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Climate change, the crisis in the Middle East, the continuing war in Ukraine, combating global poverty.
All of these are critical issues for Britain and beyond; all of them up for discussions at the G20 summit in Rio de Janeiro this week, and all of them very much in limbo as the world awaits the arrival of president-elect Donald Trump to the White House.
Because while US President Joe Biden used Nato, the G7 and the G20, as forums to try to find consensus on some of the most pressing issues facing the West, his successor is likely to take a rather different approach. And that begs the question going into Rio 2024 about what can really be achieved in Mr Biden's final act before the new show rolls into town.
On the flight over to Rio de Janeiro, our prime minister acted as a leader all too aware of it as he implored fellow leaders to "shore up support for Ukraine" even as the consensus around standing united against Vladimir Putin appears to be fracturing and the Russian president looks emboldened.
"We need to double down on shoring up our support for Ukraine and that's top of my agenda for the G20," he told us in the huddle on the plane. "There's got to be full support for as long as it takes."
But the election of Mr Trump to the White House is already shifting that narrative, with the incoming president clear he's going to end the war. His new secretary of state previously voted against pouring more military aid into the embattled country.
Mr Trump has yet to say how he intends to end this war, but allies are already blinking. In recent days, German Chancellor Olaf Scholz has spoken with Mr Putin for the first time in two years to the dismay of the Ukrainian president Volodymyr Zelenskyy, who described the call as "opening Pandora's Box".
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Sir Keir for his part says he has "no plans' to speak to Putin as the 1,000th day of this conflict comes into view. But as unity amongst allies in isolating Mr Putin appears to be fracturing, the Russian leader is emboldened: on Saturday night Moscow launched one of the largest air attacks on Ukraine yet.
All of this is a reminder of the massive implications, be it on trade or global conflicts, that a Trump White House will have, and the world will be watching to see how much 'Trump proofing' allies look to embark upon in the coming days in Rio, be that trying to strike up economic ties with countries such as China or offering more practical help for Ukraine.
Both Sir Keir Starmer and French President Emmanuel Macron want to use this summit to persuade Mr Biden to allow Mr Zelenskyy to fire Storm Shadow missiles deep into Russian territory, having failed to win this argument with the president during their meeting at the White House in mid-September. Starmer has previously said it should be up to Ukraine how it uses weapons supplied by allies, as long as it remains within international law and for the purposes of defence.
"I am going to make shoring up support for Ukraine top of my agenda as we go into the G20," said Sir Keir when asked about pressing for the use of such weaponry.
"I think it's important we double down and give Ukraine the support that it needs for as long as it needs it. Obviously, I'm not going to get into discussing capabilities. You wouldn't expect me to do that."
Ukraine war latest: Russia sending 'clear message to Washington'
But even as allies try to persuade the outgoing president on one issue where consensus is breaking down, the prospect of the newcomer is creating other waves on climate change and taxation too. Argentine President Javier Milei, a close ally of Trump, is threatening to block a joint communique set to be endorsed by G20 leaders over opposition to the taxation of the super-rich, while consensus on climate finance is also struggling to find common ground, according to the Financial Times.
Where the prime minister has found common ground with Mr Trump is on their respective domestic priorities: economic growth and border control.
So you will be hearing a lot from the prime minister over the next couple of days about tie-ups and talks with big economic partners - be that China, Brazil or Indonesia - as Starmer pursues his growth agenda, and tackling small boats, with the government drawing up plans for a series of "Italian-style" deals with several countries in an attempt to stop 1000s of illegal migrants from making the journey to the UK.
Italy's Prime Minister Giorgia Meloni has struck financial deals with Tunisia and Libya to get them to do more to stop small-boat crossings, with some success and now the UK is in talks with Kurdistan, semi-autonomous region in Iraq, Turkey and Vietnam over "cooperation and security deals" which No 10 hope to sign next year.
The prime minister refused on Sunday to comment on specific deals as he stressed that tackling the small boats crisis would come from a combination of going after the smuggling gangs, trying to "stop people leaving in the first place" and returning illegal migrants where possible.
"I don't think this is an area where we should just do one thing. We have got to do everything that we can," he said, stressing that the government had returned 9,400 people since coming into office.
But with the British economy's rebound from recession slowing down sharply in the third quarter of the year, and small boat crossings already at a record 32,947, the Prime Minister has a hugely difficult task.
Team Trump: Who is in, and who is out?
Add the incoming Trump presidency into the mix and his challenges are likely to be greater still when it comes to crucial issues from Ukraine to climate change, and global trade. But what Trump has given him at least is greater clarity on what he needs to do to try to buck the political headwinds from the US to the continent, and win another term as a centre left incumbent.