text:
Discipline: Immune Engineering
46 Results for 'Immune Engineering'
Customizable scaffolds for faster, higher-quality T cell production
Immunotherapy, or tweaking the body's own immune system to treat disease, is attracting significant attention in the medical field for its potential to offer long-lasting cures with fewer side effects than chemotherapy or other drugs. One type of immunotherapy involves isolating T cells (a type of white blood cell) from a patient's body, sometimes modifying...
Pathogen Capture Technology for Infectious Disease Therapeutics and Diagnostics
Microbial infection is the cause of life-threatening cases of sepsis, meningitis and multiple other diseases that are major causes of death world-wide. Equally prevalent are pathogenic contaminants in our environment, food, and manufacturing processes. In each case, the presence of dangerous microbes must be confirmed, and when they are found, they need to be removed,...
T cell traps
T cells, a subtype of white blood cells, play key roles in cell-mediated immunity, be it to fight infections and cancer or, when corrupted, to react against the body's own cells in more than 80 autoimmune diseases, including type I diabetes, multiple sclerosis, rheumatoid arthritis and others. However, isolating disease-related T cells from the body...
Implantable cancer vaccine
The Wyss Institute's implantable, biodegradable cancer vaccine leverages immunotherapeutic methods and could one day help overcome melanoma, other cancers, infectious diseases, auto-immune diseases, as well as vaccinate against specific peptides, proteins, or antigens. The implant is a biodegradable polymer scaffold containing growth factors and components of each patient's tumors. The technology was initially designed to...
Research Spotlights Harnessing Nature to Beat Cancer
Press Release Platelet "Decoys" Outsmart Both Clots and Cancer
Press Release Small molecules come into focus
Disruptive: Cancer Vaccine and Immuno-Materials
Immunotherapy – treatment that uses the body's own immune system to help fight disease – has groundbreaking and life-saving implications. In an effort to make immunotherapy more effective, Wyss Institute researchers are developing new immuno-materials, which help modulate immune cells to treat or diagnose disease. In this episode of Disruptive, Dave Mooney, Wyss Core Faculty...
Wyss Focus: Immuno-Materials
Wyss Core Faculty, Dave Mooney, explains our new Immuno-Materials Focus Area, which adds a new dimension to immunotherapy in that it harnesses materials to make treatments more efficient and effective. These material-based systems are capable of modulating immune cells and releasing them into the body where they can treat diseases.
David and Mary Mooney: Seeing Is Believing-Therapeutic Cancer Vaccines
Wyss Core Faculty member David Mooney presents a talk with Mary Mooney, titled Seeing Is Believing: Therapeutic Cancer Vaccines. Marshalling a patient's immune system to recognize and destroy cancerous cells is an exciting strategy to attack cancer, and this talk will explore materials that engage the immune system through science and artistic representation. Mary K....
ArtScience Talks @ Le Lab – Seeing Is Believing: Therapeutic Cancer Vaccines
Wyss Core Faculty member David Mooney presents a talk with Mary Mooney, titled Seeing Is Believing: Therapeutic Cancer Vaccines. Marshaling a patientÍs immune system to recognize and destroy cancerous cells is an exciting strategy to attack cancer, and this talk will explore materials that engage the immune system through science and artistic representation. Mary K....
William Shih: Lego-Style Construction of Future Therapeutics From DNA
Listen to Wyss Core Faculty member William Shih's lecture on how custom molecular shapes can be designed using DNA building blocks and how these minuscule devices could have a profound impact on fields ranging from molecular biophysics to therapeutics to nano-optics for decades to come. Shih's lecture is part of the ArtScience lecture series at...
Disruptive: Molecular Robotics
How can DNA be programmed to build novel structures, devices, and robots? We have taken our understanding of DNA to another level, beginning to take advantage of some of DNA's properties that have served nature so well, but in ways nature itself may have never pursued. Humans can now use DNA as a medium for...


text:
#include <iostream>
#include <string>
#include <vector>
#include <list>
#include <utility>

#ifndef SRC_VARIABLES_MULTIPART_FILE_NAME_H_
#define SRC_VARIABLES_MULTIPART_FILE_NAME_H_

#include "src/variables/variable.h"

namespace modsecurity {

class Transaction;
namespace Variables {

class MultiPartFileName_DictElement : public Variable {
 public:
    explicit MultiPartFileName_DictElement(std::string dictElement)
        : Variable("MULTIPART_FILENAME" + std::string(":") +
            std::string(dictElement)),
        m_dictElement(dictElement) { }

    void evaluate(Transaction *transaction,
        Rule *rule,
        std::vector<const collection::Variable *> *l) override {
        transaction->m_variableMultiPartFileName.resolve(m_dictElement, l);
    }

    std::string m_dictElement;
};

class MultiPartFileName_NoDictElement : public Variable {
 public:
    MultiPartFileName_NoDictElement()
        : Variable("MULTIPART_FILENAME") { }

    void evaluate(Transaction *transaction,
        Rule *rule,
        std::vector<const collection::Variable *> *l) override {
        transaction->m_variableMultiPartFileName.resolve(l);
    }
};

class MultiPartFileName_DictElementRegexp : public Variable {
 public:
    explicit MultiPartFileName_DictElementRegexp(std::string dictElement)
        : Variable("MULTIPART_FILENAME"),
        m_r(dictElement) { }

    void evaluate(Transaction *transaction,
        Rule *rule,
        std::vector<const collection::Variable *> *l) override {
        transaction->m_variableMultiPartFileName.resolveRegularExpression(
            &m_r, l);
    }

    Utils::Regex m_r;
};

}  // namespace Variables
}  // namespace modsecurity

#endif  // SRC_VARIABLES_MULTIPART_FILE_NAME_H_

redpajama_set_name: RedPajamaGithub


text:
[![Circle CI](https://circleci.com/gh/Bowery/exportfs/tree/master.png?style=badge)](https://circleci.com/gh/Bowery/exportfs/tree/master)

[![GoDoc](https://godoc.org/github.com/Bowery/exportfs?status.png)](https://godoc.org/github.com/Bowery/exportfs)

Go package to handle exports(e.g. `/etc/exports`) files for NFS servers.

## License

exportfs is MIT licensed, details can be found [here](https://raw.githubusercontent.com/Bowery/exportfs/master/LICENSE).


Nicola Sturgeon is the First Minister of Scotland.
Nicola Sturgeon (born 19 July 1970 in Irvine, Scotland) is a Scottish politician. On 19 November 2014, she became the 5th First Minister of Scotland. She became the leader of the Scottish National Party on 14 November 2014. She was previously the Deputy First Minister of Scotland, Cabinet Secretary for Health and Wellbeing, and Deputy Leader of the Scottish National Party (SNP). She is a Member of the Scottish Parliament (MSP) for Glasgow Govan.
Nicola Sturgeon studied at the University of Glasgow and attempted to become a Member of Parliament at the 1992 and 1997 General Elections. In 1999, she became an MSP representing the Glasgow region. She became the Deputy Leader of the Scottish National Party in 2004 and because Alex Salmond was still an MP, she was the SNP's leader in the Scottish Parliament until the 2007 Scottish Parliament election. At the 2007 election, Nicola Sturgeon became the MSP for Glasgow Govan and her party formed a minority government with Alex Salmond as First Minister.
On 19 November 2014, Nicola Sturgeon became First Minister of Scotland, succeeding Alex Salmond, who had resigned after defeat in the Scottish independence referendum. She is the first woman to hold this position.
This page was last changed on 11 September 2018, at 20:06.


Why Is Insurance Worth It (Analytically)?
Re: Why Is Insurance Worth It (Analytically)?
What if all my relatives and myself forego insurance and save the premiums as additional contributions into our Asset Allocations with the understanding that we can loan money to each other? Is it functionally similar to insurance then?
And you're worried about the insurance company defaulting?
It is because the costs of economic disasters do not follow a normal distribution. They are like the distribution of economic wealth in a society, earthquakes, and financial crises, with a few tail cases one one side constituting a significant portion of the total damage. Most (of the time) people will never have a big need for insurance, but when they do, it will be so much swifter and greater than daily affairs could possibly lead them to believe that they will scarcely be able to comprehend it. In fact advancing along the income scale will also increase your need proportionately. "Fat insurance claims are relatively more common than fat millionaires" -Mandelbrot, probably out of context for this but still a good quote that seems like it should be in context and helps me win the argument by appealing to authority.
For that reason, I don't bother with deductibles less than a half year's income unless I have no choice. If I survive I can recover from those. However I do insure against liability, health, and other fat tail risks to the extent I can imagine them, and like Han Solo, I can imagine quite a bit. I pay $0.65/month for $1m renter's liability insurance, probably a joke and a total loss of $0.65 but hey ain't nobody touching the $1M I don't have . Plus I think it was the same $0.65 for most of the way down the scale, so I just maxed it out since the price didn't increase.
Why do people have such a strong belief to promote a product with a statistically negative return (and negative risk) that isn't even 100% reliable on paying out in the event of a claim anyway?
Keeping with OP's numbers-based framing of this question, I'd argue insurance purchase could hold positive expected value for someone with what economists call a declining marginal utility function. In other words, our millionth dollar does less for us, we feel like, than our first one did.
Normally, when we talk about risk-adjusted return we're implicitly confining our thought experiment to a localized region of possibility where utility-per-dollar is quasi-constant. Here, Bogleheads tend to think like OP. Do we need, e.g., the car extended warranty? Perhaps not, if we're confident we could cover the repairs and would no more mourn those dollars' loss than we'd celebrate the foregone warranty premium.
For most of us, though, medical/automotive/liability events can be large enough to take us much lower on the utility-per-dollar curve. There, each lost dollar is much more painful than the one we'd have spent in insurance premiums prevent its loss. As a result, with the right utility curve shape, insurance purchase can be mathematically correct even while carrying negative expected value in dollars.
One of the hats I wore in the corporate world was risk management. There are essentially four ways to deal with a risk.
Accept the risk. You recognize that there is the risk of some event, and you choose to deal with the event when it happens. Usually this is the correct choice for a small risk. Going without an extended warranty for that new car would fit in this category. If the car breaks down, you can usually afford to fix it without too much heartache.
Avoid the risk. You recognize the risk, and avoid doing the risky thing. I've never taken up skydiving for exactly this reason.
Mitigate the risk. You take actions to reduce the risk. Eat healthy, wear seatbelts, etc. Note that this doesn't completely remove the risk. It only reduces either the risk, or the impact if the risk occurs.
Transfer the risk. This is where insurance comes in. You transfer the risk to another party, in this case, an insurance company.
When you're analyzing a risk, you have to evaluate not only the probability of the event occurring, but the impact if it does occur. Some of the things being talked about in this thread are low probability, but very high impact. As in catastrophic financial failure that will follow you for the rest of your and your family's life. In the context we're talking about, "self insure" isn't a real thing, it's a euphemism for accepting what could be catastrophic risk.
I personally would much rather pay a few hundred dollars per year for liability insurance that transfers the risk of me being wiped out by a lawsuit than risk being completely wiped out because of some freak moment of stupidity when I'm driving somewhere. And absolutely, I'll pay a few thousand a year to keep from being wiped out if someone in my family gets cancer. The cost is high, but the cost reflects the fact that the probability of a large medical bill isn't actually all that low.
I like this explanation. Basically, the first 1k lost hurts a lot less than the last one, and insurance has a very high chance of losing the first one (or several), but a very low chance of losing the last ones.
It's still missing the bullet point that one's net worth can go negative and liabilities can go unpaid, but with the explanation that some have a moral obligation to pay debts, I can see why some are adamant about carrying insurance for events with the potential to severely reduce or wipeout net worth.
My main problem of understanding was that I don't value each 1k of my net worth (even the negative ones) differently, and I don't feel morally obligated to pay large debts...but I am probably in a minority in both aspects.
I think insurance is one of the biggest scam jobs on the average American out there today. They are as effective (arguably more) as lenders at marketing their product. You can easily give 10-20-25% of your income away on these products (many of which you'll rarely if ever use).
Joe 6pk has no money because premiums eat it up, so he has to buy more insurance like extended warranties because there isn't any money left to fix his car when it breaks down, etc. At some point you have to say enough.
Health insurance is the real gotcha because you have to have it or bankruptcy could easily occur over something relatively minor. There needs to be more education in high schools on this topic. Life insurance alone can be so scamy, how's a lay person to navigate that type of product alone?
There are insurance like products that are terrible values which don't protect against low probability, high value events ie extended warranties. I think that's a separate issue most people can agree should not be bought.
You buy insurance to protect for low probability but ruinous events that you can't handle - or would prefer not to handle - by yourself.What happens if you experience multiple low probability but high value claims, ie, you end up being nowhere near the statistical average? Say you have assets of $5 million and claims of $6 million? You're now bankrupt. Then you die. Your family's now destitute. Your family's life will end up being far different from what they've experienced to date. Saying you're self insured really means that your plan for low probability but high value events is to be destitute. For slightly more probable events, you plan to surrender a signficiant portion of your net worth. Meanwhile, you could have purchased insurance for a small fraction of that cost.
I don't think you really understand all of the potential liability outcomes you are exposing yourself to by foregoing all insurance. You are too focused on the average outcome or small time (not far from the average) claims, not the type that bankrupt you and leave you and/or your family in penuary. Insurance has a cost and the purpose it to pool risk because not everyone's outcome will be average. You get insurance for the catastrophic tail risks that will ruin you or your survivors. Are you really 'self insured' from all potential perils, or just some of them, as you're too focused near the average and not at the extremes? Look at the worst outcomes and be realistic about how much they would cost. Now consider that multiple bad outcomes can occur simultaenously.
As an example, your decision to forego health insurance might be intelligent if you (and your family) are average. What if, instead, you're not average and require a major surgery, extended stay in the hospital, a transplant, cancer treatment, etc while simultaenously being unable to work? Those could wipe out all of your savings and more. It will also wipe you out even more than you would expect because you will not benefit from a negotiated rate. One of your examples was a $8000 bill. That's peanuts compared to what you could be hit with.
What if all those health issues happened, your ran down your savings ('self insurance') to fund it, and then in the end you still died? Since you also decided to forego employer provided life insurance, your family would be left destitute. No savings, no life insurance, and maybe even stuck with extra bills as your family went into debt to try to save your life? Those are possible outcomes that you are ignoring. Some people would then say that if it would cost too much, they just wouldn't go through with the treatment. I've seen that on here before. That's not a clever answer, since that means the cost of foregoing life insurance is one's actual life or one's quality of life. Your family might also not be too pleased with your decisions to forego all insurance, leave them with nothing as a result, and end up having to move to a crummy area, kids have a hard time, can't pursue their dreams to the extent they could otherwise have, etc etc.
Now what if the reason you were in the hospital in the first place is because you were in a very bad car accident, for which you were at fault? There is a person filing a claim against you who was permanently disabled as the result of your actions. How will that go? If you have lots of assets, you won't have any after just this one incident. You'll also be worrying about a lawsuit while in the hospital when you'd be worrying less if you were insured.
Sometimes homes are protected from creditors. What if, at the same time you are undergoing a very expensive treatment and not working, your house burns down? Now your family has nowhere to live and has to pay for an apartment/house while also having to pay to clear the property of the burnt remains. Now let's say that at the same time, someone was injured or died or - the worst outcome financially - permanently disabled trying to save your family from the burning house or was hit by falling debris, etc and files a claim against you?
On top of all this, you might owe taxes and/or penalties for converting your assets into dollars you can use to pay off your creditors. If you have illiquid assets (rental properties, house if it gets that bad, etc), you might also be subject to a liquidity discount, ie, you accept the first offer rather than waiting because you need the money now, not later.
If it were me, I would at least carry health insurance for you and your family, regardless of level of income. This is protecting your human capital that you can use to rebound. It's also not replaceable once extinguished.
because any catastrophic event without it can bankrupt you.
Do you have a plan if you are diagnosed with cancer or are severely injured in an accident?
One option is to (EDIT: not receive care). I'm sorry if that sounds offensive to anyone. Another is to not pay the medical bills. Another is Bankruptcy.
This is incongruent with my moral values.
But, your hypothesis has made me reconsider my insurance needs. I think I will look at higher deductibles and maybe dropping comp/collision on my cars. Been paying those for decades and made one claim. Now I can afford a new car without help from insurance. And why do I have a 1% deductible on my home owner's insurance? I have a mortgage, so have to have it, but I will look at increasing the deductible.
Other than the above statement, a very helpful thread.
If it's any consolation, I feel I understand your point of view better, and see why holding yourself accountable for your debts has value that's not monetary...a huge intangible benefit of insurance.
I feel it has a second, perhaps more important aspect. If, by my actions or inactions, I injure somebody, or even just damage their property, the responsible thing, the right thing, is for me to compensate them, although money can never completely compensate for an injury or a death.
Therefore, I view insurance as a way to protect myself from adverse events, and as a way to protect my fellow human beings from me.
A fair bit of the insurance that I purchase is for the benefit for third parties. I have a very small car; however, 3,000 lbs @ 65 mph can still do a lot of damage depending what I hit! Should I survive the accident, I hope that I can be an advocate for any victims and their families, working with them to help them recover / replace what was lost (to the extent possible).
Then your underwriters are mispricing the business to obtain market share.
I don't see what I am missing.
You are missing the whole point of insurance - to protect against catastrophic loss.
For most insurance, maybe all if you are lucky it is a losing deal. You pay premiums for home insurance and never have a fire, major theft etc. Pay for health insurance and all you get is an occasional cold. Never have more than a fender bender but paid all that auto insurance.
I think most people try to pay a modest price to protect their families/assets from a major setback. I buckle my seat belt, try to buy cars rated high for safety others feel they don't need to buckle and are ok driving older, less save vehicles even though they could afford to own safer ones.
If you have an car accident that is your fault and severely injure a person or two it could wipe out all your assets or enough to make you weep. If you get a life threatening illness it could drain your assets and limit your ability to earn a living.
Usually, young, healthy, talented people that haven't experienced much in the way of risk gone bad undervalue protection. that is why they are the most likely not to see the need for health insurance -- until they get really sick and can't get it or lose a job and can't get one because of illness.
Not having basic insurance coverage is rolling the dice and hoping you don't get snake eyes.
This is a neat post. We did something very similar in the world of aviation. We didn't have the option to transfer the risk, but the rest of the thought process was the same.
Because the real world doesn't work analytically. Eating, can be considered negative EV, from a purely analytical mindset. Protections against catastrophic risks is worth it when you add in emotions.
The health insurance market in the US (considering both ACA/private and employer provided, not to mention outright govt provided like Medicare/Medicaid) functions too much differently than the other types of insurance to be compared directly in general.
-medical insurance pricing is much more tightly regulated than life, auto, home, etc. insurance such that many people (older and less healthy) *do* get positive expected value from health insurance, sometimes even if they are paying full price for the insurance.
-there are pricing arrangements between health ins co and health providers that have no broad analog in other insurance markets. As mentioned above you can be charged 2>10 times as much for a health service if not insured, even if you didn't hit the insurance deductible. You don't get a bill 10 times higher from the home repair contractor because you don't have homeowners insurance.
Taking those together, you can't make a blanket statement that insurance has negative expected value when it comes to health insurance, compared to the actual avoided cost of not buying it. As a result of the positive expected value for some, it's even more negative in expected value for others (paying the full freight, younger, healthy). But some of the positive expected value for some people is made up by taxes/govt borrowing so is exogenous to individual insurance purchase analysis.
For the other types of insurance it tends to be more straightforward: can you afford the financial hit of an uninsured loss? Although for liability it's also somewhat more complicated, because the potential financial damage increases the more you have. Anyway when it comes to car comprehensive/collision it's pretty simple: you shouldn't have it if you can take the total loss of your car in financial stride, and assuming there's no lender requiring it (a drawback to the anyway disappearing case of '0% financing').
And even with health insurance for some people the question comes down to the same. We'll pay around $18.5k for health insurance for a couple in 2019, $3k/$6k deductible $6.5k/$13k out of pocket limit, HSA compatible. The HSA feature saves $2k+ in income tax. There's a further state income tax deduction for all in medical costs including the insurance, though typically we wouldn't reach the federal deduction level. There's some $100's to a few $k savings in years of no major illness due to the 'list price'/'insured price' thing. But $10k+ at least is to get that $13k out of pocket limit, when $100'ks to few $mil medical treatments are not that far fetched a possibility. If there was a much cheaper plan with say a $100k out of pocket limit we'd buy it, but there isn't. Medical insurance is also a much less complete market in terms of product offerings that some other kinds of insurance.
I consider myself to have enough assets (and not too much-for liability) to be "self-insured".
I have the legal minimum for car insurance and nothing else. I have even turned down employer sponsored health because I am currently statistically likely to pay in more than I claim out (including tax breaks). I would consider adding liability insurance as my after-tax holdings increase.
EDIT: I have kids and wife. Forgot to add kids have free gov't health insurance. Inconsequential, as I'd gladly drop it (or add it) as income changes.
- You have sufficient assets to pay high costs in absence of insurance.
- Your children receive free government insurance?
Regarding the possibility of bankruptcy and other forms of debt avoidance, I have sat in post-judgment discovery depositions before (as a lawyer, not as a debtor, thankfully), and it's not a pretty sight: "Does your wife own any jewelry? How many televisions are there in your home? Have you given anything of value to any family members in the last five years? What did you give your children for Christmas last year? Do you have any mistresses or paramours to whom you have given gifts in the last five years?" Most people describe the experience as "proctological," for lack of a more polite word. Lawsuits and bankruptcy are messy, chaotic, and very frequently embarrassing. These effects are often far worse than the financial effect of going back to merely zero. This indignity can span years, during which some people close themselves up in their homes, dodging subpoenas and creditors, hoping for a few days of peace. I've seen a lot in my years of legal practice, so I won't judge you for saying that you feel no strong moral calling to pay the "big debts" --- I get what you mean. But please don't think that anyone will make that process easy on you. Insurance can help avoid losing years of your life and your sanity to this process. You might (or might not) reasonably place some value on that.
Yes, at least more so. You have created a larger pool. You have essentially described the basic process of creating a mutual insurance company (ie. Liberty/Amica, etc).
Of course insurance companies also take care of things like writing up forms and contracts, processing and adjudicating claims, etc. Managing a pool of common assets with your relatives and managing the disputes that may arise sounds like a nightmare. Like probate court but worse.
"Analytically" should also include common sense. If you can afford to self insure, you can easily pay for insurance.
With a wife and kids you might want to add life insurance.
Or underestimating the risk. Merced Property & Casualty is a recent example that went under because of the fire damage in Paradise, CA.
I'm sorry, but if your plan for the unexpected is to let a doctor and medical facility treat you, then blithely say you plan to not pay the medical bills, I consider that theft. Unethical and despicable behavior.
After reading a few more of your posts, I can only hope you are trolling. That would be the generous assumption.
It's not theft. It's not illegal. It's unethical. No I am not trolling. I am honest about being unethical. If you have a 100k liability policy, get sued for 10 billion, and don't pay, is that theft too? Is declaring Bankruptcy theft too?
Just like to point out that I agree that in the case originally presented (emergency medical care) that this is not theft nor is it illegal. Most hospitals are legally required to stabilize emergency patients. It could, however, be very expensive to do as you suggest. If you choose not to pay someone your legally owed debts, they can pursue legal action against you. So I would not call you a thief, but I would probably call you broke (potentially forever broke if you get sued for 10 billion).
True - mispricing occurs when companies attempt to garner more marketshare and/or fail to account for the true cost of replacement.
If you can't honestly answer the question of what would I do if I came home from work and my house was gone? What would I do if I was diagnosed with a rare and expensive to treat illness? You are not self-insuring your self-deluding.
Also with the new tax law it will be harder to claim a casualty loss essentially eliminating the small backstop on loss of personal property built into the tax code.
And as for morals of not paying your bills, realize that the legal system operates in legality, not morality. There are people who do not owe a bill because of identity theft but are forced to pay anyways because they could not make a legal argument to not pay. There are others who owe money but get out of legally being forced to pay because they have a legal argument which allows them to not pay.
That said, if you do not pay a medical bill OR if you injure someone in an accident that is your fault, you will eventually be taken to court and if you cannot come up with evidence or a legal argument on why you are not liable for the bill/injuries, the judge (or jury) will issue a judgement against you. Inability to pay is not a legal argument BTW. Now you can hire a lawyer but that will be money out of your pocket and does not guarantee that the judge (or jury) will not rule against you. If a judgement against you is issued, the creditor then can legally start to take your assets, starting with the easiest to find (local bank accounts and wages). At this point, there will not be any warning. If the creditor cannot find any assets, they can then force you into a debtors exam (and you legally cannot refuse to do that under penalty of jail) where you can be forced to divulge any assets you may have or any that you may have tried to hid. Another poster explained what can be asked in a debtors exam. You really lose control of your financial life at this point.
Now you mention Bankruptcy. I just love how people throw out declaring Bankruptcy as if it is a simple easy thing to do and then you can get on with your life. It is neither simple, easy, and you certainly cannot move on with your life. It is a painful experience that I rank right up there with divorce. I know this from the personal experience of having gone through the process many many years ago.
2) Chapter 13 - You can use this if you are not eligible for Chapter 7 or if you want to try to protect assets. In this case, you use up any extra income that is above poverty level (and trust me, they use the IRS numbers to figure disposable income which means you are barely subsisting). This can last for up to 5 years and then anything left over might be discharged.
To declare bankruptcy, you have to fill out a voluminous amount of forms which get into every aspect of your personal financial life. You do not want to try to hide anything either. The trustees get paid based on what they can collect for the creditors so they are experts in finding assets and if you lie on your forms, you can end up in prison. Ask Denny Hecker about that one. He may be on parole by now. Once the forms are filed, you will have to meet with the trustees and any creditors who show up where it will be like a debtors exam.
If you get through all that, as I said before, your debts might be discharged. If you have any debts that were secured by collateral (home and car), you either have to reaffirm those or give up the asset. There are also certain debts that by law you cannot discharge such as certain taxes and student loans. There is another group of non-dischargable debts where the debt was incurred due to negligence. Now if you are trying to avoid paying hospital bills, this will not apply to you. However, if the bill is a liability bill from an accident that you were found negligent, you an sure that the creditor and/or their attorney will fight to have the Bankruptcy Court declare the debt non-dischargable. Now you will have to pay your attorney even more try to get the debt discharged (how much I cannot say but I would assume a couple of thousand more). If you fail, then you went through the whole process above and still owe the debt/judgement so you are back at square one.
If you manage to get through the process, then you cannot declare bankruptcy again for 8 years. That means if something else happens in the meantime, you will have to pay them back.
In the end, I would rather have insurance than go through all that above.
This would depend on the situation. If you are not work $10B and have no chance to make that amount of income, then no it would not be theft. If you are worth $20B and tried this, even if not theft, it would be morally wrong.
So if you are worth 200k. 100k in home equity and 100k in retirement plans, is it horribly unethical to not caryy health insurance and not pay a 50k ER visit. What about 500k. Paying how much is ethical? Charging how much is ethical? While I agree the more you pay (are insured to pay), the more ethical your behavior, it is irresponsible and incorrect to arbitrarily draw a line in the sand and say one legal action is ethical and one is not. That is "trolling" on your part big time.
In the end, not having insurance puts your assets at risk. If you want to take the risk, that is fine but if you have assets to pay the bill that you did not insure against, don't expect much sympathy from others when you have to pay the bill. I would rather pay the small, known risk (the insurance premium) to transfer the large unknown risk (the peril) to the insurance company in situations where it makes sense (Health, Liability, Life, and Disability).
To me it's buying access to a huge pot of money that I don't have. Or renting it, whatever.
Especially true with Medigap insurance, but I guess it applies to all insurance.
A lot of debtors will just write it off. I know many people who have not paid bills and never had any consequences. I know people who have not paid court judgements as well...although they have had negative consequences. I also have a family member who has declared bankruptcy and foreclosure. They are currently very wealthy (without illegally hiding assets). They made it back.
There is a third reason besides incremental value of wealth varying and ethics I'm starting to see. It's fear of the drastic financial situations you discussed. Probably promoted by the Insurance companies.
- Real property destroyed in fire or flood.
You forgot a massive drop in the stock market which has happened (several times to some) to 100% of people.
Death will also happen 100% of people.
Why don't they sell insurance for those...oh wait, THEY DO!
Property insurance doesn't cover floods, and automobile liability coverage is typically 20-100k depending on state.
Which is why you get flood insurance if you live in an area that could flood, and proper amounts of liability insurance.
This thread has jumped the shark. Peace out.
What seems even stranger to me is that many Bogleheads are adamant about holding insurance policies as well.
What logical reason does a Boglehead have for holding an insurance policy?
Can a policy actually increase your risk-adjusted returns (Mathematically)?
The logic is based on reducing tail risk and reducing variance of future net worth, not maximizing risk-adjusted return of the cost.
Auto liability minimum required by law is $20K to $100K (and in NH, you don't have to use insurance at all). You can purchase higher liability amounts however above the state minimums. In fact, between auto policies and umbrella policies, you can insure liability into the multi million dollar range.
Right, I would rather someone else take the risk of a catastrophe that could wipe me out financially, mentally, and/or emotionally. Having been through the bankruptcy process once, I don't want to do it again, ever.
And yes, some creditors to not pursue bills while others do. People do make it from bankruptcy to become very wealthy (and even President of the USA). Some people do not pay on court judgements either. That does not mean that I do not want to gamble on dealing with all that when it is avoidable.
If you want to deal with those situations, that is your business. However, you asked to analyze why insurance was worth it and to me, that is why.
If the discussion focuses on ethics/morality it will get shut down before long.
I would say though that medical pricing in the US is so complicated and opaque that it's much more difficult to assess what's a fair price or fair payment than some other cases. And it's all contingent on *if* among widely ranging hypothetical illnesses and prices charged. It's related to why, steering back away from pointless moral/ethical debate, it's more difficult to assess the value of health insurance to begin with than other types. You can pay on your own...except the prices you initially get charged are likely to be a multiple of what they'd be under the provider/HI company network agreement. You might negotiate down from those list prices...but hard to say how much. You might get inferior treatment...though hard to say how much (in some cases that would be prevented by law or by the medical provider's policies independent of the law, but not in every case).
Relatively speaking it's far more straightforward to predict what it would cost you to repair or rebuild your home in case of uninsured damage or destruction. And altogether straight forward to assess the cost of replacing your car if it's destroyed or stolen uninsured. And there's a limited amount at stake in those cases also. OP has something of a point comparing medical cost to a liability judgement. That's very hard to assess also. Just because somebody won a judgement against you doesn't mean they were actually right or the amount is fair. It's just what you are obligated to pay with certain exceptions (of what assets they can claim against). It's pointless IMO to debate whether you really 'deserve' to pay that much when it's all hypothetical.
But reducing that uncertainty would tend to weigh in the direction of getting medical or liability insurance.
Your question comes up every now and then.
Many here discuss insurance as a method of decreasing their own risks. That's true, it does.
I realize mine is a minority view.
In some countries it's and eye for an eye. I think having insurance to compensate the injured is a better system.
Last edited by goodenyou on Wed Dec 05, 2018 3:44 pm, edited 1 time in total.
While I've argued a bit, I feel the original question posed has been answered. Mathematically, insurance is usually not worth it. However, one could calculate different values for incremental wealth that make insurance mathmatically worth it for them. Insurance also has the value of allowing someone to prevent acting in a way they feel is unethical. Insurance is also valuable becuase it can reduced fear, stress, and anxiety (most of the time).
While the benefits can be intangible...each benefit can be valued financially for each person, and if the benefit value exceeds the cost of the coverage, a perfectly logical investor will pay for the exact amount of insurance coverage that results in the highest value to them specifically.
Even a perfectly logical investor could disagree with another perfectly logical investor on the value of the coverage because both (in a perfectly logical way) have assigned different values to those benefits.
When you add in that none of us are perfectly logical investors (though we may strive to be). It is easy to see why insurance discussion can lead to disagreement and misunderstanding.
Thanks all, for the responses. I feel like the next time I increase or decrease insurance coverage, I will consider the decision more logically and correctly for my needs based on the discussion in this thread.
Update: Several off-topic posts have been removed.


text:
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text:
Nick Shaxson ■ More than $12 trillion stuffed offshore, from developing countries alone
More than $12 trillion stuffed offshore, from developing countries alone
Nick Shaxson
James S. Henry
"More than $12tn has been siphoned out of Russia, China and other emerging economies into the secretive world of offshore finance, new research has revealed, as David Cameron prepares to host world leaders for an anti-corruption summit.
The analysis, carried out by Columbia University professor James S Henry for the Tax Justice Network, shows that by the end of 2014, $1.3tn of assets from Russia were sitting offshore."
David Cay Johnston, writing in The Daily Beast in the U.S., adds:
"The $12.1 trillion estimate—which amounts to two-thirds of America's annual GDP being taken out of the economies of much poorer nations—is for flight wealth built up since 1970. Add to that flight wealth from the world's rich regions, much of it due to tax evasion and criminal activities like drug dealing, and the global figure for hidden offshore wealth totals as much as $36 trillion."
See also Henry writing in Foreign Affairs on this topic.
Cay Johnston goes into detail, and is worth reading. For the raw data behind the numbers, you'll need to contact Henry directly: he expects to publish some further details soon. We'll carry updates in the Reports section of our website.
The initial document is here. More data will be uploaded in due course.
Also see this Guardian story: Tax havens have no economic justification, say top economists. This is a letter co-ordinated by Oxfam, which is reproduced in full here. The list of 300 signatories is here.
Nicholas Shaxson is a journalist and writer on the staff of Tax Justice Network. He is author of the book Poisoned Wells about the oil industry in Africa, published in 2007, and the more recent Treasure Islands: Tax havens and the Men who Stole the World, published by Random House in January 2011. He lives in Berlin.


text:
Armenian Academy Of Sciences Supports Turkey Deal
Armenia's National Academy of Sciences has officially given its support for its country's proposed normalization of diplomatic ties with Turkey during a closed-door session with Foreign Minister Eduard Nalbandian and more than 150 academics, RFE/RL's Armenian Service reports.
Armenian Currency Continues To Slide
The Armenian dram has lost nearly 6 percent relative to the euro and 3 percent to the U.S. dollar in the last three weeks, falling below the target level set by the authorities in March, RFE/RL's Armenian Service reports.
Nationalist Armenian Party Rebuffs Call For Unity
A leader of the Armenian Revolutionary Federation (Dashnaktsutyun) scoffed at former President Levon Ter-Petrosian's call for the creation of a coalition of opposition parties, telling Ter-Petrosian that "it's very nice to say something that you know won't happen," RFE/RL's Armenian Service reports.
Former Armenian Foreign Minister Slams Turkey Deal
Former Armenian Foreign Minister Vartan Oskanian has said that the proposed agreement normalizing relations between Ankara and Yerevan will give the Turks "everything they have wanted for 17 years," RFE/RL's Armenian Service reports.
Armenia's Hovannisian Blasts Feuding Party Members
Armenian opposition leader Raffi Hovannisian broke nearly two weeks of silence on September 22 by calling a bitter dispute between senior members of his opposition Zharangutyun (Heritage) party "unacceptable," RFE/RL's Armenian Service reports.
Clinton, Sarkisian Discuss Rapprochement With Turkey
U.S. Secretary of State Hillary Clinton has again telephoned Armenian President Serzh Sarkisian to discuss Yerevan and Ankara's ongoing rapprochement, which has been facilitated by the United States, RFE/RL's Armenian Service reports.
Erdogan Urges Progress On Nagorno-Karabakh
Turkish Prime Minister Tayyip Erdogan has urged international mediators to speed up efforts to resolve a dispute over the Nagorno-Karabakh enclave as Ankara aims to normalize ties with long-time foe Armenia.
Armenian Police Curb Travel To Yerevan Ahead Of Rally
Armenia officials again restricted transportation between Yerevan and its surrounding regions before a major opposition rally in the capital on September 18, RFE/RL's Armenian Service reports.
Yerevan Warns Ankara Over Fresh Karabakh Linkage
Armenia has criticized Turkish Prime Minister Recep Tayyip Erdogan for saying again that the normalization of Turkish-Armenian relations is conditional on an acceptable resolution of the Nagorno-Karabakh conflict with Azerbaijan, RFE/RL's Armenian Service reports.
Sarkisian Meets With Party Leaders Over Turkey Deal
Armenian President Serzh Sarkisian held a five-hour meeting on September 17 with more than 50 opposition party leaders concerned about the process of rapprochement with Turkey, RFE/RL's Armenian Service reports.
Armenian Opposition: President Weakened By Deal
A leading Armenian opposition leader says President Serzh Sarkisian will lose power if he presses head with the signing of controversial agreements normalizing relations with Turkey, RFE/RL's Armenian Service reports.
Turkish-Armenian Deal Looks Set For October 13
Armenian officials are not denying that the landmark agreements aimed at normalizing Turkish-Armenian relations will be signed on October 13, a date that has been reported in the press, RFE/RL's Armenian Service reports.


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Leonard John Fraser (27 June 1951 – 1 January 2007), also known as The Rockhampton Rapist, was an Australian convicted serial killer.

Biography
Fraser was born in Ingham, Queensland.

Raised in Ingham, Queensland.

Crimes
Before a life sentence on 7 September 2000 for the abduction, rape and murder of a 9-year-old girl, Keyra Steinhardt, in Rockhampton, Queensland, Leonard Fraser had spent almost 20 of the preceding 22 years behind bars for the rape of women. He even raped a terminally ill cancer patient, with whom he had been living in early 1997. He was subsequently charged with four murders. Police found many trophies of his victims in his flat and ponytails from three different women, which could not be traced to any of his known victims.

Fraser originally confessed to five murders in an apparent deal with police to avoid general population in prison, but one of those victims was 14-year-old Natasha Ryan, who was found to be alive and living secretly with her boyfriend in a nearby town after being listed as a missing person for five years. Although there was an obvious inconsistency with his confessions, his defence did not file for a mistrial. Nor did his defence object to the prosecution using the same confession made in custody, which included the Ryan confession, for three other victims whose remains were found. The Ryan 'murder' was also based on testimony from a fellow prisoner who alleged that Fraser drew detailed maps showing where Ms. Ryan's remains could be located. The judge in the case, Justice Brian Ambrose, heavily criticised the media for commenting on the value of confessions to crimes made to police under duress or to other prisoners while in custody, which might have affected the trial.

In 2003 Fraser was sentenced to three indefinite prison terms for the murders of Beverley Leggo and Sylvia Benedetti, and the manslaughter of Julie Turner in the Rockhampton area in 1998 and 1999. At his trial, the judge described him as a sexual predator who was a danger to the community and his fellow inmates.

Death
Fraser was being held at the Wolston Correctional Centre and, after complaining of chest pains, he was taken to a secure section of the Princess Alexandra Hospital in Woolloongabba, on 26 December 2006, where he died of a heart attack on 1 January 2007.

Media
Fraser's murders are the focus of the Crime Investigation Australia series 2 episode "The Predator: Leonard John Fraser" and Crime Stories episode "Leonard Fraser: the Rockhampton Rapist".

See also
List of serial killers by country

References

Bibliography

External links

1951 births
2007 deaths
Australian murderers of children
Australian people convicted of child sexual abuse
Australian people convicted of murder
Australian people who died in prison custody
Australian prisoners sentenced to life imprisonment
Australian rapists
Australian serial killers
Male serial killers
People convicted of murder by Queensland
People from North Queensland
Prisoners sentenced to life imprisonment by Queensland
Prisoners who died in Queensland detention
Serial killers who died in prison custody
Violence against women in Australia

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We hear a lot about the poor treatment of women in prostitution, but we seldom hear much about the men who are involved in the same thing. There are, however, a large number of male prostitutes as well, all of whom have suffered from abuse at the hands of other men.
One of the things that johns do is to beat up on the streetwalkers they see around. If you know anyone who has been robbed or attacked by a john, then you know that it happens more often to women than to men. That's why johns will sometimes attack or rob the prostitutes that are nearby just to cause them to go away. A john will go after these guys just for kicks, but it does happen on a regular basis.
Johns can do all sorts of things to get the most out of their prostitution. One of them is to get the prostitutes to have unprotected sex with them. This is a common practice among Johns, because it gives them the most opportunity to use violence. They can beat the women unconscious or hurt them enough to get them to do whatever they want them to.
Many of the prostitutes that are beaten have been arrested before, so when they are put on the street, there is very little they can do to defend themselves. That is one of the reasons why johns are much more violent toward the prostitutes than against the men who are working the streets as well.
A man who beats up another john does so because he has been forced into the same situation in the past. The john wants to continue to abuse the prostitute so he will let him beat her up, but he doesn't have to. The john doesn't feel like doing anything more about what happened to him, because he knows that he will be leaving his victim in jail, not in jail himself.
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If you have had problems with johns, then you should take some time to think about how to stop it. You can do this by stopping the john and telling him that you won't be dealing with him anymore. and that you are going to take your issues to a different area.
You can tell the john that you're going to take care of his problems and that you don't wish to deal with him. his behavior any longer.
In the meantime, if you still feel the need to deal with johns, you have several options. You can tell the john that you want to work in another area, which means that you are going to offer him sex with other women.
In many cases, johns will still try to fight you for the prostitutes you work with, but there will be some that will agree with you because they feel like you will never leave them alone after you tell them that you will no longer be coming around. with them. This is something that you need to remember.
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I am sharing my Pass It On Passport Mini Album today!
We are excited to announce that Eileen Hull now has a Fan Club!!!
Eileen Hull's Journal Fan Club was originally started to share the "New" Journal that she recently released with Sizzix but we discovered quickly that we needed to change the name to Eileen Hull's Fan Club since she has a very large following that is equally as excited about her dies as we are.
I began by die cutting the Passport Book and pages using Sizzixcream mat board.
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text:
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Giovanni Ferraguti (born 1939)
Professione Reporter (Profession Reporter)
30 x 40 cm. Signed by photographer. Giovanni Ferraguti, an Italian photographer and journalist, became interested in photography at the age of 13, when his mother gave him a camera as a present. This gave a start to a great passion that prompted him to learn the first rudiments of Photographic Art in a studio in Parma. In 1965, he was hired by the Gazzetta di Parma as the first official photographer of the city newspaper. Later, after obtaining a degree in journalism in Rome in 1979, he was hired by the same newspaper as professional journalist. With the Gazzetta di Parma, he worked as a journalist reporter for thirty-five years, from 1965 to 2000. He was also a correspondent for the international Associated Press agency for thirty years and for five of the newspaper Secolo XIX in Genoa.


text:
Q: Standard deviation of function of two RVs I've stumbled upon a problem that basically reduces to having two random variables
$$X \sim N(\mu_X,\sigma_X)$$
$$Y \sim N(\mu_Y,\sigma_Y)$$
and defining the third as
$$Z = \sqrt{X^2 + Y^2}$$
Although it would be convenient to have the exact expressions for mean and standard deviation I can safely assume the coefficients of variation $V_X$ and $V_Y$ are small, therefore I deduced
$$\mu_Z \approx \sqrt{\mu_X^2+\mu_Y^2}$$
but the standard deviation is giving me a hard time
$$\sigma_Z \approx \;??$$
Does anyone have any pointers on how to determine it?
Answer:
It turns out using a multi-variate Taylor expansion about $X = \mu_X, Y = \mu_Y$ leads to the best result, a first order approximation writes
$$Z \approx \sqrt{\mu_X^2+\mu_Y^2} + \frac{\mu_X}{\sqrt{\mu_X^2+\mu_Y^2}}(X-\mu_X) + \frac{\mu_Y}{\sqrt{\mu_X^2+\mu_Y^2}}(Y-\mu_Y)$$
such that
$$\mu_Z \approx \sqrt{\mu_X^2+\mu_Y^2}$$
$$\sigma_Z \approx \sqrt{\frac{\mu_X^2 \sigma_X^2 + \mu_Y^2 \sigma_Y^2}{\mu_X^2 + \mu_Y^2}}  $$

A: I'm not sure I understand how you got $\mu_Z$ but assuming you have it, by definition:
$$\sigma_Z^2 = Var(Z) = \left<Z^2\right>-\mu_Z^2$$
Now
$$\left<Z^2\right> = \left<X^2+Y^2\right> = \left<X^2\right>+\left<Y^2\right>$$
Which, using the difintion, $\sigma_X^2 = \left<X^2\right>-\mu_X^2$ becomes
$$\left<Z^2\right> = \left(\sigma_X^2+\mu_X^2\right) + \left(\sigma_Y^2+\mu_Y^2\right)$$
Therefore
$$\sigma_Z^2 = \sigma_X^2 + \sigma_Y^2 +\mu_X^2 +\mu_Y^2 - \mu_Z^2$$

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text:
The Guadalcanal American Memorial is a World War II monument  on Guadalcanal in Solomon Islands. Dedicated on August 7, 1992, it was established as a tribute to the Americans and their allies who lost their lives during the Guadalcanal Campaign from 7 August 1942 to 9 February 1943. The capital city of Honiara is to its north. To mark the 50th anniversary of the Red Beach landings, the U.S. War Memorial was dedicated on 7 August 1992. An account of this is also inscribed on red marble tablets inside the monument compound. The memorial was a joint effort of the American Battle Monuments Commission (ABMC) and the Guadalcanal-Solomon Islands Memorial Commission, and was at the initiative of Robert F Reynolds, Chief of Valors Tours Ltd. The memorial is maintained by the ABMC. Every year on 7 August, a commemorative ceremony is held to mark the first day of the battle. Another monument, erected by the Japanese on Mount Austen, is a tribute to the Japanese who lost their lives.

Background
The US Navy, Marine Corps, Army and their allies fought the forces of the Empire of Japan at Guadalcanal during World War II from August 7, 1942, to February 9, 1943, to take control of the island where the Japanese had established a strong base. During the six-month period, bitter fighting took place on land, in the air, and at sea, until the Japanese voluntarily withdrew after several setbacks in the seven major naval battles and clashes in the air. The American forces were ultimately victorious. The Japanese evacuated the island from Cape Esperance on the north west coast in February 1943.

The bitter struggle that took place in which both "slugged it out toe to toe", resulted in loss of 1200 aircraft, 49 ships and as many as 35,000 American and Japanese men. It was uncertain as to who would ultimately prevail. When the Japanese capitulated and withdrew, the Japanese Major General Kiyotake Kawaguchi who was assigned the task of destroying the American Marines said "Guadalcanal is not the name of an island. It is the graveyard of the Japanese Army". The conflict turned the tide against Japan and it was a decisive battle of the Pacific War, won by the effective joint action of all arms and services of the United States, and in which the marines played a crucial part.

Japanese losses were immense, including 800 aircraft and 2362 pilots and crew. The Americans lost 24 warships totaling 126,240 tons, but had the resources to recoup their losses, and American dead were one tenth of the total 50,000 deaths in the battle. It was in this battle that the legend of "the invincibility of the Japanese soldier and Zero fighter plane" were destroyed.

In this longest campaign of the Pacific War, 65,000 American forces committed were from the US Marine Corps, US Ground Forces and US Navy construction units. The combined losses of all these forces amounted to: Killed including from injuries and missing were 1,342 of the Marine Corps and wounded were 3,170; US Navy lost 4,737 including missing at sea and 2,344 were wounded; US Army's Americal Division lost 344 while 855 were wounded; US 25th Infantry division (late entrant into the battle) lost 216 with 439 wounded; USAAF Thirteenth Air force lost 93 while many were injured; US Navy lost 41 airmen and the Marine corps air arm lost many but their number has not been disclosed. Americans who were taken prisoner were never heard of again.

Features

The memorial is located on Skyway Drive on a hillock (the first hill that was occupied by the US forces) overlooking the Pacific Ocean. It is to the west of the Matanikau River, which was the battle front for many months between the Americans and the Japanese, with a commanding view of Mount Austen and Ironbottom Sound. In the shape of a pylon, the memorial is spread over a large area. The main memorial is  in size and  in height. The four fascia of the monument are oriented towards the four directions where the battles were fought. The details of the five battles and the names of ships (of the US and its Allies) that were lost during the operations are inscribed on marble plaques. The plaques give a brief description of the five battles fought – Bloody Ridge ("Edson's Ridge"), Tassafaronga at Ironbottom Sound, New Georgia Island (which was the Solomon Island campaign), Cape Esparance and  Mount Austen.

The memorial inscription reads:

"This memorial has been erected by the
United States of America
in humble tribute to its sons and its allies
who paid the ultimate sacrifice
for the liberation of the Solomon Islands
1942–1943"

References

Bibliography

Honiara
Guadalcanal Campaign
1992 establishments in the Solomon Islands
Monuments and memorials in Oceania


text:
J Crohns Colitis. 2016 Apr;10(4):462-71. doi: 10.1093/ecco-jcc/jjv223. Epub 2015 Dec 9.
Mucosal Barrier Depletion and Loss of Bacterial Diversity are Primary Abnormalities in Paediatric Ulcerative Colitis.
Alipour M1, Zaidi D1, Valcheva R2, Jovel J2, Martínez I3, Sergi C4, Walter J5, Mason AL2, Wong GK6, Dieleman LA2, Carroll MW7, Huynh HQ7, Wine E8.
Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada Department of Medicine, University of Alberta, Edmonton, AB, Canada.
Department of Agriculture, Food, and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada Department of Agriculture, Food, and Nutritional Science, University of Alberta, Edmonton, AB, Canada Department of Biological Sciences, University of Alberta, Edmonton, Canada.
Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada Department of Medicine, University of Alberta, Edmonton, AB, Canada Department of Biological Sciences, University of Alberta, Edmonton, Canada Beijing Genomics Institute-Shenzhen, Beishan Industrial Zone, Yantian District, Shenzhen, China.
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, Canada Department of Pediatrics, University of Alberta, Edmonton, AB, Canada wine@ualberta.ca.
BACKGROUND AND AIMS:
Ulcerative colitis [UC] is associated with colonic mucosa barrier defects and bacterial dysbiosis, but these features may simply be the result of inflammation. Therefore, we sought to assess whether these features are inherently abrogated in the terminal ileum [TI] of UC patients, where inflammation is absent.
TI biopsies from paediatric inflammatory bowel disease [IBD] subsets [Crohn's disease [CD; n = 13] and UC [n = 10]], and non-IBD disease controls [n = 12] were histologically graded, and alcian blue/periodic acid-Schiff stained biopsies were quantified. The mucosal barrier was assessed for mucin [MUC2], immunoglobulin [Ig]A, IgG, and total bacteria (fluorescence in-situ hybridisation [FISH probe EUB338]) by immunofluorescence. The regulation of mucin secretion was investigated by NLRP6 gene expression and immunofluorescence. The composition of the active mucosa-associated microbiota was explored by sequencing the 16S rRNA amplicon generated from total RNA.
Despite the absence of ileitis, UC patients displayed ileal barrier depletion illustrated by reductions in mucin-containing goblet cells and mucin production and altered epithelial NLRP6 expression. In both CD patients with ileitis and UC patients with normal histology, bacteria coated with IgA and IgG penetrated the TI mucin layer. Biopsy 16S rRNA sequencing revealed a reduction in α-diversity by three methods [Shannon, Simpson, and Equitability indices] between UC and non-IBD paediatric patients.
These findings suggest an underlying defect in the UC-afflicted intestinal tract even in the absence of inflammation, implicating barrier and microbial changes as primary abnormalities in UC that may play a causative role in disease development.
Copyright © 2015 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Ulcerative colitis; mucin; mucosal barrier
10.1093/ecco-jcc/jjv223
Ulcerative colitis [UC] patients demonstrate mucous barrier reduction and an elevated mucosa-bacterial interaction even in the absence of ileitis. [A] Scatterplot representation of histology showed ileitis in Crohn's disease [CD] and its absence in UC and non-inflammatory bowel disease [IBD] groups. [B] Compared with the non-IBD and CD groups, the mean numbers of mucin-containing goblet cells per villous crypt were significantly reduced in the terminal ileum [TI] of the UC group. [C] Compared with the non-IBD group, mucous production expressed as % of epithelial surface covered with mucin [see Supplementary Figure S1, available as Supplementary data at ECCO-JCC online] in the epithelia-lumen was significantly reduced in the UC group. [D] Representative AB/PAS-stained TI biopsies showing reduced mucin in UC. Bar is 100 µm; inset image is 400X. [E] Immunostaining for mucin [MUC2], IgA, IgG, and bacteria, showing bacteria virtually absent from the mucosal layer in non-IBD patients. In contrast, in CD and UC bacteria were in close proximity to the epithelial lining with an increase in association with IgA and IgG. Lu, lumen; images showing mucin or Ig [top right] and bacteria [bottom right] were cropped digitally using the ZEN software, and the dashed lines were digitally added to mark the epithelial surface; bar is 50 µm. Statistically significant differences between two groups are indicated by an asterisk [p < 0.05] or double asterisk [p < 0.01]; ns, not significant. Note: the epithelial tissue structures visualised [shown in orange] are caused by autofluorescence resulting from fluorescence in-situ hybridisation [FISH]; in contrast, bacteria appear as clear orange clumps.
Mucosal Barrier Depletion and Loss of Bacterial Diversity are Primary Abnormalities in Paediatric Ulcerative Colitis
J Crohns Colitis. 2016 Apr;10(4):462-471.
Ileal NLRP6 location is altered in inflammatory bowel disease [IBD]. [A] NLRP6 gene expression in ileal biopsies as measured by quantitative reverse-transcription polymerase chain reaction [qRT-PCR] [relative quantification, RQ]. Data are expressed as median with interquartile range, minimum and maximum. [B] Representative immunofluorescence of biopsies stained for NLRP6 protein showed expression in the lamina propria and proportionately distributed throughout epithelial cells of non-IBD group, with lower and intermittent epithelial distribution in both IBD subsets. Lu, lumen; LP, lamina propria; arrowhead, NLRP6-expressing cell in the LP; bar is 50 µm. The dashed lines were digitally added to mark the epithelial surface.
Perturbations in ileal microbial composition in inflammatory bowel disease [IBD]. [A] Principal coordinates analysis [PCoA] of BrayCurtis dissimilarity showed approximately half of Crohn's disease [CD] and ulcerative colitis [UC] samples had a microbiota composition that was different from most non-IBD patients. [B] Relative abundance at the phylum level for each individual patient [identified by the patient study code number] showing extensive changes in several CD patients. [C] Relative abundance at family level [calculated as change in total fraction compared with non-IBD] showed gains in Enterobacteriaceae in IBD subsets, with Bacteroidaceae loss in CD and gain in UC. No statistically significant difference between the groups was found using BenjaminiHochberg false discovery rate correction.
Bacterial α-diversity comparison and heatmap of relative bacterial species abundance. [A] Bacterial α-diversity of individual patients. Statistical comparison between groups, made by one-way analysis of variance with Bonferroni's multiple comparison post-test, indicated reduced diversity in ulcerative colitis [UC] compared with non-inflammatory bowel disease [IBD]. Asterisk, p < 0.05; double asterisk, p < 0.01. Statistical comparison between non-IBD and CD, as well as CD and UC, did not show significance. [B] Minimum entropy decomposition nodes were identical [100% similarity; coverage 100%] to the reported species/strain. However, in many cases, more than one identical sequence was found in the subject database and therefore the reported taxa represent only taxonomical approximations. Data represented as log2. Patterns of alterations at the species level are observed; however, no statistically significant difference was found between the groups when using Benjamini-Hochberg false discovery rate correction.
Publication type, MeSH terms, Substance, Grant support
Colitis, Ulcerative/microbiology
Colitis, Ulcerative/pathology*
Crohn Disease/microbiology
Crohn Disease/pathology
Gastrointestinal Microbiome*/genetics
Ileum/microbiology
Ileum/pathology
In Situ Hybridization, Fluorescence
Intestinal Mucosa/pathology*
RNA, Ribosomal, 16S/genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Ribosomal, 16S
Canadian Institutes of Health Research/Canada
Ulcerative Colitis - Genetic Alliance
Ulcerative Colitis - MedlinePlus Health Information


Hi gorgeous! As I was creating this meditation in my living room (with Monkey on my lap 😻), I stopped to reflect on the Love Your Body Series and how powerful it's been to meditate with you each week. Meditation allows us to connect with ourselves, heal our mind, and let more positivity and joy into our lives. It's been life-changing for me, and I feel so grateful that I've been able to share it with you. So THANK YOU for joining me!
This is the final week of the Love Your Body Series but it's not the end of caring for our minds, bodies, and souls together ~ it's just the beginning for us! This week's intention is momentum. After six weeks of this Series, you have SO MUCH incredible momentum. You've been showing your body all the love it deserves, you're feeling strong and confident, and you have a community of girlfriends who support you. Take all that with you into the next part of your journey, and you have everything you need to live your best life!
These mindful meditations have been my absolute favorite lately! Karena you are so inspiring! Thank you for sharing your wisdom and these amazing meditations with us! They have been so awesome.
Karena, this one was the best yet. I know I should listen to it every single morning – and afternoon (because I seem to forget all of these things at 4:30). Could you please put these on Spotify? I'd love to listen as I'm walking in the morning – and as afternoon alternative to scrounging around the office kitchen.
Thank you so much for these beautifully inspiring meditations, Karena! I love how they help me set the tone for my day. Looking forward to every day with you .
Karena I love these meditations. Thank you so much for making them.I have never meditated before but have been feeling very stressed and anxious lately. These meditations have helped tremendously. Are there any other meditations your recommend while I anxiously await you to do more for the bikini series?
Thanks for the wonderful meditation session!
thank you so much for these meditations, its a great way to start my day!


text:
Work begins on North East's first rail academy
By Ruth Lognonne
The region's first railway academy is taking shape, bringing the future of rail engineering to the North East
Principle of Newcastle College, Carole Kitching in the new rail academy
The region's first railway academy is taking shape, bringing the future of rail engineering to the North East.
Work has started on Newcastle College's £5m state-of-the-art training facility which is being built on land between Heworth and Pelaw.
The school will be up and running by September and aims to train 800 students over the next five years.
The Government has already pledged billions of pounds to improving Britain's rail infrastructure and the college says the region's rich rail heritage and engineering prowess stand it in good stead to take advantage of future job opportunities.
Carole Kitching, principal of Newcastle College, said: "It's exciting to see our ambitious plans to develop a rail academy taking shape so quickly.
"It's become clear that young people and adults in the North East are just as excited by the training and employment opportunities in the rail industry as we are. Applications for places in September are pouring in daily and we are encouraging people to apply as soon as possible.
"We are delighted to see industry support continue to grow as this involvement is critical in ensuring we deliver exactly the right training for the skilled employees they need."
The college is working with a number of key stakeholders on the project, including Network Rail and The National Skills Academy for Railway Engineering (NSARE). It will train people from GCSE through to degree level and will include qualifications in electrification, signalling and telecommunications.
The project has already won support from the North East's own light rail system, Nexus, and London Underground, which is donating equipment to the new academy.
The college's deputy principal, Robin Ghurbhurun, said more than 1,000 rail workers across the region will be ready to retire in the next five years.
And with Hitachi due to open its £82m train-building facility in Newton Aycliffe, County Durham, in three years, Mr Ghurbhurun believes now is the time to train a workforce ready for the plant when it arrives.
He said: "Our aim is to up-skill individuals to take advantage of jobs available in the future. It's really about bringing the future of rail to the North East. There's a real buzz around the region's manufacturing community, what with Hitachi's confirmed location here.
"There's also the plethora of job opportunities that will come on the back of the Government's proposed High Speed Rail project. The existing workforce within the region's rail industry, with no growth at all, is 1,000 workers and they're due to retire over the next five years.
"Nationally, more than 25,000 people in the rail industry are due to retire in the next 10 years. It's vital to ensure we replace that workforce with the level of skills that will be required."
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