported by Trump and a media empire, suggests that we are entering a Trumpian-infused second act that in its triumphal revanchism is seeking to create an international right-wing populist, or even authoritarian front. This is about politics, media, but also money – something European populist parties have been short of. As Marine Le Pen explained to French voters, her party is so poor it had to borrow money from a Russian bank.  

As some have pointed out, the Russian aggression against Ukraine has complicated matters when it comes to Russian funding of disinformation to the West. Many routes have been shut down. But a new route between the US and Hungary as a platform to floss Europe with dirty money is a good replacement to the old Russian route. 
 




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Culture notes: Will the EU find its voice at last?

Culture notes: Will the EU find its voice at last? The World Today mhiggins.drupal 30 January 2023

Russia’s invasion of Ukraine has galvanized the bloc, but doubt remains about how it can capitalize on this moment, writes Catherine Fieschi.

Despite its reticence to believe that Russia would attack Ukraine, once Vladimir Putin’s tanks rolled across the Donbas, the European Union finally grasped the momentous nature of the events unfolding on its eastern flank. The immediate reaction of Europe’s member states was one of unity, resolve and uncharacteristically rapid decision-making, at least on sanctions and energy policy.

That they would need to act in concert across a concatenation of crises that would be either triggered (energy), worsened (inflation) or heightened (geopolitical instability) by Putin’s move was obvious. And so, Europe’s collective narrative of this past year slid into place, and it goes something like this: We gave Russia the benefit of every doubt, including after their invasion of Crimea when we still tried to bring them back to the negotiating table, but Putin has made the fundamental choice of turning away from democracy and the rule of law.

Europe had long been in need of an arc to follow

Now, the narrative goes on, we have to treat them as enemies and give ourselves the means to become resilient in the face of aggression as Ukraine is all that stands – both symbolically and geographically – between us and the chaos of a Europe-wide war.

Like any good narrative, it is anchored in previous trials and exploits. Having learnt from its failure to coordinate action during the eurozone crisis and then the migration crisis, Europe was keen to make the most of its resilience in the face of the Covid pandemic in the form of the joint vaccine purchases and a massive recovery plan.

The Russian invasion of Ukraine is an added – albeit dramatic and costly – opportunity to pursue further collective action and discover the next chapter of its shared purpose, as a political and perhaps even a defence alliance.

Europe had long been in need of an arc to follow. In the aftermath of the Second World War, peace and prosperity seemed enough. But the new multipolar world that emerged from the ashes of the Cold War and then 9/11 were more difficult to navigate for a largely commercial and regulatory alliance.

Could the EU, then, ever find its political voice?

David vs Goliath

While Brexit and Covid created rallying points, the shock and tragedy of the invasion delivered everything the EU needed in narrative terms: a David and Goliath story, with the opportunity to feature on Team David in European terms while allying with the United States, and a ‘band of brothers’ element to shore up a union bruised by the defection of a key but troubled member. Above all, the appearance of an arch-villain in the form of Vladimir Putin put Europe back into the familiar and mythical territory of the 1940s and then the Cold War.

When on May 28, 2016, Putin seated himself on the throne of the Byzantine emperors in Mount Athos’ Protaton Church in Greece in a scene truly worthy of Game of Thrones, the writing should have been on the wall. That day he explicitly laid out his aim to appoint himself as the new Eastern emperor who would fight the decadence of the West.

‘Today,’ Putin told the world, ‘we restore the values of patriotism, historical memory and traditional culture.’ Later, he cited Ukraine as the biggest unfinished mission of his years in power. That Europe – and Germany in particular – had taken so long to decipher Putin’s dark designs only adds to the narrative’s epic quality, positioning Europe as a victim of its own good faith and open heart.

Cracks in the narrative

But the narrative is not free from cracks. The Baltic states would argue that they had long warned of Putin’s nefarious intentions; and Poland has always been convinced of the threat posed by its neighbour.




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Theranostic GPA33-Pretargeted Radioimmunotherapy of Human Colorectal Carcinoma with a Bivalent 177Lu-Labeled Radiohapten

Radiolabeled small-molecule DOTA-haptens can be combined with antitumor/anti-DOTA bispecific antibodies (BsAbs) for pretargeted radioimmunotherapy (PRIT). For optimized delivery of the theranostic - and β-emitting isotope 177Lu with DOTA-based PRIT (DOTA-PRIT), bivalent Gemini (DOTA-Bn-thiourea-PEG4-thiourea-Bn-DOTA, aka (3,6,9,12-tetraoxatetradecane-1,14-diyl)bis(DOTA-benzyl thiourea)) was developed. Methods: Gemini was synthesized by linking 2 S-2-(4-isothiocyanatobenzyl)-DOTA molecules together via a 1,14-diamino-PEG4 linker. [177Lu]Lu-Gemini was prepared with no-carrier-added 177LuCl3 to a molar-specific activity of 123 GBq/μmol and radiochemical purity of more than 99%. The specificity of BsAb-177Lu-Gemini was verified in vitro. Subsequently, we evaluated biodistribution and whole-body clearance for [177Lu]Lu-Gemini and, for comparison, our gold-standard monovalent [177Lu]Lu-S-2-(4-aminobenzyl)-DOTA ([177Lu]Lu-DOTA-Bn) in naïve (tumor-free) athymic nude mice. For our proof-of-concept system, a 3-step pretargeting approach was performed with an established DOTA-PRIT regimen (anti-GPA33/anti-DOTA IgG-scFv BsAb, a clearing agent, and [177Lu]Lu-Gemini) in mouse models. Results: Initial in vivo studies showed that [177Lu]Lu-Gemini behaved similarly to [177Lu]Lu-DOTA-Bn, with almost identical blood and whole-body clearance kinetics, as well as biodistribution and mouse kidney dosimetry. Pretargeting [177Lu]Lu-Gemini to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177Lu]Lu-Gemini for blood, tumor, liver, spleen, and kidneys of 3.99, 455, 6.93, 5.36, and 14.0 cGy/MBq, respectively. Tumor–to–normal tissue absorbed-dose ratios (i.e., therapeutic indices [TIs]) for the blood and kidneys were 114 and 33, respectively. In addition, we demonstrate that the use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT leads to improved TIs and augmented [177Lu]Lu-Gemini tumor uptake and retention in comparison to monovalent [177Lu]Lu-DOTA-Bn. Finally, we established efficacy in SW1222 tumor-bearing mice, demonstrating that a single injection of anti-GPA33 DOTA-PRIT with 44 MBq (1.2 mCi) of [177Lu]Lu-Gemini (estimated tumor-absorbed dose, 200 Gy) induced complete responses in 5 of 5 animals and a histologic cure in 2 of 5 (40%) animals. Moreover, a significant increase in survival compared with nontreated controls was noted (maximum tolerated dose not reached). Conclusion: We have developed a bivalent DOTA-radiohapten, [177Lu]Lu-Gemini, that showed improved radiopharmacology for DOTA-PRIT application. The use of bivalent [177Lu]Lu-Gemini in DOTA-PRIT, as opposed to monovalent [177Lu]Lu-DOTA-Bn, allows curative treatments with considerably less administered 177Lu activity while still achieving high TIs for both the blood (>100) and the kidneys (>30).




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FDA says commonly used decongestant 'not effective,' proposes removal

The U.S. Food and Drug Administration has determined commonly used oral phenylephrine is "not effective" and has proposed its removal from over-the-counter nasal decongestants.




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Former Notre Dame football coach Gerry Faust dies at 89

Gerry Faust, who won five Ohio high school football state titles before taking over as coach at Notre Dame in the early 1980s, has died, his family announced. He was 89.




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Blood tests for colon cancer screening not ready to replace colonoscopy, study indicates

New blood tests screen for colorectal cancer in a much less invasive way than colonoscopy, but deaths will increase if many people choose this alternative, a new study indicates.




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FDA says commonly used decongestant 'not effective,' proposes removal

The U.S. Food and Drug Administration has determined commonly used oral phenylephrine is "not effective" and has proposed its removal from over-the-counter nasal decongestants.




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Veterans Day: Biden expands benefits, urges Americans to 'keep faith' in one another

President Joe Biden on Monday addressed a Veterans Day crowd at the national cemetery in Virginia where he revealed newly-expanded veteran benefits and urged Americans to "come together" and "keep faith."




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SpaceX launches another 23 satellites into low-Earth orbit

SpaceX launched another batch of 23 Starlink V2 Mini satellites into low Earth orbit aboard a Falcon 9 rocket from Cape Canaveral Space Force Station Thursday at 3:19 p.m. EST.




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A hypnotic exploration of movement | JA Collective

Jordan Johnson and Aidan Carberry, the choreographic duo known as JA Collective, give a performance of dance and visual arts, alternating between abrupt and fluid, tense and dreamlike.




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Luxury, not landfill — the waste-free future of fashion | Joon Silverstein

Fashion is a huge part of the world's waste problem, but it doesn't have to be. Coachtopia founder Joon Silverstein shows how her company creates new designs from the waste products of another, a circular process that cuts the need for new raw materials — and rethinks what qualifies as "luxury." (Made in partnership with Coachtopia)




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7 Tips for Not Personalizing

If you want more tips for not overly personalizing events, comments and actions, and decreasing rumination, you’ll find heaps of simple, practical solutions in , especially in chapter 5 (rumination) and chapter 7 (fear of feedback and criticism). 1. Don’t catastrophize knock backs – If you get a rejection, it doesn’t mean you’re never going […]

The post 7 Tips for Not Personalizing appeared first on Dr Alice Boyes.




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How Hybrid Learning Is (and Is Not) Working During COVID-19: 6 Case Studies

The mix of hybrid learning approaches is dizzying, but schools are learning valuable lessons about what is worth replicating.




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Teaching's 'New Normal'? There's Nothing Normal About the Constant Threat of Death

As the bizarre becomes ordinary, don't forget what's at stake for America's teachers during the COVID-19 pandemic, writes Justin Minkel.




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Audit: Maryland Dept. Did Not Properly Store Data for 1.4 Million Students

The Maryland State Department of Education "inappropriately stored" personal information of 1.4 million students and more than 230,000 teachers, leaving them vulnerable to potential bad actors, according to an audit published earlier this month.




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No More Snow Days, Thanks to Remote Learning? Not Everyone Agrees

An increasing number of schools are replacing snow days with remote learning, but some plan to stick with the snow day tradition for now.




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Students' notes offer encouragement to health care workers




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Tennessee Teachers Have Warmed to Evaluation System, But Not State Tests

Tennessee improved its teacher evaluation and training systems by integrating data and teacher voice, according to a new report. But value-added measures that evaluate teachers based on student test scores remain controversial.




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Virtual Teaching: Skill of the Future? Or Not So Much?

Leaders in some districts say remote teaching will now be a skill they will build even more in their existing teacher corps. Others are more skeptical.




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Dyslexia Is Not a Bad Word, Advocates Say. Schools Should Use It

A push to get dyslexia defined in state law and persuade educators to use the term has translated to new laws in 40 states.




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Education Dept.: High Court Ruling Does Not Support Transgender Athletes

The Trump administration argues that the U.S. Supreme Court's decision that federal law protects transgender employees does not apply to transgender athletes in school.




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Help for Rural S.C. Schools Likely Delayed Another Year

Legislation to provide funds to poor and rural school districts will likely die in the legislative session this year.




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Another Former Sharks Goalie Goes On NHL Waivers

Former San Jose Sharks goalie James Reimer was placed on NHL waivers today by the Anaheim Ducks.




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See where Notre Dame football projects in latest College Football Playoff bracket

Notre Dame football has one remaining game against a CFP-ranked team: Nov. 23 at Yankee Stadium against No. 24 Army (9-0).




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West Virginia Teacher Strike Not Over Yet

Public schools in West Virginia are closed despite a deal that was supposed to end the teacher strike today.




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Women's basketball: Slow start dooms Purdue in 102-58 loss to Notre Dame

Purdue women's basketball suffered its first defeat of the season on Sunday night as No. 6 Notre Dame came into Mackey Arena and handed the Boilermakers a 102-58 loss. The Boilermakers have now lost nine straight games to the Fighting Irish, since taking a 14-5 lead in the series back in 2005. The in-state rivalry was halted, playing just once between 2012 and 2023, but the Fighting Irish resumed their success over the Boilermakers in each of the last two seasons.




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Notre Dame women's basketball clobbers Purdue on road for second win

If an opponent isn't contending for an ACC or national championship, Notre Dame is likely to run it out of the gym. That's exactly what happened during the Irish's first road game of the season against Purdue. Much like with the football team less than two months earlier,…




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Hidalgo scores 28 to help No. 6 Notre Dame women cruise to 102-58 win over Purdue

Hannah Hidalgo scored 11 of her 28 points in the first 7-plus minutes and No. 6 Notre Dame led by double figures for more than 35 minutes Sunday night as the Fighting Irish beat Purdue 102-58 for their 10th consecutive win over the Boilermakers. Notre Dame (2-0) has a 15-14 lead in its all-time series with Purdue. Olivia Miles added 17 points and Sonia Citron scored 14.




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Notre Dame WBB puts up highlight-reel performance in dominating Purdue

Dazzling first with a relentless hawking defense that helped force 22 turnovers, then adding an almost frantic-paced offensive assault, the 2-0 No. 6-ranked Irish overwhelmed Purdue (1-1), 102-58, at Mackey Arena in West Lafayette, Ind. Dynamo guard Hannah Hidalgo was slapping, diving and picking pockets all night, making life miserable for any Boilermaker stuck bringing the ball up the floor. ► Snap Counts: Here's who played for Notre Dame football against Florida St.




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No. 2 UConn women not just relying on Bueckers, top South Florida 86-49

Nov. 10—STORRS — Paige Bueckers headed to the bench for her first break of the game just 35 seconds before halftime Sunday at sold-out Gampel Pavilion. Judging by the way the UConn star almost effortlessly dominated play, Bueckers still looked fairly fresh. She already had piled up 19 points. Then again, South Florida certainly must have been tired of watching Bueckers score in a variety of ...




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Notre Dame women's basketball is No. 5 in USA Today Coaches Poll

Some big games on the horizon as Notre Dame women's basketball is at No. 5 in latest Coaches Poll




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Hannah Hidalgo added to another key award watch list

Notre Dame sophomore guard Hannah Hidalgo is on the Women’s Basketball Coaches Association (WBCA) Wade Watch List. She's among 15 players being watched as a potential winner of the oldest, most prestigious player of the year award. She was a Region I finalist for…




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Women's basketball notebook: Gonzaga got the best from a motivated Stanford team, a sign of respect for Bulldogs

Nov. 12—The Gonzaga women's basketball team has much to learn after a challenging loss at Stanford on Sunday. Losses have a way of exposing a team's shortcomings. And there is much to learn from the worst loss (89-58) in coach Lisa Fortier's 11 seasons. Stanford, unranked in the preseason poll for the first time since 1999-2000, is unranked no more. The Cardinal (3-0) entered at No. 24 in the ...




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To See or Not to See: Prestimulus {alpha} Phase Predicts Visual Awareness

Kyle E. Mathewson
Mar 4, 2009; 29:2725-2732
BehavioralSystemsCognitive




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TRIM46 Is Required for Microtubule Fasciculation In Vivo But Not Axon Specification or Axon Initial Segment Formation

Vertebrate nervous systems use the axon initial segment (AIS) to initiate action potentials and maintain neuronal polarity. The microtubule-associated protein tripartite motif containing 46 (TRIM46) was reported to regulate axon specification, AIS assembly, and neuronal polarity through the bundling, or fasciculation, of microtubules in the proximal axon. However, these claims are based on TRIM46 knockdown in cultured neurons. To investigate TRIM46 function in vivo, we examined male and female TRIM46 knock-out mice. Contrary to previous reports, we find that TRIM46 is dispensable for axon specification and AIS formation. TRIM46 knock-out mice are viable, have normal behavior, and have normal brain structure. Thus, TRIM46 is not required for AIS formation, axon specification, or nervous system function. However, we confirm that TRIM46 is required for microtubule fasciculation. We also show TRIM46 enrichment in the first ~100 μm of axon occurs independently of ankyrinG (AnkG) in vivo, although AnkG is required to restrict TRIM46 only to the AIS. Our results highlight the need for further investigation of the mechanisms by which the AIS and microtubules interact to shape neuronal structure and function.




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PDE4B Missense Variant Increases Susceptibility to Post-traumatic Stress Disorder-Relevant Phenotypes in Mice

Large-scale genome-wide association studies (GWASs) have associated intronic variants in PDE4B, encoding cAMP-specific phosphodiesterase-4B (PDE4B), with increased risk for post-traumatic stress disorder (PTSD), as well as schizophrenia and substance use disorders that are often comorbid with it. However, the pathophysiological mechanisms of genetic risk involving PDE4B are poorly understood. To examine the effects of PDE4B variation on phenotypes with translational relevance to psychiatric disorders, we focused on PDE4B missense variant M220T, which is present in the human genome as rare coding variant rs775201287. When expressed in HEK-293 cells, PDE4B1-M220T exhibited an attenuated response to a forskolin-elicited increase in the intracellular cAMP concentration. In behavioral tests, homozygous Pde4bM220T male mice with a C57BL/6JJcl background exhibited increased reactivity to novel environments, startle hyperreactivity, prepulse inhibition deficits, altered cued fear conditioning, and enhanced spatial memory, accompanied by an increase in cAMP signaling pathway-regulated expression of BDNF in the hippocampus. In response to a traumatic event (10 tone–shock pairings), neuronal activity was decreased in the cortex but enhanced in the amygdala and hippocampus of Pde4bM220T mice. At 24 h post-trauma, Pde4bM220T mice exhibited increased startle hyperreactivity and decreased plasma corticosterone levels, similar to phenotypes exhibited by PTSD patients. Trauma-exposed Pde4bM220T mice also exhibited a slower decay in freezing at 15 and 30 d post-trauma, demonstrating enhanced persistence of traumatic memories, similar to that exhibited by PTSD patients. These findings provide substantive mouse model evidence linking PDE4B variation to PTSD-relevant phenotypes and thus highlight how genetic variation of PDE4B may contribute to PTSD risk.




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Information note - July 2023

The importance of Ukraine and the Russian Federation for global agricultural markets and the risks associated with the war in Ukraine. 




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The Architect of Notre Dame's Astounding Football Success

Under exuberant coach, Knute Rockne, Notre Dame set the standards for football excellence. But off the field, the Fighting Irish was a PR sensation, capturing the hearts of a riveted nation.




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Eating the Amputated Arm of Another Octopus

The octopus places the arm in its mouth, treating it like food.




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He's (Not) Just Ken: The True History of Barbie’s Beau

He is (K)enough… or is he? With filmmaker Greta Gerwig's Barbie breaking box-office records—and devoting much of its story to Ken's existential crisis—we wondered if there's any more to Barbie's perennial plus-one. Journalist and lifelong Barbie fan Emily Tamkin talks us through Ken’s development, or lack thereof, over the decades. Read Emily’s “A Cultural History of Barbie,” and Chris’s brief Ken history “Not Your Average Beau,” here (https://www.smithsonianmag.com/arts-culture/cultural-history-barbie-180982115/) or in the June 2023 issue of Smithsonian. Emily is the author of The Influence of Soros: Politics, Power, and the Struggle for an Open Society and Bad Jews: A History of American Jewish Politics and Identities. Learn more about Emily and her work here (https://www.emilytamkin.com/) , or subscribe to her Substack newsletter (https://emilyctamkin.substack.com/) . There’s More to That is a production of Smithsonian magazine and PRX Productions. From the magazine, our team is Chris Klimek, Debra Rosenberg and Brian Wolly. From PRX, our team is Jessica Miller, Genevieve Sponsler, Adriana Rozas Rivera, Terence Bernardo, and Edwin Ochoa. The Executive Producer of PRX Productions is Jocelyn Gonzales. Episode artwork by Emily Lankiewicz. Music by APM Music.




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Easter Island's Ancient Population Never Faced Ecological Collapse, Suggests Another Study

New DNA analysis adds to growing research indicating the famous Pacific island did not collapse from overuse of resources before the arrival of Europeans




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Archaeologists Say They've Solved the Mystery of a Lead Coffin Discovered Beneath Notre-Dame

New research suggests the sarcophagus' occupant, previously known only as "the horseman," is Joachim du Bellay, a French Renaissance poet who died in 1560




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Voyager 1 Breaks Its Silence With NASA via a Radio Transmitter Not Used Since 1981

The farthest spacecraft in the universe went momentarily rogue, but scientists breathed a sigh of relief when it reconnected at an unexpected radio frequency




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Postal union gives 72-hour strike notice, putting rural N.L. Christmas deliveries at risk

After a year of negotiations, the postal union has given Canada Post a 72-hour strike notice. At a solidarity rally in St. John's last week, local president Craig Dyer says a strike could mean parcels — including Christmas presents — won't make it to rural communities.



  • News/Canada/Nfld. & Labrador

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Doctors said her gangrenous appendix was just anxiety. She's not alone

A woman who says she was repeatedly denied emergency care last spring is blasting the Newfoundland and Labrador health-care system, saying she’s been left psychologically scarred after being told several times that her gangrenous appendix was simply anxiety or constipation.



  • News/Canada/Nfld. & Labrador