Month: January 2019

Stuck in the wrong paradigm

gettingwell4 2-3 stars Required further work, Epigenetics, Stress ,

This 2019 article questioned the paradigm of determining substance carcinogenicity:

“In the absence of robust epidemiological data, the final arbiter of whether a chemical is considered to be a carcinogen or not has been based on the outcome of long-term rodent bioassays. This approach is incompatible with the current knowledge of the etiology of cancer. The current view of the etiology of cancer suggests that it is not useful to consider carcinogenicity as a single hazardous property with its own hazard category.

There is no bright line between carcinogens and non-carcinogens but rather there is a continuum with some chemicals having high potential, some having no potential, and others having potential at a point along the continuum. This continuum exists alongside other adverse effects. One problem is being stuck in the old practice of wishing to reproduce the binary “carcinogen/non-carcinogen” results of the long-term bioassay rather than move to a new paradigm in assessing the chemical’s position on the spectrum of carcinogenic potential.

The two-year bioassay has such high variability (because of the variability of the carcinogenic process it is trying to measure and the interplay between dose limiting toxicity and cell proliferation inducing toxicity) that the outcome of the assay for compounds with low to intermediate carcinogenic potential is little more than a lottery. After half a century, it has only been used to evaluate less than 5% of chemicals that are in use. It is not reproducible because of the probabalistic nature of the process it is evaluating combined with dose limiting toxicity, dose selection, and study design.”

Unscientific research paradigms will eventually collapse because they can’t withstand the scrutiny of the scientific method. Too bad the coauthors didn’t kill off this one while they were still in positions at the US Environmental Protection Agency, World Health Organization, etc.

https://www.sciencedirect.com/science/article/pii/S0273230019300248 “Chemical carcinogenicity revisited 2: Current knowledge of carcinogenesis shows that categorization as a carcinogen or non-carcinogen is not scientifically credible” (not freely available)

Random events

gettingwell4 Just me

This floated into my backyard overnight:


Later, from Turn of a Friendly Card:

Time flowing like a river
Time beckoning me
Who knows when we shall meet again
If ever
But time keeps flowing like a river
To the sea

Goodbye my love
Maybe for forever
Goodbye my love
The tide waits for me
Who knows when we shall meet again
If ever

But time keeps flowing like a river
On and on to the sea
To the sea
Til it’s gone forever
Gone forever
Gone forevermore

Goodbye my friend
Maybe for forever
Goodbye my friend
The stars wait for me
Who knows where we shall meet again
If ever

But time keeps flowing like a river
On and on to the sea
To the sea
Til it’s gone forever
Gone forever
Gone forevermore

Epigenetic causes of sexual orientation and handedness?

gettingwell4 2-3 stars Required further work, Brain development, Brain hemispheres, Cerebrum, Epigenetics, Testosterone , , , , , , ,

This 2018 Austrian human study subject was various associations of prenatal testosterone levels to fetal development:

“The available evidence suggests, albeit not conclusively, that prenatal testosterone levels may be one cause for the association of sexual orientation with handedness. Associations among women were consistent with predictions of the Geschwind–Galaburda theory (GGT), whereas those among men were consistent with predictions of the callosal hypothesis. However, research on the associations between sexual orientation and handedness appears to be compromised by various methodological and interpretational problems which need to be overcome to arrive at a clearer picture.

The GGT posits that high prenatal testosterone levels cause a delay in the fetal development of the left cerebral hemisphere which results in a right-hemisphere dominance and hence in a tendency for left-handedness. According to the GGT, high prenatal testosterone levels entail not only a masculinization of the female fetus, but also a feminization of the male fetus (contrary to neurohormonal theory). Overall, the male fetus is subjected to higher levels of intrauterine testosterone than the female fetus. The GGT is thus consistent with the higher prevalence of left-handedness among men than among women.

The callosal hypothesis applies to men only and assumes, in line with neurohormonal theory, that low prenatal testosterone levels are associated with later homosexuality. According to the CH, high prenatal testosterone enhances processes of cerebral lateralization through mechanisms of axonal pruning, thereby resulting in stronger left-hemisphere dominance and a smaller corpus callosum. Consistent with this, women have a larger corpus callosum than men.”

The study’s Limitations section included the following:

  1. “Limitations of the current study pertain to the self-report nature of our data. Behavioral data may provide differing results from those obtained here.
  2. Assessment of sexual orientation relied on a single-item measure. Utilization of rating scales (e.g., the Kinsey Sexual Orientation Scale) or of multi-item scales, and assessing different components of sexual orientation, would have allowed for a more fine-grained analysis and for a cross-validation of sexual orientation ratings with sexual attraction.
  3. Albeit both our samples were large, the proportions of bisexual and homosexual individuals were, expectedly, only small, as were effects of lateral preferences. Thus, in analysis we could not differentiate bisexual from homosexual individuals. Bisexual and homosexual individuals may differ with regard to the distribution of lateral preferences.
  4. Some effect tests in this study have been underpowered. Independent replications with even larger samples are still needed.”

The largest unstated limitation was no fetal measurements. When a fetus’ epigenetic responses and adaptations aren’t considered, not only can the two competing hypotheses not be adequately compared, but causes for the studied phenotypic programming and other later-life effects will also be missed.

https://link.springer.com/article/10.1007/s10508-018-1346-9 “Associations of Bisexuality and Homosexuality with Handedness and Footedness: A Latent Variable Analysis Approach”

Burying human transgenerational epigenetic evidence

gettingwell4 < 0 Detracted from science, Beliefs, Cerebrum, Epigenetics , ,

The poor substitutes for evidence in this 2018 US study guaranteed that human transgenerational epigenetically inherited effects wouldn’t be found in the generations that followed after prenatal diethylstilbestrol (DES) exposure:

“A synthetic, nonsteroidal estrogen, DES was administered to pregnant women under the mistaken belief it would reduce pregnancy complications and losses. From the late 1930s through the early 1970s, DES was given to nearly two million pregnant women in the US alone.

Use of DES in pregnancy was discontinued after a seminal report showed a strong association with vaginal clear cell adenocarcinoma in prenatally exposed women. A recent analysis of the US National Cancer Institute (NCI) DES Combined Cohort Follow-up Study showed elevated relative risks of twelve adverse health outcomes.

We do not have sufficient data concerning the indication for DES in the grandmother to determine whether adverse pregnancy outcomes in the third generation might resemble those of their grandmothers. Fourth generation effects of prenatal exposures in humans have not been reported.”

https://www.sciencedirect.com/science/article/pii/S0890623818304684 “Reproductive and Hormone-Related Outcomes in Women whose Mothers were Exposed in utero to Diethylstilbestrol (DES): A Report from the US National Cancer Institute DES Third Generation Study” (not freely available)

This study had many elements in common with its poor-quality reference [25] “Transgenerational effects of prenatal exposure to the 1944–45 Dutch famine” which is freely available at https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/1471-0528.12136.

That study’s Methods section showed:

  1. Its non-statistical data was almost all unverified self-reports by a self-selected sample of the F2 grandchildren, average age 37.
  2. No detailed physical measurements or samples were taken of the F2 grandchildren, or of their F1 parents, or of their F0 grandparents, all of which are required as baselines for any transgenerational epigenetic inheritance findings.
  3. No detailed physical measurements or samples were taken of the F3 great-grandchildren, which is the generation that may provide transgenerational evidence if the previous generations also have detailed physical baselines.

That study’s researchers drew enough participants (360) such that their statistics package allowed them to impute and assume into existence a LOT of data. But the scientific method constrained them to make factual statements of what the evidence actually showed. They admitted:

“In conclusion, we did not find a transgenerational effect of prenatal famine exposure on the health of grandchildren in this study.”

The current study similarly used the faulty methods 1-3 above to produce results such as:

“We do not have sufficient data concerning the indication for DES in the [F0] grandmother to determine whether adverse pregnancy outcomes in the [F2] third generation might resemble those of their grandmothers.

Fourth [F3] generation effects of prenatal exposures in humans have not been reported.“

Zero studies of probably more than 10,000,000 F3 great-grandchildren of DES-exposed women just here in the US?

Who is against funding these studies? Who is afraid of what such studies may find?

One plausible hypothesis of these human studies would be of inherited effects that skipped generations! The rodent studies Epigenetic transgenerational inheritance mechanisms that lead to prostate disease and Epigenetic transgenerational inheritance of ovarian disease found inherited diseases that didn’t manifest until the F3 great-grand offspring:

The F3 generation can have disease while the F1 and F2 generations do not.

Ancestral exposure to toxicants is a risk factor that must be considered in the molecular etiology of ovarian disease.

For the current study:

  • What could be expected from a study design that didn’t include F3 women and men, which is the only generation that didn’t have direct DES exposure?
  • What a nonsensical study design to permit NON-evidence like educational level!

Human studies of possible intergenerational and transgenerational epigenetic inheritance are urgently needed. There will be abundant evidence to discover if researchers will take their fields seriously.

Fear of feeling?

gettingwell4 2-3 stars Required further work, Beliefs, Brain development, Cerebrum, Epigenetics, Limbic system, Lower brain, Primal Therapy , , ,

Here’s a 2018 article from two researchers involved in the Dunedin (New Zealand) Longitudinal Study. They coauthored many studies, including People had the same personalities at age 26 that they had at age 3.

The paper’s grand hypothesis was:

“A single dimension is able to measure a person’s liability to mental disorder, comorbidity among disorders, persistence of disorders over time, and severity of symptoms.”

The coauthors partially based this on:

“Repeated diagnostic interviews carried out over 25 years, when the research participants were 11, 13, 15, 18, 21, 26, 32, and 38 years old, and include information about seven diagnostic groups: anxiety, depression, attention deficit hyperactivity disorder, conduct disorder, substance dependence, bipolar disorder, and schizophrenia.”


https://ajp.psychiatryonline.org/doi/full/10.1176/appi.ajp.2018.17121383 “All for One and One for All: Mental Disorders in One Dimension” (not freely available)

More about the coauthors:

Two psychologists followed 1000 New Zealanders for decades. Here’s what they found about how childhood shapes later life

“Dunedin and other studies show that most people have at least one episode of mental illness during their lifetime.”

What compels people to manufacture “universal” truths? Aren’t such beliefs poor substitutes for feeling? For understanding historical, factual, personal truths?

What if the price we pay for avoiding and pressuring down our feelings is: A wasted life?

What if the grand hypothesis worth proving is: For one’s life to have meaning, each individual has to regain their feelings?

Fitting data

gettingwell4 4-5 stars Advanced knowledge, Cerebrum, Limbic system, Lower brain ,

Let’s start out the new year with a repost of a cautionary reminder:

“Both “predict and “explain” imply that investigators have uncovered a reliable structure to phenomena, the latter involving hypotheses describing unseen mechanisms, leading to a new ability to control events and produce formerly unpredicted/unpredictable outcomes. This is clearly not a fair description of post hoc correlation-fishing.

The current publication system almost forces authors to make causal statements using filler verbs (e.g. to drive, alter, promote) as a form of storytelling (Gomez-Marin, 2017); without such a statement they are often accused of just collecting meaningless facts.”

https://mythsofvisionscience.wordpress.com/2018/12/30/neuroscience-newspeak-or-how-to-publish-meaningless-facts/ “Neuroscience Newspeak, Or How to Publish Meaningless Facts”