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Yaama I'm Jack Evans and you're watching BTN. Here's what's coming up. We uncover the story behind this famous photo, learn about First Nations seasons and find out the history of Book Week. What is Statehood? Reporter: Tatenda Chibika INTRO: But first, the Prime Minister Anthony Albanese has announced that Australia will join other countries in recognising Palestine as an independent state. So, what does that mean? Tatenda found out. Anthony Albanese, Prime Minister: Australia will recognise the state of Palestine. Australia will recognise the right of the Palestinian people to a state of their own. We will work with the international community to make this right a reality. Tatenda Chibika, Reporter: That's the moment our Prime Minister said Australia would recognise Palestine as an independent state at the upcoming United Nations General assembly next month. It's something other countries, including France and Canada, have said they'll be doing too. So, what does that mean exactly? To be considered an independent state under international law a place needs to have its own land or territories with defined borders, it needs to have people who permanently live there, have a working government and it has to be able to talk and make deals with other countries. Once a place meets all those rules, it can ask to be recognised by other independent states and countries. But a big step in becoming an independent state is being fully recognised by the United Nations. To do that you first need to get approval from at least nine members of the UN's Security Council. That's a group of countries responsible for maintaining international peace and security. But even then, that tick of approval can still be blocked by one of the Security Council's five permanent members Russia, China, the UK, the US and France. If the Security Council approves, the decision then goes to the UN's General Assembly where at least two thirds of the UN's 193 members have to agree to make it official. Yeah, it's a pretty complex process which is why we've only seen a handful of countries recognised by the UN in recent years like South Sudan and Montenegro. Others like Kosovo are only 'partially' recognised which means they have some recognition but not enough to become a full member state at the UN. Right now, Palestine is recognised by more than 140 countries — that's more than two thirds of the UN General Assembly. So, why hasn't it become a UN member state yet? Well, it came pretty close last year when 12 members of the Security Council voted in favour of it. VANESSA FRAZIER, AMBASSADOR OF MALTA, APRIL 2024 UNSC PRESIDENT: I shall now put the draft resolution to the vote. But the US, a close ally to Israel, used its special powers to block Palestine from becoming a member state. VANESSA FRAZIER: Those against? At the time, the U.S said Palestine and Israel needed to come to an agreement on their own first. Throughout the years, there have been attempts to figure out a way for both Palestine and Israel to exist peacefully alongside each other but that hasn't happened yet. And now Israel has said that recognising Palestine as an independent state would be rewarding Hamas the group in charge of Gaza which was responsible for the terror attacks on October 7th, 2023. But the Palestinian Authority which governs parts of the West Bank says Hamas won't have a role in any future state of Palestine which will exist peacefully alongside Israel. Australia, like the US, had previously said that it wanted Israel and Palestine to figure out things by themselves first but because of how the war has been going the Australian government is worried that if it continues to wait, there might not be a Palestinian state to recognise. ANTHONY ALBANESE, PRIME MINISTER: There has been too many lives lost, both Israeli's and Palestinians and the world is saying we need a solution to this conflict, we need to end the cycle of violence and the way to do that is to have a two-state solution. News Quiz Russia's President Vladimir Putin stepped foot on American Soil for the first time in a decade to meet with US President Donald Trump. What state did they meet in? Alabama, Alaska or Arizona?It's Alaska. The two leaders met to discuss a way to end the war in Ukraine but weren't able to make any final agreements. DONALD TRUMP, US PRESIDENT: There were many, many points that we agreed on. Most of them, I would say, a couple of big ones, that we haven't quite got there, but we've made some headway. There's no deal until there's a deal. A lot of people criticised the two world leaders for not including Ukraine's president Volodymyr Zelenskyy in the meeting. But that didn't seem to worry Mr Trump who said the meeting was a success and Mr Putin even invited the US President to meet up again in Russia. DONALD TRUMP: We'll see you again very soon. Thank you very much, Vladimir. VLADIMIR PUTIN, RUSSIAN PRESIDENT: Next time in Moscow. DONALD TRUMP: Oh, that's an interesting one. No, no, no. I'll get a little heat on that one. Last week thousands of people marked the 80th anniversary of VJ Day. What does VJ Day commemorate? The victory of Allied forces in Europe, the surrender of Japan and the end of World War II or the dropping of the first atomic bomb? VJ Day or Victory over Japan day commemorates the surrender of Japan and the end of World War II on the 15th of August 1945. Around the world, and here in Australia, people marked the anniversary with ceremonies remembering those who fought in the war. REPORTER: Who will you be remembering today? VETERAN: Oh, a lot of fellows that I knew that never made it home. Scientists in the UK have created toothpaste that includes which of these ingredients? Hair, eye lashes or fingernails? Yeah, they're all a bit random and gross but the answer is hair. According to scientists from King's College in London, hair could be the key to good oral health because it contains a protein called Keratin which they say when mixed with saliva forms a crystal-like protective coating similar to enamel. And Swifties rejoice because Taylor Swift has announced her 12th Studio album. It's called life of a show what? Is it show pony, show girl or show bag? It's Life of a Showgirl and it'll be released October 3rd. Vincent Lingiari Reporter: Joseph Baronio INTRO: Now to this very famous photograph. It was taken 50 years ago and depicts a really significant moment in Australian history. Joe found out about the story behind it. On the 16th of August 1975, this famous photo was taken. It shows the former Prime Minister Gough Whitlam pouring sand into the hand of Aboriginal leader Vincent Lingiari. A simple gesture that symbolised handing the land at Wave Hill in the Northern Territory back to the Gurindji people. But the journey to get there was far from simple. It started back in the 1960s. At the time, Wave Hill was the biggest cattle station in the world, controlled by British landowner Lord Vestey. The Gurindji people, who had lived on the land for generations, worked for Vestey, but they weren't paid fairly, and conditions were tough. NEWS REPORTER: The station's 100 aboriginal stockmen, with their 100 dependents, are camped in the dry bed of the Victoria River with little shade from 90-degree heat, dust and flies. Eventually, Gurindji leader Vincent Lingiari said it was time to act. VINCENT LINGIARI: I said, "What was it before Lord Vestey born and I was born?" It was blackfella country. So, on August 23rd, 1966, Mr Lingiari and his fellow Aboriginal workers went on strike. It became known as the Wave Hill Walk Off. They moved their camp away from the Wave Hill station to a sacred site called Daguragu on Wattie Creek. They wanted to set up their own cattle station, and said they wouldn't move until their land was returned to them. For years, petitions and negotiations went on between the Gurindji people, the NT Administration, and the Australian Government in Canberra. CLAPPERS: 31. 32. 33. DAVID QUINN, ABSCOL: Well, it's basic justice that their land is recognised. PROTESTORS: Equal rights! As the news spread across the country, thousands of Aussies joined the campaign, including the leader of the Labor Party, Gough Whitlam, who made this promise during his 1972 election campaign. GOUGH WHITLAM: We will legislate to give Aborigines land rights. Not just because their case is beyond argument, but because all of us as Australians are diminished, while the Aborigines are denied their rightful place in this nation. Later that year, Gough Whitlam became Prime Minister. (Song From Little Things Big Things Grow, Song by Kev Carmody and Paul Kelly, 1993) From little things big things grow,from little things big things grow… But it wasn't until 1975, 9 years after the Wave Hill Walk Off started, that he followed through with his promise. Eight years went by, eight long years of waiting'Til one day a tall stranger appeared in the landAnd he came with lawyers and he came with great ceremony GOUGH WHITLAM: I solemnly hand to you these deeds as proof in Australian law that these lands belong to the Gurindji people. And through Vincent's fingers poured a handful of sandFrom little things big things grow 50 years on, and The Wave Hill Walk Off is seen as a pivotal moment in Australia's history. It led to significant legal and social changes for First Nations people, which is something many agree is worth celebrating. First Nations Seasons Reporter: Saskia Mortarotti INTRO: Recently, Melbourne's Lord Mayor suggested ditching the four-season calendar that most of us are familiar with and adopting a six-season Wurundjeri calendar instead saying it gives a better description of what the weather's actually like there. Sas found out more about the different seasonal calendars used by First Nations people. SASKIA MORTAROTTI, REPORTER: Right now, in most of the country, it's pretty cold. COLD GIRL: Think of somewhere warm. What? It's 32 degrees in Darwin in the middle of winter? But ah, yeah. There are some places where it's, well, quite warm. Which makes you wonder whether the weather actually matches the seasons. You see, Australia is pretty big, and we have lots of different weather patterns. Which is something First Nations people have tracked for thousands of years with their own seasonal calendars. KARL WINDA TELFER, CULTURAL CREATIVE KANYANYAPILLA: Why have we got four seasons when you know that don't make any sense here. It doesn't relate to the country here. This is Karl Telfer. He's an artist and storyteller who produced the Kuri Kurru exhibition at the Museum of Discovery in Adelaide that explores the 6 different seasons of the Kaurna Meyunna. SASKIA MORTAROTTI: So, how do you know when you're in one of those six seasons? KARL WINDA TELFER: Well, there are stars that rise. So, you know, there are certain stars, like in Parnatti, for example. There's a star called Parna, and we know what that star is. So, that talks to us about, okay, the time now is going to be cold on the ground. First Nations calendars like the Kaurna one don't just tell us what's happening with the weather; they're also used to track when certain plants and animals are around. KARL WINDA TELFER: It teaches you about what plants you can, you know, what you can eat what you can't and all that what is ready certain times a year and fruit everything, bird shows you the right time to eat the fruit, perfect time, if you try and go get them the next week they're gone. Karl says we can also use these calendars to see how the environment has changed over time. KARL WINDA TELFER: Kudlilla is the season we're in now and Kudlilla that talks about like the rain but we're not having enough rain these days, well, these times. And this is due to climate and the climate changing. There are many different First Nations seasonal calendars around the country. Like Ngan'gi calendar from the Northern Territory which has 13 seasons that follow the life cycle of the native spear grass. Or the Wurundjeri Calendar in Victoria which has 6 seasons. And recently, Melbourne's Lord Mayor, Nicholas Reece, said Melbourne, or Naarm, would be better off adopting the Wurundjeri calendar because it's more in tune to what's happening with the weather. Something many, including Karl, think we should be doing right across the country. KARL WINDA TELFER: I'm talking about the English four seasons. So, this is totally different systems that we're talking about and weather patterns and currents and all sorts of different things, because it's the sea country too. So, my question is, well, why do we have that? If that doesn't work, you know? Quiz How many seasons are there in the Tiwi Island Calendar? 1, 2 or 3? It's 3, although they also have 13 minor seasons. Book Week Reporter: Wren Gillett INTRO: This week, kids across Australia have been dressing up as their favourite characters to celebrate Book Week. Wren finds out why Book Week began 80 years ago and why it's still important today for getting young Aussies into reading. STUDENT: I read an hour every night, maybe even two hours some nights. STUDENT: My favourite book series are the Harry Potter series and the Keeper of the Lost City series. STUDENT: Probably Bad Guys and Weirdo. STUDENT: I like the Amulet, I've been reading that. STUDENT: I love reading Dork Diaries and Exploding Endings. Whether it's Fantasy, mystery, history — whatever you're into. Book week is a time to celebrate, well, books. STUDENT: Me and my friends are dressing up as Inside Out. STUDENT: I was thinking SpongeBob. STUDENT: I'm dressing up as Winnie the Pooh and it's just a fun way to express what kind of books you like. And guess what, book week has actually been a thing for many, many years. WREN GILLETT, REPORTER: Once upon a time, in a land not so far away, literacy lovers noticed a problem. The year was 1945. The second World War had just ended, and kids were mainly reading books from overseas, in particular the UK. Because, at the time, there weren't many Aussie authors writing books for children. WREN GILLETT: So, a group of passionate teachers, librarians, booksellers, publishers, and book-loving volunteers, decided to create what we now know as The Children's Book Council of Australia. Familiar logo, right? Together, they launched book week, all in an effort to get Aussie kids' reading more. And it seemed to work. The 1960s saw a boom in Australian children's books being published. REPORTER: How many books do you read a week? STUDENT: Well, it really depends on the week. If there's exams, I might read only one or two. But if there's no exams and if I've got plenty of time, I might read up to five or six. WREN GILLETT: But today, it's a slightly different story. Studies show that less than one in five eight to 18-year-olds are reading in their free time, and that only one in three actually enjoy reading for fun. WREN GILLETT: Why do you reckon we're seeing this trend? STUDENT: People are getting sucked into screens and they're like spending hours just scrolling through TikTok and stuff, and they're getting so attached to it that they don't feel the need to pick up books and read them. Yeah, there's a lot of different things competing for our attention these days, but many think books are still worth our time. PETER HELLIER, AUSSIE COMEDIAN AND AUTHOR: Books are the exact opposite of boring. And if you think they're boring, I'm sorry, but you're wrong. This is Peter Hellier, he's a pretty famous Aussie comedian, actor, and the author behind these books. And he's just released another one called Detective Galileo, about a trail horse who dreams of solving crimes. PETER HELLIER: He joins the police force and quickly finds out that the horses don't actually solve the crimes, it's the police officers who solve the crime. So he promptly gets thrown out of the force and begins his own detective agency, which I'm reliably told is the only detective agency in the world run by a horse. Peter actually started writing books when he was a kid. PETER HELLIER: I started writing when I was six, seven, eight years old. In fact, I started my own publishing company called Better Books. And I would write these books, and then I would get a parent or one of my parents or teachers to type them up. And I would read them in front of the class. And, you see, each has the logo, the Better Books logo, there it is — the famous Better Books logo. WREN GILLETT: You weren't mucking around. PETER HELLIER: There all on all of them. There we go. There we go. Many, Including Peter, say there's plenty to get from a good book. They help us learn new words and phrases, get a better understanding of the world around us, and strengthen our imaginations. PETER HELLIER: Books can take you absolutely anywhere. They can take you to countries that you never dreamed about going. Countries that exist, countries that don't exist. Reading just makes the world a much bigger place. It's why for the past 80 years, schools around the country have been taking part in book week. STUDENT: Reading is a place where you can have your own world just to yourself. STUDENT: It's like watching a movie inside your head, but you can choose how it goes. STUDENT: Picking up a book is a good idea, maybe you should start with something that you're interested with and then you can start exploring from there. Quiz What is the title of the book that took out this year's Book of the year Award for younger readers? It's Laughter is the Best Endingby Maryam Master. Some other winners included I'm not really here by Gary Loneborough which took out book of the year for older readers and best picture book went to The Truck Cat, by Deborah Frenkel. Sport Australia's men's national basketball team — the Boomers — have won their third Asia Cup in a row, with an epically narrow victory over China. COMMENTATOR: It is Australia who are celebrating! China started strong, leading 25-17 at quarter time. But Aussie Xavier Cooks led a fierce comeback, shooting 30 points and collecting nine rebounds, earning him the title of MVP. And there seriously couldn't have been a tighter finish. Just as the final buzzer went off, China missed a shot that would have won them the game, leaving Australia with a 90-89 victory. COMMENTATOR: An unbelievable finish. The 2025 AFLW season kicked off last week, and so did a new trick. Yeah, 19-year-old Ash Centra from Collingwood, pulled out this move in the warm-up before their season-opener to Carlton, and since then, a lot of people have been trying to do it, with some success, kind of? FOOTY PLAYER: No, I'm not doing it on camera. But despite the epic warmup, Carlton did end up beating Collingwood by 24 points. Now, the moves from these athletes in China weren't quite so graceful but give 'em a break, okay, they're robots. For the first time ever, humanoid robots from all over the world, competed in their very own games, which featured, soccer, boxing, running, and ahh, lots of falling over. Lots. Luckily though, they did bring their own cheer squad. Young Rapper Reporter: Rylie INTRO: Finally, we're going to meet another winner of this year's Heywire competition — which asks young people in regional areas to share their stories. Rylie's going to tell us how music helped to transform his life. Check it out. Mum and I were homeless. We lived at a caravan park, in motels and tents around Warrnambool. It wasn't pretty. I'm First Nations, and I remember feeling like, my own country is failing me right now. So, we camped right along here. I remember pitching a tent right here and this was actually around the same time I started to get into music which was a good way for me to have something to look forward to. I was raised by the SoundCloud era, listening to a lot of trap music. When I was in school, I'd rap along to songs by Juice World, then I started to make my own. My first track was recorded on my phone. It was bad but a lot of fun to make. Some kids in my school heard it and shamed me. That put me off music for the next couple of years, until a friend of mine bought a microphone and encouraged me to give it another go. There was something about that mic and the energy of the crew around me that gave me confidence. It lit a fire in me. Over time, I was able to focus my flow. My songs are about escapism, living the life, being a success. I rap about stuff that takes me to a better place in my head. I'm manifesting my future. My stage name is Hundo Milli, it's short for hundreds of millions. Money's not really the end goal; it's more about having the freedom to dream big. Mum taught me to never stop believing. Even when times were tough, she kept pushing for us to get housing and eventually we did. We're some of the lucky ones. Today, I'm in a Melbourne studio recording my next single. I remember living in my tent dreaming about this very moment and now I'm here, doing what I love. Ain't nothing going to stop me. Closer Well, that's all we've got for you today, but we'll be back before you know it. In the meantime, you can head to our website, there's plenty to see and do. You can also catch Newsbreak every weeknight and there's BTN High for all you highschoolers out there. Have an awesome week and I'll see you next time. Bye.
Key Word Definition
Aid Assistance in the form of grants or loans at below market rates. For example, the UK provided aid to Nepal after the 2015 earthquake to help with reconstruction efforts.
Barriers to Trade Government constraints on the flow of international goods and services, such as tariffs and quotas. For example, the European Union imposes tariffs on certain agricultural products to protect its farmers.
BRICS An acronym for an association of five major emerging nations: Brazil, Russia, India, China, and South Africa. For example, BRICS nations often meet to discuss economic cooperation and development strategies.
Demographic Aging The rise in the median age of a population. For example, Japan is experiencing demographic aging, with a significant increase in the elderly population.
Economic Core Region The most highly developed region(s) in a country. For example, London is considered an economic core region in the UK due to its high level of development and economic activity.
GNP (Gross National Product) GDP plus overseas earnings, also known as GNI (Gross National Income). For example, the GNP of the United States includes the value of goods and services produced domestically and the income earned by its citizens abroad.
HIC (Higher Income Country) A country with a high level of income and development. For example, Germany is classified as a higher income country due to its high GDP per capita and advanced infrastructure.
NEE (Newly Emerging Economy) A country that is experiencing rapid economic growth and industrialisation. For example, China is an example of a newly emerging economy, having rapidly industrialised and grown economically over the past few decades.
LIC (Lower Income Country) A country with a low level of income and development. For example, Malawi is considered a lower income country, with a low GDP per capita and limited access to healthcare and education.
GDHI (Gross Disposable Household Income) The amount of money that households have available for spending and saving after taxes and social contributions. For example, in the UK, the GDHI varies significantly between regions, with London having one of the highest levels.
Gini Coefficient A measure of income inequality within a population, ranging from 0 (perfect equality) to 100 (perfect inequality). For example, South Africa has a high Gini coefficient, indicating significant income inequality within the country.
Trade Unions Organisations that promote trade between member countries, such as the East African Community (EAC). For example, the East African Community (EAC) works to promote economic integration and trade among its member states.
Fair Trade A movement aimed at helping producers in developing countries achieve better trading conditions and promote sustainability. For example, Fairtrade coffee ensures that farmers receive a fair price for their product and work under safe conditions.
FDI (Foreign Direct Investment) Investment made by a company or individual in one country in business interests in another country. For example, Toyota's investment in manufacturing plants in the UK is an example of foreign direct investment.
Debt Relief The partial or total remission of debts, especially those owed by developing countries to external creditors. For example, the Heavily Indebted Poor Countries (HIPC) initiative provides debt relief to eligible countries to help them achieve sustainable development.
International Aid Voluntary transfer of resources from one country to another, often in the form of financial assistance, goods, or services. For example, the UK provides international aid to various countries through its Department for International Development (DFID).
Top-Down Development Large-scale development projects led by national governments or international organisations. For example, the construction of the Three Gorges Dam in China is an example of a top-down development project.
Bottom-Up Development Small-scale development projects led by local communities or NGOs, focusing on the needs of the poorest and most vulnerable. For example, WaterAid's installation of hand pumps in rural villages in Africa is an example of a bottom-up development project.
Urbanisation The increase in the proportion of people living in urban areas compared to rural areas. For example, rapid urbanisation in India has led to the growth of megacities like Mumbai and Delhi.
Geopolitics The study of the effects of geography (human and physical) on international politics and relations. For example, the geopolitics of the Arctic region involves disputes over territorial claims and access to natural resources.
Quality of Life The general well-being of individuals and societies, outlining negative and positive features of life. For example, Scandinavian countries are often ranked high in quality of life due to their strong social welfare systems and high levels of happiness.
Poverty Cycle A set of factors or events by which poverty, once started, is likely to continue unless there is outside intervention. For example, lack of education and healthcare can trap families in a poverty cycle, making it difficult for future generations to improve their living standards.
Sustainable Development Economic development that is conducted without depletion of natural resources. For example, the use of renewable energy sources like wind and solar power is a key aspect of sustainable development.
Humanitarian Aid Material or logistical assistance provided for humanitarian purposes, typically in response to crises including natural disasters and man-made disaster. For example, humanitarian aid was provided to Haiti after the devastating earthquake in 2010 to help with immediate relief efforts.
Economic Growth An increase in the production of goods and services in an economy over a period of time. For example, China's economic growth over the past few decades has lifted millions of people out of poverty.
Social Indicators Measures that describe the well-being of individuals or communities, such as health, education, and income. For example, life expectancy and literacy rates are common social indicators used to assess development.
Environmental Sustainability Responsible interaction with the environment to avoid depletion or degradation of natural resources and allow for long-term environmental quality. For example, practices like recycling and conservation of natural habitats contribute to environmental sustainability.
Infrastructure The basic physical and organisational structures and facilities needed for the operation of a society or enterprise. For example, good infrastructure, such as roads, bridges, and schools, is essential for economic development.
Globalisation The process by which businesses or other organisations develop international influence or start operating on an international scale. For example, the globalisation of technology companies like Apple and Google has led to their products being available worldwide.
Microfinance Financial services provided to low-income individuals or groups who are typically excluded from traditional banking. For example, microfinance institutions like Grameen Bank provide small loans to entrepreneurs in developing countries to help them start or expand their businesses.
Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty Desirée Nieuwenhuis | Natàlia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. 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FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including ‘onset of puberty and adiposity/obesity’, ‘onset of puberty’, ‘children with obesity’, ‘adipose tissue’, ‘childhood obesity’, ‘adiposity’, ‘obesity’, ‘adipokine(s)’, ‘HPG axis’, ‘adipokines ovary/ova- ries’, or ‘adipokines testes’, either alone or in combination. 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The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study. BMC Pub- lic Health. 2017;17:664-673. 81. Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expres- sion of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 2007;39(1):22-27. 82. Martins AD, Moreira AC, Sa R, et al. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta. 1852;2015: 1824-1832. 83. Morash BA, Willkinson D, Ur E, Wilkinson M. Resistin expression and regulation in mouse pituitary. FEBS Lett. 2002;526(1-3):26-30. 84. Cabrera SM, Bright GM, Frane JW, Blethen SL, Lee PA. Age of thelarche and menarche in contemporary US females: a cross- sectional analysis. Journal of pediatric endocrinology & metabolism: JPEM. 2014;27(1-2):47-51. 85. Herman-Giddens ME, Steffes J, Harris D, et al. 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Obesity Reviews. 2020;21:e13005. https://doi.org/ 10.1111/obr.13005 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are gover
According to 1 Corinthians 15:1-4, the three key parts of the gospel message are that Christ died for the world's sins according to the Scriptures, that He was buried, and that He rose again on the third day according to the scriptures. Evangelism is the process of sharing the gospel with others. Christians should evangelize so others can have faith and salvation in Jesus Christ. Proverbs 11:30 says that it is wise to win souls. The Great Commission is Jesus' command for believers to evangelize all nations. Wherever Christians go, they are supposed to make disciples, baptize believers in the name of each Person in the Trinity, and teach about Jesus and how to live God's way. According to 2 Corinthians 5:20, Christians are ambassadors for Christ. An ambassador for Christ should be a good example through words and actions, such as inviting a friend to church, being friendly to new people, and being obedient and truthful. A witness is a person who gives evidence or proof of something he or she has seen or experienced. Christians can be a witness of Jesus by giving proof of their faith through evidence from the Bible. A Christian can give a testimony of what he or she has seen Jesus do in his or her life. Evangelism should include the following points: everyone is a sinner; a person must believe, repent, and receive eternal life; and a person must choose Jesus as Lord.
A piece that’s sung as opposed to played. Answer: Cantata A hymn tune of the Lutheran church. Answer: Chorale A part for keyboard (harpsichord or organ) and cello or bass. The keyboard player reads the cello line and provides an accompaniment based on the figured Bass. Answer: Basso continuo The numbers written under the cello part indicating chords and their positions to the keyboard player. Answer: Figured Bass A piece for choir. Answer: Chorus A style of singing that is more related in pitch and rhythm to speech than song. In the 18th Century it was used extensively in Opera as “Dialogue” between Characters. Answer: Recitative (Dry) Accompanied only by continuo. Answer: Recitativo secco More expressive and accompanied by the orchestra. Answer: Recitativo stromentato Contrapuntal device whereby a motif or phrase is presented successively by different voices. Answer: Imitation To turn a motif or phrase “up-side down”. Answer: Inversion A song for 1 or more voices, popular in Opera and Cantata as a contrast with Recitative. Answer: Aria A type of piece that was written as a set of variations on an Ostinato. Answer: Chaconne A musical idea repeating many times. Answer: Ostinato A sustained or repeated note over which the harmonies change. Answer: Pedal Point Point of rest. Answer: Cadence Change of key. Answer: Modulation Where the composer gives prominence or illustrates words in musical terms. Answer: Word Painting A motif that has more than 1 note per syllable is said to be melismatic. Often used as word painting. Answer: Melisma Where 1 note per syllable is used. Answer: Syllabic A polyphonic composition in which a part is imitated by 1 or more parts so that successive statements of the melody overlap. Answer: Canon Any rhythmically independent movement between parts. Answer: Polyphony A combination of 2 or more independent melodies. Answer: Counterpoint A structure consisting of 3 sections-ABA. Answer: Ternary Form Back to the beginning as in the Da Capo Aria. Answer: Da Capo (D.C.) Back to the sign. Answer: Dal Segno (D.S.) A motif which is repeated at a different pitch in the same part. Answer: Sequence
Research: Scientific Attitudes These are the traits that scientists and researchers practice to ensure reliable results and good research work: Curiosity – Desire to ask questions and seek answers. Drives exploration and discovery. Example: Wondering why leaves change color in autumn. Intellectual Honesty – Reporting observations and results truthfully, even if they don’t support your hypothesis. Open-Mindedness – Willingness to accept new ideas and consider other perspectives. Perseverance – Continuing research despite difficulties or failures. Objectivity – Avoiding bias; basing conclusions only on evidence and facts. Positive Attitude Towards Failure – Viewing mistakes as opportunities to learn and improve. Skepticism – Questioning results and not accepting claims without sufficient evidence. Observation and Inference Observation – Using the senses (or tools) to gather information. Qualitative Observation → Describes qualities (color, shape, texture). Quantitative Observation → Uses numbers or measurements (height, mass, temperature). Inference – Logical explanation or conclusion based on observations and prior knowledge. Example: Seeing smoke and inferring there is fire. 🔎 Science Process Skills These are steps used in scientific investigations: Observing – Using senses and instruments to gather data. Inferring – Making explanations based on observations. Predicting – Stating what you think will happen based on patterns or evidence. Communicating – Sharing results through words, graphs, charts, or reports. Classifying – Grouping objects or data according to similarities and differences. Ordering/Sequencing – Arranging objects or events in correct order (time, size, importance). Measuring – Using standard units and instruments to describe length, mass, volume, time, etc. 📏 Measurement and Measuring Instruments Measurement – The process of comparing an unknown quantity with a standard unit. Common Quantities and Instruments: Length/Distance – Ruler, Meter Stick, Vernier Caliper, Tape Measure. Mass – Balance (triple beam, electronic). Volume – Graduated Cylinder, Measuring Cup, Pipette, Burette. Temperature – Thermometer. Time – Stopwatch, Clock. Electric Current – Ammeter. Voltage – Voltmeter. Key Idea: Accurate measurement requires using the correct instrument and unit (SI Units).
Management and Globalization Global Management Why companies go global How companies for global Global Business environments Global Business Types of global business Pros and cons of global businesses Ethnic Challenges for global business Culture and Global Diversity Cultural intelligence Silent language of culture Tight and loose cultures Values and national cultures Global Management Learning Are management theories universal? Intercultural competencies Global learning goals Key concepts of the challenges of globalisation: Global economy Resources, markets and competition are worldwide in scope Internationalisation The process of increasing involvement in international operations Globalization/Deglobalization Glob- the growing interdependence among elements in the global economy The worldwide interdependence of resource flows, product markets and business competition World 3.0 Different views: World flat vs. round Distance is a metaphor that represents the degree of dissimilarities between countries Balancing cooperation in the global Global Management Global management - managing things in different countries Managing business and organizations with interests in more than one country What do we expect from global Managers Knowing how to adapt Knowing the language Global Manager Is culturally aware and informed on international affairs International Business Conducting for-profit transactions of goods and services across national boundaries International Motive Why do firms internatioalize their activities Cheaper labour Labour tax Natural resources Enrolments to do business Clientele Exclusive materials Personal benefits: Taxes Reasons why businesses go global Customers Suppluers Capital During (1993) - 4 motive 1. Market seeking 2. Efficiency Seeking 3. Resource seeking 4. Strategic Asset Seeking Cuervo Cazurra, Narula and un (2015) - 4 motive s Internationalization Motives A company may also explore the opportunities in different markets in order to take advantage and in some cases extend the product life cycle What is a Market Entry Strategy Involves the sale of goods or services to foreign markets but do not require expensive investments Franchising Exporting and importing Involve the sale of goods or services to foreign markets but do Types of market entry strategies Global sourcing Exporting Importing Licensing agreement Franchising Types of Foreign Direct Investment (FDI) strategies: Joint venture Strategic alliance Owned Subsidiary (sometimes called WOS) How to go abroad What conditions will affect the decisions of firms on how to internationalize their activities? During (1978)- Eclectic paradigm OLI model OLI- Ownership, Location and Internalization Advantages Ownership advantages Resources owned by the organization that can be transferred across locations include trademarks, production techniques and processes, managerial skills and other resources not available to the competitors Location Advantages Represent the implications of choosing to produce or to perform activities in a specific location (country or region) Internalization Advantages: The ability to internalize or to incorporate activities that add value to its business Evolution of Concepts- New Elements Although economic factors are certainly important to explain the formation, growth and expansion of firms within and across national borders, they are not sufficient to explain the additional complexity when a firm decides to expand its activities across national borders Economic factors Investigate the economic elements that affect the internationalization of firms Behavioural Elements Explaining the additional challenges (and perhaps opportunities) a firm faces in foreign host countries when compared to indigenous (local) firms Behavioural theories Johanson and Wiedersheim-Paul (1975) and Johanson and Vahlne (1977) Included the psychic Distance concept (beckerman,1956) to explain the internationalization behaviour of firms The Uppsala internationalization model Psychic distance is: the sum of factors preventing the flow of infomatio from and to the market Psychic Distance is a broad concept that includes several elements such as: language, culture, political systems, level of education, level of industrial development Firms behave in a “Risk Averse” manner It means that when the perceived risk goes down, the firm increase its commitment to the foreign market \ The Haier Group Data Strategy Big DATA and Small DATA The use of small data to satisfy individual customers’ needs, however, the book mentions a huge cultural shock at the plant in Camden, south caroline Ex: top down, hard hat colors and hierarchy Culutral Differnces can have a huge impact on the internationalization of firms Kogut and Singh (1988)- Cultural Distance Index First statsical study on the implication of ciltiral distance to the selection of entry mode When investigating in culturally distant countries, foreign firms can choose to partner with foreign firms in order to gain local knowledge and share the risk associated to the investment (higher commitment = higher risk) How Companies Go Global Global sourcing The process of purchasing materials or services around teh world for local use Exporting Selling locally made products in foreign markets Importing Buying foreign made products and selling them domestically Exports correspond to what percentage of Candain GDP What countries are the major trending partners of Canada Management and Globalization How Companies Go Global Licensing Agreement One firm pays a fee for rights to make or sell another company’s products What are the potential risks associated to licesning The case of new balance in China Franchising A fee is paid for the rights to use another firms name, branding and methods Insourcing Insourcing: refers to local job creation that results from foreign direct investment Types of insourcing Joint ventures: operate in a foreign country through co-ownership by foreign and local partners Strategic alliances: A partnership in which foreign and domestic firms share resources and knowledge for mutual gains Foreign subsidiaries: local operation completely owned by a foreign firm Criteria for choosing a joint venture partner: Familiarity with your firm’s major business String local workforce Values its customers Future expansion possibilities Strong local market for partner’s own products Good Profit potential Sound financial standing Global business environments Legal and poliical systems Trade agreements and trade barriers Regional economic alliances Legal and political systems Differing laws and practices regards Business ownership Negotiation and implementation of contracts Foreign currency exchange Protection of intellectual property rights Counterfeit merchandise Political risk Potential loss in value of foreign investment due to instability and political changes in the host country Political risk analysis (expertise/experience) Forecast political disruptions that threaten the value of a foreign investment Changes in the rules of the game Brexit US Trade Wars-mexico-China Other examples Bolivia, Venezuela, China De-globalization The process of weakening interdependence among nations Trade Agreements and trade Barriers World trade organization Most favourd nation status Tariffs Nontariss barriers (quotes, restrictions, etc.) Protectionism Regional Economic Alliances USMCA (replacment for the NAFTA-North American Free trade Agreement) EU- European Union APEC- Aisa Pacific Economic Copperation ASEAN - Association of Southeast Asian Nationas SADC - Southern Africa Development Community MERCOSUR- Chapter 5- Global Management and Cultural Diversity (part 2) Review Types of global business Global corporation MNE (multinational enterprise) or MNC (multinational corporation) with extensive business operations in more than one foreign country Transnational corporation A global corporation that operates worldwide on borderless basis Some host country complaints about MNCs Host Country companits about MNCs: Excessive profits Interference with local government Domination of local economy Interference with local government Hiring the best local talent Limited technology transfer Disrespect for local customers Examples - War in Ukraine Disruption in global -value chains and increased pressure and interference of MNCs with local government Fertilizer imports in Brazil (one of the major producers of agricultural commodities) We must consider the triple bottom line and the impact in society, the environment and the economy $2.5 billion invest in potash mine in Brazill What about Globalization gap Large multinationals adn industrilizednaitons gaining disporoportinonally form globalization Globalization gap: Large multinational and industrialized nations gaining disproportionally from Globalization Some MNC complaints about host countries MNC Complaints about host countries: Profiit limitations Laws and regulations Overpirce resources Exploitative rules Foreign exchange restriction Failure to uphold contracts Mutual benefits for host countries and multinational companies Mutual benefits for host country and global corporation of MNC: Shared growth opportunities Shared income opportunities Shared learning opportunities Share development opportunities Develop projects together What are some of the ethical challenges for global business Ethincal challenges for global business Child labour Employmnet of children for worl otherwise done by adults Sweatshops Employment of workers at very low wages for long hours in poor working conditions Ex: Nike bad labour prices Unsafe working conditions Corruption Illegal practices that further one’s business interests Corrupiotn of froeign public officials Act makes it illegal for Candain firms and their representatives to engage in corrupt practices overseas Bribes to foreign officials Excessive commissions Non-monetary gifts Sweatshops Conflict materials What is culture Culture : The shared set of beliefs, values, and patterns of behvaiourr common to a group of people Food preferences Values and traditions Language and beliefs Religion Art music Life style Hofstede defines culture as: “The collectiv programing of teh mind distinguishing the members of one group or category of people from others” What is culture shock Culture Shock: Confusion and discoumfert a person experiences in an unfaamiliar culture Stages to adjusting to a new culture Confusion Small vitorires The honeymoon Irritation and anger Reality Cultural Intelligence The ability to adapt and adjust to new cultures What is Ethnocentrism Tendency to consider one’s own culture as superior others Slinet languages of culture Contect Low context High context Space Proxemics Ex: personal space Time Monochronic Polychronic High and low contexts cultures Edward T.Hall (1959) Def: Part of a discourse that surround a word or passage and can throw on its meaning Low context cultures Emphizes communication via spoken or written words Countries like United States, Canada and Germany High context cultures Rely on nonverbal and situational cues as well as on spoken or written works Thailand Malaysia Time Monochronic cultures People tend to do one thing at a time Canda Polychronic cultures Time is used to accomplish many different things at once Egypt Space Proxemics Study of how people use space to communicate In North American people value “personal space’ Many Latin and Asian cultures expect much less personal space Tight and Loose Cultures Cultural tightness-looseness Tight = Strength of norms that govern social behvaviour Japan, Korea, Malaysia Loose = tolerance for any deviation from norms Australia, Brazil, Hungary Values and national cultures (Hofstede) Power distance Uncertainty avoidance Individalism-collectivism Masculinity-femininty Time Orientation Indulgence vs. Restraint Comparative management How management pratices systematically differ among countries and /or cultures Intercultural competencies Skills and personal characteristics that help us be successful in cross cultural situations Global Managers (know how to adapt) Need to successfully apply management functions across interantional boundaries Global Learning goals Not universal Engage critical thinking Look everywhere for new management ideas Always consider culture
In this video we take a look at the 0:02 fetch to code 0:03 execute cycle including its effect on 0:06 the various registers we've previously 0:12 [Music] 0:14 discussed a computer is defined Definition 0:17 as an electronic device that takes an 0:20 input 0:22 processes data 0:25 and delivers output 0:29 in this simple example you can see we're 0:31 taking the input 5 0:35 we're multiplying it by 2 that's our 0:37 process 0:39 and we're outputting 10. 0:44 but this could be way more complex for 0:46 example of a game console 0:48 the input could be the buttons you press 0:50 on a controller 0:53 the processes would then be carried out 0:55 by the console itself 0:59 and the output would be some form of 1:01 update to a monitor 1:02 and sound out for a speaker possibly 1:04 vibration feedback through the 1:06 controller 1:10 to process data a computer follows a set 1:13 of instructions 1:14 known as a computer program 1:18 if we take the lid off a typical desktop 1:20 computer we can identify 1:22 two critical components the memory 1:26 that stores the program and the central 1:29 processing unit or processor 1:31 which is under this large fan and 1:33 carries out the instructions 1:37 a computer carries out its function by 1:40 fetching 1:41 instructions decoding them and then 1:43 executing them 1:44 in a continuous repetitive cycle 1:46 billions of times a second 1:48 let's look at each of these stages in a 1:50 little more detail Fetch 1:53 so let's start with the fetch stage the 1:55 very first thing that happens 1:57 is the program counter is checked as it 2:00 holds the address 2:01 of the next instruction to be executed 2:07 the address stored is then copied into 2:09 the memory address register 2:14 the address is then sent along the 2:16 address bus to main memory 2:18 where it waits to receive a signal from 2:21 the control 2:22 bus so it knows what to do 2:27 as we want to read the data that's 2:29 stored in memory address 2:30 0 0 0 0 the control unit sends 2:34 a read signal along the control bus to 2:36 main memory 2:41 now main memory knows the data needs to 2:44 be read 2:45 the content stored in memory address 000 2:49 can be sent along the data bus to the 2:51 memory data register 2:56 now as we're currently in the process of 2:58 fetching an instruction 3:00 the data received by the memory data 3:03 register gets copied 3:04 into the current instruction register 3:11 the instruction effectively has now been 3:14 fetched from memory 3:16 just before we proceed to the decode 3:18 phase we now 3:19 increment the program counter so that 3:22 the address it contains 3:24 points to the address of the next 3:26 instruction which will need to be 3:30 executed 3:32 the instruction now being held in the 3:33 current instruction register 3:35 is ready to be decoded 3:39 now as we mentioned in the previous 3:41 video the instruction is made up of two 3:43 parts 3:44 we have the op code that's what it is we 3:47 need to do 3:50 and we have the operand what are we 3:53 going to do it to 3:55 now the operand could contain the actual 3:57 data 3:58 or indeed it could contain an address of 4:01 where the data is to be found 4:06 by decoding this instruction we can see 4:08 the operation we need 4:10 is a load operation so we need to load 4:14 the contents of memory location0101 4:18 into the cpus accumulator 4:25 in the exam a simple model will be used 4:27 to describe the 4:29 structure of any given instruction 4:32 you're not going to be expected to 4:34 define how an opcode is made up 4:36 but simply to interpret opcodes in the 4:39 given context of an exam 4:40 question in the example here 4:44 you can see there's a total of 16 4:46 different opcodes available 4:48 and this is because we're using four 4:50 bits for our representation 4:56 so now we've fetched the instruction and 4:59 we've decoded it so we know what we need 5:00 to do 5:01 we're finally ready to execute it 5:05 so we now send address 0101 5:08 to the memory dress register 5:13 now we're in the memory address register 5:15 we can finally send the address 5:18 down the address bus to main memory 5:24 this time we want to read the data 5:26 that's stored in memory 5:28 and so the control unit again sends a 5:30 read signal along the control bus 5:36 so main memories now receive an address 5:38 and a read signal 5:40 so the content stored at memory location 5:43 0101 5:44 can now be sent along the data bus back 5:46 to the cpu 5:47 and into the memory data register 5:54 finally the contents of the memory data 5:56 register are copied to the accumulator 5:59 and this is one of a number of general 6:00 purpose registers found in the cpu 6:04 this first instruction is now complete Branching 6:11 so what does this program actually do 6:14 you should be able to work it through 6:16 carefully and figure it out 6:19 we're now pointing instructions zero 6:21 zero zero one in the program counter 6:23 and we're ready to fetch the second 6:25 instruction 6:27 at the end of this video we're gonna 6:29 provide you with the answer 6:34 so let's talk a second about programs 6:37 that branch 6:40 on the left here we have a very simple 6:42 piece of pseudo code 6:44 line zero says first execute this line 6:46 of code 6:47 line 1 now execute this line and then 6:50 line 2 says 6:52 if the age is greater than 18 then 6:56 we're going to execute lines 3 and 4 6:58 otherwise 6:59 we're going to execute lines six and 7:02 seven 7:03 so this program doesn't necessarily 7:05 follow strictly in sequence from line 7:07 zero through to seven there's a chance 7:10 here the program may branch and jump 7:14 around 7:16 so we're going to pretend that this 7:17 program has been loaded into memory 7:20 each line of code on the left here has 7:23 ended up 7:24 as a location in memory now this is not 7:27 strictly how this would happen in this 7:28 one-to-one way 7:29 but for the purpose of example it's 7:31 absolutely fine 7:35 so the program counter starts by 7:37 pointing to memory address zero 7:39 and we fetch the first instruction 7:41 decode it and execute it 7:44 it then updates and tells us the next 7:47 instruction 7:48 is zero zero zero one because remember 7:50 the program counter is being incremented 7:52 so we fetch it decode it and we execute 7:55 line one of our program 7:59 we then fetch line two which in binary 8:01 is one 8:02 zero 8:06 now at this point depending on what 8:10 happens during the execution 8:11 of line two the program may be required 8:15 to fetch line three from memory or 8:18 line five from memory 8:25 so let's look at how this actually works 8:27 because we've said the program counter 8:28 simply gets incremented 8:31 well in the current instruction register 8:33 we have an instruction with the op code 8:36 0 1 1 0. 8:41 now when we look this up in the decode 8:43 unit we discover that this 8:45 code means branch always 8:51 this replaces the value held in the 8:54 program counter 8:56 with the contents of the operand that's 8:58 the second part of the instruction 9:01 from the current instruction register so 9:03 this case 9:04 one zero zero one 9:09 now when the next fetch cycle begins the 9:12 program counter is obviously checked 9:14 and as its contents have been previously 9:16 updated to a new memory location 9:19 and not simply incremented the program 9:22 effectively is able to jump 9:24 around memory 9:28 so having watched this video you should 9:30 be able to answer the following key 9:32 question 9:33 how does a cpu work 9:39 okay so let's um answer the question we 9:41 posed 9:42 earlier what did that program actually 9:48 do 9:50 so this is the first fetch to code 9:53 execute cycle 9:55 and this is the one that we ran through 9:57 in detail earlier 9:58 it effectively loaded the contents of 10:01 the memory 10:02 stored at location location0101 10:05 into the accumulator in other words 10:08 the dna number 3 is moved 10:11 from memory into the cpu 10:18 we then proceed onto the second fetch 10:20 decode execute cycle 10:23 now this one adds the contents of memory 10:27 located at 0 1 1 0 10:30 to the current contents of the 10:32 accumulator 10:34 so in other words the dna number one 10:38 because that's what's stored at address 10:40 zero one one zero 10:43 is added to the number three that was in 10:45 the accumulator 10:46 the results are stored back over the 10:48 accumulator 10:49 so effectively we've done three plus one 10:53 equals four 10:58 the third fetch to code execute cycle 11:00 stores the contents which are in the 11:02 accumulator 11:03 into memory location zero one one one 11:07 and that's because the op code the first 11:09 part of this current instruction 11:10 zero zero one one is the command to 11:13 store when we look it up in the decoder 11:15 unit 11:16 so in other words the result of the 11:17 previous calculation three plus one 11:19 equals four 11:20 is now written back into main memory 11:28 the fourth fetch decode execute cycle 11:30 outputs the contents of the accumulator 11:33 remember they were copied into main 11:34 memory but they're still held in the 11:35 accumulator 11:37 so in this simple abstraction the number 11:40 four is now 11:41 output to the user so they can see the 11:43 result of the calculation 11:49 the fifth and final fetch code execute 11:51 cycle 11:52 brings a halt to the current program 11:58 so this very simple program which has 12:01 five 12:02 fetch decode execute cycles has 12:04 performed the calculation 12:06 three plus one is then stored the result 12:09 in main memory 12:10 and displayed the result four to the 12:12 user 12:13 and in a high-level language this may 12:15 look something very similar to the 12:17 following two lines of code 12:20 sum variable equals num1 plus num2 12:24 print sum to the user 12:27 so you can start to get an appreciation 12:29 here of how the high level code you 12:32 write actually ends up being fetched 12:34 decoded 12:35 and executed inside a processor 12:38 of course your processor is doing 12:40 billions and billions of these 12:42 operations a second 12:43 which when you think about it is really 12:45 very impressive 12:52 [Music] 13:03 you. make 10 questions for a standerd of a level