Skip to content

Author: Sima

Published on

We can't see them, but we all have little face mites that live in our faces, specifically in hair follicles. The scientific name of the face mites: Demodex folliculorum. There are at least 4 lineages of face mites that correspond to different regions of the world. Good thing they're harmless (we think).Gross but fascinating. From Wired:

Your Face Is Covered in Mites, and They’re Full of Secrets

WHEN YOU LOOK in the mirror, you’re not just looking at you—you’re looking at a whole mess of face mites. Yeah, you’ve got ‘em. Guaranteed. The little arachnids have a fondness for your skin, shoving their tubular bodies down your hair follicles, feeding on things like oil or skin cells or even bacteria. The good news is, they don’t do you any harm. The better news is, they’ve got fascinating secrets to tell about your ancestry.

New research out today in the Proceedings of the National Academy of Sciences reveals four distinct lineages of the face mite Demodex folliculorum that correspond to different regions of the world. African faces have genetically distinct African mites, Asian faces have Asian mites, and so too do Europeans and Latin Americans have their own varieties. Even if your family moved to a different continent long ago, your forebears passed down their brand of mites to their children, who themselves passed them on down the line.

Looking even farther back, the research also hints at how face mites hitchhiked on early humans out of Africa, evolving along with them into lineages specialized for certain groups of people around the planet. It seems we’ve had face mites for a long, long while, passing them back and forth between our family members and lovers with a kiss—and a little bit of face-to-face skin contact.

Leading the research was entomologist Michelle Trautwein of the California Academy of Sciences, who with her colleagues scraped people’s faces—hey, there are worse ways to make a living—then analyzed the DNA of all the mites they’d gathered. “We found four major lineages,” says Trautwein, “and the first three lineages were restricted to people of African, Asian, and Latin American ancestry.”

The fourth lineage, the European variety, is a bit different. It’s not restricted—it shows up in the three other groups of peoples. But Europeans tend to have only European mites, not picking up the mites of African, Asian, or Latin American folks. (It should be noted that the study didn’t delve into the face mites of all the world’s peoples. The researchers didn’t test populations like Aboriginal Australians, for instance, so there may be still more lineages beyond the four.)

So what’s going on here? Well, ever since Homo sapiens radiated out of Africa, those four groups of people have evolved in their isolation in obvious ways, like developing darker or lighter skin color. But more subtly, all manner of microorganisms have evolved right alongside humans. And with different skin types come different environments for tiny critters like mites.

Published on Leave a comment on Periodontal Disease Associated With Increased Breast Cancer Risk

Image result for teeth, wikipedia Research found that postmenopausal women with periodontal disease (gum disease) were more likely to develop breast cancer than women who did not have the chronic inflammatory disease. And it's a bigger risk among those who currently smoke or quit smoking within the last 20 years. The interesting part is the fact that periodontal disease is a bacterial disease and that it results in inflammation. An earlier post discussed research that found that the human breast microbiome (microbial community) and specifically the bacteria, is different in healthy breasts (in the breast tissue) as compared to cancerous breasts. From Science Daily:

Periodontal disease associated with increased breast cancer risk in postmenopausal women

Postmenopausal women with periodontal disease were more likely to develop breast cancer than women who did not have the chronic inflammatory disease. A history of smoking significantly affected the women's risk, researchers report. Periodontal disease is a common condition that has been associated with heart disease, stroke, and diabetes. Previous research has found links between periodontal disease and oral, esophageal, head and neck, pancreatic, and lung cancers, so the researchers wanted to see if there was any relationship with breast cancer.

Jo L. Freudenheim, PhD, and colleagues monitored 73,737 postmenopausal women enrolled in the Women's Health Initiative Observational Study, none of whom had previous breast cancer. Periodontal disease was reported in 26.1 percent of the women. Because prior studies have shown that the effects of periodontal disease vary depending on whether a person smokes, researchers examined the associations stratified by smoking status.

After a mean follow-up time of 6.7 years, 2,124 women were diagnosed with breast cancer. The researchers found that among all women, the risk of breast cancer was 14 percent higher in women who had periodontal disease.

Among women who had quit smoking within the past 20 years, those with periodontal disease had a 36 percent higher risk of breast cancer. Women who were smoking at the time of this study had a 32 percent higher risk if they had periodontal disease, but the association was not statistically significant. Those who had never smoked and had quit more than 20 years ago had a 6 percent and 8 percent increased risk, respectively, if they had periodontal disease.

"We know that the bacteria in the mouths of current and former smokers who quit recently are different from those in the mouths of non-smokers," Freudenheim explained. One possible explanation for the link between periodontal disease and breast cancer is that those bacteria enter the body's circulation and ultimately affect breast tissue. However, further studies are needed to establish a causal link, Freudenheim said.

Published on Leave a comment on Drinking Coffee May Improve Athletic Endurance and Performance

A University of Georgia review study of the research literature shows that drinking coffee (instead of a caffeine supplement) improves athletic endurance performance. Also, that caffeine from coffee has ergogenic benefits—that it enhances physical performance. More beneficial effects of coffee! From Medical Xpress:

Coffee may improve athletic endurance performance, review finds

The caffeine in a morning cup of coffee could help improve athletic endurance, according to a new University of Georgia review study....To research the issue, Higgins reviewed more than 600 scholarly articles and screened them for those that focused only on caffeinated-coffee conditions, measured the caffeine dose and measured an endurance performance. Of these, nine randomized control trials specifically used coffee to improve endurance."Previous research has focused on caffeine itself as an aid to improve endurance," Higgins said.

 Looking at the nine trials, Higgins found that between 3 and 7 milligrams per kilogram of body weight of caffeine from coffee increased endurance performance by an average of 24 percent. The amount of caffeine in a cup of coffee can vary from 75 mg to more than 150, depending on the variety and how it's roasted and brewed. 

In the nine trials, participants either cycled or ran after drinking coffee. They then exercised vigorously and the results were measured. In a majority of cases, endurance was noticeably improved after the use of coffee.When researching the effects of caffeine from coffee, Higgins found two important discoveries: that caffeine from coffee has ergogenic benefits—that it enhances physical performance—and that more research is needed on the use of caffeine from coffee versus pure caffeine use.

"While there is a lack of high-quality research on coffee as a source of caffeine, there is an abundance of research on pure caffeine," he said. "It's surprising how little we know about caffeine from coffee when its endurance effects could be just as beneficial as pure caffeine."

Higgins said that coffee shouldn't be dismissed as less beneficial for endurance. He found that coffee appears to be just as helpful as taking caffeine in the form of powder or tablets.... Higgins says that more research is needed before giving official recommendations to athletes, especially since the amount of caffeine in a cup of coffee can vary depending on how it's prepared.

Published on Leave a comment on Millions of Bacteria In Our Water and Water Pipes

Interesting, but in some ways horrifying - the hidden world of microbes teeming around us. With new techniques such as genetic sequencing we now know that at least a couple of thousand different species live in our water pipes in biofilms (concentrated microbial communities) that coat our water pipes. About eighty thousand bacteria per milliliter are in our drinking water, with one glass of clean drinking water containing ten million bacteria! And same as with microbes in human bodies, researchers think that a number of these bacteria and other microbes are beneficial and actually help purify the water. From Science Daily:

Our water pipes crawl with millions of bacteria

Researchers from Lund University in Sweden have discovered that our drinking water is to a large extent purified by millions of "good bacteria" found in water pipes and purification plants. So far, the knowledge about them has been practically non-existent, but this new research is about to change that.

A glass of clean drinking water actually contains ten million bacteria! But that is as it should be -- clean tap water always contains harmless bacteria. These bacteria and other microbes grow in the drinking water treatment plant and on the inside of our water pipes, which can be seen in the form of a thin, sticky coating -- a so-called biofilm. All surfaces from the raw water intake to the tap are covered in this biofilm.

Findings by researchers in Applied Microbiology and Water Resources Engineering show that the diversity of species of bacteria in water pipes is huge, and that bacteria may play a larger role than previously thought. Among other things, the researchers suspect that a large part of water purification takes place in the pipes and not only in water purification plants.

"A previously completely unknown ecosystem has revealed itself to us. Formerly, you could hardly see any bacteria at all and now, thanks to techniques such as massive DNA sequencing and flow cytometry, we suddenly see eighty thousand bacteria per millilitre in drinking water," says researcher Catherine Paul enthusiastically.

At least a couple of thousand different species live in the water pipes. According to the researchers there is a connection between the composition of bacteria and water quality."We suspect there are 'good' bacteria that help purify the water and keep it safe -- similar to what happens in our bodies. Our intestines are full of bacteria, and most the time when we are healthy, they help us digest our food and fight illness, says Catherine Paul.

Although the research was conducted in southern Sweden, bacteria and biofilms are found all over the world, in plumbing, taps and water pipes. This knowledge will be very useful for countries when updating and improving their water pipe systems."The hope is that we eventually may be able to control the composition and quality of water in the water supply to steer the growth of 'good' bacteria that can help purify the water even more efficiently than today," says Catherine Paul.

1

Published on 1 Comment on Physical Therapy Best For Carpal Tunnel Syndrome?

So many people I know complain of carpal tunnel syndrome, especially those who spend hours every day at a computer keyboard. Carpal tunnel syndrome is a hand and arm condition of numbness, pain, tingling, etc. caused by a pinched nerve in your wrist (pressure or compression of the median nerve). Treatments vary from physical therapy to steroids to surgery, with surgery being the recommended option by many doctors. So what is best?

A study with women randomly assigned to manual (physical) therapy or surgery suggests that from months one to 3 physical therapy was better and more effective, especially in pain relief. At the 6 months and one year follow-up, both groups were similar in outcome - in improvements in pain, symptoms, and functioning of the hands. What was nice in this study was that all assessments, baseline and follow-ups, were done by a blinded assessor - that is, a person who did not know what treatment was used on the patient.  Bottom line: a major intervention (surgery) may be unnecessary. From Medical Xpress:

PT beats surgery for quick relief of carpal tunnel pain

For women with carpal tunnel syndrome (CTS), physical manual therapies are similarly effective to surgery in the medium and long term, and may be more effective in the short term, according to a study published in the November issue of The Journal of Pain.

César Fernández-de-las Peñas, P.T., Ph.D., from the Universidad Rey Juan Carlos in Madrid, and colleagues compared the effectiveness of surgery versus physical therapy consisting of manual therapies, including desensitization maneuvers, in CTS. The interventions were either three sessions of manual therapy (physical therapy group; 60 patients) or decompression/release of the carpal tunnel (surgical group; 60 patients).

The researchers found that 55 women in the physical therapy group and 56 in the surgery group completed follow-up at 12 months. In adjusted analyses there was an advantage for the physical therapy group at one and three months in mean pain, the worst pain, and function. At six and 12 months, the changes in pain and function were similar between the groups. At all follow-ups the two groups had similar improvements in the symptoms severity subscale of the Boston Carpal Tunnel Questionnaire.

"This study found that surgery and physical manual therapies, including desensitization maneuvers of the central nervous system, were similarly effective at medium-term and long-term follow-ups for improving pain and function, but that physical therapy led to better outcomes in the short term," the authors write.

Published on Leave a comment on Could Apigenin Be Considered a Brain Food?

The important thing learned from this study (though it was done in the laboratory and not directly on humans) is that it supports that apigenin (in the same chemical group as flavonoids) is important for neuron formation and for strengthening connections between brain cells. Flavonoids are known to positively affect memory and learning, and to preserve and enhance brain function. Apigenin is found in many fruits and vegetables, but common sources are parsley, celery, celeriac, thyme, chamomile, grapefruit, onions, oranges, red wine, and spices such as rosemary, oregano, thyme, basil, and coriander. Another good reason to eat a variety of fruits and vegetables. From Medical Xpress:

Plant compound found in spices and herbs increases brain connections

Brazilian researchers from D'Or Institute for Research and Education (IDOR), Federal University of Rio de Janeiro (UFRJ) and Federal University of Bahia (UFBA) have demonstrated in laboratory that apigenin, a substance found in parsley, thyme, chamomile and red pepper, improves neuron formation and strengthens the connections between brain cells.

Previous experiments with animals had already shown that substances from the same chemical group as the apigenin, known as flavonoids, positively affect memory and learning. Many studies highlight the potential of flavonoids to preserve and enhance brain function. While the effectiveness of flavonoids for brain health is not an entirely new concept, this research is the first to show the positive effects of apigegin directly on human cells and the first to unraveling its mechanism.

The scientists observed that just by applying apigenin to human stem cells in a dish they become neurons after 25 days - an effect they would not see without the substance. Moreover, the neurons that were formed made stronger and sophisticated connections among themselves after being treated with this natural compound."Strong connections between neurons are crucial for good brain function, memory consolidation and learning", says neuroscientist from IDOR and UFRJ Stevens Rehen, leader author of the paper published today atAdvances in Regenerative Biology.

The research team conducted by Rehen demonstrated that apigenin works by binding to estrogen receptors, which affect the development, maturation, function, and plasticity of the nervous system. This group of hormones is known to delay the onset of psychiatric and neurodegenerative disorders such as schizophrenia, depression, Alzheimer's and Parkinson's disease. However, the use of estrogen-based therapies is limited by the increased risk of estrogen-dependent tumors and cardiovascular problems.

Researchers believe apigenin can be used as an alternative approach on future treatments for neurodegenerative diseases as well as in neuronal differentiation strategies in laboratory. "We show a new path for new studies with this substance", points out Rehen. "Moreover, flavonoids are present at high amounts in some foods and we can speculate that a diet rich in flavonoids may influence the formation of neurons and the way they communicate within the brain."

Published on Leave a comment on Appendicitis in Children Can Be Treated With Antibiotics
Drawing of colon seen from front (appendix is colored red). Credit: Wikipedia

This is the second time I've seen research finding that antibiotics  alone could be used (instead of surgery) for the treatment of uncomplicated appendicitis (June 17, 2015 post), but this time in children. Appendicitis is inflammation of the appendix.  At the one year follow-up the researchers found that 75.7% of patients with uncomplicated appendicitis had been successfully treated with antibiotics alone and had not had any recurrences of appendicitis.

This is a major finding because for years the gold standard for appendicitis treatment has been an appendectomy. The times are a changing.

From Science Daily: Antibiotics alone can be a safe, effective treatment for children with appendicitis

Using antibiotics alone to treat children with uncomplicated acute appendicitis is a reasonable alternative to surgery when chosen by the family. A study led by researchers at Nationwide Children's Hospital found that three out of four children with uncomplicated appendicitis have been successfully treated with antibiotics alone at one year follow-up. Compared to urgent appendectomy, non-operative management was associated with less recovery time, lower health costs and no difference in the rate of complications at one year.

"Surgery has long been the 'gold standard' of care for treating appendicitis because by removing the appendix we eliminate the chance that the appendicitis will ever come back," said Dr. Deans. "However, early in our careers we noticed that patients with appendicitis who were placed on antibiotics overnight until their surgery the following morning felt better the next day. So, Pete and I asked ourselves: do they really need to have surgery?"

In the first study conducted and published in the United States examining non-operative management for appendicitis, they enrolled 102 patients age 7 to 17 who were diagnosed with uncomplicated acute appendicitis at Nationwide Children's between October 2012 and October 2013. Participants had early/mild appendicitis, meaning that they experienced abdominal pain for no more than 48 hours; had a white blood cell count below 18,000; underwent an ultrasound or CT scan to rule out rupture and to verify that their appendix was 1.1 centimeter thick or smaller; and had no evidence of an abscess or fecalith, which is hard stone-like piece of stool.

Thirty-seven families chose antibiotics alone and 65 opted for surgery. Those patients in the non-operative group were admitted to the hospital and received IV antibiotics for at least 24 hours, followed by oral antibiotics after discharge for a total of 10 days. Among those patients, 95% showed improvement within 24 hours and were discharged without undergoing surgery. Rates of appendicitis-related medical care within 30 days were similar between the groups with two patients in the non-operative group readmitted within 30 days for an appendectomy. At one year after discharge, three out of four patients in the non-operative group did not have appendicitis again and have not undergone surgery.

Appendicitis, caused by a bacterial infection in the appendix, is the most common reason for emergency abdominal surgery in children, sending more than 70,000 young people to the operating room each year. Although many of these cases are severe and require surgery, there are a good number that would be candidates for treatment with antibiotics alone, Dr. Minneci said.

According to the study results, patients who were transferred to Nationwide Children's from other institutions expressed concerns about the distance and time necessary to come back if the appendicitis recurred. These families opted for surgery more often. Patients whose families spoke primary languages other than English were more likely to choose antibiotics as a course of treatment due to cultural values to avoid surgery if at all possible.

Published on Leave a comment on Taking Antidepressants During Pregnancy and Autism

A large study found that using antidepressants during the second or third trimester of pregnancy increases the risk that the child will have autism by 87%,  especially if the mother takes selective serotonin reuptake inhibitors (SSRIs). A drawback was that the study looked at associations rather than actual cause (which would have meant randomly assigning women to either treatment or no treatment - which is unethical). From Medical Xpress:

Taking antidepressants during pregnancy increases risk of autism by 87 percent

Using antidepressants during pregnancy greatly increases the risk of autism, Professor Anick Bérard of the University of Montreal and its affiliated CHU Sainte-Justine children's hospital revealed today. Prof. Bérard, an internationally renowned expert in the fields of pharmaceutical safety during pregnancy, came to her conclusions after reviewing data covering 145,456 pregnancies.

"The variety of causes of autism remain unclear, but studies have shown that both genetics and environment can play a role," she explained. "Our study has established that taking antidepressants during the second or third trimester of pregnancy almost doubles the risk that the child will be diagnosed with autism by age 7, especially if the mother takes selective serotonin reuptake inhibitors, often known by its acronym SSRIs." Her findings were published today in JAMA Pediatrics.

Bérard and her colleagues worked with data from the Quebec Pregnancy Cohort and studied 145,456 children between the time of their conception up to age ten. In addition to information about the mother's use of antidepressants and the child's eventual diagnosis of autism, the data included a wealth of details that enabled the team to tease out the specific impact of the antidepressant drugs. 

"We defined exposure to antidepressants as the mother having had one or more prescription for antidepressants filled during the second or third trimester of the pregnancy. This period was chosen as the infant's critical brain development occurs during this time," Prof. Bérard said. "Amongst all the children in the study, we then identified which children had been diagnosed with a form of autism by looking at hospital records indicating diagnosed childhood autism, atypical autism, Asperger's syndrome, or a pervasive developmental disorder. Finally, we looked for a statistical association between the two groups, and found a very significant one: an 87% increased risk." 

The findings are hugely important as six to ten percent of pregnant women are currently being treated for depression with antidepressants. In the current study, 1,054 children were diagnosed with autism (0.72% of the children in the study), on average at 4.5 years of age. Moreover, the prevalence of autism amongst children has increased from 4 in 10,000 children in 1966 to 100 in 10,000 today. While that increase can be attributed to both better detection and widening criteria for diagnosis, researchers believe that environmental factors are also playing a part.

"It is biologically plausible that anti-depressants are causing autism if used at the time of brain development in the womb, as serotonin is involved in numerous pre- and postnatal developmental processes, including cell division, the migration of neuros, cell differentiation and synaptogenesis - the creation of links between brain cells," Prof. Bérard explained. "Some classes of anti-depressants work by inhibiting serotonin (SSRIs and some other antidepressant classes), which will have a negative impact on the ability of the brain to fully develop and adapt in-utero".

Published on Leave a comment on Endocrine Disrupting Chemicals and Male Infertility

Recent research looked at environmental causes of male infertility, specifically endocrine-disrupting chemicals. Poor semen quality contributes to increases in infertility and the use of assisted reproductive technology.The researchers also discuss the higher incidence of testicular cancer worldwide, lower levels of testosterone in men, and poor semen quality among men aged 20 to 25 (with the average man having up to 90% abnormal sperm). From Science Daily:

Endocrine-disrupting chemicals may be threatening fertility in industrialized countries

The birth rate is declining in all industrialised countries, and socioeconomic factors and women's age are not solely to blame. Male reproductive health and environmental factors are also significant, as concluded in a new scientific review article. ...Behind the article are fertility researchers from Denmark, the US and Finland. The researchers studied a number of factors related to fertility, and one of the main conclusions of their study was that poor semen quality contributed to increases in infertility and the use of assisted reproductive technology.

The study also revealed higher incidence of testicular cancer worldwide, with the greatest frequency among Caucasian populations. Moreover, the researchers also observed lower levels of testosterone in average men. "I was surprised that we found such poor semen quality among young men aged 20 to 25. The average man had up to 90% of abnormal sperm. Normally, there would be so many sperms that a few abnormal ones would not affect fertility. However, it appears that we are at a tipping point in industrialised countries where poor semen quality is so widespread that we must suspect that it results in low pregnancy rates," said first author of the article, Professor Niels E. Skakkebaek from the Department of Growth and Reproduction (EDMaRC) at Rigshospitalet and the University of Copenhagen.

"The article also demonstrates the impact of the increasing number of male reproductive problems on low birth rates. There is no doubt that environmental factors are playing a role. These are the correlations we are researching at the new research centre EDMaRC at Rigshospitalet," added Professor Anders Juul, who is the last author of the article.

Many of the male reproductive problems could be due to damage to the testes during embryonic development. While the reproductive problems could arise from genetic changes, "recent evidence suggests that most often they are related to environmental exposures of the fetal testes," the researcher team wrote."Since the disorders in male genitals have increased over a relatively short period of time, genetics alone cannot explain this development. There is no doubt that environmental factors are playing a role and that endocrine-disrupting chemicals, which have the same effect on animals, are under great suspicion. The exposure that young people are subjected to today can determine not only their own, but also their children's, ability to procreate," explained Professor Skakkebaek.

Published on Leave a comment on Male Infertility Linked to Other Chronic Medical Conditions

A recent study found that men with infertility have a much higher risk for a variety of other chronic medical conditions, including diabetes, heart disease, renal disease, alcohol abuse, and drug abuse. Thus, it appears that male infertility may be a symptom or a clue that there may be other health problems. One example is that male infertility is linked to an 81% greater risk of diabetes, and the greatest risk for renal disease occurred among men with azoospermia (zero sperm counts, the most severe form of male infertility). From Medscape:

Infertility in Men Tied to Heart Disease, Chronic Conditions

Men with infertility have a higher risk for a variety of other chronic medical conditions, including diabetes, heart disease, alcohol abuse, and drug abuse, according to a retrospective cohort study published online December 7 in Fertility and Sterility."The results suggest that male factor infertility has more than just reproductive implications," write Michael Eisenberg, MD, assistant professor of urology and director of male reproductive medicine and surgery at Stanford University School of Medicine in California, and colleagues.

The researchers used insurance claims data from 2001 to 2008 from the Truven Health MarketScan to identify more than 115,000 patients for the study population. They compared outcomes among 13,027 men diagnosed with male factor infertility (average age, 33 years), with outcomes among 23,860 men (average age, 33 years) who received semen or infertility testing and with outcomes among 79,099 men who had received vasectomies.

The authors looked for 16 conditions: hypertension, diabetes, hyperlipidemia, renal disease, chronic pulmonary disease, liver disease, depression, peripheral vascular disease, cerebrovascular disease, ischemic heart disease, other heart disease, injury, alcohol abuse, drug abuse, anxiety disorders, and bipolar disorder.

The men with infertility had higher rates of obesity and smoking, but even after adjustment for these covariates and for age, follow-up time, and healthcare use, men with infertility had a higher risk for multiple conditions compared with vasectomized men or those receiving only fertility testing. Specifically, compared with the men who received fertility testing, men with infertility had a 30% increased risk for diabetes (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10 - 1.53), a 48% increased risk for ischemic heart disease (HR, 1.48; 95% CI, 1.19 - 1.84) and for alcohol abuse (95% CI, 1.07 - 2.05), a 67% increased risk for drug abuse (HR, 1.67; 95% CI, 1.06 - 2.63), and a 19% increased risk for depression (HR, 1.19; 95% CI, 1.04 - 1.36).

Compared with men who received vasectomies, those with infertility had a 9% higher risk for hypertension (HR, 1.09; 95% CI, 1.02 - 1.17), a 14% greater risk for hyperlipidemia (HR, 1.14; 95% CI, 1.07 - 1.22), a 41% greater risk for ischemic heart disease (HR, 1.41; 95% CI, 1.19-1.67), and a 16% greater risk for other heart disease (HR, 1.16; 95% CI, 1.04 - 1.29). Further, men with infertility, compared with vasectomized men, had an 81% greater risk for diabetes (HR, 1.81; 95% CI, 1.57 - 2.08), a 60% greater risk for renal disease (HR, 1.60; 95% CI, 1.14 - 2.24), a 53% greater risk for liver disease (HR, 1.53; 95% CI, 1.31 - 1.80), and a 52% greater risk for peripheral vascular disorders (HR, 1.52; 95% CI, 1.12 - 2.07).