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Tuberculosis and COVID-19 lung lesions revealed by high-resolution three-dimensional imaging

BIRMINGHAM, Ala. – Gross anatomy reveals three-dimensional shapes of pathology at a large scale. Histology, in contrast, reveals the microscopic anatomy…



BIRMINGHAM, Ala. – Gross anatomy reveals three-dimensional shapes of pathology at a large scale. Histology, in contrast, reveals the microscopic anatomy of biological structures. But that magnification comes at a cost — histology shows only two-dimensional shapes because it studies small, flat slices of stained tissue.

Credit: Africa Health Research Institute

BIRMINGHAM, Ala. – Gross anatomy reveals three-dimensional shapes of pathology at a large scale. Histology, in contrast, reveals the microscopic anatomy of biological structures. But that magnification comes at a cost — histology shows only two-dimensional shapes because it studies small, flat slices of stained tissue.

This lack of three dimensions means histology can miss important pathophysiologies in the damaged lungs of patients with tuberculosis, or TB, and COVID-19, the two deadliest infectious diseases of mankind in recent years.

Now researchers report that a powerful imaging tool called microCT can be used to create a three-dimensional, or 3D, atlas of the spectrum of lung lesions in both tuberculosis and COVID-19, at near-microscopic levels. This gives unexpected insights into the unseen microarchitecture of the lesions within the context of the whole lung.

The research, published in the journal EMBO Molecular Medicine — with one of the 3D images featured on the journal cover, was led by Adrie Steyn, Ph.D., a professor in the Department of Microbiology at the University of Alabama at Birmingham and member of the Africa Health Research Institute, or AHRI, University of KwaZulu-Natal, in Durban, South Africa, along with UAB and AHRI researchers and colleagues at various South African institutions.

“To the best of our knowledge, this is the first study to use microCT to elucidate macro- and microscopic features of tuberculosis lesions such as cavitation, calcification and necrosis, as well as COVID-19 pathophysiology across large lung samples in three dimensions,” Steyn said. “A major new contribution of this study is the characterization of obliterated airways in TB and hemorrhage from ruptured blood vessels in COVID-19 lungs that would not be possible with conventional two-dimensional platforms. Further, microCT analysis of an entire COVID-19 lung lobe in 3D represents a technical advance that enabled us to contextualize vascular pathology within the greater lung architecture and visualize vascular micro-architecture in remarkable detail.”

One of the benefits of microCT is creating a 3D image of a lesion. In a tuberculosis paper last year, Steyn and colleagues showed that power. For 70 years, they said, clinicians thought TB granulomas in the lungs of patients were spherical or ovoid because conventional histology showed round features, and researchers intuitively assumed those meant the granulomas were spherical or ovoid. But such round images are similar to cutting a very thin slice through a thick tree branch and assuming the branch is round or oval.

Instead of spheres, the 3D images revealed the larger granulomas as anything but round — they had complex, branched shapes. One looked somewhat like a ginger root, and another like a cluster of early buds on a cherry tree, before the blossoms appear.

In Steyn’s current study, researchers also identified an unusual spatial arrangement of vasculature within an entire lobe of a COVID-19 lung, and 3D images of blood vessels revealed microangiopathy associated with hemorrhage.

Notably, Steyn says, this imaging of pathological anomalies revealed hidden pathological structures that might have been disregarded, demonstrating a powerful method to visualize pathologies in 3D in TB lung tissue and whole COVID-19 lobes.

The researchers compared microCT with two lower-resolution clinical imaging platforms that do not yield accurate three-dimensional images of TB lesions — high-resolution computed X-ray tomography, which is used to aid diagnosis of tuberculosis, and low resolution, low-energy “soft” X-ray CT, commonly used in mammography. MicroCT imaging provides higher resolution compared to the other two; but its samples must be close to the X-ray source, so microCT analysis is limited to post-mortem or resected lung tissue.

Worldwide, a vast number of formalin-fixed, paraffin-embedded tuberculosis lung specimens from decades of research are available. The Steyn research team showed that microCT is able to directly characterize calcium deposits, as well as necrotic and partially calcified necrotic granulomas in those specimens. Further, they found that removing the paraffin allowed visualization of more detailed microanatomical features.

“We anticipate that microCT could be used to establish a three-dimensional reference atlas of the human tuberculous lung derived from digitized 3D image libraries of tissue, organs from new patients and existing fixed-tissue libraries,” Steyn said. “This atlas could be used to identify novel imaging biomarkers. Also, we expect an atlas of tuberculosis and COVID-19 lesion types will inform our understanding of the failure of localized immunity and be an important resource for therapeutic and diagnostic development.”

Co-authors with Steyn on the study, “A high-resolution 3D atlas of the spectrum of tuberculous and COVID-19 lung lesions,” are Gordon Wells, Kievershen Nargan, Kapongo Lumamba, Alex Sigal and Threnesan Naidoo, AHRI; Joel N. Glasgow, UAB Department of Microbiology; Rajhmun Madansein and Kameel Maharaj, Inkosi Albert Luthuli Central Hospital and University of KwaZulu-Natal, Durban, South Africa; Leon Y. Perumal and Malcolm Matthew, Ahmed Al-Kadi Private Hospital, Durban, South Africa; Robert L. Hunter, University of Texas Health Sciences Center at Houston, Houston, Texas; Hayden Pacl and Jacelyn E. Peabody Lever, UAB Medical Scientist Training Program; Denise D. Stanford, Satinder P. Singh and Steven M. Rowe, UAB Department of Medicine; Prachi Bajpai, Upender Manne and Paul V. Benson, UAB Department of Pathology; Stephan le Roux, Bruker Belgium NV, Kontich, Belgium; Muofhe Tshibalanganda, Anton du Plessis and Carlyn Wells, Stellenbosch University, Stellenbosch, South Africa; and Mpumelelo Msimang, Inkosi Albert Luthuli Central Hospital, Durban, South Africa.

Support came from National Institutes of Health grants AI111940, AI134810, AI137043, AI138280 and A127182; Bill and Melinda Gates Foundation award OPP1130017; the Wellcome Leap ΔTissue Program; and pilot funds from the UAB Marnix E. Heersink School of Medicine  .

Microbiology, Medicine and Pathology are departments in the Heersink School of Medicine. The paper by Steyn and colleagues is highlighted in an accompanying editorial in the journal, “Giving volume to the elephant in the imaging room,” by pulmonologist Anurag Agrawal, Ph.D.

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Hamas Delegation Arrives In Moscow As Russia Blames US For Escalation

Hamas Delegation Arrives In Moscow As Russia Blames US For Escalation

In a somewhat unexpected development, a delegation of Hamas leaders…



Hamas Delegation Arrives In Moscow As Russia Blames US For Escalation

In a somewhat unexpected development, a delegation of Hamas leaders have arrived in Moscow for talks, the Russian Foreign Ministry has confirmed Thursday evening (local time). "I can confirm that representatives of the [Hamas] Palestinian movement are visiting Moscow,” Foreign Ministry spokeswoman Maria Zakharova said in a press briefing, vowing to provide relevant details as the talks unfold.

The visit had not been previously announced by either side, and the Hamas delegation is being led by a senior member of the group, Moussa Abu Marzouk. Hamas is a designated terror organization in the US, European Union, and some other countries; but it has official relations with countries like Iran, Turkey, Syria, and now apparently Russia.

A 2019 meeting involving Hamas, Fatah, and Russian representatives, via Reuters

Russia, however, has said it remains willing to talk to all sides of the conflict in hopes of achieving ceasefire and peace. After the US exit from Afghanistan, Moscow had similarly hosted a Taliban delegation. 

It's as yet unclear whether Russia's top diplomat, Sergei Lavrov, will meet with the Hamas representatives, given he's said to currently be in Minsk. 

RIA Novosti has reported that Hamas has during opening meetings with Russian officials "commended Putin’s position and the efforts of Russia’s diplomacy."

The Kremlin has said it is engaged in crisis diplomacy talks with both the Hamas and Israeli sides, at a moment that over 220 hostages are still being held in Gaza. Four have been released thus far, including two Americans, due in large part to the mediation of Qatar. Will Russia press the delegation to release more captives? Likely this is high on the agenda for Moscow. 

Just days ago Russia blamed the United States for stoking escalation by positioning Navy warships in the Mediterranean near Israel. FM Lavrov said Monday during a meeting in Tehran that "the more a state takes this kind of proactive measures, the greater the risk and the danger of an escalation of the conflict".

He called out Washington as "already among the countries intervening the most" since the October 7 Hamas terror attack. The Biden administration as of course rejected the charge, and blamed Iran for ultimately being behind Hamas and regional terror.

At the UN in New York, Russia and China have also just vetoed US drafted UN Security Council resolution on Gaza. The dueling sides have rejected the proposals of the other given Washington's pro-Israel stance, and the willingness of Moscow and Beijing to heap criticism on Tel Aviv for the humanitarian crisis and soaring death toll among Palestinians.

Turkey has also been a foremost critic of Israel's assault on Gaza, as the death toll surpasses 7,000 - with President Erdogan blasting the West's double standard on the crisis. 

He said in his most recent speech at a Thursday conference, "Is it possible not to react while seeing what happens in Gaza? Nothing justifies such savagery. Unfortunately, so-called 'civilized' countries watch it. We heard that the EU is still hesitating to call for a cease-fire. How many children should die before you decide on a call? Let us know when the cease-fire should be declared. I have been in politics for 40 years, but I never sat idly in the face of such savagery,” Erdoğan said.

Tyler Durden Thu, 10/26/2023 - 12:05

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Ukraine recap: future of US support for Kyiv in question as Israel conflict reshapes Washington’s priorities

A selection of the best of our coverage of the conflict from the past fortnight.



There was some worrying news for Volodymyr Zelensky this week when the US House of Representatives finally elected a new speaker. Mike Johnson, a Republican congressman from Louisiana, has consistently opposed US funding for the Ukrainian war effort. Now he’s the second most powerful man in US politics behind the president, Joe Biden.

As Thomas Gift, the director of the Centre on US Politics at UCL spells out, Johnson’s cooperation will be vital if Biden is to get his latest US$105 billion (£86.5 billion) national security aid package through Congress. More than$60 billion of that is earmarked for Ukraine and if it doesn’t come through, Kyiv will struggle.

Of course, Washington has other fish to fry. Whether you can call the Israel-Hamas war a “bigger fish” remains unclear. Only $14 billion has been earmarked to go to Israel so far. But for most people in the US events in Israel and Gaza are seen as being of the highest importance. Israel has replaced Ukraine as the lead story on most news channels and knocked the European war off the front pages. With Donald Trump relentlessly demanding a moratorium on aid to Ukraine, Kyiv has clear grounds for concern as its counteroffensive grinds on in the south with still no end to the killing in sight.

Read more: Funding for Ukraine is anything but certain after US elects new speaker

Russia meanwhile is struggling with its own offensive in the east. According to a recent report published by the UK’s Ministry of Defence, the Russian push around the town of Avdiivka in the Donetsk Oblast has run into heavily fortified Ukrainian defensive positions (similar to what Ukrainian forces in the south are experiencing with entrenched Russian troops).

Since Vladimir Putin sent his war machine into Ukraine on February 24 2022, The Conversation has called upon some of the leading experts in international security, geopolitics and military tactics to help our readers understand the big issues. You can also subscribe to our fortnightly recap of expert analysis of the conflict in Ukraine.

The MoD update, dated October 17, says that heavy casualties have forced Russia from the offensive into what it calls “active-defence”. Death tolls vary widely and should be taken with a grain of salt, but Newsweek claimed in a report on October 20 that Russia’s death toll was approaching 300,000 men, including 1,300 killed in a single day.

Map showing the state of the war in Ukraine as at October 25.
The state of the war in Ukraine as at October 25 according to the Institute for the Study of War. Institute for the Study of War

But plenty of men still appear to be joining up – at least, according to Dmitry Medvedev, former Russian president, deputy national security minister and outspoken Putin mouthpiece, who said 385,000 men had enlisted so far this year. So the burning question is whether and when the Russian public will get tired of the bodybags and the news from friends or relatives that a loved one has been killed or maimed at the front.

Ben Soodavar, of the Department of War Studies at King’s College London, believes that military loss is deeply embedded in the Russian psyche. Most Russians are brought up with tales of self-sacrifice in the second world war – the heroes of the Red Army who made the world safe from fascism. “For Russia, every dead soldier in Ukraine constitutes a step towards victory and reclaiming the great power image of the country’s Soviet past,” he writes.

It helps, of course, that the head of the Russian Orthodox church is as good as promising soldiers the keys to the kingdom of heaven if they are killed in the line of duty.

Read more: Ukraine: Russia's losses mount -- but self-sacrifice in war is part of the country's mythology

War at sea…

If the war on land continues to grind on, with every metre of land bitterly contested, the sea war took an interesting turn recently when it was revealed that Russia has relocated many of the vessels in its Black Sea fleet from its base in Sevastopol in Crimea to safer bases in Novorossiysk and Feodosia, on either sides of the Kerch strait connecting eastern Crimea with the Russian mainland. There are even reports of plans to build naval facilities in the breakaway Georgian region of Abkhazia.

Zelensky claimed on October 24 that: “The Russian fleet is no longer able to operate in the western part of the Black Sea and is gradually fleeing from Crimea. And this is a historic achievement.”

Map of the Black sea.
Strategic hotspot: Ukraine is claiming that Russia has lost control of the northwestern Black Sea. Peter Hermes Furian/Shutterstock

Basil Germond, a researcher in maritime strategy at the University of Portsmouth, believes this is a significant moment, marking Russia’s inability to properly enforce any blockade of Ukraine’s grain shipments. It also makes Russia look weak in Crimea itself, which, as Germond points out, “is a big problem, given the central role that Crimea plays in Putin’s imperialist narrative”.

Read more: Russia's plan to relocate its Black Sea naval base from Crimea is priceless for Ukraine's morale

… and in cyberspace

Another theatre of war not much discussed thus far is cyberspace. Russia has long been thought of as a master of cyberwarfare, spreading disinformation, launching attacks against western systems and disrupting communications. But now Kyiv has formed its own “IT army”, launching disruptive cyber-attacks and data thefts against the Russian government and other high-profile targets such as energy giant Gazprom.

Launched in February by the deputy prime minister, Mykhailo Fedorov, it is thought to be the first time that a state official has openly called on hackers from around the globe to join a nation’s military defensive efforts against an invading force. Vasileios Karagiannopoulos, who researches cybercrime and security at the University of Portsmouth, says the army has pulled off a number of coups, including hacking into Russian state TV channels to broadcast a message that: “the hour of reckoning has come.”

Karagiannopoulos believes this is the tip of the cyberwar iceberg and that a great deal of work is needed to incorporate activities in cyberspace into the rules of war.

Read more: Ukraine's IT army is a world first: here's why it is an important part of the war

Putin and Xi, a new world order?

Putin may not have been able to travel to South Africa for the Brics summit earlier this year for fear he might be and face war crimes charges at the International Criminal Court. But when China celebrated the tenth anniversary of the Belt and Road Initiative (BRI) in Beijing last week, Putin was there, front and centre, taking every opportunity to bask in the reflected glory of his apparently “no-limits friendship” with Chinese president Xi Jinping.

Stefan Wolff, an international relations expert at the University of Birmingham, noted the asymmetry of this friendship. While Xi travelled to Moscow in March for a one-on-one with the Russian leader, Putin had to content himself with being one of many leaders in Beijing, and while he made the most of it for the Russian press, the occasion was all about Xi and his Belt and Road project.

Read more: Xi-Putin meeting: here's what it says about their current, and future, relationship

Writing after the summit, Natasha Kuhrt, a senior lecturer in international peace & security at King’s College London and Marcin Kaczmarski, who lectures in security studies at the University of Glasgow, observed what they described as “Putin’s explicit acknowledgement of the different roles played by Moscow and Beijing in international politics”.

They note that despite the presence of a number of high level representatives of Russian business, no contracts of note were announced, perhaps a sign of China’s wariness of openly deriding the west’s sanctions regime. And, for all Putin’s boasts of the volume of trade between the two countries, the bulk of this trade consists of export of Russian hydrocarbons and other raw materials to China. In the 1990s, Russia feared becoming a “raw materials appendage” to China. As Kuhrt and Kaczmarski note, this appears to be becoming a reality.

Read more: Putin and Xi: Beijing Belt and Road meeting highlighted Russia’s role as China’s junior partner

Trapped doing business in Russia

Meanwhile, more than 600 days since Putin sent his war machine into Ukraine and Russia was hit by increasingly stringent western sanctions, more than 1,400 international companies are still operating in Russia, many of them unwillingly.

Simon Evenett, a professor of international trade and economic development at the University of St Gallen, and Niccolò Pisani, a professor of strategy and international business at the International Institute for Management Development (IMD), have explored why some multinationals have been trapped in Russia, finding it very difficult, if not impossible, to exit the country. They explore four push and pull factors that have help explain why this is.

Read more: Four reasons why western companies have been 'trapped' in Russia since it invaded Ukraine

Ukraine Recap is available as a fortnightly email newsletter. Click here to get our recaps directly in your inbox.

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Electrifying offshore platforms targets a tiny fraction of the oil industry’s emissions

The use of fossil fuels carries a much heavier greenhouse gas penalty.




David Nixon/Shutterstock

We are all familiar with the greenhouse gas emissions that come from burning fossil fuels in car engines, central heating systems and power stations. Little discussed is the climate footprint of producing oil and gas in the first place.

Extracting, refining and distributing oil and gas requires energy. Pumps, compressors, heaters and drilling units treat and move the fuels from many kilometres underground using electricity typically generated by gas turbines. Clearly, burning gas at offshore production sites will result in local emissions of climate-heating CO₂.

The North Sea Transition Authority (NSTA) regulates the UK’s oil and gas industry and has a remit to reduce the amount of greenhouse gas emissions from UK operations. This does not, however, extend to emissions arising from the subsequent use of that oil and gas.

With what little scope it has to reduce the industry’s emissions, the NSTA is keen for oil and gas platforms to be electrified. In essence, converting these offshore production sites from running on gas turbines to imported electricity from renewable sources like wind turbines.

Conventional oil production only accounts for roughly 5-10% of the emissions associated with the fossil fuel. By far the bulk of these emissions come from when it is used in transport, heating and power generation.

A UK motorway with cars and lorries travelling in one direction.
Burning oil and gas for energy emits far more than producing these fuels. Jarek Kilian/Shutterstock

It’s clear that, by pursuing platform electrification, the NSTA is focusing on the wrong emissions source.

Open heart surgery at sea

I worked in the oil and gas sector for over 40 years and know from experience that modifying an existing installation can be a risky undertaking. When dealing with equipment that is several decades old, unforeseen issues can emerge.

Shell’s UK chief Steve Phimister has compared the complicated process of converting oil and gas platforms to renewable electricity to open heart surgery. Some oil and gas companies have described electrification as a “huge concern”.

The configuration and location of some of the older installations mean that electrification will prove to be prohibitively expensive. On some installations, access to relevant equipment is limited.

Electrification is being proposed for clusters of platforms so that costs can be shared. For more remote platforms, sharing costs will not be feasible, so not all offshore platforms will be suitable for the switch to renewable electricity. Future North Sea oil and gas production would be a mix of electrified platforms and those which continue to burn gas.

For those offshore platforms that can be electrified, my experience tells me that costs are likely to be in the billions of pounds. Electrification costs are not quantified in the NSTA’s 2022 report on the industry’s emissions – in fact, there is only one mention of cost.

But even without cost and schedule overruns, electrifying a platform does not tackle all of its emissions. According to the NSTA itself, a large portion of the emissions from producing oil and gas will be unaffected by electrification. The authority estimates that around 35% of platform emissions come from activities unrelated to energy generation, mainly flaring and venting gas.

An offshore oil platform flaring gas.
Gas flaring allows operators to alleviate pressure on equipment. AzmanMD/Shutterstock

The NSTA does estimate that an electrification campaign could save 1.2 million tonnes of CO₂ a year. That might sound like a big number, but the UK emits greenhouse gases equivalent to around 420 million tonnes of CO₂ annually. The climate benefit of the UK oil and gas industry shedding 1.2 million tonnes of CO₂ from its offshore operations amounts to just 0.3% of the country’s yearly emissions.

Cut fossil fuel use instead

I believe electrifying offshore oil and gas platforms is a wrong-headed use of taxpayer and industry money and fails to address the wider picture.

The UK would cut far more CO₂ per pound spent if the billions earmarked for offshore electrification were directed at reducing the much larger carbon footprint from fossil fuel use instead. The government could cut these emissions by improving building insulation, building more electric vehicle charging points, investing in wind and solar installations and expanding the electricity grid.

But shifting money from offshore electrification to abating fossil fuel use will not be straightforward. Perhaps the NSTA could agree to let oil and gas firms operate without electrification, provided they can demonstrate they are operating their equipment in such a way as to reduce these emissions to as low as reasonably practical. This would not cut emissions as much as electrification, but it would free up money for more effective decarbonisation elsewhere.

And in this scenario, oil and gas companies would not need to undertake open heart surgery at sea. That sounds like a win-win for everyone.

Tom Baxter does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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