text:
Roadblocks to Intimacy and Trust II
Psychological Defenses: Often Our Salvation
Note to Reader: As a licensed psychologist, I strictly adhere to the ethics of confidentiality; therefore, I do not use/make reference to any patient/client information in the pieces I write. The only data I use to explore these psychological issues is my own. The Roadblocks to Intimacy & Trust Series will include several pieces related to the effects of early relationships on the development of trust and intimacy.
With an ambivalent mother as the barometer of mood and well-being (often it's opposite), our home was a threatening place. She knew all and saw all, and though there's still a part of me that wants to refute it, her responses were violent. But the young Joan didn't know that; in fact, this is the first time in my life that I've described my mother as violent. I can feel the trembling in my chest as I write this. My impulse is to soften that word—to insist that I'm overstating. Certainly, violent is not the way I want/wanted to see her. Nor the way I was taught to view her. Because she had presented such a positive persona to us, Dad, and the world (My kids are my life), I didn't see her treatment as abuse. Nor was I angry with her: it wasn't her fault. It was a flaw (more likely several) in me that caused her to erupt or refuse to speak. Clinically speaking, I had introjected her. Simply put, I saw myself as she saw me (as I believed she saw me). Her behavior told me that something was wrong with me—I didn't love her enough or I was inherently bad. And I swallowed that whole. This introjection of the parent, particularly the mother, is the cornerstone on which the child's sense of herself is constructed and the bedrock of what we come to know as the superego or conscience.
Hence the damage occurs very early in a child's life. He/she has learned to dislike, disapprove of, even hate him/herself. It became my quest to monitor what seemed to please and displease my mother and to tailor myself according to that template—what would make her love me? Though there were times when her love was apparent, the opposite was also true, so I could never be sure (and according to Skinner's theory of reinforcement, it is intermittent reward that is the most effective. The subject continues to behave at the highest level when the pattern of reward is irregular. The outcome cannot be predicted so the effort must be constant). Thus began my unrelenting effort to discover what she wanted and to become that person. Anything to end the silences or quiet the rage.
And Mom's anger was lethal. Initially, my three siblings got regular beatings with the belt. I was spared for several years because I was 'nervous' and diagnosed as such by our doctor when Mom took me to see him to explain the belly pains I was getting regularly. These started with a 'spastic colon' and accelerated into colitis as I got older (I also developed other physical problems which will be explored in a later chapter of this series). The other reason I escaped the strap, (besides the fact that I was as close to a perfect kid as she could have imagined) was that I responded to her rages with uncontrollable trembling—until one day she turned on me yelling, Maybe this will stop the shaking! and flung the strap at me as well. After that, I got beat just like everyone else (though not as often because I was obsessive in my attempts to be good). Mom was convinced that I'd been faking, and there was no way she'd let me 'pull the wool over her eyes'! The attack succeeded—even I believed I was pretending. To this day, I'm not sure what the truth is.
One wonders how these children and the multitudes of abused children (many under the guise of spare the rod, spoil the child brand of parenting) cope with the dissonant messages from parents. They're loved, not loved; they're good, bad; they belong; they're outsiders. They can do little or nothing to combat the physical abuse (other than, as discussed in an earlier chapter, to enlist the more loving parent or grandparent, uncle or aunt, perhaps teacher or clergy person who might potentially intervene. But that seldom happens; the child has to have a sense of his/her own rights to complain about his/her parent's treatment. Most do not. To do that would be a betrayal. [Yes, despite all of the abuse, the child still remains faithful to the parent]. Instead, they keep trying to escape the wrath and appease the angry parent. The fault is with them; it's their badness that keeps the parent enraged).
On the other hand, there are psychological tools or defenses that the child naturally (unconsciously) reverts to to make sense of their world. In fact, these defenses are essential in protecting ("defending") against the loss of sanity. One cannot maintain sanity believing two opposite realities. Our brains demand stasis, logic, order. As is the case with the child mentioned above, he/she cannot live with the truth that the parent is cruel; rather, it's less traumatic to identify with the aggressor and see the self as flawed. In my own case, though my home was, in reality, a dangerous place, I'd never have admitted it was anything but idyllic. That's the power of psychological defenses. Profound in their facility to rewrite history, they assist the child/adult in avoiding truths too painful to know/admit consciously: i.e. the awareness that one's family is troubled and unsafe, that a parent is mean or evil, that they hate their cruel brother or envy their sister. Denial buries these from the conscious mind and replaces them with fictions that are easier for the child to tolerate. Thus, I was convinced that ours was a loving mother and a loving home.
(Particularly impressive is the power of dissociation in children/adults who have been sexually abused. The knowledge that his/her parent has violated the child in such a heinous way is close to impossible to assimilate. Add to that the fact that in most cases the parent continues to be a presence in the child's life (often displaying otherwise parent-appropriate behavior and affection)—perhaps sitting across the table for breakfast or dinner. How does that child not explode or disappear into insanity? He/she splits off separating the intact self from the one violated).
And it's not just children who employ defenses. We all do. Certainly my father was insulated by denial in continuing his delusion that Mom was a loving mother who harbored no ill will against her children. My mother's defenses remained intact as well (I will explore her psychological development in a further chapter); with reaction formation she was able to convince herself that she was who she wanted to be. She needed to see herself as a good mother who gave all for her children and found her happiness in mothering. And so she did. She died believing that.
It's important to note, however, that though these truths disappear from the conscious mind, they are not erased completely; they still exist in the unconscious mind [psychology teaches that we have a conscious, a preconscious and an unconscious mind] and can wreak their own havoc on the psychological development of the child continuing their erosion into adulthood until such time that they become conscious and are worked through—most likely in psychotherapy. (That process is complicated and involves teasing out the source of the person's misperceptions and confronting them; the patient/client and the therapist become partners in a kind of research project aimed at discovering who this person is and where he/she came from—making conscious the unconscious. That's the goal of therapy. The decision to enter therapy usually stems from the individual's dissatisfaction with his/her ability to achieve happiness—be it in relationships, professional life or overall peace with one's life and self).
Finally, though defenses develop unconsciously out of a need to make sense of a dissonant reality, and are therefore essentially good, they often become problematic (outdated, if you will) when they continue to protect us in environments that are actually safe, in other relationships that may well be loving. When the young man or woman continues to see all potential partners as replacements of the parents—forbidding, demanding acquiescence, hypercritical—and to respond as such, intimacy and trust with another becomes virtually impossible. Our defensive response is no longer appropriate. We expect the world to treat/view us as our parents did. But the world isn't our parents. Some may be like them, but not all. It becomes our challenge and that of therapy to recognize the difference.
The following is a list of commonly used defense mechanisms many of which will be discussed further in subsequent sections of The Roadblocks to Intimacy and Trust series:
Repression: "Keeping distressing thoughts and feelings buried in the unconscious"
Denial: "Refusing to accept reality or fact, acting as if it isn't so/didn't happen"
Rationalization: "Creating false but plausible excuses to justify unacceptable behavior"
Identification: "Bolstering self-esteem by forming an imaginary or real alliance with some person or group"
Displacement: "Diverting emotions (usually anger) from their original source to a substitute target"
Projection: "Attributing one's own thoughts, feelings, or motives to another"
Regression: "A reversion to immature patterns of behavior"
Reaction Formation: "Behaving in a way that is the exact opposite of one's true feelings"
Sources: Weiten, Wayne. Psychology: Themes and Variations. Thomas Wadsworth
Upcoming: Roadblocks to Intimacy and Trust III: The Passive Father
About cre8d
Talk with Joan
Bryant Park Reading Room Celebrates CavanKerry Press
Roadblocks to Intimacy and Trust III


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Q: Distinct counts from large table are too slow I have a table with 1.2 billion rows. The table has 60-70 columns, the vast majority of which are empty.
The table is indexed on subscription_id, among other indexes.
My query is:
SELECT count(distinct listing_id)
FROM apps
WHERE subscription_id = 1298;

This particular subscription_id is going to have roughly 30M rows to count. Unfortunately I am unable to do so as the query takes in excess of one hour just to  get that count.
I know there must be some way to improve it. Would it be improved if I created an index on subscription_id and listing_id together?

A:
Would it be improved if I created an index on subscription_id and listing_id together?

Possibly yes, an index on (subscription_id, listing_id) (columns in this order!) might very well allow a cheaper index-only scan. You did not provide enough information to say more.
If it's all about this particular subscription_id, then a partial index would help a lot more:
CREATE INDEX ON apps (listing_id) WHERE subscription_id = 1298;

If there are more than a few duplicate listing_id per subscription_id, use
this adapted query with a recursive CTE:
WITH RECURSIVE rcte AS (
   (
   SELECT listing_id
   FROM   apps
   WHERE  subscription_id = 1298
   ORDER  BY listing_id
   LIMIT  1
   )

   UNION ALL
   SELECT a.listing_id
   FROM   rcte r
   JOIN   LATERAL (
      SELECT a.listing_id
      FROM   apps a
      WHERE  a.subscription_id = 1298
      AND    a.listing_id > r.listing_id
      ORDER  BY a.listing_id
      LIMIT  1
      ) a ON a.listing_id IS NOT NULL
   )
SELECT count(*) FROM rcte;

Requires index from above to be fast. For many duplicates it can be faster by orders of magnitude. The point is to work around a still missing (up to Postgres 12) index skip scan. See:

*

*Fast way to count distinct column values (using an index?)

*Optimize GROUP BY query to retrieve latest row per user
If, OTOH, there are no duplicate listing_id, then get rid of DISTINCT to make it a lot faster.

redpajama_set_name: RedPajamaStackExchange


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Texas gunman escaped mental health facility in 2012, threatened military superiors
by Matt Pearce, Los Angeles Times Nov 7, 2017 2 minutes
The gunman who killed 26 people at a Texas church last weekend escaped a mental health facility in 2012 and made death threats to his superiors in the U.S. Air Force, according to newly revealed El Paso, Texas, police records.
The Comal County Sheriff's Office also announced Tuesday that gunman Devin Kelley had been accused of sexual assault
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Chicago Tribune3 min readSociety
Father Pushes Teen Son Out Of Way As Gunfire Erupts In Chicago: 'He Thought His Daddy Tripped'
CHICAGO - Darnell Simmons was walking out of a West Side store with his teenage son and another boy when the gunfire started. Simmons pushed his son out of the way and then fell to the ground, the teen later told Simmons' cousin, Dedrick Wilborn. "He
People2 min readSociety
U.s.a. Gymnastics Scandal Facing Down A Monster
Scores of young athletes confront the team doctor who sexually abused them, as a judge sentences him to up to 175 years in prison
Nightmare at the Airport
Friends and family share stories of the loved ones who were killed when a gunman attacked a Florida airport
More from Los Angeles Times
Los Angeles Times4 min readPolitics
Fantasy collided with reality when the nominations for the 71st Emmy Awards were announced Tuesday: The Television Academy overwhelming chose to fly with dragons and tackle real-world racism, all in the same election cycle. The final season of "Game
Los Angeles Times2 min read
Xxxtentacion's Estate Teases New Song, 'Royalty,' One Year After His Death
The estate of the late rapper Xxxtentacion is expected to release a new track by the artist on Friday, called "Royalty," feeding a demand that shows no signs of slowing down a year after his death. A snippet of the song has been floating around the i
Team In No Hurry To Move Julio Urias From His Current Bullpen Role
PHILADELPHIA - The Los Angeles Dodgers' need for a reliable, conventional left-handed reliever was never more obvious than in the ninth inning against the Boston Red Sox on Sunday night. The score was tied with Jackie Bradley Jr., a left-handed batte

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E3 Spark Plugs >> Results of NHRA 4-Wide Action at the Strip
Salinas, Todd, and Butner Win Four-Wide Nationals at the Strip
Northern California native Mike Salinas picked up his first career NHRA win in Top Fuel dragster at Las Vegas Motor Speedway when the Strip hosted the 20th annual DENSO Spark Plugs NHRA Four-Wide Nationals.
Having built his California-based scrap metal and garbage hauling business from scratch, Salinas has applied the same winning philosophy of surrounding himself with lots of talent. For the 2019 Mello Yello Drag Racing season, the 57-year old hired former Brittany Force crew chief Brian Husen to join his long-time tuning advisor Alan Johnson at Scrappers Racing. As an added bonus, Husen was able to bring several John Force Racing teammates with him, as JFR announced their intention to move in a new direction.
Reigning Funny Car world champion J.R. Todd drove the DHL Toyota Camry to a 3.970 ET at 319.07 mph to claim the win in Funny Car at the Las Vegas track. Todd eliminated an impressive threesome that included number one qualifier Tim Wilkerson, "Fast Jack" Beckman and eventual runner-up Tommy Johnson Jr. on his way to the victory podium. It was J.R. Todd's third consecutive events win at the Strip. When he returns to Las Vegas Motor Speedway in the fall, Todd will attempt to join Greg Anderson and Erica Enders as the only Pro Stock drivers to win four consecutive events at the Vegas track.
Driving for Las Vegas businessman Ken Black, seasoned Pro Stock veteran Bo Butner relied on a triple holeshot in the Finals to claim victory over runner-up Matt Hartford. Butner's .030 RT may not have been the fastest light of the weekend but it was good enough to earn him another Wally for the trophy case. Butner now owns three of the first four Wallys handed out in Pro Stock for NHRA 2019 season. It was Butner's first win four-wide competition and his second win at the Strip in Las Vegas. With ten Pro Stock wins, Butner and his K.B. Racing Camaro will be sidelined for three races as Pro Stock division's reduced class schedule for 2019 returns to action at Richmond on May 17-19 for the Virginia NHRA Nationals.
The rest of the NHRA teams will travel east for the Mopar Express Lane NHRA SpringNationals presented by Pennzoil on April 12-14 at Houston Raceway Park.


text:
Canadian Minister of the Environment and Climate Change, Steven Guilbeault (L) speaks with the delegate for Costa Rica before the plenary for the tail end of the United Nations Biodiversity Conference (COP15) in Montreal, Quebec, Canada on December 19, 2022. (Photo by ANDREJ IVANOV / AFP)
After years of negotiations, the world has agreed on a landmark deal to protect vanishing species and ecosystems, dubbed a "peace pact with nature" at the UN meeting in Montreal called COP15.
After years of negotiations, the world has agreed on a landmark deal to protect vanishing species and ecosystems, dubbed a "peace pact with nature" at the UN meeting in Montreal called COP15.
Here are some of its strengths, as well as where it fell short.
– '30 by 30′ –
The cornerstone of the agreement is the so-called 30 by 30 goal — a pledge to protect 30 percent of the world's land and seas by 2030.
Currently, only about 17 percent of land and seven percent of oceans are protected. The oceans target had reportedly been opposed by some countries but made it into the final text.
And some experts had said 30 percent is a low aim, insisting that protecting 50 percent would be better.
– Indigenous rights –
About 80 percent of the Earth's remaining biodiverse land is currently managed by Indigenous people, and it's broadly recognized that biodiversity is better respected on Indigenous territory.
Activists wanted to make sure their rights are not trampled in the name of conservation — previous efforts to safeguard land have seen Indigenous communities marginalized or displaced in what has been dubbed "green colonialism."
In the end, Indigenous rights were addressed throughout the text, including in areas covered by the 30 by 30 pledge — safeguarding Indigenous peoples' right to remain stewards of the land they use and ensuring they are not subject to mass evictions.
The International Indigenous Forum on Biodiversity praised the text for its "strong language on respect for the rights of Indigenous Peoples and local communities."
– Finance –
Finance remained the overriding question.
Developing countries say developed nations grew rich by exploiting their resources and the South should be paid to preserve its ecosystems.
In the end, the text approves the objective for rich countries to provide "at least US$20 billion per year by 2025, and … at least US$30 billion per year by 2030," approximately double and then triple the current international aid for biodiversity.
It also includes new language that mentions funding from "developed countries, and from countries that voluntarily assume obligations of developed country parties," which a Western source told AFP was meant to involve the United States.
Washington is not formally a part of the Convention on Biological Diversity but is supportive of its goals.
Developing countries were also seeking a new funding mechanism, as a signal of the rich world's commitment to this goal, but developed nations said it would take several years to create.
In the end, a halfway solution was adopted: creating a "trust fund" within an existing financial mechanism called the Global Environment Facility, as a stepping stone to a new fund in the future.
– What was missing –
An overriding concern by campaigners was that the final text did not contain enough "milestones" — key statistical measures countries should achieve before the year 2050.
For example, the text says human-induced extinction of known threatened species is halted, and, by 2050, the extinction rate and risk of all species are reduced tenfold — but there aren't targets that countries must hit before that year.
Also watered down was a mandate for businesses to assess and report on the biodiversity impacts — instead, they are merely "encouraged" to do so.
bur-ia/rlp/mtp
Tags: biodiversity environment extinction human rights indigenous people
Foxconn ends 'closed loop' at iPhone megafactory in China


text:
James A. Feldman
David W. Lee
Brandon M. Feldman
Katherine M. Chrostowska
Patrick J. Feldman
Trang H. Nguyen
Kent Office
Marysville Office
Contact Us Click to Call
Drug Defense Attorneys in Washington
Washington Drug Lawyer Serving Kent, Lynnwood, and Marysville
Washington law enforcement and prosecutors vigorously pursue drug crimes. While in some states, possession of illegal drugs is a misdemeanor, in Washington it's a felony–the only exception is small quantities of marijuana. As authorities recognize that there is an ongoing problem with illegal drugs in Washington State, they have invested greatly in resources that identify illegal drug distribution channels.
A drug charge is serious business. For years, states have been increasing the penalties for everything from simple drug possession to felony drug trafficking. At Feldman & Lee, our lawyers defend clients with all types of drug charges ranging from possession of marijuana or paraphernalia to felony VUCSA or intent to distribute. If you or a family member faces drug charges, you need a tenacious, knowledgeable lawyer to defend you. Contact Feldman & Lee to talk to an experienced criminal defense lawyer.
Drug Offenses in Washington
Drug offenses in Washington state can range from simple possession of illegal drugs in small quantities to very serious felonies that involve the manufacture, trafficking, and sale of controlled substances including heroin, cocaine, steroids, methamphetamines, and other illegal narcotics. The possession of drug paraphernalia and drug fraud (the unauthorized sale, use, or distribution of prescription medicines) are also seen as drug crimes by the law.
Washington State's Initiative 502 (I-502) has decriminalized the use of recreational marijuana in November 2012. This law has allowed a regulated, licensed system, of marijuana production and distribution. But I-502 does not preempt federal law. Therefore the possession, production, sale, distribution, and use of marijuana is still against US federal law and may still be subject to prosecution. Also note that one must be at least 21 years old to be able to legally consume marijuana.
The penalties for drug offenses will depend on the quantity of drugs involved, the nature of the charge, and whether you have any criminal history. They are often severe and are likely to have adverse effects on your life and your future. Court-mandated consequences for drug charges include:
Heavy Fines
As any drug charges will remain on your permanent criminal record, it can jeopardize future employment or career advancement. A drug conviction may also disqualify an individual for receiving state or federal aid in the form of student loans.
In the face of life-altering penalties, it's imperative to retain the services of an attorney who has knowledge and actual experience handling drug defense cases. At Feldman & Lee, PS, our skillful attorneys handle drug cases that involve:
Intent to distribute
Illegal prescriptions
Possession of Marijuana, Cocaine, Ecstasy, Meth, and Illegal Prescriptions and Narcotics
Drug misdemeanor or felony charges will adversely affect your relationships — they will alter your career, your life, and your future. When facing charges for illegal drug possession or any other narcotic crime, seek the legal advice and service of Feldman & Lee PS.
The success of a drug case hinges largely on the evidence presented by the prosecution. Another factor that determines the case's success is whether the prosecution can use that evidence to convince the jury or judge that an individual is guilty beyond a reasonable doubt. As such, any pieces of evidence that have been found and seized by authorities can play a pivotal role in the success or failure of the case.
A skillful defense lawyer will dutifully investigate the manner in which the prosecution collected evidence. This is to make sure your rights have not been violated at any point in the process.
The attorneys at Feldman & Lee analyze a DUI and drug arrest in a similar fashion—Was the initial search and seizure leading to the arrest legitimate? The Washington State Constitution provides greater protection against unreasonable search and seizures by law enforcement. Simply being at the wrong place at the wrong time is not a legitimate basis for an arrest. Therefore, a motion can be brought before the court to get the case dismissed if Miranda Rights were not timely read, consent was not knowingly, intelligently or voluntarily given, or constructive possession cannot be proven. If your case falls into one of these categories call an attorney at Feldman & Lee. We zealously pursue all legal angles on our clients' behalf to reach the best possible resolution whether that be in negotiations or trial.
If you or a family member faces drug charges, it is important to talk to an experienced lawyer as soon as possible. The sooner you contact us, the sooner we can begin building your defense.
Contact a drug possession defense lawyer at Feldman & Lee for a free initial consultation.
Are you a new or current client?*
New/Potential Client
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604 West Meeker Street
Suite 206, Kent, WA 98032
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Colleen Schaan shares her technique for testing paper to determine what type will work best for different artistic style. She tests out 19 papers and divides them into sketch & drawing paper and marker-specific papers. Follow along and find out which papers sound like they'd work best for your artwork.
While Copic Markers are an exceptional art tool, some people can find them challenging or downright frustrating. The good news is that it's not you or the markers… it's probably the paper! There are a variety of art papers that range in weight, density, content, and thickness. Each of these variables affects the overall look when using them with Copic Markers. While we may say some papers aren't compatible, it's really about learning how a paper reacts to Copic inks and what techniques work well (or don't work well) with them.
So how do you know what paper is best? Test them! I recommend testing a lot of papers. Raid your stash and test out every paper you can get your hands on, even if you don't typically think of using it with markers. You never know what you will find.
How smoothly does the ink lay down?
Does layering the same color create deeper shades?
How much ink does it take to saturate the paper and cause feathering?
How easily does it blend? Overblend?
What kind of special effects can I achieve with the Colorless Blender?
For this post, I've tested 19 different papers using the technique shown in the video above. Some of them I tested in the past and some are new to me. As my inking and coloring technique changes, my paper preferences do too, so I like to retest papers periodically to see how they stand up to my current inking style.
Sketch and drawing papers are not typically recommended for use with markers because they are generally soft papers, but you might be surprised to find one you like.
Overall Thoughts - The rough surface and the quick saturation make this a paper that I would not use with my Copics.
Overall Thoughts - I love the way the marker glides across the Copic Sketchbook's smooth surface and the blending is almost effortless. Great blender effects!
Overall Thoughts - Due to the quick saturation point of this paper, I would not use it with my Copic markers.
Overall Thoughts - I like the feel of this paper with the markers, but the fact it saturates so quickly makes it one I wouldn't use with Copics.
Similar to sketch and drawing papers, bristols are generally soft. The variation in surface treatment gives a number of options, so make sure to add them to your testing list.
Overall Thoughts - I like the blending ability of this paper, but the fact that it saturates pretty quickly makes it one I would not use with my Copic markers.
Overall Thoughts - While this paper is a bit softer than I prefer, I love the blendability. I would recommend this paper with Copics with the note to be aware of saturation point.
Overall Thoughts - If this paper could hold more ink before feathering, I'd love it. The blendability is wonderful and the Colorless Blender effects are nice. This may be a good choice for someone who doesn't use a lot of layers.
Overall Thoughts - This paper feels much softer and absorbs ink more quickly than the Strathmore smooth surface. The immediate blending makes controlling color placement difficult, so I would not use this paper with my Copic markers.
I knew going into this test that the mixed media papers probably wouldn't be a favorite. They were made to handle a lot of different mediums and layers, so I wanted to add them to my test list anyway.
Overall Thoughts - This paper has a very low saturation point and the difficult blending make it a paper I would not use with my Copic markers.
Overall Thoughts - While this paper gives easy blends, the very low saturation point makes it one I would not use with my Copic markers.
Marker papers are generally thinner, denser papers than sketch or bristols. Some marker papers have a right side and a wrong side. On these, the markers will react differently on each side.
Overall Thoughts - This is an excellent paper for use with Copic markers. Care needs to be taken when layering darker shades as the ink sits on the surface and may turn shiny or sticky.
Overall Thoughts - I love the .Too PM paper pad! I am used to card weight, so this is much thinner, but it reacts much like the softer paper I'm used to. I love the blending and the unbelievable saturation point.
This category is a mix of marker-type papers and the heavier weight card-type papers.
Overall Thoughts - I like the saturation point of this paper and the final blending results. With effort, this paper works with Copic markers.
Overall Thoughts - This is not a paper I would use due to my blending style, but if more traditional marker rendering techniques are used, the Copic Manga illustration paper is excellent to use with Copic markers.
Overall Thoughts - With practice and patience, this paper can be used successfully with Copic markers.
These papers include the card weight papers and the ones I consider "other" surfaces that aren't typically used with markers.
Overall Thoughts - I love this paper! It's heavy like a bristol, but smooth and tightly woven so the saturation level is higher. The ease of blending and Colorless Blender effects make this a paper that is top on my list.
Overall Thoughts - I would not use this paper to do my normal marker coloring. BUT, this surface can be used brilliantly with Copic markers and inks with a different approach.
Overall Thoughts - X-Press It blending is my number one paper! I love the blendability, the Colorless Blender effects and the high saturation point. (the super smooth surface is a plus too).
Colorless Blender creates crisp, vibrant effects.
Overall Thoughts - I would not use this paper to do my normal marker coloring. But, this surface can be used brilliantly with Copic inks for painting or directly out of the bottle.
Remember, these are results from my own testing, using my own inking and blending style. To find the papers that are best for you, I recommend that you do your own testing with a variety of papers and brands. I'm sure you will quickly find the ones that support your technique and style.


If you are a bull, the past week's action has been very kind. Tight action, over an extended period, favors a big reaction move. The resulting move should come in the direction of the prior trend, which in this case is bullish. New longs can look to place a stop below the 5-day low. Aggressive players may wish to play a short on the break of the 5-day low as it would mark a 'fake out' of the bullish thesis (stops coming in above the 5-day high in this case).
The S&P shows the bullish flag which 'should' break higher. Technicals are bullish (with the exception of On-Balance-Volume, although this is likely to turn bullish on the next up day).
Notice how the breakout gap in the Nasdaq hasn't been violated; another bullish sign. The only ugly is down trending On-Balance-Volume.
While the Russell 2000 is pressuring its high even within the tight consolidation. Look for this index to lead out the others.
For Thursday, keep an eye on the Russell 2000. If it can push above 881 in early trading it will offer a momentum scenario to drive buying for the rest of the day. This will bring the other indices along for the ride.


Much of the insurance industry business is driven by contract requirements. Two specific areas that come up quite often are the need for Contractors Pollution Liability (CPL) for non-environmental contractors and higher limits of insurance for any type of contractor.
When a non-environmental contractor bids a job and is required to provide evidence of CPL coverage, it's often a last minute request with some urgency in order to get their bid submitted on time. To obtain a quotation, the agent will typically need project specs, including the name, location, duration of the job, scope of services, and revenue associated with the project. Most carriers have minimum premiums per layer of insurance requested and don't pro-rate project specific policies. The premium is based on the job details and not on the job duration.
On the other hand, practice policies are written to provide coverage for all the applicant's projects over the policy term. The total revenue is used to calculate the rate and in theory, the higher the revenue, the lower the rate. This translates to paying a lower premium per $1,000 of revenue.
To illustrate the benefit of a practice policy vs. a project policy, let's examine a $6,000,000 plumbing contractor. PartnerOne Environmental was recently asked to quote CPL for a contract based on $685,000 of revenue. The project was the construction of a new apartment complex and the contractor was hired to install all cold and hot water systems and fixtures, sanitary and waste systems, electric water heaters, sump pumps, and other plumbing operations. The job duration was scheduled to last 12 months. After underwriting the risk, PartnerOne was able to offer a $2,500 minimum premium quote for this project, but also provided terms for a practice policy for $5,238 annual premium, which also included Mold coverage. Had this client purchased the project specific option, the $2,500 premium may have been attractive when actuality, they'd be paying $3.65 per $1,000 of revenue. With the practice policy option, the rate is $ .87 per $1,000 of revenue. If the client intends to bid multiple projects requiring CPL coverage, it's much more cost effective to buy a practice policy. Additionally, with the practice policy, the insured no longer has to worry about last minute bids for jobs and can actually present their bid showing the coverage is already in place. This may make them more marketable to clients if they are proactive with their insurance.
The second frequent contract requirement deals with midterm increased limits. Insurance carriers and their reinsurers typically have a minimum premium charge per $1 million dollars of coverage limit. The following is an example of an account that would have benefited from binding a higher limit at inception. A tank contractor bound a Commercial General Liability/Contractors Pollution Liability policy with a $2,000,000/$4,000,000 limit for roughly $24,500 annual premium. During the policy term, they were asked to provide higher limits of insurance for various projects. The first project required another $3,000,000 occurrence limit for a $30,000 project that was to last one week and the second was a project for $3,000 to last one day. Because of the minimum premium per layer, each job rated up to anywhere from $4,500-$6,000. Had they purchased a policy at inception with a $5mil/$5mil limit, they cost would have been about $28,500. Now, because it's a midterm request, it's actually costing $6,000 for each job.
By having a policy in place with the broadest coverage and the limits usually requested in the industry, your client will be more marketable, the agent won't have to scramble for last minute quotes or endorsements to prove the limits are in place, and the insured will actually save money in the long run.
To learn more about the differences in insurance policies, or to discuss a specific risk, please contact us.


text:
Police appeal for help in finding missing 17-year-old girl believed to be in Skelmersdale
Jade Kao went missing from an address in Lancaster at around 3.15pm on Saturday, December 12
Francesca Fitzsimmons
Jade Kao went missing from an address at around 3.15pm on Saturday, December 12
Police have asked for the public's help to find a missing 17-year-old girl who is believed to be in Skelmersdale .
Jade Kao went missing from an address in Lancaster at around 3.15pm on Saturday (December 12) and is thought to be in the company of an older male.
Sgt Steve Monk said: "We need anyone who may have seen Jade or who knows of her whereabouts to come forward.
"Similarly, if herself Jade is reading this appeal I would urge her to make contact with us."
Police said they are becoming increasingly concerned for Jade's welfare.
She is described as white, 5ft 3in, slim build, with dark brown shoulder length hair and was last seen wearing a dark navy jacket, jeans and a green bobble hat.
Jade is originally from Skelmersdale and officers believe she could be there.
Police said: "We are becoming increasingly concerned about her and would urge anyone who has seen her or has any information on her whereabouts to call 101."
Ormskirk police issue burglary warning after homes targeted
Southport's Chapel Street is booming, as last empty shopping unit is filled in time for Christmas


According to The Winnipeg Free Press, a new study published by the Historica-Dominion Institute, indicates feelings Canadians have towards Americans.
According to CBC Manitoba, the Winnipeg Police Department said a number of headstones in a Winnipeg cemetery were knocked over by Halloween vandals,.
Rev. Marcel Damphousse told the CBC Sunday that someone passing by phoned police at roughly 9 p.m. on Saturday to report the vandalism that had occurred.
"I guess it's kind of a game for them, a challenge somebody put them up to or, I don't know, they're maybe [on] alcohol or drugs," said Damphousse.
Even though the graveyard was the same cemetery where Louis Riel was buried, his grave was not targeted.
"Many regions will continue to provide vaccine to people in the first priority group with a particular emphasis for people most at risk of severe illness," The press release continued.
According to a release by the provincial government, a long time treaty settlement has been finalized.
"The land transfers fall under treaty land entitlement agreements that require Manitoba to transfer unoccupied lands to Canada so it can fulfill treaty land entitlement obligations," the press release reported.


text:
Susan Fell
Textile artist, researcher and educator, Susan has presented many solo exhibitions of her work. This includes significant regional public galleries – Wangaratta Art Gallery, Shepparton Art Museum and Benalla Art Gallery. Group exhibitions have seen Susan's fine art textiles throughout Australia and internationally – Italy, Canada, Malaysia, Belgium, Hong Kong, Taiwan, UK and China. Her short film was screened in Musee Du Quai Branly Paris in 2008. Susan has a Master of Visual Arts from Monash University. In 2006 she was awarded the postgraduate studio residency in Italy –Palazo Vaj, Prato, Tuscany. She is an advanced level shibori practitioner. Over a number of years, Susan has researched natural dyes, particularly indigo and eucalyptus. In order to enrich her own art practice, and build her knowledge of natural dyes, she
has undertaken extensive professional development with traditional dye masters and contemporary artists in many countries
"My search for indigo has seen me folding, stitching, pleating and binding with elders and experts in many places, and peering inside
dark vats in Japan,Thailand, Borneo, Taiwan, France. In every instance I have learnt new recipes and techniques. I've learnt about the many rituals, and the challenges associated with this magic colour. I've learnt that years of experience and knowhow is
required to become a masterdyer. Indigo requires proper instruction, experience, commitment, and comprehension of what is going on in the indigo vat."
Susan has developed a globally unique plant dye from eucalyptus, now packaged and supplied to an online global market as Gondwana Colour. Her wearable art has been shown in international designer shows on the catwalk in KL, Kuching and Taiwan. She is regularly invited as a VIP, to present and exhibit at prestigious international textile conferences. Susan specializes in shibori, stitch and occasionally feltmaking and encaustic, to make works that at times are two dimensional and at others, sculptural. She challenges the ways in which contemporary
textile art is perceived and represented. Her aim is to employ textiles as sculptures and installations, to articulate a sense of place and history, connecting threads of different places, different landscapes and different times.
Susan accepted an invitation to speak at The International Festival of Plants Ecology and Colours in Antananarivo, Madagascar in May this year.
Countries represented were Columbia, Japan, China, Chile, Malaysia, South Africa, USA, Taiwan, Comoros, Thailand, France, UK, Burkina Faso, India, Mexico, Sweden, Australia and of course Madagascar.
Susan's presentation "The use of Eucalyptus for dyeing in Contemporary Australian Textiles" featured not only her own work but that of 15 other artists and demonstrated the diversity of eucalypts in Australia.
Embracing sustainability and an aesthetic vision that sees her considered by many of her peers to be a master dyer and master shibori artist, Susan integrates historical know how into contemporary textile art contexts. Susan, who has a Masters of Visual Arts, exhibits regularly with group shows in Australia, particularly with the World Shibori Network, and in 2018 has been invited to exhibit a solo show at Lismore's new art gallery and Redland Gallery.
Her recent involvement in the international conference in Madagascar will no doubt have enriched her teaching for Byron Bay Community College. Susan is offering a Textile Intensive this term, with four exciting elements. While each workshop could stand alone, these courses are designed for sequential learning and skill building. She will generously share her travel adventures and her broad knowledge of traditional and contemporary textiles with participants.
Publications: Articles about her work have been published in:
International Forum on Natural Dyes and WEFT Taiwan 2014 –
Catalogue p34-5
Art Quill Blog Art Cloth: Shroud of Ancient Echoes – Exhibition:
ArtCloth Engaging New Visions. Marie Therese Wisniowski.
http://artquill.blogspot.com.au/2011/02/shroud-of-ancient-echoes-iii.html
Textile – No 88, 2007 ' Intent and impact – textiles as Contemporary Sculpture' Sari Wawn p32-34
Textile – No 72 2003 'Nature's Memory' Benalla Art Gallery'
Tony Dyer p24-5
My Batik – Malaysia No 3 2008
Susan was author of an article on Ernabella Arts inc in Batik
Transitions – UK Batik Guild 2006.
Website: Gondwanta Textile


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text:
Renato "Cinco" Athayde Silva (Rio de Janeiro, 25 de maio de 1974) é sociólogo, ex-vereador e conhecido ativista pela legalização da maconha. Cursou o ensino médio no Colégio Pedro II e é formado em ciências sociais pela UFRJ. Foi eleito vereador do Rio de Janeiro pelo PSOL, em 2012, com 12.498 votos. A primeira lei conquistada pelo mandato foi a 5858/2015, que institui a "Campanha Permanente de Combate ao Machismo e Valorização das Mulheres" nas escolas públicas do Município do Rio de Janeiro.

Cinco participa da organização da Marcha da Maconha desde 2005. Em 21 de abril de 2008 foi preso junto com outros militantes antiproibicionistas quando distribuíam panfletos sobre a Marcha da Maconha, acusado de "apologia de fato criminoso". Entretanto, a justiça determinou o arquivamento do processo, por entender que a crítica dirigida à legislação penal e a defesa da sua modificação estavam amparadas pelo direito de liberdade de expressão. Em 2009, Renato Cinco foi um dos subscritores da Representação dirigida à Procuradoria-Geral da República que deu origem à Adpf 187. Nesta ação, por decisão unânime, o STF reconheceu a legalidade das manifestações públicas em defesa da legalização das drogas.

Nas eleições de 2014 foi candidato a Deputado Federal e recebeu 27.965 votos, ficando com a primeira suplência do PSOL para a Câmara dos Deputados. Em 2016, Renato Cinco foi reeleito para a Câmara de Vereadores com 17.162 votos. Foi presidente da Comissão Especial de Enfrentamento do Colapso Hídrico e vice-presidente da Comissão de Defesa dos Direitos Humanos, ambas da Câmara Municipal do Rio de Janeiro.

Renato Cinco também foi responsável por uma campanha online em favor da expulsão do Deputado Cabo Daciolo do PSOL, em decorrência de suas opiniões em favor da libertação de policiais acusados de tortura e homicídio.

Após a derrota eleitoral em 2020, Renato Cinco deixou o PSOL e abandonou a política partidária. https://diariodorio.com/renato-cinco-deixa-o-psol-e-se-afasta-da-politica/

Ligações externas

Naturais da cidade do Rio de Janeiro
Sociólogos do Brasil
Membros do Partido Socialismo e Liberdade
Alunos do Colégio Pedro II
Ativistas pela reforma da política antidrogas do Brasil
Vereadores da cidade do Rio de Janeiro

redpajama_set_name: RedPajamaWikipedia


text:
\section*{Abstract}

A sequence of pathological changes takes place in Alzheimer's disease, which can be assessed in vivo using various brain imaging methods. Currently, there is no appropriate statistical model available that can easily integrate multiple imaging modalities, being able to utilize the additional information provided from the combined data. We applied Gaussian graphical models (GGMs) for analyzing the conditional dependency networks of multimodal neuroimaging data and assessed alterations of the network structure in mild cognitive impairment (MCI) and Alzheimer's dementia (AD) compared to cognitively healthy controls.
Data from N=667 subjects were obtained from the Alzheimer's Disease Neuroimaging Initiative. Mean amyloid load (AV45-PET), glucose metabolism (FDG-PET), and gray matter volume (MRI) was calculated for each brain region. Separate GGMs were estimated using a Bayesian framework for the combined multimodal data for each diagnostic category. Graph-theoretical statistics were calculated to determine network alterations associated with disease severity.
Network measures clustering coefficient, path length and small-world coefficient were significantly altered across diagnostic groups, with a biphasic u-shape trajectory, i.e. increased small-world coefficient in early MCI, intermediate values in late MCI, and decreased values in AD patients compared to controls. In contrast, no group differences were found for clustering coefficient and small-world coefficient when estimating conditional dependency networks on single imaging modalities.
GGMs provide a useful methodology to analyze the conditional dependency networks of multimodal neuroimaging data.

\section{Introduction}

Alzheimer's disease is characterized by a range of pathological brain alterations that can be assessed in vivo using various neuroimaging methods, including MRI and PET.
Several studies suggest that information obtained from combining different imaging modalities could provide reliable markers of cerebral reserve capacity and might be used to predict and monitor the evolution of AD and its relative impact on cognitive domains in pre-clinical, prodromal, and dementia stages of AD (see e.g. reviews \cite{Teipel.2015,Teipel.2016b}).
However, there is still a great need for appropriate analysis methods for studying multimodal data.
Up to date, multimodal studies employ one of the following approaches:
	(i) Correlating pathology maps on a voxel level \cite{Altmann.2015,Grothe.2016b,LaJoie.2012};
	(ii) estimating linear regression models including a-priori specified regions-of-interest \cite{Buckner.2005, Seeley.2009, Villain.2010, Kljajevic.2014, Chang.2015, Grothe.2016a, Teipel.2016};
	(iii) stratifying subjects into distinct groups (e.g. amyloid positive/negative) to compare differences in other imaging modalities \cite{Buckner.2005, Kljajevic.2014, Grothe.2016a};
	(iv) comparing graph-theoretical measures and statistics between modalities \cite{Stam.2006, Buckner.2009, Zhou.2012, Sepulcre.2013, Sepulcre.2017}; and
	(v) deriving generative models estimating spreading mechanisms of amyloid-$\beta$ deposition and its contribution to neurodegeneration \cite{IturriaMedina.2017,Torok.2018}.
Commonly employed statistical models, such as linear regression analysis, provide limited ability to assess the interactions between dozens of variables in the same model, as they cannot derive reliable estimates regarding the individual contribution of highly collinear predictors and suffer from variance inflation \cite{Dormann.2013}.
Calculation of covariance/connectivity matrices based on the Pearson correlation between each pair of variables has led to practical problems in deriving meaningful results, i.e. these matrices are commonly thresholded to an a-priori defined density and binarized \cite{Buckner.2009,Zhou.2012,Sepulcre.2013}. More recently, summary statistics based on graph-theory have been proposed \cite{Watts.1998,Stam.2006} and are currently widely applied \cite{Buckner.2009,Zhou.2012,Sepulcre.2013,Sepulcre.2017}. However, this approach has limited applicability for deriving clinically meaningful results from the data, as for instance, group differences in small-worldness of the brain network might be sensitive to the specific density threshold \cite{Hlinka.2017,Martensson.2018}.

We suggest the application of GGMs, which are able to reliably estimate the \textit{partial} correlation between various multicollinear predictors \cite[ch. 7.3]{Hastie.2013}. GGMs yield sparse conditional dependency matrices, which makes them an interesting candidate for studying properties of the brain network.
The partial correlation derived from GGMs is conceptually similar to the partial correlation obtained from a series of linear regression models, providing the statistical association of the dependent and independent variables while controlling for the confounding variables.
In GGMs, this concept is being extended such that the association between each pair of variables is estimated while controlling for all other variables included in the model.
Technically, GGMs are naively realized by matrix inversion of the covariance matrix or, in more robust and efficient approaches, by applying regularization techniques \cite{Ravikumar.2011,Ryali.2012,Cai.2013,Wang.2016} or efficient sampling schemes \cite{Mohammadi.2015}.

In this paper we assessed inter-regional statistical associations within and between three main imaging markers of Alzheimer's disease using GGMs based on a whole-cortex parcellation of the brain. The assessed imaging markers included amyloid-$\beta$ deposition (florbetapir/AV45-PET), glucose metabolism (FDG-PET), and gray matter volume ($T_1$-weighted MRI).
Based on our previous results with only six representative brain regions \cite{Dyrba.2017}, we hypothesized that regional amyloid deposition has low contribution to gray matter atrophy, whereas hypometabolism was expected to be stronger related to atrophy.
Further, we expected a few hub-nodes influencing pathology in other regions.
For graph-theoretical measures, we expected a linear trajectory of decreasing clustering coefficient and increasing path length with stronger disease severity, as previously reported in the literature for connectivity analyses based on Pearson correlation \cite{He.2008,Yao.2010,Li.2012,Morbelli.2012,Tijms.2013,Pereira.2016,John.2017,Titov.2017}.

\section{Material and Methods}

\subsection{Study participants}

Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (\url{http://adni.loni.usc.edu}). The ADNI was launched in 2003 by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, the Food and Drug Administration, private pharmaceutical companies, and non-profit organizations, with the primary goal of testing whether neuroimaging, neuropsychological, and other biological measurements can be used as reliable in vivo markers of Alzheimer's disease pathogenesis. A complete description of ADNI and up-to-date information is available at \url{http://www.adni-info.org}.
For this study, 403 subjects with amnestic mild cognitive impairment (MCI), 85 patients with Alzheimer's dementia (AD), and 179 cognitively healthy control subjects (CN) were selected from the ADNI-GO and ADNI-2 extensions of the ADNI project, based on the availability of concurrent structural MRI at 3 Tesla, FDG-PET, amyloid-sensitive AV45-PET, and neuropsychological assessments. In ADNI, two MCI subgroups exist, which only differ by the less severe impairment of memory function for \textit{early MCI} (EMCI) compared to \textit{late MCI} (LMCI) subjects.
Detailed inclusion criteria for the diagnostic categories can be found at the ADNI website (\url{http://adni.loni.usc.edu/methods}, ADNI2 manual page 27).
Demographics and neuropsychological profiles of the different diagnostic groups are summarized in Table~\ref{tab:sample}.

\subsection{Imaging data and feature extraction}

ADNI-GO/2 MRI, FDG- and AV45-PET data was downloaded from the ADNI image archive and processed as previously described in \cite{Grothe.2016a,Grothe.2016b}.
MRI T1 scans were segmented and spatially normalized to an aging/AD-specific reference template \cite{Grothe.2013} using SPM8/VBM8 and the DARTEL algorithm.
FDG- and AV45-PET scans were registered to the T1 scan and spatially normalized by applying the deformation fields of the T1 scan.
Mean gray matter volumes and mean FDG- and AV45-PET uptake values were calculated for 108 cortical and subcortical regions defined by the Harvard-Oxford atlas \cite{Desikan.2006} after projecting the atlas to the aging/AD-specific reference space.
Regional gray matter volumes were proportionally scaled by total intracranial volume (TIV), regional FDG-PET values were proportionally scaled to pons uptake, and regional AV45-PET values were proportionally scaled to whole-cerebellum uptake.
To be able to directly compare the different modalities, all values were normalized using the control group as reference \cite{Dormann.2013}.
As described previously \cite{Dyrba.2017}, we used the so-called $W$-scores, which are analogous to $Z$-scores but are adjusted for specific covariates; age, gender, and education in the present case.
Like $Z$-scores, $W$-scores have a mean value of 0 and a standard deviation of 1 in the control group, and values of $+1.65$ and $-1.65$ correspond to the $95^{th}$ and $5^{th}$ percentiles, respectively.
To calculate the $W$-scores, regression models were estimated for the control group using age, gender, and education as independent variables and the mean value of each region as dependent variable.
Then, $W$-scores were computed using $W=(x_{ij}-e_{ij})/s_{res,j}$; with $x_{ij}$ being the $i^{th}$ subject's raw value for region $j$; $e_{ij}$ being the value expected for region $j$ in the control group for the $i^{th}$ subject's age, gender, and education; and $s_{res,j}$ being the standard deviation of the residuals for region $j$ in controls.

\subsection{Statistical modeling}

Graphical models provide an effective way for describing statistical patterns in multivariate data  and for estimating the conditional dependency between the various brain regions and imaging modalities based on GGMs \cite{Lauritzen.1996,Mohammadi.2015}.
For data following a multivariate normal distribution, undirected GGMs are commonly used.
In these graphical models, the graph structure is directly characterized by the precision matrix, i.e. the inverse of the covariance matrix: non-zero entries in the precision matrix show the edges in the conditional dependency graph.
Notably, simple inversion of the covariance matrix usually does not work in real world data sets, as already slight noise or selection bias in the empirical data causes the precision matrix to contain almost no zero entries.
To overcome this problem, regularization techniques or efficient sampling algorithms have been proposed that reduce the effect of noise by additionally employing a sparsity assumption and, thus, only detect the most probable conditional dependencies.
For our analyses, we employed a computationally efficient Bayesian framework implemented in the R package BDgraph. More specifically, this framework implements a continuous-time birth-death Markov process for estimating the most probable graph structure and edge weights that correspond to the observed partial correlations \cite{Mohammadi.2015,Mohammadi.2018}.
For this study, BDgraph was substantially extended by multithreaded parallel processing and marginal pseudo-likelihood approximation to speed up computations.

\subsection{Experimental setup}

First, we estimated GGMs based on the combined data of EMCI, LMCI and Alzheimer's dementia patients to study the conditional dependency between brain regions and modalities. Second, we estimated GGMs for each diagnostic group separately to assess alterations of the graph structures.
For the combined model, regional $W$-scores of all MCI and Alzheimer's dementia patients ($N=488$) and all three imaging modalities were entered. Initially, we took all $108$ cortical and subcortical regions included in the Harvard-Oxford atlas \cite{Desikan.2006} into consideration, corresponding to $P=3*108=324$ variables. The sampling process included 2,000,000 burn-in iterations, starting from a random estimate for the inverse covariance matrix and converging to estimates with higher posterior probability giving the training data. These burn-in iterations were then discarded, and subsequently 100,000 sampling iterations followed to obtain the estimates for the inverse covariance matrix used in the analyses.
Because results were showing a strong left--right hemisphere symmetry, we repeated model estimation including only the 54 regions in the left hemisphere, resulting in $P=3*54=162$ variables. We thus applied the same settings as before but finally sampled 500,000 iterations to increase model stability.
From the final model we set a probability threshold of $P_{avg}>0.5$ for selecting the edges, that means that a specific edge was estimated to be present if it existed in at least half of all model iterations \cite{Madigan.1996}.
For the second analysis of group differences, we estimated individual GGMs for each group based on the multimodal data of the left hemisphere. Sampling was performed with 1,000,000 burn-in iterations followed by 100,000 sampling iterations.

\subsection{Comparison of conditional dependency matrices}

For comparing the different models, we calculated various similarity measures. The Jaccard coefficient is formally defined as $J=M_{11}/(M_{10}+M_{11}+M_{01})$, that is the number of edges being present in both graph structures $M_{11}$, divided by the total number of occurring edges $M_{10}+M_{11}+M_{01}$, where $M_{10}$ is the number of edges being only present in the first graph but not in the second graph and vice versa for $M_{01}$.
The Jaccard coefficient only takes the graph structure into consideration but not the edge weights. Therefore, we additionally calculated the Pearson correlation and the cosine distance between the edge weights of two graphs. The cosine distance is defined as the cosine of the angle between the two vectors created from the edge weights of each graph, i.e. taken the edge weights of one graph structure as the components of the vector. The cosine ranges from $1$ for perfect match over $0$ for two orthogonal vectors to $-1$ for vectors with opposing direction, similar to the Pearson correlation.
For comparing the edge weights, we took only the edges into consideration that existed in both graphs.

\subsection{Graph-theoretical analyses}

To assess group differences of the estimated graph structure we calculated the three graph-theoretical measures clustering coefficient, characteristic path length, and their ratio small-world coefficient that were commonly reported in the literature.
The path length quantifies the distance of connections between two nodes along the shortest path. The weighted characteristic path length is the average minimum distance between a node $i \in N$ and all other nodes, $L_i=\sum_{j\in N,j\neq i}d_{ij}/(n-1)$, where $d_{ij}=\sum_{a_{uv}\in g_{i \leftrightarrow j}}\omega_{uv}$ is the shortest weighted path length between $i$ and $j$, $g_{i \leftrightarrow j}$ defines the shortest path, and $\omega_{uv}$ defines the distance between two nodes. Here, the distance matrix was defined as $\Omega=1-abs(\Theta)$, that is one minus the absolute pair-wise partial correlation \cite{Rubinov.2010}.
The weighted clustering coefficient indicates the inter-connectedness of neighboring nodes $C_i=2t_i/(k_i(k_i-1))$, where $t_i=0.5\sum_{j,h\in N}(\omega_{ij}\omega_{ih}\omega_{jh})^{1/3}$ is the geometric mean of triangles around node $i$, and where $k_i=\sum_{j\in N}a_{ij}$ is the number of nodes connected to node $i$ \cite{Onnela.2005,Rubinov.2010}. $k_i$ is often referred to as the \textit{degree} of the node $i$, and the link status $a_{ij}=1$ if node $i$ is connected to another node $j$, or $a_{ij}=0$ otherwise.
The small-world coefficient is defined as the ratio of the clustering coefficient $C$ and characteristic path length $L$ in comparison to a random network, $S=(C/C_{rand})/(L/L_{rand})$, with $S\gg1$ in small-world networks \cite{Rubinov.2010}. To simplify calculations, we omitted defining a random network to estimate $C_{rand}$ and $L_{rand}$, and directly took the ratio $S_i=C_i/L_i$ for group comparisons.
Graph metrics were compared between diagnostic groups using pairwise t-test, controlled for the false discovery rate using the Benjamini and Hochberg \cite{Benjamini.1995} procedure.

\section{Results}

\subsection{Conditional dependency of Alzheimer's pathology}

Initially, we calculated the Pearson correlation matrix for all imaging data (Figure~
\ref{fig:corr-mat-whole-brain} left).
More than $19.5*10^3$ correlations, corresponding to a network density of $37\%$ of the total number of possible edges, were found to pass the significant threshold of $P<0.05$, Bonferroni corrected.
The conditional dependency matrix obtained using the GGM approach is given in Figure~\ref{fig:corr-mat-whole-brain} (right).
For the partial correlation between all pairs of brain regions, we obtained 1,905 significant associations ($4\%$ network density) surviving the posterior probability threshold of $P>0.5$.
We obtained high associations between homologous brain regions of the left and right hemisphere, visible as the shifted diagonals in each modality block of Figure~\ref{fig:corr-mat-whole-brain}.
The mean partial correlation between homologous regions on the left and the right hemisphere was $\rho=0.42$.
Thus, we repeated the analyses using only the left hemisphere data, which significantly reduced the number of possible edges and, therefore, increases model stability.

When estimating the model only for the left hemisphere, we obtained 901 associations ($7\%$ network density) exceeding the posterior probability threshold of $P_{avg}>0.5$.
The model estimates reached a stable level after approximately $120*10^3$ iterations, corresponding to the first fifth of the total number of iterations.
In general, the estimated conditional dependencies between all regions in the left hemisphere were consistent compared with the previous results obtained for both hemispheres. Comparing both models, the Jaccard similarity coefficient for the adjacency matrices was relatively low with $j=0.52$, which was driven by approximately four hundred additional edges included in the model based on the left hemisphere data and missing in the model based on the combined data of both hemispheres.
However, comparing the magnitude of partial correlation for the five hundred edges being present in both models, we obtained a cosine similarity of $cos=0.95$ and a Pearson coefficient of $r=0.93$.

For intra-modal associations of amyloid-$\beta$ deposition and glucose metabolism, brain regions directly adjacent to each other formed smaller clusters of high partial correlation around the main diagonal (Figure~\ref{fig:parcor-mat-lh-fdg-fdg} and Supplementary Figure~\ref{sfig:parcor-mat-lh-amy-amy}). For gray matter volume, such patterns also appeared but with lower density and inter-cluster partial correlation (Figure~\ref{sfig:parcor-mat-lh-vol-vol}).
When considering the associations between different imaging modalities, we obtained a consistent pattern of significant positive intra-regional conditional dependency for the pairs amyloid-$\beta$ deposition and metabolism with a mean partial correlation of $\rho=0.27$, and between metabolism and gray matter volume (mean $\rho=0.23$). These associations are visible as the higher intensities in the diagonal of Figure~\ref{sfig:parcor-mat-lh-amy-fdg} and Figure~\ref{sfig:parcor-mat-lh-fdg-vol}. For the pair amyloid-$\beta$ deposition and gray matter volume these associations were substantially lower (Figure~\ref{sfig:parcor-mat-lh-amy-vol}); only 13 of 54 possible edges were detected with a mean of $\rho=0.08$.

\subsection{Group comparison of the graph structures}

When estimating separate models for each diagnostic group based on the multimodal data, the resulting graph structures were similar to each other with a mean Jaccard similarity of $j=0.31$. However, the estimated regional dependency differed between groups due to the different degrees of severity of amyloid pathology, glucose metabolism, and atrophy. Regarding the raw partial correlation weights between groups, we obtained an average cosine similarity of $cos=0.92$ and Pearson coefficient of $r=0.74$.\\
The graphs differed in their density, leading to significant alterations of the clustering coefficient, characteristic path length, and small-world coefficient (Figure~\ref{fig:graph_statistics}).
We observed a biphasic trajectory of the graph measures. This means that the clustering coefficient and small world coefficient initially increases when comparing early MCI and CN participants (Figure~\ref{fig:graph_statistics}). When Alzheimer's disease progresses, i.e. in the late MCI and dementia groups, both measures decrease again, with late MCI being approximately on the same level as CN participants (Figure~\ref{fig:graph_statistics}). The characteristic path length showed a similar pattern across groups, but with inverted directionality and decreasing intensity, i.e. group differences were highest in amyloid-$\beta$ deposition, intermediate for glucose metabolism, and lowest for gray matter volume (Figure~\ref{fig:graph_statistics}). P-values for post-hoc t-test between groups are given in Table~\ref{tab:pvals}.

When estimating separate models for each diagnostic group based on the single-modality data only, the resulting graph structures showed a comparable level of similarity between groups, with a mean Jaccard similarity of $j=0.35$, cosine similarity of $cos=0.93$ and Pearson coefficient of $r=0.76$. In contrast, for the single-modality data, group differences for the graph measures clustering and small-world coefficient vanished and became insignificant (Figure~\ref{sfig:graph_stats_single}, Table~\ref{tab:pvals2}).

\section{Discussion}

\subsection{Conditional dependency between brain regions.}
The GGMs estimated the strongest conditional dependencies mainly \emph{within} imaging modalities. We expected adjacent brain regions to form clusters with high inter-cluster similarity for amyloid-$\beta$ deposition (Figure~\ref{sfig:parcor-mat-lh-amy-amy}), as it is known to have low variability in spatial distribution and, therefore, is often used as a dichotomic variable after applying a certain threshold to the global amyloid tracer uptake \cite{Chetelat.2013,Landau.2013,Grothe.2017}.
We also found such clustering patterns for metabolism (Figure~\ref{fig:parcor-mat-lh-fdg-fdg}) and gray matter volume (Figure~\ref{sfig:parcor-mat-lh-vol-vol}), matching previous studies on metabolism and gray matter covariance networks based on Pearson correlation \cite{Yao.2010,Carbonell.2016,Pereira.2016} or principal/independent component analysis \cite{Di.2012,Spetsieris.2015,Savio.2017}. Clusters of high covariance have been found in the lateral and medial parietal lobe, lateral frontal lobe, and lateral and medial temporal lobe, and had been associated with simultaneous growth during brain development, functional co-activation, and axonal connectivity in the literature \cite{Gong.2012,AlexanderBloch.2013}.

Our analyses yielded only few and relatively weak associations \emph{between} different modalities (Figure~\ref{sfig:parcor-mat-lh-amy-fdg}-\ref{sfig:parcor-mat-lh-amy-vol}), except for the direct intra-regional dependency between amyloid-$\beta$ and metabolism as well as between metabolism and gray matter volume (diagonal of Figure~\ref{sfig:parcor-mat-lh-amy-fdg} and Figure~\ref{sfig:parcor-mat-lh-fdg-vol}), which matched our previous analysis with six selected regions of interest \cite{Dyrba.2017}. To check that this dependency did not result from partial volume effects in the PET data, we repeated all analyses with partial volume corrected PET scans (data and methods described elsewhere \cite{Teipel.2015b,GonzalezEscamilla.2017}), which did not significantly alter GGM structures (data not shown). The positive dependency between amyloid-$\beta$ and metabolism matches previous results for linear regression models from Altmann et al. \cite{Altmann.2015}, who reported a markedly reduced number and strength of negative associations between regional amyloid-$\beta$ and metabolism when correcting for global amyloid load. They concluded that the negative association between amyloid deposition and metabolism is more related to the global amyloid level than to the distinct regional level.
The strong pattern of direct intra-regional dependency observed in the present study might be an artifact from using the same atlas for all three imaging modalities, such that a unique amount of covariance is explained by the specific shape of the regions of interest, which becomes more relevant when partialling out the values of all other brain regions.

We observed a saturation of the GGM dependency estimates when adding many variables, meaning that adding new variables decreasingly alters the estimated interdependence of the other variables as only little new information is contributed. Actually, this problem is well-known for linear regression models \cite{Obrien.2007,Dormann.2013,Teipel.2015b}. Recent developments in stochastic block models may help to overcome these limitations, as they try to infer the underlying clustering block structure to improve estimation of dependencies between clusters \cite{Sun.2014,Hosseini.2016}.

\subsection{Alterations of graph measures}

Various studies reported a network disruption of AD in comparison to cognitively healthy controls for gray matter volume \cite{He.2008,Yao.2010,Li.2012,Tijms.2013,John.2017} and glucose metabolism \cite{Morbelli.2012,Titov.2017}, and intermediate levels for volume in MCI \cite{Yao.2010,Pereira.2016}. In contrast, Chung et al. \cite{Chung.2016} and Voevodskaya et al. \cite{Voevodskaya.2017} reported divergent increases and decreases of the global clustering coefficient in Alzheimer's disease, depending on the specific graph density threshold that was applied for the metabolic \cite{Chung.2016} or the gray matter network \cite{Voevodskaya.2017}. However, it has to be acknowledged that instead of the Pearson correlation network, we used conditional dependency networks in the present study, and that we calculated weighted graph measures instead of applying an arbitrary threshold to yield an a-priori defined network density level.

Our results suggest that the graph statistics for regional dependency networks follow a biphasic trajectory as recently proposed for cortical thinning and mean diffusivity \cite{Montal.2017}, and resting-state fMRI connectivity \cite{Schultz.2017}. For preclinical AD, two previous studies revealed regional differences of the amyloid-$\beta$ network \cite{Sepulcre.2013,Pereira.2018} and reported an increase of clustering coefficient specifically for the default-mode network regions.
In the current study, as we did not limit the sample to include only amyloid-positive subjects, the EMCI group exhibited the strongest alterations of network structure with an increase of the clustering coefficient, which could be related to the process of amyloid accumulation taking place in several regions simultaneously in this group increasing the intra-cluster correlation. Interestingly, the EMCI showed almost no alteration of the characteristic path length compared to the cognitively healthy controls.
In contrast, LMCI subjects showed a clustering coefficient comparable to controls, but the path length significantly increased for the amyloid and metabolic network ($P<0.05$, FDR corrected).
The lowest alterations of graph measures were obtained for the gray matter network. This can be easily explained by the less widespread and distributed atrophy across regions in the MCI groups than in the dementia group. The characteristic path length was almost equal for the controls, EMCI, and LMCI groups, and became significantly larger only for AD patients ($P<0.05$, FDR corrected). These results are in line with previous reports from gray matter correlation networks \cite{He.2008,Yao.2010,Li.2012,Tijms.2013}, which found a higher randomness of the graph in AD with reduced network efficiency and increased path length.

Notably, group differences in clustering and small-world coefficient where only found when estimating the models based on the multimodal data, but not when estimating individual models for each modality separately. Single-modality models showed a higher density for the conditional dependency network, with some proportion of correlations with lower magnitude, that vanished in the multimodal models as they were probably mediated by amyloid pathology or atrophy. Our findings emphasize the benefit of integrating and combining the information provided by the various imaging modalities \emph{one} statistical model.

GGMs were recently applied as clustering algorithm for brain networks in a few other single-modality applications. De Vos et al. \cite{Vos.2017} found them useful for increasing group separation between AD and controls compared to classical Pearson correlation networks in resting-state functional connectivity.
Titov et al. \cite{Titov.2017} compared metabolic networks for the differential diagnosis between AD and frontotemporal lobar degeneration (FTLD). They also proposed an algorithm to estimate if an individual subject shows a more AD or FTLD pattern of regional metabolism.
Munilla et al. \cite{Munilla.2017} systematically evaluated the influence of the number of subjects and the regularization strength on the GGM stability and graph structure. They found that the estimated GGM graph structure and small-world coefficient converged to a stable level when including 40 or more subjects in the study sample. For regularization-based approximation of GGMs, they showed that the probability of an edge to exist in the estimated graph structure almost linearly corresponds to the magnitude of their partial correlation. Thus, this finding confirms our initial decision, that sampling-based Bayesian estimation of the graph structure might be more useful for detecting even low associations.

\subsection{Conclusion}

We applied GGMs to assess inter-modal and inter-regional dependencies of high-dimensional multimodal neuroimaging data of AD-related brain alterations. Our results showed that conditional dependency networks estimated by GGMs provides more useful information than traditional brain networks based on Pearson correlation, especially when including multimodal data in the models.
As soon as large-scale tau PET data is being available, it will be interesting to assess the regional contribution of tau and amyloid-$\beta$ on the longitudinal trajectory of brain function and structure (e.g. glucose metabolism and gray matter volume). Multivariate models such as GGMs will then help us to determine key determinants of disease progression and support us to better understand Alzheimer's disease pathophysiology.

\section*{Acknowledgment}
The authors have no conflicts of interests to declare. This project was supported by the Rostock Massive Data Research Facility (RMDRF) funded by the German Research Foundation (DFG) (FKZ INST 264/128-1 FUGG).
Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). The ADNI was launched in 2003 by the National Institute on Aging (NIA), the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the Food and Drug Administration (FDA), private pharmaceutical companies and non-profit organizations, as a \$60 million, 5-year public-private partnership. ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research \& Development, LLC.; Johnson \& Johnson Pharmaceutical Research \& Development LLC.; Lumosity; Lundbeck; Merck \& Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institute of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuroimaging at the University of Southern California.

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