Very good evening to all of our friends and welcome to the Hindu News Analysis of Shankar IAS Academy for the date 10th November 2020. The list of the relevant news articles taken up for today's discussion from five different editions of the Hindu newspaper along with their page numbers is given here for your reference. Also, the handwritten notes in the PDF format and time stampings for all the news articles taken up for today's discussion is given in the description box and also in the comment section for the best interest of the viewers. Let us now begin our news analysis for today. Now, this discussion is based on this news article and an editorial that mentions about the directions issued by the National Green Tribunal. See, the NGT directed that there would be a total ban on sale or use of all kinds of firecrackers till November end in all cities and towns across the country where the average ambient air quality fell under the poor and above category in November 2019 that is the previous year. In places where the ambient air quality fell under the moderate or below category, only green crackers would be permitted for sale and also the timings for bursting them would be restricted to two hours. So, what are these categories? Know that these categories form the National Air Quality Index or simply NAQI. So in this regard, let us see about the NAQI and related initiatives that are present in India to curb the menace of air pollution. The syllabus relevant for this analysis is highlighted here for your reference. Please go through it. First, let us start with NAQI or National Air Quality Index. See, it was launched by the Ministry of Environment, Forest and Climate Change in October 2014 and AQI acts as one number, one colour, one description so that even a common citizen of India can understand the impact of air pollution in the place where they live in. And through this, the citizens can easily judge the air quality within their surroundings. Know that AQI is released by the Central Pollution Control Board. Eight pollutants will be monitored under AQI. They are the particulate matter 10 or PM10, then particulate matter 2.5 or PM2.5, then nitrogen dioxide, sulphur dioxide, carbon monoxide, ozone, ammonia and lead. And as you can see in this table, there are six air quality index categories which are good, satisfactory, moderately polluted, poor, very poor and severe. And as you can see here, one colour is assigned to each of these categories. And based on these categories only, the National Green Tribunal has directed for ban or regulation of firecrackers sale now. And you can also refer to the possible health impacts that can happen to an individual for each of these air quality index category. And in this regard, the National Green Tribunal has emphasised on sustainable development over employment and revenue losses to the fireworks industry. And as per this news article, the National Green Tribunal has also directed the state pollution control boards all over India and also the committees to take special initiative to contain air pollution by regulating all the other sources of pollution apart from the firecrackers ban. And this is because the pollution can aggravate the COVID-19 pandemic. Now, if you look at this editorial, though it has welcomed the decision of National Green Tribunal, there might have been some room for a limited quantity of firecrackers such that the fireworks industry is not affected. See, this editorial has also highlighted the concerns of the fireworks industry of Shivakasi region of Tamil Nadu that produces almost 90% of India's firecrackers. And it has an astonishing 2,300 crore of output. The editorial suggests that a transparent compensation scheme for workers and suitable relief for producers may be necessary in the short term. And the long-term solution is to diversify the economic activity in the Shivakasi region, such that the reliance on firecrackers is reduced. Also, the editorial has mentioned about the National Clean Air Program. In this regard, let us see some other initiatives that are present in India to curb air pollution. And this includes the National Clean Air Program. So, let us start with SUFFER or the System of Air Quality and Weather Forecasting. See, this initiative was introduced by the Ministry of Earth Sciences. The SUFFER system is developed by the Indian Institute of Tropical Meteorology, which is located in Pune, along with the India Meteorological Department or IMD, and the National Centre for Medium Range Weather Forecasting. See, SUFFER is implemented by collaborating with local municipal corporations and various local educational institutions and governmental agencies in the metro cities of India, where the air quality data is monitored. And as the name indicates, SUFFER will provide location-specific information on air quality in near real-time and it also forecast one or three days in advance. So, this is for the first time in India. And the AQI parameters which we saw previously are considered for reporting the air quality by SUFFER. And based on these values, the advisories for human health are also released by the SUFFER. See, the pollutants that are mentioned in SUFFER are PM1, PM2.5, PM10, ozone, carbon monoxide, then nitrogen oxides like nitrous oxide and nitrogen dioxide, then sulfur dioxide, black carbon, methane, non-methane hydrocarbons, volatile organic compounds, benzene and mercury. And the monitored meteorological parameters in SUFFER include ultraviolet radiation, rainfall, temperature, humidity, wind speed, wind direction and solar radiation. So, this is about SUFFER. Apart from NAQI and SUFFER, we also have the National Air Monitoring Program or NAMP in short, which is executed by the Central Pollution Control Board. See, these are the objectives of the National Air Monitoring Program. To determine status and trends of ambient air quality, then to ascertain whether the prescribed ambient air quality standards are violated, then to identify non-attainment cities, then to obtain the knowledge and understanding necessary for developing preventive and corrective measures, then finally to understand the natural cleansing process undergoing in the environment through pollution dilution, dispersion, wind-based movement, dry deposition, precipitation and chemical transformation of pollutants generated. So, under the National Air Monitoring Program, four pollutants have been identified for regular monitoring at all the locations. And they include sulphur dioxide, oxides of nitrogen as the nitrogen dioxide, then respirable suspended particulate matter that is RSPM, which is nothing but PM10 and then fine particulate matter which is PM2.5. I know that the monitoring of meteorological parameters such as wind speed, wind direction, relative humidity and temperature were also integrated with the monitoring of air quality. So, this is the prescribed air quality standards under the National Ambient Air Quality Standards or NAAQS. You can see it here. And the monitoring is being carried out with the help of the Central Pollution Control Board, then State Pollution Control Boards, Pollution Control Committees and National Environmental Engineering Research Institute which is located in Nagpur. And the Central Pollution Control Board coordinates with these agencies to ensure the uniformity and consistency of air quality data. And it also provides technical and financial support to them for operating the monitoring stations. And as we have seen now, one of the objectives of the National Air Monitoring Program is to identify the non-attainment cities that have not met the targets. And as of now, there are 122 non-attainment cities across India. Now the next initiative which we are going to see is the National Clean Air Program. And know that it was launched in 2019. So, NCAP will be a mid-term five-year action plan with 2019 as the first year. And the goal of the National Clean Air Program is to meet the prescribed annual average ambient air quality standards at all locations in the country in a stipulated time frame. The national level target for 20-30% reduction of the PM2.5 and PM10 concentration is by 2024. And here 2017 is taken as the base year for the comparison of the concentrations. And know that 102 cities across India have been chosen under this program. Now, these are the objectives of NCAP. Please go through it. It includes to augment and evolve effective and proficient ambient air quality monitoring networks across the country for ensuring comprehensive and reliable database. And it is also to have efficient data dissemination and public outreach mechanism for timely measures for preventing and mitigating the air pollution and for inclusive public participation in both planning and implementation of programs and policies of the government on air pollution. And finally, to have feasible management plan for prevention, control and abatement of air pollution. So, these are some of the programs for curbing the menace of air pollution. And see, air pollution is very high in northern India, especially during the winters. And the main reason is the climatic conditions that prevail in the northern India during this season, such as low temperature and low atmospheric circulation. And apart from this, there are anthropological activities such as stubble burning, burning of firecrackers during the festival season and also industrial activities that all aggravate air pollution. Severe air pollution and its effects are seen especially in urban areas such as the National Capital Region of Delhi. So, in order to prevent and control the air pollution in the National Capital Region, in 2017, the Centre notified Graded Response Action Plan or GRAP. And under GRAP, various measures depending on the pollution level will be taken by the concerned authorities. And you can see it in this picture. So, to summarize, we have seen about the National Air Quality Index, then the system of air quality and weather forecasting or SUFFER, then National Air Monitoring Program, and finally about National Clean Air Program and Graded Response Action Plan. So, these are some of the initiatives in India in order to curb the menace of air pollution. With this, we'll move on to the next news. Let us take up this opiate article which was written by an Indian Trade Service Officer. Here, the author focuses on the growth story of Bangladesh and Vietnam and the lessons India can learn from both these countries. The syllabus relevant for this analysis is highlighted here for your reference. Please go through it. Know that Bangladesh is the second largest apparel exporter in the world, only after China. Similarly, Vietnam's exports rose from 83.5 billion US dollars in 2010 to 279 billion US dollars in 2019. So, what could be the reasons for this? See, coming to Vietnam, its open trade policy, inexpensive workforce and generous incentives to foreign firms in order to do business in Vietnam are some of the major factors. And see, Vietnam also has free trade agreements with most of its trading partners like the US, the European Union, China and India. So, this ensures that additional import duties are not imposed on Vietnam's goods. Similarly, Vietnam's domestic market is open to its trading partners with minimal barriers. Let us understand this with an example. Know that recently, Vietnam concluded a free trade agreement with the European Union and this agreement will ultimately scrap the duties on 99 percentage of the goods traded between the two sides. Also, doing business in Vietnam will become easier for European companies. That means they will be able to invest and also pitch for government contracts with equal chances to the local competitors. And in the last decade, large brands like the Samsung, Nike and IKEA have moved their manufacturing base to Vietnam. And in 2019 itself, Vietnam received more than 16 billion US dollars as investment. So, this is what helped Vietnam's exports to grow by a massive 240 percentage in the past eight years. Now, coming to Bangladesh, its strength is the export of apparatus, which is led by low cost of production and a cheap but skilled workforce. Know that the trade has created wealth and employment in these countries and lifted millions above the poverty level. So, what can India learn from Vietnam and Bangladesh? See, the author says that Bangladesh models stresses on the need to support large firms for a quick turnover. This is because large firms are better positioned to invest in brand building, meeting quality requirements and marketing. It will also help small firms to grow as they will be the suppliers for the large firms. And apart from this, India could set up sectorial industrial zones with pre-approved factory spaces. And this would enable a firm to start operations in a few weeks and that too without spending much time on searching for the lands and getting approvals. So, this would improve the ease of doing business and promote manufacturing and investment in our economy. But there are some issues as well. India cannot follow the extreme liberal economic policies of one party dominated Vietnam. This is because such policies do not offer protection to the farmers or local producers from imports. Not just that, Vietnam and Bangladesh are heavily dependent on their exports. For example, Vietnam's export to GDP ratio is 107 percentage. Whereas for US it is just 11.7 percentage and for Japan it is 18.5 percentage and India says 18.7 percentage. And also note that heavy dependence on exports makes the country vulnerable to global economic uncertainty. So, what India needs is an organic economic growth. For this, we need a mix of open trade policies, balanced free trade agreements and we should also restrict our unfair imports and have a healthy mix of domestic champions as well as multinational corporations. Finally, let us see about the Economic Complexity Index or ECI which is mentioned in this op-ed article. See the Economic Complexity Index is released by the Harvard University's Growth Lab, which is a centre for international development works to understand the dynamics of growth. And see this index ranks a country based on how diversified and complex its manufacturing export basket is. That means countries can improve their ECI by increasing the number and complexity of products they successfully export. The author says that ECI rank for India is 43. It is for 79 for Vietnam and 127 for Bangladesh. So, this indicates that India's export basket is more diversified compared to Vietnam and Bangladesh. So, in order to have a healthy and balanced economic growth, we should diversify our exports more by incentivising them and at the same time we should also ensure that we have a good industrial strength and also that our domestic market is healthy as well. And for this, as told before, we should have more balanced trade agreements than pro-business policies and restrictions on unfair imports etc. So, this is all about this op-ed article. With this, we'll move on to the next news. Now, let us take up this editorial which talks about the Indo-US bilateral relations in the wake of Joe Biden's victory as the President of the United States of America. In the last two days, we have covered various aspects of foreign policy like India-Iran relations and the US role in climate change etc. So, today we will see how foreign policy of Biden may impact India. The syllabus relevant for this analysis is highlighted here for your reference. Please go through it. See, for India, there are two foreign policy issues which are of great concern and interest. One is China and the other is Iran. And for the world, the relations between the United States and China may be the relationship of the greatest consequence. But for India, the most consequential relationship is not with the US, but with China. See, we know that in Trump years, the India and US became very close and India even signed all the four foundational agreements with USA, General Security of Military Information Agreement, then Logistics Support Agreement, then Communications Interoperability and Security Memorandum of Agreement and finally, the Basic Exchange and Cooperation Agreement for Geospatial Cooperation. And it is also to be noted that India bought billions of dollars worth of military hardware from US instead of Russia. And with respect to China, India resisted in converting the Quad into a military grouping like NATO, mainly not to make India-China relations hostile. But how far this Quad grouping will be successful in containing China is always a worrying question to Indian government. And though we are resisting from making Quad a military alliance like NATO, the US is trying hard to formalize and institutionalize it by adding more members from South Asia and also bringing military dimension to Quad. In other words, the US wants Quad to be institutionalized and expanded by adding additional members such as Taiwan and South Korea. Here the author says that in future, India will be forced to agree to some form of military alliance in South Asia because the other three countries which are US, Japan and Australia are already in strategic alliance with one another and also with the US. Here we should remember that all these initiatives such as the Quad are maritime agreements and do not have much bearing on our disputes with China, which is a continental or land border dispute. The author further says that no external power would want to support India in case of major hostilities with China. On the other hand, if there is a major issue in the South China Sea, the other members of the Quad would expect us to join them in fighting China. And we know that it is far from our borders. As a few policy makers suggest, if Mr Biden adopts a more lenient approach towards China, then India may find herself in a difficult position to counter China. And we know that US is also known for swiftly changing its policies. So if US wishes to get closer to China to reduce tensions, India will be left alone in our confrontation with China. With India already having a permanent enemy in the form of Pakistan, we do not want China to be permanently hostile to us. And this is because it will absorb huge resources, human and material. So smooth bilateral relations with China is more beneficial to India. Next we'll see the issue with Iran. See what happens in greater West Asia will always remain a concern to us, since we have huge stakes in that region. We know that under Trump, US and Iran relations went too hostile and US even withdrew from the JCPO agreement and imposed sanctions on Iran. See the Joint Comprehensive Plan of Action or JCPOA was signed in 2015 and it imposes restrictions on Iran's civilian nuclear enrichment program. And China, France, Russia, the United Kingdom and the US, which are the five permanent members of this UN Security Council, negotiated this agreement alongside Germany. And together they were known as the P5-plus-1. It may be difficult for Mr Biden to quickly reverse Mr Trump's policy towards Iran. But know that Joe Biden was the vice president of the US when JCPOA was signed. So it is expected that Mr Biden may engage with Iran in talks and negotiations to reduce the tensions in the region. We should also hope that the new president will not maintain the harsh unilateral sanctions that Mr Trump imposed on Iran. If sanctions are continued, we can't buy Iranian oil or sell our pharma and other goods to Iran. And the government may also feel less constrained in investing openly in oil and other infrastructure projects in Iran, including the rail project in which the Indian railways construction limited has interest in. So the aspects of foreign policy like containing China, then US policy on Iran as well as US role in climate change are the current hot topics across the world. So as Indians, we hope that the US should act more responsibly when it comes to climate change and maintaining stable relations with Iran and China. So this is all about this news article. And in this discussion, we saw how the foreign policy of the new US president, that is Mr Joe Biden, may impact India's relation with other nations. With this, we'll move on to the next news. Now have a look at this question. It is based on this news article, which is regarding the Finance Commission. See, the news is that the Finance Commission has submitted its report to the President of India with separate section on states finances. So in this context, we shall see about the constitutional provisions of the Finance Commission and then about the 15th Finance Commission. See, Finance Commission is a constitutionally mandated body under article 280 of our Indian constitution. And this finance commission shall consist of a chairman and four other members, and they will be appointed by the President of India. See, the Indian constitution authorized the parliament to determine the qualifications of the members of the commission and the manner in which they should be selected. And accordingly, the parliament has specified the qualifications for the chairman and the members of the commission through the Finance Commission Miscellaneous Provisions Act of 1951. And under this act, the chairman should be a person having experience in public affairs, and the four other members should be selected from amongst the following. First one, a judge of a high court or one qualified to be appointed as one. Second, a person who has specialized knowledge of finance and accounts of the government. And third, a person who has wide experience in financial matters and in administration. And finally, a person who has special knowledge of economics. Now, talking about the duty of the commission. See, it is the duty of the commission to make recommendations to the President with respect to the distribution of the net proceeds of the taxes between the Union and the States, which are to be divided between them, and also the allocation of shares of such proceeds between the States. And the Finance Commission can also make recommendations on the principles which govern the grants in need of the revenues of the States out of the consolidated fund of India. Then it can recommend the measures that are needed to augment the consolidated fund of a State in order to supplement the resources of the panchayats in that State. And this should be on the basis of the recommendations made by the Finance Commission of the particular State. And the Finance Commission also recommends the measures needed to augment the consolidated fund of a State to supplement the resources of the municipalities in the State on the basis of the recommendations made by the State Finance Commission. And it can also make recommendations on any other matters referred to the Commission by the President in the interests of sound finance. So generally the Finance Commission will be constituted at the end of five years or before. And accordingly the 15th Finance Commission was constituted by the President in 2017. The 15th Finance Commission was asked to make recommendations covering a period of five years from the financial year 2020-21 to financial year of 2024-25. And later it was decided that the Finance Commission will submit its first report for the first financial year that is 2021, first by November 2019. And this was because it was difficult to make projections for five years when the economy is slowing down after the structural reforms like the GST and the Insurgency Corp. And the interim report had reduced the State's share in the divisible pool of taxes from 42% to 41% for the current year after Jammu and Kashmir was made a Union territory. And now today's article says that the Finance Commission has submitted its recommendations for financial year 2021-22 to 25-26. But one important point to be noted here is that the recommendations made by the Finance Commission are only advisory in nature and not binding on the government. Hence, it is up to the Union government to implement its recommendations on granting money to the States. Next, the President lays the recommendations of the Finance Commission before both the Houses of the Parliament along with an explanatory memorandum on the actions taken on its recommendations. And once the report is tabled in the parliament, we will get to know more about the new recommendations. So we might be seeing more about news articles related to the Finance Commission in coming days. So this is all about Finance Commission. Now see this question. Consider the following statements. Finance Commission is a permanent constitutional body. See, this statement is wrong. Even though it is a constitutionally mandated body, it is not a permanent body and it is usually constituted at the end of five years or before. Now the second statement reads, The members of the Finance Commission are appointed by the Prime Minister on the recommendation of Appointments Committee of the Cabinet. See, this statement is also incorrect. The members of the Finance Commission are appointed by the President of India. So in this question, we are supposed to identify the correct statement or statements here. Both the statements are incorrect. So the correct answer is option D neither one nor two. With this, we'll move on to the next news. Now have a look at this question. It is based on this news article which talks about the Competition Commission of India probe on Google abusing its dominant position in the digital market. It is alleged that Google has abused its dominant market position primarily with regard to its digital payments application that is Google Pay. So let us discuss in detail about the Competition Commission of India and specifically the Section 4 of Competition Act. First of all, let us understand about the Competition Commission of India. See, it was established under the Competition Act of 2002 and it comes under the Ministry of Corporate Affairs and CCA consists of a chairperson and not less than two and more than 10 other members. Coming to the qualification, the chairperson and the members shall be a person of ability, integrity and standing and who has been or is qualified to be a judge of a High Court or they shall have special knowledge and professional experience of not less than 15 years in international trade, economics, business, commerce etc. And know that they are appointed by the center based on the recommendations of a selection committee and this committee is chaired by the Chief Justice of India or his nominee. It also includes the secretaries of the Ministry of Corporate Affairs and the Ministry of Law and Justice. Then two experts from international trade, economics, business, commerce etc. Now coming to the duties of the Competition Commission of India, its priority is to eliminate practices which are having adverse effect on competition and to promote and sustain competition. It shall also protect the interests of the consumers and ensure freedom of trade carried on by other participants in markets in India. See, an important section of the 2002 Act subject to 2007 amendment is section 4. It is about preventing abuse of dominant position. Here, dominant position means a position of strength engulfed by an enterprise in Indian market and this position enables it to operate independently of the competitive forces prevailing in the relevant market. In this case, it is Google and we all know about the dominance of Google and its products in the digital market. So, it is clear that this dominant position also affects its competitors or consumers or the relevant market in its favor. So, regulating their predatory activities is essential to ensure fairness in the market and here section 4 clearly states that no enterprise shall abuse its dominant position. See, there shall be an abuse of dominant position if an enterprise directly or indirectly imposes discriminatory condition in purchase or sale of goods or services and this also includes predatory prices. Here, predatory price means the sale of goods or services at a price which is below the cost of production of the goods or services and this is done with a view to reduce the competition or to eliminate the competitors. So, this is all about competition commission of India. Now, see this question with respect to competition act of 2002. Consider the following statements. An enterprise in Indian market is said to enjoy a dominant position if the position enables it to operate independently of competitive forces prevailing in the market. Yes, this statement is correct and the second statement reads an enterprise is said to impose predatory price if it sells goods at a price below its cost of production to reduce competition in the market. Yes, this statement is also correct. So, in this question we are supposed to identify the correct statement or statements. Here, both statements are correct. So, the correct answer is option C both 1 and 2. With this, we have discussed all the relevant articles from today's newspaper. Now, let us move on to the practice questions discussion based on today's news analysis. Now, see this first question. The national air quality index is released by which of the following? Here, the correct answer is option B central pollution control board and see the second question. Consider the air pollutants PM10, PM2.5, sulphur dioxide and nitrogen oxides. Which of the above mentioned air pollutants are targeted under the national clean air program? See, we have seen that PM2.5 and PM10 are targeted under the national clean air program and the national level target is for 20 to 30% reduction of PM2.5 and PM10 concentration by 2024. And the base here taken for the comparison of concentration is 2017. So, the correct answer is option A 1 and 2 only. Now, see the third question. Consider the following statements regarding the economic complexity index. See, it is a two statements question. The first statement reads, it ranks a country based on how diversified and complex its manufacturing export basket is. Yes, this statement is correct. Now, the second statement reads, it is released by the World Economic Forum. See, this statement is incorrect. See, we have seen that the economic complexity index is released by the Harvard University's Growth Lab. Here, we are supposed to identify the correct statement or statements. Statement 1 is correct and statement 2 is incorrect. So, the correct answer is option A 1 only. Now, we have this means practice question. Please write your answers and post it in the comment section. Our feedback will be given in a reasonable time frame. So, friends, with this, we have come to the end of analysis of all the news articles taken up for today's discussion and also the discussion of practice questions. If you like this video, please press the like button, comment, share, and do subscribe to Shankar Iyer's Academy YouTube channel for more updates related to civil service preparation.


okay I have a genuine question that I need someone to answer for me so my very first boyfriend I don't even count him because we didn't date that long but you know I f*** with him I liked him he cheated on me and it wasn't until after he cheated on me where I was like oh my god like I like him you know I love him my second boyfriend was my longest relationship and my last relationship I remember somewhere in the middle he like texted his ex and I was like oh my god it wasn't after he texted his ex where I really started f***ing with him and then we broke up and it wasn't until he stopped giving me attention when I was like I love this man he was my first love but when I was in a relationship with him I didn't even see long term with him like I liked him but it wasn't like that so my question is what does that mean for me what is the underlying issue why don't we f*** with guys more when they do me so I did this thought experiment on what the opposite of a patriarchy would look like and came up with a really insidious thought experiment the first is I took away all genuinely effective birth control from men and then gave them no reproductive rights after conception gave them the bulk of the dull dirty and dangerous jobs and some ridiculous percentage of workplace deaths like 97% made them feel so disposable that four to five hundred percent more men would commit suicide than women and in the cases of divorce a thousand percent stigmatized their sexuality and their ability to express their emotions and then I gaslight him and say that any men who would speak out about this hates women or is a misogynist and it would wait wait a second oh my sugar daddy sports cars two years old so we decided to trade it in for a newer model just like he's going to do with me when I turn 30 when we arrived to the Porsche dealership he had his eyes set on the white car because it reminded him of my skin before I get a spray tan all pasty and pale though I had my eyes set on the bright orange car to represent the love I have for him until it burns out just like his money he saw no difference in the colors because he is colorblind so I went to the car to pout until I got what I wanted to make up for it he took me a laser hair removal so I could be a naked mole rat in March 2020 I broke up my partner and then two days later planned to go to Amsterdam with a girl from Tinder she said she went to the University of Leeds she said she was some Australian girl only here for a year or something like that and that she was going on holiday in Amsterdam I said it and I booked a ticket people wearing face masks and stuff even back then so I fly there by myself he's supposedly already out there when I land I message her and she's like yeah come and meet me and when I get to Amsterdam City she blocks me I've just flown to a different country to go on a date and I've been stood up not only did I get stood up right but I was staying in a hostel because I'm cheap bastard with a load of Italian people who all had very bad coughs and when I got back to the UK I also had a very bad cough I actually just killed my baby I'm popular opinion I got my master's last year I started paying on my student loans I consider myself to be a pretty ambitious person I don't have credit card debt my cards paid off I haven't bought a house yet but I am I don't think about the student loans I don't give them a second thought I make whatever the minimum monthly payment is and I live my life I feel like this is gonna come back to haunt me but I don't care I don't care at all sometimes I think it's just cuz I don't have the mental capacity to like process that I owe nearly a hundred thousand dollars in loans whatever it is I don't give a shit I don't I don't care guys I am blown away my buddy from high school sent me this on Facebook and this is literally my my 10th grade English high school teacher Mrs. Robinson is on TikTok and has an only fans are you kidding me I can make all of my my high school fantasies come true so let's talk about why this super straight nonsense is problematic first of all being super straight isn't really real like Antifa Cog said if you find women attractive then you probably also find trans women attractive and saying that you prefer someone assigned female at birth like this trans man or this trans man doesn't really make much sense if you're straight as someone who's attracted to men I've been attracted to trans men because they're men and Natalia preference is totally different you can prefer a kitty over a cucumber if you're attracted to a trans woman have sex with her and it's going really great you like her and then you find out that she's trans and that changes how you think of her that indicates you've some internalized transphobia that feeling alone does not make you a bad person but what you choose to do with that feeling can make you a bad person so working on yourself trying to figure out why you feel that way that's okay if you go back and harass that woman that makes you transphobic and a bad person and at the end of the day no one is forcing you to date trans women this whole super straight thing doesn't accomplish anything it's just a way of telling trans people that they're not wanted trans people have to go through so much you're telling me they can't just open this app without seeing an entire movement dedicated to shit on them we're gonna meet our people at a certain time in our lives this town is too small for us to meet our soulmates I'm sorry he might be one of them but like you have many soulmates throughout your whole life like that you never have one soulmate I don't care what anyone says you never have one soulmate I finally attract an alpha male who treats you like a queen before I tell you how to do this though let's talk about what you keep attracting boys here's the thing real men want to do things for you okay they want to plan the date pick up the bill call you an uber so if you start getting all defensive and being like no no no I can do that for myself then he's gonna feel like he adds no value into your life you're gonna end up attracting people who use you so instead what you need to do is stop resisting and start receiving it's as easy as saying thank you for the smile okay so is anyone single and free tomorrow night because I have two four if they're 14 or 16 ounce revise their bone in and then I have like I think a pound a pound and a half maybe of scallops and I'll go buy vegetables and buy me a bit of okra um do you want to have like a dinner date and maybe cuddle watch some Netflix I'm gonna cook it this is so hard to find here's why I am not paying my wedding off early so what I mean is that we are paying for our wedding in cash the first deposit is due today and the team emailed me and said hey do you want to just make the deposit amount that is due which is like five thousand dollars or do you want to make the full amount it might be easy to think well might as well I have the money might as well make the full amount might as well get it taken care of but but here's the reason why I'm not doing that the rest of the amount due is fifteen thousand dollars don't come at me for how much I'm spending my wedding mind your business if I were to pay that off today cool it's done with but the alternative option is to keep that money because it's not due until next year and put it into a high yield savings where I'm averaging about 1.9 percent let's round it up and say two percent so over the next year by holding on to that money before making that payment I'm making an extra 300 which is why you should open a high yield savings account if you are in a sexless marriage or relationship this is just a reminder that well yes you cannot force your significant other to sleep with you or be intimate with you nor should you course them into it because it's their body they have autonomy over it it goes both ways meaning if you are in a monogamous relationship and they're saying that you can't see other people but they're also not sleeping with you they are now also controlling your body so it's perfectly acceptable to leave the relationship if they're not willing to work on it


You to who? Team keeping clean. Hey, what's going on? It's a engraving here with another video and man Well, what a day today has been And it just got that much more crazier Earlier the Raven sign Nate McCrary to a future reserve deals like I yeah running backs We run running backs been rough this year. Our main guys were hurt So this gives us a nice insurance policy just in case Then before that they signed Keevon Seymour to a future reserve deal or cornerbacks been hurt Well, this gives us a nice insurance policy just in case but now back again Because he was drafted by the Ravens They drafted them in the fifth round from Michigan So shout out to the hardball hardball connection.  So we'll see what happens now Just to give you a quick back story on been Mason just in case y'all forgot He was a fifth round draft picked by the Ravens and they cut him and They didn't come out and flat out say it, but you kind of figure like they weren't gonna keep two full backs on the roster They weren't gonna do that. So we knew that he was well We thought he was headed and I think the Ravens thought he was headed to the practice squad and So they drafted him they cut him and probably in hopes that he would clear waivers and then he will go to the practice squad But he didn't come back He did not come back and I remember the presser I will never forget the way that John Harbaugh came out there in that presser because you knew he was upset He was upset with been Mason upset And he was like, oh you could ask him Because they asked hey, what's going on with been Mason? We're having a been Mason. You could ask him you can ask him And when I'll say something like that. Oh, yeah But anyway, they cut him probably in hopes that he will come back to the practice squad So he could stay there, but then he went and signed with the New England Patriots practice squad and That was that that was the end of the two full backs in Baltimore So then now this this this whole situation It kind of makes you wonder about two huge things when it comes to the Baltimore Ravens two very very big subjects Because they've been quiet. They've been extremely quiet like we have not heard a peep out of the Ravens for a long Time they gave us that in the year presser. Well, it wasn't it will kind of the end of year player presser We haven't heard from the front office anything like that But they gave they gave us that into the year player presser and after that Not a peep Not one peep But this makes you kind of I mean a lot of our questions had already not necessarily been confirmed But this kind of confirms it in a way because One would think that if the Ravens were going to go in a different direction on Offense then they would probably eliminate the full back position We know there's they will still be able to run the ball, but they will probably eliminate the full back position If they were going to be really opening up the offense and really just doing some new things But with them signing been mason to a future reserve deal This is not it's not gonna be any crazy guaranteed money and this does not mean that he would even make the team Nothing is guaranteed when it comes to this deal but It kind of lets you know like hey Greg Roman ain't going nowhere and I don't really know anybody who really anticipated Greg Roman going anywhere Especially with how quiet the Ravens have been even though I've seen some people say well Maybe the Ravens are trying to figure out a way. They still got stuff going on in the building who knows But we just got to wait and see but to me This gives me a nice reminder that a G row is here to stay this year and okay Cool, we already talked about what the Ravens need to improve on with G row stand. That's fine But something else that it also lets people know Yeah, I mean it ain't it ain't over till it's over but Patrick record This kind of lets you know like that could be it for project Pat when it comes to the Ravens Because project Pat undrafted rookie free agent defensive tackle They flipped in the full back so they changed his position It worked out this time which was great for him Which was great for the Ravens and then he ended up earning a second contract It's like all right Pat record would keep him project Pat and it's crazy because I feel like he just got that contract like yesterday This contract went by it flew by literally flew by But with Patrick record, I just I didn't envision a scenario where you pay a fullback a third contract I just I didn't see that happening. I really didn't and As far as a fullback safe for instance because again been Mason is not guaranteed to remain on the roster Say for instance, if they don't even keep been Mason You could use a tight end at fullback and that that'll save your roster spot Especially on game day when you can only have what 46 active that'll save you a spot there So you can use that for somebody else Maybe James pro-shame might be active for Anyway Anyway But yeah, so been Mason is back Hope it's not too awkward like like him and him and how about like I know John They had to get on a three-way FaceTime with John Ben Mason and Jim Harbour there There's no way that they had to have got on that FaceTime call with the three of them So they could really mend this relationship between John Harbour and Ben Mason because John Harbour is probably like nope. I don't want him back. EDC was like not not John. Now John look We we're probably not gonna sign back record. Let's bring back been Mason. He's a little familiar with us and what John like. Nope. No He said he was gonna come back. We had a handshake deal and he didn't honor it I don't want him then all of a sudden you heard that through the little FaceTime noise And it was Jim. It was Jim and EDC said look It's Jim and then they then they brought in been Mason to him. They make some light look man I just wanted to go play for my hometown team. I grew up a Patriots fan Always been rocking with them. I just wanted to see what that life was like on the opposite end of just not just being a fan But being a player for the New England Patriots playing for Bill Bell I just wanted an opportunity for that and I took it I had to Don't know when that opportunity is gonna come again That's it. So they squashed it and now been Mason. He's back with the pack Well, I shouldn't say pack because that's something like Packers, but you get what I meant So welcome back Welcome back Now moving forward We got a lot of hopes for this Ravens this 2022 team We have hopes and we also have Expectations and the two they can be different from one another Now we would hope that our expectations in the meeting our hopes. I mean, excuse me our hopes Well, no, what am I saying? We would hope that our Expectations. Yeah, reach our hopes. There we go The brain fart there. So because well, what a lot of us expect is not what we hope happens We but Man, this this this whole offseason is just it's crazy and this is it's not even fully started yet That's the craziest part about this offseason. It's not even fully started yet We haven't even reached free agency.  That's of course in the middle of March free agency Um, but man Ravens they uh, they got a lot of eyes on them and With them not saying anything at all It makes it seem like they're saying a lot all at the same time, but anyway, we'll see What happens next? Cuz hey, you never know Patrick.  Go test the market and see what the market is for for a blocking fallback. You can catch two though But what's the market for a blocking fallback because with juice juice was a nice fallback But he wasn't just a blocking fallback juice. He he could move too. He can move He's like a he was like a little short tight end The juice. Hey, that boy is nice man. And I think what that was his last game as Raven, right? Was it the uh? No, it wasn't the Steelers game when he um when we took the lead No, that oh, that was it. No, that was it. I think yeah Was that game y'all remember the game I'm talking about when um When the Ravens were down and they drove down the field Then they did like a draw to cow use check He took the ball off He ran somebody over and he kind of like stumbled then got his balance back and ran it in for a touchdown Was that week six that week 16 or week 17 of that season because I don't remember but then I think the Steelers they ended up Driving down the field and they end up taking a lead after that. I believe because I'm not yeah We didn't we didn't win that game. We took the lead, but we didn't win I just don't remember if it was at the steelers of the Bengals. I Don't even remember what team it was. I don't remember what year it was, but I remember that being one of cow juice checks one of his Last and one of his best plays all in one So we're gonna see man. Like I said, we're gonna see but like Ben Mason Isn't anymore when it comes to being a Baltimore Raven we out Oh But it's all season just been it just been so fun already man already and we even get started yet I love it team. Keep it clean


I'm very happy to be able to join you all today and I appreciate the opportunity. So I, in preparing for this presentation, I spoke with some of the folks at the Blue Cross Blue Shield Association. And the idea of this presentation is to give you a sense of an approach to genetic testing, like testing strategies. I have lots of clinical examples. I touch on next generation sequencing panel, but it isn't necessarily the focus of this discussion and I think you perhaps will be having another talk on that as well. So let me just move forward here with the slides. So I wanted to give, I know you've had, this is now your seventh webinar on this topic. Very briefly, just to kind of set the stage, let's a couple slides on some basic principles around genetic testing and then jump into some case examples to try and illustrate the pre-analytic phase or process that is involved in thinking about selecting a genetic test. This is a slide showing some common reasons for genetic testing. I think you all are probably familiar with this. I'm going to focus my comments today on arriving or trying to arrive at a diagnosis of a genetic disorder and what I mean by that is an inherited single gene Mendelian disorder. I'm not going to talk about multifactorial conditions and gene associations, et cetera. There are lots of reasons to try and make a genetic diagnosis. Maybe it's a patient who's already had signs and symptoms and you suspect a specific condition. So ordering a genetic test or test is confirmed as a diagnosis and many talk about ending that diagnostic odyssey and sometimes there are definite changes in management downstream from that. And then the other area is if there's a family with a suspected genetic condition and there's an unaffected family member for whom understanding their predisposition would be helpful in guiding surveillance, prevention, management options. Prenatal diagnosis is another subset of diagnostic workup. It's just in a fetus. I'm not going to touch on any of the examples today around that. Carrier screening for recessive conditions to inform reproductive decisions. I don't have examples for that today. And then there's a whole area of pharmacogenetics, pharmacogenomics to inform response to certain treatments and to inform prognosis of either an inherited or acquired condition. Genetic testing is pretty fundamental to diagnosis, although it's not always necessary, but it is being used I would say more and more as we discover more and more of the genes that cause Mendelian disorders, of which I think now there are about 6,000 to 7,000. We've identified, I think, 2,500, 3,000 of the genes contributing to those conditions. There are different types of genetic tests. I think most commonly we all think of molecular genetic tests that interrogate DNA or RNA and those assess a genotype. We also look at a higher level and look at chromosomes and order a karyotype. And then, of course, we can look at metabolites or proteins that are the product of these genes or involved in the biochemical processes. Today, there's a little bit of noise on the phone that I don't think it's me, but I wanted to make sure it's not just me hearing it. I just wanted to interject there. It's on the molecular genetic testing for the most part. Molecular techniques that I think they have heard about, sequencing is the quote-unquote old-fashioned approach where we do one gene at a time. Now we, for the last couple of years, have had massively parallel sequencing technologies. It's called next generation sequencing. This is similar in terms of it's a sequencing process, but it can be done on thousands to millions of pieces of DNA all at one time. And so we get lots of throughput, lots of output on one patient, and it improves the efficiency of testing and reduce the cost of testing. The deletion duplication is complementary typically to sequence analysis so that if the condition, the gene you're looking at, if there isn't a point mutation or involving just a few nucleotides, but larger deletions or duplications of the pterilina gene, you need to do some other tests to investigate that. On the single gene level, there's a variety of types of studies. I've listed this example here, MLPA. And then if we want to look across the entire genome, there's a range of hybridization that can look for copy number variants. And then of course we still use very often targeted mutation analysis. So this is important when there's a known mutation in a gene that's causing a disease in a family. You would like to try and exclude that in an at-risk family member for example. But there are also common mutations in genes that are for the most part based on a person's ancestry that can be tested or targeted initially. Now here I have what's called the ACE framework. This framework, I got this image from the CDC's website. And this is the analytic validity, clinical validity, clinical utility and ethical legal social issues to consider when you're evaluating a genetic test. And I know that the blues have many health frameworks when they look to the literature for evidence of these issues around validity and utility. I'm not going to go over this with you. I think perhaps you've heard about this. Maybe we could talk more about it afterwards. But I think what I wanted to point out is this middle here, this bullseye, where we have a disorder and setting. So the context is extremely important when you're trying to apply a genetic test clinically. Of course we need to understand the analytic validity, the clinical validity, the clinical utility. But it's also important when you're using it to think about disorder for what you're testing. And the setting, and I think primarily these are patient characteristics and provider characteristics. So for example, with regards to the disorder and genetics, there are common, how should I say, common tenants, common individuals that need to be considered like penetrants. If I have a gene mutation, what's the probability I'm going to develop the disease in my lifetime? Also variable expressivity. If I have a gene mutation associated with the diagnosis, what types of conditions am I at risk for? Because typically it will be more than one manifestation. So these are important things to consider. And as I mentioned, the patient's characteristics, their age, their gender, their preferences, and the provider that's involved in offering the testing, what is their expertise, how familiar are they with the condition that's of concern, but also the genetic testing technologies that can be utilized to investigate that disorder. So with that, let's see. Okay, I think this is my last introductory slide, and then we can get into some clinical cases. So this is a diagram that I've used to try and illustrate what happens in a genetic evaluation. I'm a clinical geneticist. I get referrals from primary care, from specialists to help evaluate a genetic diagnosis in a patient. And I'm a physician trained in genetics, also trained in internal medicine, and I oftentimes work together with genetic counselors, and I wanted to differentiate what the medical geneticist or clinical geneticist's role is and the counselor's role. So in this line here would be the physician's responsibility. And again, this is the more traditional model of a geneticist working with a genetic counselor, but there's also an emerging model of genetic consultation and evaluation where a non-geneticist works together with a counselor or a non-geneticist works on their own to kind of achieve these goals that I've outlined here on this slide. So I think that, again, gets back to who's providing these services. Now, so the key thing in my mind is coming up with a differential diagnosis. That's what we do in medicine. So we have to consider all this stuff over here. The medical history, family history, developmental history is sometimes very important with genetic conditions, reproductive history, habits, et cetera, et cetera. Physical exam, sometimes looking for specific stigmata associated with a known genetic syndrome, and of course reviewing labs, procedures, imaging, et cetera. Then with that information we can look to see if there are genetic tests available that could address that differential diagnosis. And maybe it's one diagnosis, one gene, or many genes, and a series of decisions that are made, or we do a panel or an ex-home. And it kind of depends. Now, the clinical decision-making really relates to, you know, how will management change? Is there a specific treatment that's available? Will there be surveillance that will be ongoing for this patient? Or are there preventive options available? And then reproductive options. If the patient is still of reproductive age, then if we make a genetic diagnosis, this could be relevant to their future offspring, and they may want to know about that and make decisions either not to have children to adopt, to use a donor sperm, donor egg, or if they get pregnant, think about prenatal diagnostic options. The genetic counseling and education side is sometimes very important. It's not always, but for complex genetic conditions, it typically is a critical piece where we consider patients' motivations for understanding a diagnosis, cultural norms, beliefs, educational level, what's going on in their family, what they've experienced. All of this comes into play in terms of what they can understand and how they relate to what this diagnosis may mean. And then when it comes to their decision-making, their preferences, values, their knowledge, risk perception, all of these things will play into their decision about having a genetic test or entering into certain intervention or surveillance programs, and it should be the shared decision. Okay, so let's... I do have a couple more slides here, I think, so introductory slides. So genetic testing errors. Lots of studies done. Genetics is no different from any other laboratory test. Most of the errors are made in the preanalytic phase before we order a test because we don't have enough information about the patient to select the right test or because we might have the right diagnosis, but we don't know enough about the genetic test and their limitations when we select the wrong test. And this results in an inappropriate... that test selection could result in, you know, a compromised informed consent process, which is very important to patients. Overutilization of tests that aren't indicated, at least to misdiagnoses, and then, of course, underutilization of indicated tests, which could result in delayed or misdiagnoses. Two cases I wanted to present that illustrate the importance of getting the differential diagnosis right. And I think you're all... as I understand physicians, clinicians, and I don't think this will be too much of a big surprise that this is a really key step, but I can't emphasize it enough, and I doesn't really get discussed enough as far as I'm concerned. So I have...this is not unusual. I'm pretty much a gatekeeper for all the genetic testing services where I work. I get referrals from physicians of all types requesting genetic testing for their patients. And here's an example of a case I recently saw, a case of a 38-year-old girl. He was referred from the gastroenterology clinic, and it said genetic testing desired. And this case was in a resident, probably, or a fellow submitted a case. He said it was discussed with the biliary attending, and they describe a patient who may have chronic pancreatitis. And they were requesting hereditary pancreatitis gene testing, requesting a panel specifically of the genes listed here. So I met with a patient. This is the family history I ascertained. So here he is at age 38. He also has some reflux, and it looks like, at least on imaging and by history, he has some pancreatitis, but never really hospitalized with acute bouts. And then his brother has, quote, pancreas problems, and I've shaded him a little lighter blue, not sure if he's similarly affected. But the father died from abdominal cancer at age 66, and we always worry about that because pancreatic cancer is increased risk in people with chronic pancreatitis. So possibly that's related. The other history that was interesting to me is there's this cousin over here with pretty early onset type 2 diabetes we clarified, but otherwise, and mom has diabetes at a later onset, but nothing else too exciting going on here. So in reviewing his labs and so forth, you'll see here everything looks pretty okay, except his renal function is not so great for a young guy with no history of any reason to have any kidney problem. But I saw, again, there's this A genesis of the pancreas, prominent side with calcifications, common bile ducts are normal, nothing else going on there, but there are these multiple bilateral renal cysts and the liver, spleen, and adrenal are okay. So in talking about that and the family history, I thought, okay, this is unusual. He's got A genesis of the pancreas. This is not acquired. It's most likely congenital. And there's that. He's got bilateral renal cysts with renal incidences and he has this maternal family history of diabetes of early onset and a first cousin. So these are the things that were, you know, that kind of popped out at me. And I thought, well, could these all be related? And I thought, well, I know something that could, you know, account for all of these. And let me go look it up again. And so I did. And I remember, yep, you were right. You know, renal cysts and diabetes of early onset. There's a condition called MODI 5 or maturity onset diabetes of the young 5. It's due to heterozygous mutations in the A10S1B gene. And it features all of the stuff that we saw. My patient doesn't have diabetes, however, but he does have this dorsal a genesis of the pancreas with pancreas and gynecological disease. And so there were a couple of other things that I found and kind of looking at the databases that might explain some of these features, but not all of them, including the hereditary pancreatitis and these other things could just be a red herring. So in thinking of a genetic therapy strategy, rather than doing what the GI doc requested, I said, you know, I think we should look into this MODI 5. I talked to the patient about it. He was on board. And if that was normal, then we could talk about testing for hereditary pancreatitis. And the test was to include sequencing and deletion duplication testing. And so it has a pathogenic mutation in the A10S1B gene. Essentially, the entire gene from exon 1 to the whole plate of research has been deleted. It's missing. So this is a huge deletion. And there are many other cases in the literature that are described that have this phenotype and are diagnosed with MODI type 5. Patient implications and management. Whatever's going on here, and has a genesis of the door sold part of the... is, I would say, due to this HNF1BG patient. He's at risk for diabetes. He's at sentence endocrine clinic. He's at risk for extrinsic function. I sent him to nephrology. He's never seen a kidney doctor. And this is likely coming from a terminal side of the family. And now we have the other family members who could ask for to determine if they have the same condition. So that was the first. Lauren, I'm going to interrupt just because there's somebody on the line who hasn't muted, and it seems to be something quite difficult to hear you. So if everybody can check, it's going to be great. Thank you. Great. This next case, Mr. SH, he's a 54-year-old male. He's referred by primary care. And the patient himself requested genetic testing. He informed his primary care doctor that his brother recently quote-unquote screened for defects due to arrhythmia, and his information is as follows. He has arrhythmogenic right ventricular cardiomyopathy. The other information that was provided is here, lots of PBCs, but no specific arrhythmia, aside from that, was known. And he has sleep apnea. And the brother provided a specific test that was performed and his obsession number, because if any family member wanted to get tested, they're going to need this number. So I met with this patient, and he was just expecting to get his blood drawn. And I said, no, no, no, I need to go over the history with you and really understand what's going on and make sure you yourself don't have similar symptoms, et cetera. So I spoke with him, and he himself, my patient is really doing really well, no cardiac symptoms whatsoever, very active. He had not had an echo, but he does have a normal EKG. And in further questioning, he offered, yes, my brother has a large heart, and my uncle said we all have it because we're all athletes, we were wrestlers. My brother's doctor recommended an ICD genetic test. And then he saw a specialist at Johns Hopkins, and he was told something different. So then we looked at the family history, and this is what I learned. So here's my patient here. He's unaffected age 54. It's his younger brother, age 46, who has this quote-unquote enlarged heart and the ARVC diagnosis. And the other history that's of concern is the father who died at 72. The family thought it was from a stroke, but it is known that he had a pacemaker and had some kind of arrhythmia. So something may be going on here, possibly paternally inherited, although hard to know for sure. So we then, I was able to get the brother's test results. The patient brought them with him, and he said this is his test report. And this is what his doctor ordered was this next-gen sequencing panel with these genes on the panel. And my brother is heterozygous for a variant of uncertain significance, so in the RYR2 gene. So I explained to the patient that this variant, the lab, is not calling it pathogenic. They don't know if it's the cause of anything. It's like it could be a polymorphism. It could be pathogenic. They just don't have enough information to really interpret it as pathogenic. And this patient, you know, it's not appropriate to test other family members who, you know, certainly those who are not affected because it couldn't change anything. It really has no clinical significance right now, this variant. We don't know enough. And so I explained that there. And the other thing is, so there's no genetic testing. There's nothing that my patient came wanting a test, expecting his blood to be drawn. I said no, there's no reason to do that. What's more important is that we really understand what is going on with your brother. You know, does he have a cardiomyopathy? What is his arrhythmia? I need to review his medical records to really understand what he has so I can understand if you are at risk. So the one thing I did is I ordered an echo because of this history of cardiomyopathy and we didn't have that information. And then I said I'll follow up with you in a couple months. So that's case number two, illustrating that maybe it's not the patient himself with the genetic diagnosis, but it's something in the family. And before we go ordering tests, we need to really understand what is going on in the family and make sure we understand the phenotype. Okay, so selecting the right test depends on the right diagnosis and it requires the synthesis of all this information as I discussed before. So we'll go on to selecting the right test. So this is kind of the next step, I would say kind of in the pathway or the preanalytic phase before the informed consent process, which we won't get into. I have, I think, three or four cases here and they're all kind of quick and then I think we'll have plenty of time to answer questions. So case three is Ms. T. So she's 47 years old, referred by primary care and she's just been diagnosed with invasive lobular carcinoma of the right breast. And I learned from the referring physician that her maternal aunt also had breast cancer. And so when I met with a patient or I think the counselor met with this patient, she was diagnosed with invasive lobular and carcinoma, as I said. She had two foci, but it was small together, no more than 15 millimeters. And she elected to undergo bilateral mastectomy with reconstruction just because of her own personal history of this happening and she does have some family history. She had a sentinel node biopsy negative and her tumor was ERPR positive and her two new negatives. So in just talking to the patient about what are your expectations? What do you understand about genetic testing and what would you do with that information? The patient said if it's positive I would get everything taken out and what she meant by everything was her uterus, fallopian tubes and ovaries. She reported that she's had this problem with adenomyosis. She's had a lot of vaginal bleeding. And she said it would just be better to get everything out instead of just a hysterectomy, which was planned as we understood. Or at least on the table. So this is her pedigree. So here she is. We knew about this breast cancer. We don't know the age of diagnosis in this maternal aunt. She died in her 70s, that's the extent of it, but she's alive. And the mother is age 66, no cancer history that we knew of. Her father, this should have a slash here, died at age 32 from a primary brain tumor of some kind. We don't know more than that, but it wasn't early death from brain tumor and probably not metastatic disease, probably a primary. And then it's the maternal aunt over here. Also had breast cancer in her 50s. She's currently 71. No one else in the family had ever undergone genetic testing and there's no Jewish ancestry. We always ask about Jewish ancestry with breast cancer because of three common mutations in BRCA 1 and 2. And if we were to offer a patient testing, we would start there, and if that were normal, we would think, you know, is it worthwhile to do any additional testing. In this case, the patient was not Jewish. So in terms of a differential diagnosis, given her somewhat early age and onset under 50 and multifocal lesions with, you know, this invasive lobular cancer, she could have hereditary cancer and it may be, you know, I'm more suspicious of the paternal, the father's side of the family, given his cancer diagnosis with brain cancer and his sisters than the maternal side, but it could be coming from either if it is genetic, if it is hereditary. And then if it is hereditary breast cancer, we know of a number of genes these days that do contribute to breast cancer. Some are of higher risk than others. And I want to point out that CDH1 is associated with lobular breast cancer specifically, which our patient had, and also diffuse gastric cancer. Whereas I'm sure you're familiar with BRCA1 and 2, it can be early onset, typically it's ductile but it could be lobular and of course there's an increased risk for ovarian cancer. So because the patient had bilateral mastectomy, you know, her decision making about dealing with any increased risk from these genes related to that, that decision has already been made. So testing would really potentially be helpful to understand her risk for other cancers and then to offer her other preventive and surveillance options depending on those test results. So we went forward with testing and we found that she has a BRCA2 gene mutation, pathogenic. At position 199, there's a deletion of a guanine, a G nucleotide, and that leads to an early stop in the production of the amino acid chain. And so this is known to be a pathogenic mutation. And it has been observed in the literature and other families it's actually likely a founder mutation from Northwest England. So I hadn't even looked back to see which site. So here her grandfather is from England. You know, this is the first time I put two and two together on this. So it is likely that this is paternally derived possibly from this grandfather, although we don't know the country of origin of these maternal grandparents, but just thought I'd throw that in there. So anyway, for this patient, she has maximally reduced her risk for another breast cancer with the mastectomy. But we did recommend that she remove her tooth and ovaries to reduce her ovarian cancer risk. We referred her to GI because of the BRCA2. There is an increased pancreatic cancer risk and there are some surveillance options, although, again, you know, how well they do at detecting pancreatic cancer at an early stage is debatable. There is also an increased risk for melanoma with BRCA2 and we advised her about that. And of course we recommended that she speak with family members. And then follow-up, we knew, we learned that she had hysterectomy with bilateral selpigo urectomy. She was seen in GI clinic at a scopic ultrasound. And her mother and both sisters have tested negative. So yes, it's coming from the paternal side of the family. So good news there for mother and sisters. The next case is Ms. CJ. She's 30 years old, referred by primary care. She's got a family history early on that breast cancer. And genetic testing was desired to evaluate for her risk of breast and ovarian cancer, specifically requested with testing for BRCA1 and 2. And we were informed by the primary care doc that she would consider preventive surgery after childbearing. So let's show you a little bit more about this patient. So here she is, age 30. She is currently pregnant at this time. She has a paternal first cousin, a female cousin with breast cancer diagnosed recently, just at age 28. And that's really the extent of the history here. We have lung cancer in this paternal grandfather. So if this is hereditary, and it sounds like it, when you see breast cancer at 28, that's a huge red flag. And we did verify that it was an invasive ductal carcinoma, as I recall. So this could be, there are three uncles here. So men can certainly carry these mutations. They have a much lower risk for developing cancer as a result. You can see pedigrees where it's male to male to male, and then eventually a daughter is inherent that you'd see breast cancer or ovarian cancer or whatever. So this definitely is a sign. Now, but this is a third degree relative to our patient. So, and always, we always want to identify the mutation in the affected family member rather than offering her testing first, because a normal test result would be somewhat reassuring, especially given the genetic distance of this history. But it just would be so much more informative if we would know this cousin's genetic test results. It so happens a cousin lived in Germany, and my patient thought, well, do they have genetic testing in Germany? And I said, yes, they have genetic testing in Germany. So she corresponded with her cousin, and her cousin did undergo testing. And so this is reflected here in this slide, the conversation that we had. The testing strategy is to hold off on our patient and see if her cousin would undergo testing. And her cousin did test, and now my patient is pregnant, which kind of was a little bit of a wrinkle, and most women don't really want to know about this stuff while they're pregnant. But her cousin has a BRCA2 mutation. Now, we also learned that her cousin's mother, unrelated to my patient, died from breast cancer at an early age. So now I strongly suspect that this woman's mother was the person who transmitted this BRCA2 mutation to this cousin. But I can't prove that. And because I have a known familial mutation, we offered our patient that test. It would have been good for her dad to test, but it's hard to get men tested. So the insurers typically will not pay. And so we offered this familial mutation to our patient. And the good news is that no mutation was detected. So that was good news all around for her. So she's not at increased risk for breast and ovarian cancer. There's no indication for enhanced surveillance or prevention. And there's no risk to transmit this familial risk to offspring. So this illustrates the importance of, you know, if you have someone at risk to try and work with that family to get that familial mutation known. And sometimes it takes a while and it takes effort. And lots of clinicians don't have that time, but that's something that we often do in genetics. Okay, case number five, Mr. MC, a 46-year-old man referred by GI clinic and all they said was Possible Linge Syndrome. So let's see, this is his story. He was diagnosed with synchronous colorectal cancer at 2 centimeters and 18 centimeters on his first colonoscopy at age 46. I believe he had a colonoscopy because he has a family history in his father and paternal aunt. So he had it at an earlier age than typical. Both tumors were screened for Linge Syndrome. So maybe you've had some discussions about Linge Syndrome. We know that there are at least four mismatched repair genes that code for these proteins that fix mismatches that occur during DNA replication. If you have a mutation in one of these genes, you can't fix these mistakes and mutations accumulate in tissue becoming a tumor. And so immunohistochemistry can be done looking at the proteins that are made from these genes. And if there's absence staining of a protein, it suggests that there's loss of heterosegosity. It suggests that there's a germline mutation in the gene where there's loss of protein expression. We also can do microsatellite instability testing. And in my hospital, we tend to do both, especially in a case like this, where what ends up happening is the immunohistochemistry was normal. So we went on to do microsatellite instability testing. And there, all five markers, these are molecular markers, showed high instability. And there was no promoter methylation of the MLH1 gene, which could be a somatic reason for having the MSI high phenotype. So I know this is... I went a little bit into Lynch syndrome. It's a lot of detail, maybe more than you needed, but just wanted to kind of explain the process there and those results.  And then we have some family history. So here's what he told us. He has a sister from whom he is estranged. He hasn't spoken with her in quite a while. His mother died at age 40, maybe from cancer or possibly AIDS. And he knew nothing about his maternal family, only that his grandparents were white. His father, he knew died at 54. He had colorectal cancer diagnosed at age 38. His father's sister also is deceased possibly. He wasn't even sure if she was alive or dead, but he had heard that she had colorectal cancer as well, but doesn't know the age or anything. So he's kind of estranged from his family. He doesn't have a lot of information, but enough here, especially with his own history, which is sufficient to be concerned about an inherited predisposition to colorectal cancer. Genetic testing strategy for him. Given his personal family history, it is consistent with Lynch syndrome. He meets what are called these Amsterdam criteria where you have three family members. I could go back to the pedigree. Three family members, first-grade relatives to one another, and at least one of them diagnosed before age 50 with colon cancer. Now, I know this is a question mark, but he said his aunt did have colon cancer. He just didn't know at what age and if she's even living. But if we go by this history and the fact that his tumor had micro-satellite instability, it meets clinical criteria for Lynch syndrome, which is the most common cause of hereditary colorectal cancer. But there are many other hereditary colorectal cancer syndromes that could feature this, but we could never exclude Lynch syndrome because it meets these clinical criteria. And furthermore, making the genetic diagnosis with a molecular test isn't going to impact his cancer surveillance or prevention. We're going to have to recommend that he follow Lynch syndrome recommendations for surveillance, which are listed here. And we emphasize for him to quit smoking, to start aspirin. There was a big study that showed taking aspirin reduces the incidence of colorectal cancer in these patients. So in this case, we didn't do genetic testing because the clinical phenotypic information was sufficient to make a diagnosis. I think I might have time for one more case. Maybe this is the last case anyway. 33-year-old female referred by GI. Again, lots of referrals from GI. She had colonoscopy today, so the day they sent the consult in for rectal bleeding, lots of polyps removed, two more than a centimeter. Grandmother had breast cancer, question of whether we should be sending the polyps for some special testing. That was what was on the consult request. Some more history. Abdominal pain. Polyps were found throughout the colon. She also had a cyst removed from her back. And with these hereditary cancer syndromes, we're always asking about dermatologic findings and other things that could be related. The migraine acne and back pain, I don't think are related. These are her meds. She's taking a vitamin, not aspirin, not smoking drug or alcohol use, and she walks every day in terms of exercise. So here's her pedigree. She's an only child. She has a son age 13. Unfortunately, her mother died from a drug overdose at age 37. She's a strange from her maternal aunt. This is the grandmother with breast cancer of Guatemalan ancestry. Grandfather was African-American, and her grandparents on the father's side are both African-American. Dad is 59 and had a normal colonoscopy, and she doesn't know much about these four uncles and this paternal aunt over here. So the family history really isn't that helpful. You know, this could just be... I mean, having nine tubular adenomas at such a young age is definitely concerning. I would say for apolloposis phenotype. Clearly, it's not classical familial adenomas apolloposis because she doesn't have hundreds to thousands of polyps, which you would expect at age 33 in the classical familial adenomas apolloposis, but she could have an attenuated form of familial adenomas apolloposis due to a mutation in the APC gene, or she could have MUTYH-associated polyposis. MUTYH is another gene. The phenotype looks exactly the same as APC, but it's due to recessive inheritance so that it would mean that the father and mother were both carriers. She inherited the two abnormal gene copies, and now she's at risk for developing multiple adenomas. It's also possible that she has Lynch syndrome because we do see polyps in Lynch syndrome adenomas much more frequently than the average, even though it's been called non-polyposis colon cancer. Clearly, the colorectal cancers develop in polyps, and patients do have multiple of them. So there is a relatively broad differential diagnosis for her, and again, I've listed that here. There really wouldn't be much utility to test her adenomas for Lynch syndrome, as I described in the previous case. It's pretty low yield. So if we wanted to arrive at a genetic diagnosis for her, the best thing would be to order a series of genes one at a time or to do a gene panel that has a combination of the genes that I've mentioned to you to try and sort this out, and it would be important because, for example, the APC gene is associated with other malignancies a little bit of pancreatic cancer risk, thyroid cancer, but really gastric and small bowel, those are the areas that we would be mostly concerned about. M-E-T-Y-H associated polyposis, there are some other cancers associated with this, but less is really understood about this particular one. And of course, with Lynch syndrome, we know that women would have a very significant increased risk for endometrial cancer, ovarian cancer, also gastric cancer, ureter cancer, several other cancers are increased with Lynch, but I think if we were to diagnose Lynch syndrome with genetic testing, then we would advise her at some point she needs to have her uterus and tubes and ovaries removed as a preventive measure. So we ended up with a panel of genes. You'll see a lot of genes on this panel. That's because the laboratory that we have a contract with. In order to get the genes of interest, this was like the best approach for us. And, you know, there are some of these genes that, you know, really don't pertain at all, and I wouldn't even think are relevant, like CHEC2 or CDH1, but they just happen to be on the panel. But when you do panel testing, as in this case you see here, we did find a pathogenic mutation in the APC gene, and we also found a variant of uncertain significance. So these variants, they, you know, we need to explain them to our patients and we need to tell them that they can change over time and sometimes family studies can be done to inform what these variants mean. In this case, I guess you could say we were lucky because we found a pathogenic mutation that we suspected, and it helps us with making the diagnosis of attenuated FAP for this patient. So here are the, you know, what we recommended to her in terms of surveillance, et cetera, and of course now there's a test for her son and relatives to understand, you know, who else is at risk in the family, and she may be the first in the family, she may be a de novo mutation, but certainly her son would be at risk and when he's older could look into this. This is, I'm at the end now, so we'll have at least 15 minutes for discussion. So selecting the right test, I want to emphasize that if you think about that ACE framework and the disorders and setting, that's in the middle of all of that, that, you know, the clinical context is so important. It's so important to understand the patient characteristics that are going to contribute to the diagnosis and differential diagnosis, the characteristics of the genetic disorder that you're contemplating, and they're listed here, inheritance pattern, the prevalence, penetrance, variable expressivity, the clinical heterogeneity so that it might look genetic, but it might be quote-unquote non-genetic, or there may be lots of genetic genes or genetic diagnoses that have the same phenotype, genetic heterogeneity. The genetic tests that you might want to order to kind of work this up, you know, it depends on, is there even a genetic test available? Even in this day and age, even though we know a disease is Mendelian, is hereditary, there may not be a clinical test. And then this idea of targeted versus comprehensive testing, one unit of time or panels, exomes, and understanding the limitations of all of that. And then the provider, you know, who is arriving at this differential diagnosis and how much do they really understand about the disease of concern and how much do they understand about the genetics and the limitations of genetic testing and what it can really offer. So, in summary, genetic diagnosis can end a diagnostic odyssey, it can help guide management and surveillance recommendations, it can inform reproductive and life-planning decisions for the patient, and it can have health and reproductive implications for the family members. Making a diagnosis can be complex and it relies heavily on genetic testing these days, and selecting the right tests relies on the accurate diagnosis, et cetera. So, I...