Time doesn’t heal all wounds: how DNA damage as we age causes cancer


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Our risk of cancer is determined by a complex mix of genes, environment and lifestyle factors.
Claudia van Zyl

Ian Majewski, Walter and Eliza Hall Institute and Edward Chew, Walter and Eliza Hall Institute

As we age, our bodies inevitably deteriorate. Some changes, like grey hair and wrinkles, are easily visible. Others, like high blood pressure, often go unnoticed, but can be deadly.

Just as our body shows signs of ageing, so does our genome. Damage comes from chemical reactions that alter our DNA, and from errors introduced when it is copied. Our cells protect against these ravages, but these mechanisms are not foolproof and cells gradually accumulate DNA damage over a lifetime.

As a consequence of this damage, your genome is not the same in every cell; you are a patchwork of cells with subtle differences in their DNA. When a cell divides it will pass on these changes, and as they accumulate there is more and more likelihood that there will be consequences.

If these changes – we call them mutations – chip away at the systems that govern cell proliferation and survival, this can lead to cancer.

Our latest research, published today in the journal Blood, provides new clues about how our cells protect their genome and guard against cancer.

Guarding the genome

Nearly 10% of cancers have a familial component. Genes like BRCA1 and TP53 are among the best known cancer susceptibility genes, and both are involved in coordinating the cell’s response to DNA damage.

BRCA1 helps to repair a specific type of DNA damage, in which both strands of DNA are broken. Inheriting a defective BRCA1 gene elevates the lifetime risk of both breast and ovarian cancer.




Read more:
Angelina Jolie has had a double mastectomy, so what is BRCA1?


When DNA repair mechanisms break down, cells can accumulate staggering numbers of mutations, and cancer becomes almost inevitable.

Beyond genetics, a complex mix of environmental and lifestyle factors modify cancer risk.

When we read the genome of a cancer it is possible to attribute mutations to certain types of stress. UV radiation, for example, will fuse certain DNA bases. The UV damage signature is writ large in melanoma, a cancer linked to sun exposure.

Lung cancers from smokers and non-smokers have different mutation patterns because of the action of chemicals in cigarette smoke that attack the DNA.

We can also use this approach to diagnose defective DNA repair, as each defect triggers a characteristic pattern of mutations. In this way, mutation signatures can help us understand why a cancer has developed.

A ticking genetic clock

Smoking, UV radiation and X-rays all damage your DNA, but damage also comes from reactive molecules present within the cell. These molecules are fundamental to the chemistry of life – take water, for example.




Read more:
Chemistry Nobel DNA research lays foundation for new ways to fight cancer


Water is a very reactive molecule and can do damage to our DNA. One of the most common mutations, either in cancer or in normal cells, results from water molecules reacting with methylated DNA.

DNA methylation is a small chemical modification that acts as a signpost on top of our genetic code. It helps to control which genes are switched on or off. This fine-tuning is essential for normal development, but methylation also makes DNA more susceptible to damage. Most of these events are quickly repaired, but the damage is unrelenting and some sneak through.

Cells accumulate mutations when DNA repair mechanisms break down.
K.D.P/Shutterstock

Methylation damage is the most prominent feature of an ageing genome. It’s so pervasive and reliable it has been proposed as a molecular clock that marks ageing. But our new research shows this process occurs more rapidly in some people.

We found and studied three people whose pathways to repair methylation damage had broken down. They all lacked a DNA repair protein called MBD4, which led to a marked accumulation of methylation damage – as though their cells were ageing prematurely.

All three developed an aggressive form of leukaemia in their early 30s, a cancer which usually wouldn’t be seen until the person is in their 60s or 70s.

Methylation damage plays a role in most cancers, but in these cases it was the primary driver of the disease.

While complete inactivation of MDB4 – as occurred in the three participants – is extremely rare, our findings raise the question of how more subtle differences in DNA repair shape cancer risk, particularly in the context of ageing.

Turning back the clock

Ageing contributes to cancer risk in myriad ways. While we’ve focused here on the buildup of DNA damage, our immune system also plays an important role and tends to fade as we get older.

Lifestyle factors – such as obesity, stress and diet – also provide a cumulative risk that builds over a lifetime.




Read more:
What does DNA sound like? Using music to unlock the secrets of genetic code


Understanding the interplay between these factors is key to finding strategies that will effectively diffuse the health consequences associated with ageing.

Our research is helping to tease apart the contribution of DNA damage in different disease processes. Our findings suggest that some people accumulate more DNA damage than others – their clocks are ticking a little faster – and measuring these differences may help to spot people at risk of developing cancer, or help match them with more effective treatments.The Conversation

Ian Majewski, Laboratory Head & Victorian Cancer Agency Fellow, Cancer & Haematology Division, Walter and Eliza Hall Institute and Edward Chew, PhD candidate, Cancer and Haematology Division, Walter and Eliza Hall Institute

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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The faster you walk, the better for long term health – especially as you age



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OK, you don’t need the poles. But you should pick up the pace.
from http://www.shutterstock.com

Emmanuel Stamatakis, University of Sydney

Some of us like to stroll along and smell the roses, while others march to their destination as quickly as their feet will carry them. A new study out today has found those who report faster walking have lower risk of premature death.

We studied just over 50,000 walkers over 30 years of age who lived in Britain between 1994 and 2008. We collected data on these walkers, including how quickly they think they walk, and we then looked at their health outcomes (after controlling to make sure the results weren’t due to poor health or other habits such as smoking and exercise).

We found any pace above slow reduced the risk of dying from cardiovascular disease, such as heart disease or stroke. Compared to slow walkers, average pace walkers had a 20% lower risk of early death from any cause, and a 24% lower risk of death from heart disease or stroke.

Australian Science Media Centre.



Read more:
We asked five experts: is walking enough exercise?


Those who reported walking at a brisk or fast pace had a 24% lower risk of early death from any cause and a 21% lower risk of death from cardiovascular causes.

We also found the beneficial effects of fast walking were more pronounced in older age groups. For example, average pace walkers aged 60 years or over experienced a 46% reduction in risk of death from cardiovascular causes, and fast walkers experienced a 53% reduction. Compared to slow walkers, brisk or fast walkers aged 45-59 had 36% lower risk of early death from any cause.

In these older age groups (but not in the whole sample or the younger age groups), we also found there was a linearly higher reduction in the risk of early death the higher the pace.

What it all means

Our results suggest walking at an average, brisk or fast pace may be beneficial for long term health and longevity compared to slow walking, particularly for older people.

But we also need to be mindful our study was observational, and we did not have full control of all likely influences to be able to establish it was the walking alone causing the beneficial health effects. For example, it could be that the least healthy people reported slow walking pace as a result of their poor health, and also ended up dying earlier for the same reason.

Fast walking for some might not seem it for others.
from http://www.shutterstock.com

To minimise the chances of this reverse causality, we excluded all those who had heart disease, had experienced a stroke, or had cancer when the study started, as well as those who died in the first two years of follow up.




Read more:
New study shows more time walking means less time in hospital


Another important point is that participants in our study self-reported their usual pace, which means the responses were about perceived pace. There are no established standards for what “slow”, “average” or “brisk” walking means in terms of speed. What is perceived as “fast” walking pace by a very sedentary and physically unfit 70-year-old will be very different from a sporty and fit 45-year-old.

For this reason, our results could be interpreted as reflecting relative (to one’s physical capacity) intensity of walking. That is, the higher the physical exertion while walking, the better health results.

For the general relatively healthy middle-aged population, a walking speed between 6 and 7.5 km/h will be fast and if sustained, will make most people slightly out of breath. A walking pace of 100 steps per minute is considered roughly equivalent to moderate intensity physical activity.

We know walking is an excellent activity for health, accessible by most people of all ages. Our findings suggest it’s a good idea to step up to a pace that will challenge our physiology and may even make walking more of a workout.

The ConversationLong term-health benefits aside, a faster pace will get us to our destination faster and free up time for all those other things that can make our daily routines special, such as spending time with loved ones or reading a good book.

Emmanuel Stamatakis, Professor of Physical Activity, Lifestyle, and Population Health, University of Sydney

This article was originally published on The Conversation. Read the original article.

How lowering the voting age to 16 could save democracy



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Thousands of high school students across the US walked out of their schools to protest gun violence and to call for changes to gun laws.
EPA/Tannen Maury, CC BY-ND

Bronwyn E Wood, Victoria University of Wellington and Nick Munn, University of Waikato

Former US president Barack Obama visited New Zealand this week and met with Prime Minister Jacinda Ardern. Both leaders share an interest in youth development and their discussions focused on how to keep younger generations engaged and involved.

In the wake of the school shooting in Florida last month, there have been calls in the US to lower the voting age to 16 to give high school students power to challenge gun laws. In New Zealand, too, the idea of allowing 16-year-olds to vote has again been mooted by the children’s commissioner, Andrew Becroft.

So, what are the arguments against and for a lower voting age?




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Ongoing opposition to lower voting age

Becroft argues that a lower voting age could enhance turnout, ingrain the habit of voting, and give young people more rights.

However, his comments have been met by similar responses to those former New Zealand Green MP Sue Bradford received when she initially proposed lowering the voting age back in 2007.

Opponents argue that young people lack maturity, life experience and civic knowledge. At 16 and 17, critics say, young people are heavily influenced by adults such as teachers and parents (and therefore subject to coercion), and their ability to vote doesn’t match other responsibilities young people hold as they are still largely dependent economically on adults.

This time, however, New Zealand would not be alone in giving younger people the vote. Sixteen-year-olds in Argentina, Cuba, Ecuador, Austria, Nicaragua and Brazil now have voting rights.

In the 2014 Scottish independence referendum, 16- and 17-year-olds seized the opportunity to vote; 75% of their cohort turned out to vote. In the US, high school students are showing their considerable political strength in protesting against gun violence in their schools.

Inconsistent arguments

New Zealand has a very inclusive electoral system. It allows people on benefits to vote, despite their lack of economic independence. It also allows those with cognitive disabilities to vote, regardless of the severity of their disability and the degree to which they are influenced by their parents or caregivers. And it allows that members of religious groups are given guidance on how to vote by their religious leaders.

The system ought to be more consistent in applying its reasons for preventing people from voting. If lack of maturity is a reason to stop someone voting, it applies to all who lack maturity. If being heavily influenced by others is a reason to prevent someone from voting, it applies to all who are subject to this sort of influence.

There is an even deeper problem with the objections against a lower voting age. Consider how we treat those aged above 18 and those below 18 when it comes to proving their capacity to vote.

Those over 18 are accepted as voters, and remain so regardless of their actions (short of criminal offences that see them imprisoned and their voting rights removed). Those under 18 are presumed not to have the capacity to vote, and are denied any opportunity to show otherwise. But in neither case are we actually examining whether the individual concerned has the qualities we want in a voter.




Read more:
Giving voice to the young: survey shows people want under-18s involved in politics


Young people have perhaps more opportunity than older people to develop these qualities. The younger a person the more time they have to spend in formal education, where they can develop their civic knowledge and recognise the importance of political participation – including voting.

Lowering the voting age to 16 would bring the age of political responsibility more in line with the age of criminal responsibility and the age of informed consent for medical procedures.

New Zealand’s current system is willing to hold a 16-year-old responsible for murder, but deny that same 16-year-old the responsibility to cast a vote. This isn’t right. They are either capable of acting both well and badly, or of doing neither.

Civic education

In New Zealand, discussions on lower voting ages take place alongside conversations about civic education in schools. Becroft and others recognise that both should go hand in hand. However, this is not a simple premise.

Merely learning more about civics and political processes has not been shown to lead to greater citizenship participation. The type of civic learning matters.

A large-scale longitudinal study of more than 4,000 students in the US found that civic learning in which students actually experienced involvement in civic and political issues — and particularly on issues that matter to them – had the greatest long-term impact on future political participation.

This bodes well for New Zealand, as research published last year following a two-year study on social studies students taking social action for their internal assessment credits showed the curriculum is well set up for young people to experience civic engagement.

The ConversationEncouraging younger voter participation is complex but essential if we want to maintain the health of our democracy.

Bronwyn E Wood, Senior Lecturer in Education, Victoria University of Wellington and Nick Munn, Senior Lecturer in Philosophy, University of Waikato

This article was originally published on The Conversation. Read the original article.

Customised & Personalised Bibles


The link below is to an article concerning the future ‘Bibles’ of the digital age. This article suggests that people will download customised and personalised Bibles that will be made up of what people want in their Bibles – it had to come to this eventually. The technology already exists for people to do for themselves.

For more visit:
http://www.telegraph.co.uk/culture/hay-festival/10088562/Hay-Festival-2013-Digital-Bible-will-be-personalised.html

Church in the Digital Age


The following article reports on a Christianity that is going digital – at least this ‘church’ has. The online church with 100 000 ‘members.’ Is this really the church experience of the Bible? Somehow, I don’t think it is.

http://www.christianpost.com/news/church-online-boasts-100000-viewers-a-week-72817/

Plinky Prompt: Would You Rather Be Super Intelligent or Extremely Good Looking?


Intellectual Incitement Ahead

Hmmm – this is a rather self-centered question. The answer I have for this question is that I’m really quite content with who I am. I am what God had made me to be and with that I am content.

In human terms I know I am not the most attractive/good looking guy that is getting about. I’d have to say I’m fairly average – if not below average – by this current age’s philosophy of good looks. One of the reasons why I’m still single I guess.

I also wouldn’t describe myself as super intelligent, but am thankful for having a degree of intelligence that allows me to be a little intellectual. Perhaps, another reason I am still single – lol.

So to answer this question – I am content with what God has made me to be and what he has fashioned me to be via His providential dealings.

Powered by Plinky

Victim of Orissa, India Violence Rescued from Trafficking Ring


Christians displaced by Kandhamal violence in 2008 sold for coerced labor or sex.

NEW DELHI, August 25 (CDN) — Nearly two years after large-scale anti-Christian violence broke out in India’s Kandhamal district, Orissa state, a team working against human trafficking on Aug. 9 rescued a 16-year-old Christian girl – one of at least 60 people sold into slavery after being displaced by the 2008 attacks.

The recovery in Delhi of the girl represented the cracking of a network that has trafficked Christian girls and women from Orissa to the national capital, sources said.

“Human trafficking agents operating in the tribal belt of Orissa have targeted the Christian girls who are displaced by the Kandhamal communal violence – we have been receiving complaints of missing girls from Kandhamal after the violence broke out in 2008,” said attorney Lansinglu Rongmei, one of the rescue team members. “Roughly 60 girls are estimated missing and have been trafficked to different states.”

The girl, whose name is withheld, is a tribal Christian who was sold into slavery along with her 19-year-old sister and two other girls, all victims of the 2008 violence; they were trafficked from the Daringbadi block of Kandhamal district to the capital in December 2009, according to the Human Rights Law Network (HRLN). Her sister and the other two girls remain missing.

The mother of the girl accompanied the rescue team the evening of Aug. 9 in the Rohini area of Delhi, said a source from the HRLN Anti-Human Trafficking department on condition of anonymity.

“It was only the joint efforts of the All India Christian Council [AICC], HRLN Anti-Human Trafficking and the area police that made this rescue possible,” the source said.

The rescue team took action after the minor’s mother approached the HRLN of Kandhamal for help, which in turn called the Delhi office. Team members said they were disappointed by the reaction of police, who were initially cooperative but later “just unwilling to help,” in the words of one member.

The girl was used only for labor, although she was sexually harassed, sources said.

Rongmei told Compass that police refused to file a First Information Report, telling rescue team members, “No rape of the victim took place as per the medical examination, and there was no need for a case registration against anyone.”

The rescue team was not given a copy of the report of a medical examination at Bhagwan Mahavir Hospital, Pitampura, in Delhi, but they were told it indicated no sign of rape.

“It is confirmed that she was not raped,” said Madhu Chandra, spokesperson of the AICC and part of the rescue team. “She was physically abused, with teeth bite marks and bruises on her body – her neck, leg and right hand.”

 

Tricked

The girl stated that a well-known woman from their village in Kandhamal district gave her and her sister a false promise of safe and secure work in Delhi as gardeners.

Instead, operatives brought the sisters and the two other girls to a placement agency in Ratala village in Delhi, Sakhi Maid Bureau, which was run by a man identified only as Montu.

The HRLN source told Compass that the girl was with the placement agency for six days as the owner, Montu, attempted to rape her on several occasions. She was threatened, beaten, drugged with alcohol and sexually molested, the source said.

The girl said her sister and the other two girls were treated the same way.

She was placed in a home in Rohini, Sector 11, as domestic help beginning in January. Until July, she said, she was treated relatively well there, except for a few instances of being slapped by the lady of the house. Then the family’s 10-year-old son began to hit her and their 14-year-old son tried to assault her sexually, and she tried to flee earlier this month.

The girl told the rescue team that she informed the lady of the house about the elder son’s misbehavior, but that the woman stated that she could do nothing about it.

“She bears marks from being beaten on her right hand by the younger boy,” said Chandra.

He told Compass that the owner of the placement agency collected the girl’s wages from the family who employed her, promising to send the money to her mother in Kandhamal district, but that he failed to do so.  

Compass was unable to meet with the girl as she was still traumatized and undergoing counseling sessions. The girl’s mother sobbed for her other daughter, grieved that no one knew what condition she was in.

Montu, the placement agency operator, has absconded, according to police.

 

Passive Police

Prasant Vihar Police Station House Officer Sudhir Kumar confirmed the rescue team’s accusation that he refused to register a complaint in the girl’s case.

“The victim is from Kandhamal, let her go back to Kandhamal and register her complaint there,” Kumar told Compass. “No rape of the victim took place as per the medical examination, and thus there is no need for registering a case against anyone.”

Assistant Commissioner of Police Sukhvir Singh told Compass he had no explanation why the girl’s complaint was not registered, but he insisted on having her and the rescue team return.

“We will file their complaint if they come back to us now,” he said.

Karuna Dayal, coordinator of Anti-Human Trafficking Initiatives at HRLN, led the rescue team, which also included AICC Legal Secretary Advocate Rongmei, Chandra and Ashis Kumar Subodh of the AICC, and three others from the HRLN – Afsar Ahmed, attorney Diviya Jyoti Jaipuria and one identified only as Sangram.

Dr. John Dayal, secretary general of the AICC, said large-scale human trafficking in Christian tribal and Dalit women of Kandhamal district is one of the worst problems in the aftermath of the Kandhamal violence.

“Police have made arrests in the nearby Andhra Pradesh and other states,” he said. “Because of the displacement due to the violence, they lost their future, and it is very easy for strangers to come and lure them. Community and family life has been disrupted; the children do not have the normal security that growing children must have. Trauma, unemployment and desperate measures have resulted in the loss of childhood, forcing many to grow up before their age.”

The AICC is calling on the National Commission for Women, the National Commission for Scheduled Castes and the National Commission for Scheduled Tribes to investigate, he added.

Report from Compass Direct News

‘Blasphemy Laws’ Used to Jail Elderly Christian in Pakistan


‘Blasphemy Laws’ Used to Jail Elderly Christian in Pakistan

Muslim vying for same piece of land as Christian accuses him of speaking ill of Muhammad.

FAISALABAD, Pakistan, June 29 (CDN) — A Muslim vying with a Christian for a parcel of land here has accused the elderly man of “blaspheming” Islam’s prophet Muhammad, which is punishable by death or life imprisonment, according to the Christian Lawyers’ Foundation (CLF).

Jhumray police on June 19 arrested Rehmat Masih of village No. 165/RB Jandawali in Faisalabad district under Section 295-C of Pakistan’s controversial “blasphemy laws,” and he was sent to Faisalabad District Jail on judicial remand by Magistrate Muhammad Sajawal.

Section 295-C states that “whoever by words, either spoken or written, or by visible representation, or by imputation, innuendo, or insinuation, directly or indirectly, defiles the sacred name of the Holy Prophet Muhammad (PBUH) shall be punishable with death, or imprisonment for life, and shall be liable to fine.”

Christian sources said Masih, who suffers from arthritis, is 85 years old, though the First Information Report against him lists his age as 73.

The CLF’s Rai Navid Zafar Bhatti told Compass that hard-line Muslim Muhammad Sajjid Hameed filed the charges after learning that he would not be able to secure the Punjab Province land.

“He used the weapon of last resort, the controversial Blasphemy Laws’ Section 295-C, which preponderantly unbalances the scales of justice,” Bhatti said.

CLF President Khalid Gill said local Christian residents led by Masih had applied to the Punjab government to secure it for construction of a Christian residential area, and Hameed also had applied for the same parcel for commercial projects.

Hameed has testified in court that Masih made derogatory remarks about Muhammad, the prophet of Islam, and Khadija, the first wife of the founder of the religion, Bhatti said.

Gill said Masih has testified that he said nothing “humiliating” about Muhammad or Khadija.

“I am not a blasphemer, nor I can think of such a sinister thing, which is against the teachings of Christ,” Masih testified, according to Gill.

A CLF fact-finding team found that in April the frail Masih had argued with Hameed and several other Muslim hardliners – Shahbaz Khalid, Afzaal Bashir, Muhammad Aamer, Akber Ali and Asghar Ali – about the Virgin Mary, said Gill.

“At that time the elderly Masih, who at present is languishing in Faisalabad District Jail and facing discriminatory behavior and apathy of Muslim inmates and jail wardens, did not know that this altercation with Muslim men would lead to imprisonment for him,” Gill said.

Three of Hameed’s friends who backed him during the argument, 25-year-old Aamer, 45-year-old Akber Ali and 40-year-old Asghar Ali, have testified in support of Hameed’s accusation, according to Bhatti.

The CLF fact-finding team, led by Babu William Rose, a local Faisalabad Christian representative, found that Masih was also accused because he was a politically active member of the Pakistan Muslim League-Quaid-e-Azam party (PML-Q), while Hameed supports the PML-Nawaz Sharif (PML-N).

Representatives of the National Commission for Justice and Peace also asserted that Masih’s political views played a role in Hameed having him jailed under Pakistan’s blasphemy statues, saying that Hameed was using the power of the PML-N, which rules Punjab province, to implicate Masih in the case.

Gill and Azher Kaleem of the CLF sternly condemned the incarceration of Masih and said that the blasphemy laws must be repealed at once as they are widely used to take vengeance in personal or land disputes.

Section 295-A of the blasphemy laws prohibits injuring or defiling places of worship and “acts intended to outrage religious feelings of any class of citizens.” Section 295-B makes willful desecration of the Quran or a use of its extract in a derogatory manner punishable with life imprisonment.

Masih is the father of seven adult daughters and four grown sons.

Report from Compass Direct News

A Problem with Expository Preaching?


I have recently come across an article on the Banner of Truth website that ‘deals’ with expository preaching, or rather, attempts to define the dangers of what goes by ‘expository preaching’ in this day and age. The basic explanation or definition given in the article is pretty good really – that of a preacher confining himself to the text of Scripture and making it plain to others. That in itself is a fairly good explanation of being ‘expository’ I think. I do however think that some other things are probably required to fulfill the definition of what preaching ought to be – such as there being a place for application to the listeners, etc.

My point of disagreement with the article in question, is that of the need to issue a ‘caution’ to what goes by expository preaching today, which according to the article is the method of preaching through a passage or a book of Scripture week by week. I have no issue with saying that this is not the only way of being expository, but to issue a caution about the ‘modern way’ seems somewhat extreme to me.

I wouldn’t say that the ‘modern way’ is the only way to preach, nor would I go so far as to say it is the best way of preaching. I would say that I find it the best way of preaching for me, but I wouldn’t lay it down as a rule for others. I think the method of preaching used by a preacher is best left to that preacher and between himself and the Lord. I don’t think I would even call most of the preaching of Charles Haddon Spurgeon expository, yet you cannot argue that he didn’t preach in a manner used of God. So I think caution needs to be used in laying down ‘rules’ as to what method of preaching is best for a preacher, etc.

I have heard ‘preaching’ that has been systematic in its approach to a book of the Bible and it has left me bored, dry and thinking ‘what was the point of listening to it.’ However, as a person commented on the Banner of Truth article, this has probably got more to do with the validity of the preacher’s call than anything else. Perhaps the preacher is in a not so good place before God at the time of preaching also. Who knows – but a bad experience of someone ‘preaching’ systematically through a book of the Bible or passage doesn’t necessarily mean that that method is therefore proven to be a bad one. There are other variables that come into the picture.

So the Banner of Truth article is probably leading off in the wrong direction in my opinion. Readers of this Blog can make up their own opinion by reading the said article at:

http://www.banneroftruth.org/pages/articles/article_detail.php?1777