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Saturday, September 26, 2026

Building a computer game using Grok, Purpose and Skill

 Building a computer game using Grok

While trying out the new build feature on Grok, thought about 

Finding a Purpose and Skill.

Grok: “ You do not need a purpose before you start building a skill. Purpose usually shows up later, after you notice what you want to keep doing.

What you just did is the skill. You looked at a picture, decided the circle should stay and the arrow should go, and made that happen. That is directing. You can practice it on the next small thing, without naming a life purpose first.

If you want the flight itself to have a reason — somewhere to go, or one thing to get better at — say so and I will put that in.”

Skill building and purpose are different problems. Psychology knows a lot about the first and much less about the second. Mixing them is why both stall.

What a skill actually is

A skill is a change in what you can do when the instructions are gone. Reading about steering is not the skill. Steering tomorrow, without the arrow, is.

Paul Fitts and Michael Posner described three stages that still match what labs see in motor learning:


Early progress is fast. Then it flattens. That flattening is normal. It usually means the current method is used up, not that you have no talent. The next gain comes from a smaller target, not from more of the same hour.

The practice that works feels worse

A repeated finding, called contextual interference: if you mix versions of a task, you do worse during the session and better a day later. Repeating one easy version feels smooth and teaches less. Robert Bjork called these desirable difficulties. Spacing, testing yourself, and changing the conditions all belong there.

Two limits matter. Beginners often need a few clean repetitions before mixing helps. And this is about learning, not about performing well today. A session that feels fluent can be the one you forget.

Feedback has the same twist. You need to know what happened. If every try is corrected instantly, you learn to wait for the correction. The skill falls apart when the hint is removed. Better feedback arrives, then thins out, so you start detecting the error yourself.

Where you look also matters. Gabrielle Wulf’s work on attention finds that focusing on the effect you want (“slide toward that gap”) beats focusing on your own movement (“move your finger this way”). Once a skill is automatic, turning attention inward is how people choke under pressure. They go back to the beginner’s step-by-step talk and the automatic pattern breaks.

Hours are not the method

Deliberate practice, from Anders Ericsson, means a specific aim just past what you can already do, a way to see the result, and a correction. It is not “spend a long time near the activity.”

The famous 10,000 hours is a story told about that research, not a law. Later reviews found that structured practice explains a large share of skill in things like music and games, and a much smaller share in school and professional work. Starting point, coaching, and the shape of the task all count. More hours of vague effort do not substitute for a target.

Transfer is narrow. Getting better at one named task helps nearby versions of that task. It rarely spills into a distant part of life. “Become a skilled person” is too wide to practice. “Keep the ship in the gap between two rocks” is narrow enough.

Where purpose fits

Purpose is not a stage of skill. It does not tell you what to repeat, and it does not provide the feedback. What does keep people practicing is seeing that they got slightly better, choosing the task themselves, and having a reason to come back tomorrow. A grand purpose can supply that last part. It cannot supply the first two.

So the practical order is the reverse of how it is usually sold. Name one small action. Make the result visible. Practice it until the early clumsiness fades. Let the reason for continuing show up from the fact that you want another session. The purpose can stay unnamed while the skill is already being built.


Neuroplasticity is the nervous system changing its own connections because of what it just did. It is not one switch. It is several mechanisms on different clocks, and most of the popular version skips the ones that actually save a skill.

The fast change is at the synapse

The basic unit is the synapse, the junction where one neuron signals the next. If a connection is used in the right pattern, it can become stronger. That is long-term potentiation. If it is used in a different pattern, it can become weaker. That is long-term depression. Learning needs both. A skill is not “more connections.” It is a smaller set of connections that fire together and a lot of others that stop interfering.

The usual trigger is coincidence. The sending neuron fires, the receiving neuron is already active, and an NMDA receptor lets calcium in only when both happen close together. That calcium starts a short chemical cascade. Within minutes the receiving side inserts more AMPA receptors, so the next signal gets through more easily. This early phase does not require new proteins. It fades unless a later phase builds them.

That later phase is what turns a practice attempt into something still there tomorrow. It needs gene expression and new proteins, and it enlarges the spine, the little knob where the synapse sits. Repeated, well-timed activity can grow a new spine. Unused spines shrink and disappear. Imaging studies of motor learning show this directly: training grows a set of new spines in motor cortex, then sleep keeps the ones that were strengthened and prunes the rest.

A third rule, spike timing, says the order matters down to milliseconds. If the incoming spike arrives just before the cell fires, the synapse tends to strengthen. If it arrives just after, it tends to weaken. That is why sloppy repetition is not neutral. The nervous system records the timing you actually produced.

The brain also limits its own plasticity

If every used synapse only got stronger, the circuit would saturate and nothing new could be stored. Two brakes prevent that.

Homeostatic scaling turns the whole cell’s sensitivity up or down so that overall firing stays in a workable range. One synapse can still win, but the neuron does not lock into permanent overdrive.

Metaplasticity means recent activity changes how plastic the synapse is allowed to be next. A circuit that has just changed a lot becomes temporarily harder to change again. This is one reason a second new skill, practiced immediately, can interfere with the first. The tissue is not infinitely available.

There is also a chemical support system around these events. BDNF, a growth factor released by active neurons, helps the protein-synthesis phase and spine growth. Dopamine from reward-prediction circuits tags which attempts are worth keeping, especially in the striatum, where actions are selected. Acetylcholine and norepinephrine mark moments of surprise or importance. Without a signal that this attempt mattered, many synaptic changes do not consolidate.

Slower structural changes

Over days and weeks, the change is no longer just receptor count.

Dendrites and axons sprout and withdraw. In adults this is local, not a new highway across the brain. After injury, spared axons can sprout into nearby territory. In ordinary learning, the bigger effect is which existing routes get myelinated.

Myelin is the insulation oligodendrocytes wrap around axons. It changes conduction speed. Motor learning and other practice increase new oligodendrocytes and myelin along the circuits being used. That is how a movement stops feeling assembled piece by piece: the signals arrive together because their travel times were tuned. Most myelin is laid down early in life, but activity keeps altering it in adulthood. This is also why gains that feel “in the body” take longer than gains that are only insight.

Map plasticity sits above all of this. The motor and sensory cortices devote more territory to whatever is practiced and less to what is silent. The map is competitive. Extra space for one skill is borrowed, not created from nothing.

Adult neurogenesis, the birth of new neurons, is the mechanism people most often mean and the one that matters least for ordinary skills. In rodents it is clear in the hippocampus and the olfactory system. In adult humans the hippocampal evidence is real but contested in degree, and the cortex does not add new neurons as its way of learning a movement. A new skill is mostly old neurons with new weights, new spines, and retuned myelin.

Where a skill is stored

A practiced movement is not kept in one place. Three systems change in parallel.

The cerebellum handles error. It compares the movement you intended with the sensory result and weakens the synapses that produced the miss. That is long-term depression at parallel-fiber synapses, and it is why a visible mistake teaches faster than a perfect-looking repetition you do not inspect.

The striatum handles selection. Dopamine marks the action that turned out better than expected, so that action becomes the one you reach for next time. This is the biological version of “keep the version that worked.”

The motor cortex stores the pattern once it is stable enough to run without constant correction. Early practice is cerebellum- and attention-heavy. Later practice is cortical and striatal, which matches the shift from clumsy and verbal to automatic.

Sleep is part of the mechanism, not a pause in it. During non-REM sleep, slow waves and spindles replay fragments of the trained circuit. In motor cortex, the spines that were strongly potentiated during practice are the ones retained; the weakly changed ones are depressed. Corticostriatal coupling also increases offline across days of practice, not only while you are doing the task. Cut the sleep and the synaptic work of the session is only partly saved. Aging and broken sleep both reduce this offline step, so the same practice leaves a smaller trace.

What this does and does not allow

Plasticity continues for life. It is cheaper and broader in childhood, when maps and myelin are still being set, and it gets slower, more local, and more dependent on sleep and repetition after that. Disease, inflammation, and exhaustion all narrow it further. Nothing in the mechanism says a damaged circuit can be replaced on demand by “rewiring.” Nearby circuits can take over some functions. That is compensation, and it has limits.

The behavioral counterpart is ordinary. You need a repeated action, an error signal, a marker that the result mattered, and sleep before the next competing demand. Massed practice without rest writes the early, fragile phase and then meets the brake. A single insight writes almost none of the structural phase. The lasting change is the one that survives the night.



Thursday, September 24, 2026

How to Read Virginia’s 2026 Constitutional Amendment Questions

My Chief of Staff and Writer bot explains the 2026 ballot to amend the Virginia Constitution.

Virginia voters will see three proposed constitutional amendments on the ballot for Election Day, Tuesday, November 3, 2026. Early voting began September 18. The questions are written by the General Assembly. There is no word-count or grade-level limit on what appears on the ballot, so the sentences can be long and dense.

Before you vote, it helps to know what you’re looking at—and what you’re *not* looking at—when you stand in the booth.

**Three layers of information**

A. Ballot question — The official Yes/No sentence (only thing in the booth)

B. Plain-English explanation + full amendment text — Neutral decode published by the State Board of Elections (plain English ≤500 words), plus the legal text at vote.elections.virginia.gov (read before you vote)

C. Campaign flyers and headlines — Advocacy (mailers, social posts, party materials)

Only A is on the ballot. B is the best neutral way to understand what a Yes or No actually does. C can mix real legal points the ballot left out with topics that do not appear in the amendment at all.


*A simple method for each question**


1. Break the sentence into Roman-numeral clauses — (i), (ii), (iii). Treat each as its own idea, not one endless thought.

2. Ask what one Yes covers. If several policies are bundled, a single Yes or No decides all of them together.

3. Compare the ballot wording to the full amendment text. The ballot is a summary. It can omit the legal tests courts will actually use.

4. Separate “in the text” from “campaign claim.” Some flyer points track language that exists in the amendment but not on the ballot. Others (minors, sports, bathrooms, juror eligibility, and similar) may be advocacy topics that are not in the ballot question or the amendment.

**Question 1 — Reproductive freedom**

Roughly 70 words in one sentence with three clauses (harder reading level once you account for the clauses).

What the ballot asks, in short: Protect personal decisions about prenatal care, childbirth, postpartum care, birth control, abortion, miscarriage management, and fertility care; protect doctors, nurses, and patients from punishment; allow third-trimester restrictions except when the patient’s health is at risk or the pregnancy cannot survive.

What the amendment text adds that the ballot does not fully spell out: a “fundamental right to reproductive freedom”; that the right cannot be denied, burdened, or infringed without a compelling interest achieved by the least restrictive means; that third-trimester exceptions include life or physical or mental health, or a non-viable fetus; that the provision is self-executing; and broader protections against adverse action.

Reading note: One Yes covers several care categories and the enforcement rules. The operative legal tests (“fundamental right,” “least restrictive means,” mental health, viability, self-executing) matter in court and live mainly in the amendment text, not the short ballot sentence.

**Question 2 — Marriage**

Roughly 43 words — the clearest of the three (about a ninth-grade reading level).

What the ballot asks, in short: Remove the ban on same-sex marriage; affirm that two adults may marry regardless of sex, gender, or race; require equal treatment of legally valid marriages.

Alignment: Ballot wording and amendment text are mostly aligned.

Reading note: “Gender” is not defined in either place. Neither the ballot nor the amendment mentions clergy or religious exemptions. Campaign claims about sports or bathrooms are not in the ballot question or the amendment text.

**Question 3 — Voting rights**

Roughly 92 words — the longest and densest (about a seventeenth-grade reading level).

What the ballot asks, in short: Recognize a fundamental right to vote; a person convicted of a felony is not entitled to vote while incarcerated, but the right to vote is restored automatically upon release; update “mentally incompetent” language to lack of capacity to understand the act of voting.

What the amendment text adds: Upon release, restoration of “all political rights,” not only voting — and that phrase does not appear on the ballot. “Release from incarceration” is not fully defined in the materials voters see most often (probation and parole questions remain open in public discussion).

Reading note: One Yes bundles the fundamental-right statement, automatic restoration after incarceration, and the capacity-language update. Check the full text for “all political rights” and how “release” is framed.

**Quick checklist before Election Day**

- Read the official plain-English explanation and the full amendment text at vote.elections.virginia.gov

- For each question, list the (i)(ii)(iii) clauses and note what a single Yes covers

- Ask what legal tests appear in the amendment but not on the ballot

- Treat campaign “what it actually does” boxes carefully: some points may track omitted legal language; others may be advocacy topics not in the text

- Official question wording on a flyer can be an accurate transcription even when the flyer’s “vote yes / vote no” framing is advocacy

**How ballot drafting ideals compare (optional context)**

Common reform ideals ask for shorter questions, about an eighth-grade reading level, one idea per question, and a statement of the operative legal test in neutral tone. Against those ideals: Question 3 runs long; only Question 2 comes close on reading level; all three bundle more than one idea; Questions 1 and 3 omit key tests from the ballot sentence itself. Official questions stay dry; flyers may spin.

Disclaimer: This guide is for understanding the ballot, not for telling you how to vote. Verify every claim against the official plain-English explanations and full amendment texts published by the Virginia Department of Elections.

Wednesday, September 23, 2026

Gadolinium the beat goes on

Great paper by Dr. Brent Wagner 

Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC13587227/




I saw reference to Dr. Tweedle’s study from 1995, went looking and kept going…

@grok helped with research:

Tweedle studies (date + one line)

Chemistry / development

•  1988 — Wedeking & Tweedle. 153Gd-Gd(DTPA) vs Gd(DOTA) vs free Gd acetate in mice. Free Gd → liver/bone; slow clearance.

•  1989 — US Pat. 4,885,363 (Tweedle et al.). HP-DO3A ligand family → gadoteridol / ProHance.

•  1991 — Tweedle et al. Magn Reson Imaging. Chelates vs endogenous ions (Zn, Cu, Ca): in-vitro transmetallation.

•  1992 — Wedeking, Kumar, Tweedle. Magn Reson Imaging. Seven chelates in mice; acid-dissociation rate predicted 14-day residual Gd in body/liver/femur (r > 0.99).

•  1993 — Wedeking, Kumar, Tweedle. Nucl Med Biol. Free [153Gd]acetate dose map (liver, bone saturation).

•  1993–94 — Kumar/Chang/Tweedle. Inorg Chem. DOTA/DO3A thermodynamics, kinetics, crystal structures.

•  1995 — Tweedle, Wedeking, Kumar. Invest Radiol 30:372–80. Formulated Magnevist, ProHance, Dotarem, Omniscan in mice/rats. 14-day residual: gadoteridol ≈ gadoterate ≤ gadopentetate << gadodiamide. Caldiamide cut Omniscan residual but not to macrocyclic levels.

•  1997 — Tweedle. Eur Radiol. “The ProHance story.” Nonionic + macrocyclic design.

Human / commentary

•  2006 — White, Gibby, Tweedle. Invest Radiol. Human bone ICP-MS after clinical doses: Omniscan >> ProHance.

•  2007 — Tweedle. Br J Radiol. Letter on what “stability” means.

•  2012 — Hao, Runge, Tweedle et al. JMRI. Chemistry and safety review.

•  2015 — Kanal & Tweedle. Radiology. Residual Gd in normal-kidney patients; clinical meaning unknown; choose agent and dose with that in mind.

•  2016 — Tweedle. Magn Reson Imaging. Speciation: chelated vs dissociated Gd.

•  2018 — NIH/ACR/RSNA roadmap (Tweedle co-author). Retention research agenda.

•  2020–23 — Radiology editorials (next-gen agents; Kobayashi cadaver brain/bone/skin; Le Fur rat multi-organ). Same rank order; harm from leftover fraction in normal kidneys still unproven.


Credentials

Michael F. Tweedle, PhD — inorganic/coordination chemist, not a clinician.

Inventor on gadoteridol. Long career at Squibb → Bracco Research USA (1995 paper affiliation). Later Stefanie Spielman Professor of Cancer Imaging, Ohio State University / James Comprehensive Cancer Center; emeritus. High citation count on GBCA chemistry, kinetics, and residual Gd.


Conflicts of interest

Yes, especially 1988–1997.

•  Employee of Bracco Research USA when the comparative 153Gd papers were done.

•  Inventor of the ligand that became ProHance, the agent his studies ranked as lowest residual.

•  1997 “ProHance story” is company-era product writing.

•  Later OSU editorials are academic bylines; he remains the chemist most tied to that product. Contrast research in this field was routinely company-sponsored.

The residual-Gd rank order (linear nonionic highest, macrocyclics lowest) was replicated by others. The conflict is about which product that ranking was built to support, not about whether 153Gd counts existed.


When linears were used vs when macrocyclics arrived

US first approvals (not the 2003 ProHance year on your slide — that is wrong for first US approval).

Linear (open-chain) — first wave, 1988–2008



How that played out in practice

•  1988–mid-1990s: almost all clinical MRI contrast was linear (Magnevist, then Omniscan). That is the window of many older MS protocols and of Tweedle’s rodent work.

•  1992 onward: ProHance available in the US, but Magnevist/Omniscan still dominated volume for years.

•  2006–2010 NSF crisis: FDA restricted Omniscan, Magnevist, OptiMARK in severe renal failure. Use shifted toward macrocyclics + MultiHance.

•  2013+ brain T1 papers: further shift to gadoteridol, gadoterate, gadobutrol.

•  EU 2017: linear general-purpose agents largely suspended; US still allows some linears with warnings.

•  Today: routine body/CNS MRI in the US is mostly macrocyclic; MultiHance and Eovist remain as specialty linears.

Your handwritten 1–5 look like a personal ranking or order of interest (MultiHance → Gadavist → Dotarem → Eovist), not FDA chronology.

ProHance year on the slide: first US approval was December 1992 (CNS adults), with later supplements (pediatrics, etc.). 2003 on that table is not the original approval year.


More about Dr. Tweedle’s work:

Tweedle’s work on gadolinium chelates runs from the late 1980s (chemistry and early animal biodistribution at Squibb/Bracco) through human bone data, NSF-era editorials, and later commentary on retention vs. risk. He is closely associated with gadoteridol (ProHance), the first nonionic macrocyclic GBCA (US approval 1992).

Core animal / chemistry papers (retention and stability)

•  1988 — Wedeking & Tweedle. Comparison of 153Gd-labeled Gd(DTPA)2−, Gd(DOTA)−, and Gd(acetate) in mice. Early head-to-head of linear vs macrocyclic vs “free” Gd; free Gd deposits heavily in liver and bone and clears slowly.

•  1989 — Tweedle et al. US patent 4,885,363. 1-substituted-1,4,7-triscarboxymethyl-1,4,7,10-tetraazacyclododecane and analogs — the HP-DO3A ligand family that became gadoteridol.

•  1991 — Tweedle, Hagan, Kumar, Mantha, Chang. Magn Reson Imaging. Reaction of gadolinium chelates with endogenously available ions (Zn, Cu, Ca, etc.). In vitro transmetallation / dissociation risk.

•  1992 — Wedeking, Kumar, Tweedle. Magn Reson Imaging. Dissociation of gadolinium chelates in mice: relationship to chemical characteristics. Acid-dissociation rates strongly predicted long-term whole-body, liver, and femur residual 153Gd.

•  1993 — Wedeking, Kumar, Tweedle. Nucl Med Biol. Dose-dependent biodistribution of [153Gd]Gd(acetate)n in mice. Maps where unchelated Gd goes (liver, bone saturation).

•  1993 — Kumar, Chang, Tweedle. Inorg Chem. Equilibrium and kinetic studies of lanthanide complexes of macrocyclic polyaminocarboxylates.

•  1993–1994 — Chang, Francesconi, Kumar, Tweedle et al. Crystal structures and stability of Gd/Y/Fe complexes of DO3A and DOTA.

•  1995 — Tweedle, Wedeking, Kumar. Invest Radiol 30:372–380. Formulated Magnevist, ProHance, Dotarem, and Omniscan in mice and rats. Residual 14-day Gd: gadoteridol ≈ gadoterate ≤ gadopentetate << gadodiamide; caldiamide in Omniscan lowered residual Gd but not to macrocyclic levels.

•  1997 — Tweedle. Eur Radiol. “The ProHance story.” Design rationale: nonionic + macrocyclic (lower osmolality, higher kinetic stability).

Human retention and later commentary

•  2006 — White, Gibby, Tweedle. Invest Radiol. Omniscan vs ProHance residual Gd in human bone (hip surgery samples) by ICP-MS. Linear agent left substantially more Gd in bone after clinical doses.

•  2007 — Tweedle. Br J Radiol. Short letter on what “stability” of Gd chelates actually means.

•  2012 — Hao, Ai, Goerner, Hu, Runge, Tweedle. J Magn Reson Imaging. Review: basic chemistry and safety of MRI contrast agents.

•  2015 — Kanal & Tweedle. Radiology. Editorial: residual/retained Gd in patients with normal renal function; practical implications after Kanda-type brain T1 findings.

•  2016 — Tweedle. Magn Reson Imaging. “Gadolinium deposition: is it chelated or dissociated Gd? How can we tell?” Speciation methods review.

•  2018 — McDonald, Levine, Weinreb, … Tweedle (workshop co-author). Radiology. NIH/ACR/RSNA gadolinium retention research roadmap.

•  2020 — Tweedle. Radiology. “Next-generation MRI contrast agents: still including gadolinium.”

•  2021 — Tweedle. Editorial on Kobayashi et al. human cadaver brain/bone/skin comparison (gadobenate vs gadoteridol); notes higher linear retention but argues clinical toxicity of residual intact chelate or trace ion remains unproven in normal kidneys.

•  2023 — Tweedle. Editorial on Le Fur et al. rat multi-organ ICP-MS/speciation study (gadoteridol lowest among agents tested; kidney cortex highest residual).

Development thread in one line

Linear DTPA-type agents (Magnevist, then Omniscan) → kinetic-stability problem shown in 1988–1995 rodent 153Gd work → macrocyclic HP-DO3A (ProHance) designed and marketed as more inert → later human bone (2006) and brain-signal (2013+) data confirmed the same rank order: linear nonionic > linear ionic ≥ macrocyclic, with gadoteridol often at the low end of residual Gd.


Sunday, September 20, 2026

Deck Garden

 Our garden has migrated to our deck.

Beautiful colors 

5 gallon buckets & railing planters.

Summer winding down 🍁