Article for AML News

In my last ever Post of February I had mentally moved through the 2 year post transplant tests and had believed that I had fully recovered from Leukaemia and things were moving forward well. I was in a very happy space and there would be nothing more to share – how wrong I was to be! Here’s an update…….

A Leukaemia patient should not be surprised when the disease throws you a curved ball.

For me that is now Sclerodermatous Skin GVHD (bascially my immune system (well my brothers if you must know! – attacking the soft tissues in my skin believing it is ‘foreign’).  I had recalled talking to Hugh Williams (brother of Ross, ex Wagga, now St Helens, Tas) about his Leukaemia treatment not long after I had started to recover.  Hugh is two years further advanced than me in his treatment and his main complaint was GVHD of the skin – a condition that affected his skin severely with a tightening and restriction over many areas of his body.  His way of dealing with this (apart from the drug regime) was to spend up to 2 hours each day with stretches and exercise for relief.  At that stage it was not on my radar.

Over the past two years I had often made mention of sore muscles and bones.  And a year ago I had a nasty outbreak of Lichen Planus on my hands.  As it turns out this was a pre-cursor to the Skin Sclerodermatous GVHD which has manifested itself as a nasty tightening of my skin, with scar tissue forming just under my skin layer across a large portion of my body.

The skin hardens up around your body and looks like ‘cryovac meat’ – nice vacuum sealed dimply muscles – just want you want.

This is a chronic condition and will take a long time to resolve.  Fortunately I appear to have caught it reasonable early (in my mind 4 months later than first discussed with the specialists) but never the less in time to address the issue.

Unfortunately with Sclerodermatous Skin there is no specific blood marker that easily identifies the condition – unlike say kidney or liver issues with are easily identified.

The clinical presentation of the disease is the key.  The main issue for people is loss of mobility as the skin gradually tightens up around your body.  Eventually you lose movement in your joints – so much so that you can’t bend over, touch your toes or even sit comfortably;

Luckily at this stage I am finding I still have my full range of movement but am most affected in by tightness around my legs and significant tightness around my abdomen/gut/trunk area.  The end game here if things don’t go well is loss of movement and ending up in a wheel chair – not for me!

I had been complaining to Amit for some time about feeling like I had developed a ‘beer gut’ which the associated comfortableness. We had passed this off as a side effect of the steroid Prednisolone that I was weaning off last year.

However as it turns out this was just the beginning of the Sclerodermatous Skin issue.

Amit’s response was to turn up the steroid dose initally to 10mg, then 20mg, then 40mg and after little impact 80mg a day  – which is a significant dose and one they don’t like you staying on for too long due to the many complications from side effects, including loss of bone density and muscle mass (and endless fatigue).

They add other drugs to this as long term immuno-suppressants, such as Mycophenolate   (In fact I am now back on up to 26 individual tablets a day – almost at the peak of my illness where it hit 44!).

As Amit says this will take a ‘long time’ to resolve.  Patience is once again part of the plan.

As part of seeking answers I have also consulted a Dermatologist at Melbourne City Dermatology, Emma Mooney, who first diagnosed this situation and took a biopsy to to confirm the condition.  She also referred me to a specialist Dermatology clinic at RHM with Dr Ryan De Cruz.  Emma was the first mover on this condition for me and I am grateful.

So where to from here?

Although quite worrying there are a range of treatments but as Amit says ‘unfortunately there is no clear path forward’.  We have to try the drugs and measure the clinical response looking for slow improvement.  There are a range of alternative drugs, each with various sides effects that might be used.  And as a third and final line of defence there is a process called Extracorporeal Photophersesis that involves a ‘dialysis ‘ like treatment of your blood on a regular basis over many months that is know to have a positive impact.  That would involve many months in Melbourne again for treatment.

Two Year Tests

My two year post transplant tests were all very positive. Via a comprehensive TeleHealth Session with Professor David Ritchie at Peter Mac, we talked through the tests completed in January.  This process is relatively new for RMH and it aimed at the Long Term Effects for Leukaemia patients.  It was very imformative.

Things tested and discussed included:

1. Hormonal Health Issues – testosterone levels, bone denisty, vitamin deficiencies, thyroid issues. Affect of constant steroids.
2. Cardiac Health – heart condition – response to drugs.
3. Immunologic – blood type, recovery of immune system, blood graft etc
4. Secondary Cancers – skin and other types
5. Psychological Health

David quoted numbers, ranges and test results, (largely at my request) and most if not all were in the normal range.  It was a very positive and glowing report card!

My recent blood tests showed most results in the normal range with a few outliers that the consultants were not overly concerned about at this stage.

Vaccines – I still a require the ‘live’ vaccines like measles, mumps & rubella but they have to wait until I am completely off immunosuppressants.

Where to from here

So although this blog brings you my current thoughts and concerns I see it as only a minor (and annoying) set back in my journey and one that I am determined to work through.

After such a good report at the two year mark I felt things were well underway but the life of a leukaemia patient is often unpredictable and can take many unforeseen turns.

I am sure I will get on top of this current situation and will endeavour to keep you posted on improvements from time to time – certainly not on a monthly basis but perhaps a few times throughout the year as things change.

As before, many thanks for your support and feedback.  It has been an important part of my journey and one that has meant a lot to me.

If there is anything good to come or the current COVID-19 Pandemic the ‘lock-down’ on our farm has meant plenty of time to catch up on jobs and keep well away from possible infection that would certainly take a rapid toll on my health given my current severely compromised immune system.

I am certainly enjoying my time with Jan catching up on pages of jobs around the farm, lots of reading and of course plenty of virtual drinks and ‘get togethers’ via Zoom with friends and family.  We even managed a black tie dinner for Claire’s birthday with 15 groups and 28 people.  It did get a little noisy at times!

So life goes on and compared to a lot of people I am having it easy!  When you think about it there are plenty of people much worse off – so no complaints here!

Welcome to my last blog post covering my Leukaemia journey from August 2017 to February 2020 – almost two and a half years.

In mid January I underwent a series of two year post bone marrow transplant tests including a bone marrow biopsy (to detect signs of leukaemia), a bone density test, heart test, lung function and others.  I had 13 separate blood samples taken for a range of blood tests.

My wife, Jan and I met with  Amit Khot, my haematologist in late January to receive the good news that I was technically in ‘molecular remission’ – basically cured of cancer, with less than 5% chance of relapse.  This was wonderful news – many people don’t survive this nasty disease.  I am in the lucky category!

Almost all my blood counts are now in the normal range and I feel fit and healthy – almost back to my pre-diagnosis health.  The main issues I currently deal with are quite minor and ‘at the fringe’ being GVHD, largely of the soft tissues in my mouth and some minor aches and pains of muscles and bone joints. These things can be easily managed and don’t affect my day to day activities much at all.

I must say I am eternally grateful for many things and would like to thank the many people have helped me return to health:

• The wonderful medical and support staff at RMH and Peter MacCallum – in particular Professor John Seymour and Dr Amit Khot
• My gorgeous wife (and proof reader!) Jan who stayed by my side for many months advocating for my return to health
• My wonderful family who have supported me through some pretty tough times and in particular our wonderful children Claire, Lachlan and Dougall.
• My brother Tony who donated his stem cells (bone marrow) to keep me alive
• Our friends who have wished me well and made special efforts to visit and keep in touch

I am now moving onto 3 and then 6 monthly blood tests and checkups and anticipate that my focus on leukaemia will wane as I move forward with my life.

I have recently contributed an article for the AML news – a special newsletter produced by the Leukaemia Foundation and you can read it on my Blog under the home page.

My treatment for Leukaemia has been an incredible experience, with some challenging situations and one of learning and growth.  Whilst I would not wish it on anyone I do implore those with a similar diagnosis to stay focused and positive in an attempt to manage your own recovery.

Thankyou to each and everyone who has connected with my blog and have taken the time to send messages of support.  This support was a key factor in my recovery.

I wish you all health and happiness in your own lives.

This week I will undergo my 2-year post Bone Marrow Transplant testing at Peter Mac.  This involves the following:

• 14 Different blood tests
• Bone Marrow Biopsy
• Bone Density Scan
• Lung Function Test
• Dental Check
• Gated Blood Pool Scan

And in addition I will also have the following with external specialists:

• Dermatology Checkup
• Optometry Checkup
• Physiotherapy Checkup

The results will not be available until the end of January and I will report these with my last Blog in February.

I have been feeling very well over the past few months and expect that all tests will go well – although I do remember Amit Khot’s answer when questioned what the outcome of my treatment would be.  He said “we can only apply the latest thinking and practice and in general this leads to a positive outcome, but please remember we are dealing with biology so to some extent it is unpredictable”.

Confident on one hand and non-committal on the other!

I thought I would post the results of my blood tests over the past two years.  As you can see they were very much up and down in the period immediately post my BMT but have generally settled in recent times.  The slight hiccups are due to being placed back on steroids from time to time to combat GVHD.

Blood Graphs

Over the Christmas Period

We had a great time at Mollymook with my sister Fiona and brother and law, Michael, Georgie, Oscar, our kids and all the grandparents Helen&Allen and Helen&Hugh.

Visitors over Christmas included:

• Darren and Cathy Wallace, Maddy and Ben
• Lachy and friends, Fi, Milly, Hanna and Marney.

• Andrew and Bev Irvine

• John and Sandy Hawkins
• Dougall and Celia, Charlie Youngman and girlfriend Becky.

• Brian Northcote and friend Julie

It is amazing how quickly time passes!  Who would believe it has been just over a year since we returned to Tassie after 15 months in Melbourne for treatment.  But it just goes to show that you need to keep doing things or you might run out of time!  And I more than most have seen this scenario emerge from out of nowhere!

My most recent blood tests were very encouraging.  Almost every blood count was in the normal range – Red Blood Cells  – 141, White Blood Cells – 9.1, Platelets – 162, Neutrophils – 5.1, Creatinine – 90 and Liver Markers (ALP, GGT and ALT) all in the normal range.

My consult with Amit is not for a week or so but on my reading of the blood results he should be satisfied that things are progressing well.

My steroid weaning has progressed ever so slowly and I am on a minimal does of just 2.5mg of Prednisolone daily now.

January Tests

I have been booked for a number of ‘2 year post-BMT’ tests in mid January covering Bone Marrow biopsy, bone density scan, lung function, dental, gated heart pool scan and extensive blood tests.

Following this if all is well Amit will give me the ‘all clear’ which as I say to friends will mean “I am as healthy as you!”  Some of my friends point out that I should be careful what I say as I mightn’t like that option at all!

Given the good progress I seem to have made this year I have decided that the blog will come to an end soon – probably after I receive my 2 year results.  This would be a good time to ‘hang up my boots’ if all goes well.

Other things

We have been lucky enough to make a few trips to Wagga for business and to catch up with friends and my mum and dad in Cootamundra.

On one of these trips I called in to meet up with Cathy Koning – my new found AML friend who is writing a book on her experience.  Cathy is now 7 years on from her BMT and is doing well leading very much a normal lifestyle.  It was good to share some stories and experiences.

And on top of that I have enjoyed getting back into flying spending a bit of time in our helicopter which is now based on the farm.

I am now counting down to the two year mark post Bone Marrow Transplant as this is when I will undergo another series of tests to check on my status.  If there is no sign of leukaemia the doctors will give me a ‘full clearance’ meaning I am officially cancer free.  These tests will happen early January and I am counting each day until then!

My most recent blood tests were very encouraging will all counts either in the normal range or very close to.  My Haemoglobin and Platelets were high (154 and 188) and Neutrophils 7.2.

My monthly consult with Amit was perhaps the quickest so far with just a few questions over the phone (I was driving at the time which Amit found amusing saying he’d never had a consult with a patient on the road).  I replied that my next one might be when I am flying a helicopter which he said would be another first.

Amit was cautious with my GVHD saying that the steroids were certainly doing their job (I am now weaned down to just 2.5mg per day) but he expected this treatment might come and go over the next 12-18 months.

One of the most undesirable side effects of the Prednisolone is the fat deposit I have gained around my abdominal area.  I complained to Amit that it must be very uncomfortable for men who carry a beer gut because that is how I feel and it is not nice!  He laughed it off and said that with time this will return to normal (with a little help with diet and exercise).  I’m on to it!

My health has been great over the last month and there are even days when I feel almost ‘as good as new!’.  On other days I still suffer from muscle soreness and fatigue – which of course is entirely manageable.  As I say ‘if this is my life then I have nothing to complain about’.  In fact because I have been feeling so well I am now focusing on the ‘margins’ ie. the small stuff such as the muscle soreness and my ‘beer gut’  – First World Problem I guess. It just reminds me how lucky I am  – of course 40-50% don’t make it at all!  The marvels of modern medicine.

Other stuff

The big news is I have now re-gained my helicopter licence – and what a goal.  In fact this was my first concern when I got sick – ‘when will I be able to fly again?’  So after 2 and 1/2 years I am back in the air – and thoroughly enjoying it.

We have been busy with business appointments and meetings recently which I am also thoroughly enjoying.  It is good to be back.

Things down in Tassie are going well with the drought affecting the farm (no where near the likes of NSW and QLD) but never the less it is dry for spring.

Sparky gets shorn in preparation for grass seed season and Jan shares some time with her mum.

I was contacted recently by a lady who had undergone successful treatment for AML and is writing a book on her experience.  Cathy Koning lives in Victoria and has experienced many of the things that I have and is now 7 years post transplant. Cathy still suffers from GVHD and is on and off steroids constantly.

Cathy asked me if I’d be happy for her to quote sections from my blog (namely the blog on religion!) and read her draft book.  I found it very interesting especially that her experience was similar to mine (although she spent a month in ICU due to kidney problems including dialysis and still has complications).

One of the most startling things I read was the overall survival rate for AML was just 24%.  This was quite alarming as I had always thought the statistic to be closer to 60%.  As it turns out 60% is the overall survival rate for Leukaemia but AML tends to be much more aggressive than other blood cancers.

Having checked this statistic with my Haematologist, Amit Khot, I have been reassured that this statistic has improved significantly in recent years with Stem Cell technology and other advancements – although I don’t have a more accurate statistic.  What is evident is the first 6-12 months post transplant are critical and survival in this period can be ‘touch and go’.  Luckily I am well through this and we do know that every month you survive post transplant your chances of survival increase significantly.

And once you reach 2 years post transplant you are given a full clearance with your chances of survival as good as any one else.  This is just 3 months away and I am very confident I am going to see this milestone!

My most recent blood tests were pretty encouraging although both my haemoglobin and platelets had dropped somewhat.  Amit was not too concerned indicating that these results will bounce around somewhat and both are still in the acceptable range.

Results were:

Hb – 129 (down from 152)

Wcc – 8.0

Neutrophils – 4.6

Platelets – 137 (down from 184)

In my review with Amit (over the phone) we covered my current drugs (just 8 tablets a day now) and the weaning plan for the steroids.  As expected this will be very slow taking another few months.  However I am down to just 5mg a day which is considered to be very low.

The lichen planus of my hands has almost disappeared and the only impact of GVHD that I am currently experiencing is mouth soreness from time to time and muscle pain in my legs which seems to come and go depending on the day.

So in a nutshell things are going very well – probably as good as can be expected.  And as I say to people I am now doing most if not all of the things I used to do prior to be diagnosed.  The marvels of modern medicine!

Other things in the life of the Hamiltons

I caught up with Lachy in Cairns recently (en route during the HeliSafari of FNQ).

We travelled up to Darwin for business meetings with our Business partners Mike and Kate McConachy.

Julia Ham made a visit one weekend.

We have been busy on the farm in Tassie tending to small jobs.  The weather has been superb with lovely calm spring days with cool nights.

Claire and Dougall (and multiple friends) made a visit to Tassie one weekend but we were so involved that we overlooked taking a photo!

I am now on monthly blood tests which is fantastic. My veins have taken a pounding over the past 12 months and it is good to give them some relief.

I had a consult with Amit this week over the phone and all went well. We went through the standard questions.

How do you feel? What drugs are you taking?

Amit was interested in my recent travel and movements and said I must be feeling well if I can be doing the things I listed.

And that is the key point. I have recently felt as well as ever. I’d say 80-90% of my pre diagnosis health – which is probably a great outcome. I have nothing really to complain about.

My recent blood results were all pretty good with Haemoglobin 152, Wcc 129, Neutrophils 9.5, Platelets 177 and Creatinine 78. In fact some of counts were a little high but probably due to the steroid dose I am not on (currently 10mg).

The weaning process for the Prednisolone is very slow – it will take 5 months to get back off this drug!

The Lichen Planus on my hands had recently flared up but thanks to a super strength cream it is now under control.

So now I am looking forward to the 2 year post Bone Marrow Transplant date (January 2020) as this is when the doctors will give me a full clearance.

Other things

Jan and I enjoyed a few days at Falls Creek skiing with David Foster Peter Clucas and Colin Duff. It had been 3 years since I’d been skiing so I was unsure how that would go. Apart from some massive cramps at night time (in my shins of all places) the skiing went really well – no falls and I even managed to ski the Summit.

Claire Toby and Pria helped out with tree planting at Milford. Lachy made a surprise visit from Bali.

I joined my friend Eric Saacks on a Heli Safari around FNQ. This was a trip of a lifetime.

Prednisolone is an amazing drug – just a few mgs a day and the T Cells back off allowing my body to recover from the GVHD.

Amit Khot tells me that all the effects of GVHD are not well known or documented and there are many manifestations which patients describe that are not named or well studied.  The standard response is to ‘hit it’ with Steroids (Prednisolone) and hope for the best.  A blunt instrument but one that seems to work.

Since going back on the steroids I have felt much better and I am now starting the weaning process – slowly reducing the dose every 3-4 weeks.  This will take up to 5 months this time so by the end of the year I may be completely off this drug.

Amit confirmed in my consult this week that taking Steroids will be part of my on-going treatment and this could be for a number of years.  He has patients that are on low doses (1-2mg/day) many years after their initial treatment for Leukaemia.

I have resigned myself to this fact and consider if this is the worst outcome of my recovery I am a lucky man.  The GVHD is not restricting what I do and in the big picture is a small price to pay for a return to health.  I admit it is a little annoying having to take the myriad of other drugs to counterbalance the effects of the steroids but once again a few pills a day is a small price to pay!

The lichen planus on my hands has finally started to resolve and my skin is almost back to normal.  And the only other irritation has been GVHD in my mouth with has also developed into Oral Thrush. A few more drugs and this seems to be subsiding!

My blood counts from this week’s tests were all in the normal range.  Hbs 138, Wcc 12.4 Platelets 196, Neutrophils 9.1 and Mg 0.82.  Amit has now put me on monthly blood tests rather than fortnightly – another milestone.

Earlier this month I had a ‘Flexible Cystoscopy’ of my urinary tract (ouch!).  This was to check for lesions in my bladder and urethra as I had been passing blood in my urine from time to time.  Luckily the urologist did not find anything of concern and in fact commented that it was the ‘tidiest’ he had seen in recent times!  This was a big relief as I had feared the worse.  He explained that my prostate gland had developed a slight vascular condition which was contributing to the blood.  In his opinion this was not anything to be concerned about.

So all in all things are moving ahead really well and my recovery is certainly looking very positive.  Amit indicated that apart from dealing with the GVHD issues there should not be any other new issues or matters of concern.

Other Things

We had a couple of days with Claire and Toby at Cape Leveque getting the hang of their camper trailer and we thoroughly enjoyed our subsequent camping trip across Australia travelling from Broome to Melbourne in 2 weeks via Marble Bar and the West MacDonnell Ranges.  Claire, Jan and I were joined by my sister Fiona who is married to Jan’s younger brother Michael (all very close I know!).

We made a quick trip from Alice Springs back to Camperdown in Vic to see Dougall play a game for the Port Fairy Seagulls (est. 1868!)

Space junk at Woomera

Nothing like Bacon and Eggs for breaky!

And back on the farm in Tassie the grass is green and the sheep are happy!

I guess the last blood tests were a little warning that things were not going so well and of course given more time that is exactly what the situation was.  Over the past few weeks I hadn’t been feeling so well with considerably more muscle pain and more bowel problems including diarrhoea which is an obvious sign of GVHD.  And to top if off the Lichen Planus on my hands had flared up again.  All things pointed to another bout of GVHD and although I was keen to ‘self-medicate’ I resisted the urge until I had discussed the options with Amit.

One of the first things he zeroed in on was the blood count for the Eosinophils, which normally rests at less than 0.1 but last test was up to 0.8 and this week rose to 2.2.  This is a ‘marker’ for GVHD and was enough for Amit to put me back on Prednisolone, starting at 20mg per day.

Amit had said some time ago that my journey this year would involve ups and downs with GVHD and having to continually go back on steroids as a countermeasure.  Despite this I had hoped that my recovery might have progressed a little more smoothly.

The good thing is once I had started taking the steroids again I immediately started to feel better.  The muscle pain eased within a day and I regained the energy that the GVHD had obviously been taking away.

Blood counts are now sitting at 134 for Hb, 13.4 Wcc, 154 for Platelets, 4.2 for Neutrophils.

One of the side effects of being back on Prednisolone is increasing the dose of Valaciclovir back up to 12 day!

Joe Trapani

To show our gratitude for the care and treatment received at Peter Mac (ie The Victorian Comprehensive Cancer Centre) Jan and I made a donation to research (apparently the full cost of treating a leukaemia patient is close to $1.5m – so I guess there was some room to help out!).  Through the Peter Mac Foundation we managed to sponsor some leading research under the Direction of Professor Joe Trapani who is the head of the Cancer Immunology Research program.

Joe and his team are working on a targeted therapy for GVHD, which of course was of interest to us.  We managed to meet with Joe and discuss his research which after 10 years in a laboratory with mice is about to be tested with humans.  He is hopeful of launching a new medication within a few years that will replace the need for the blunt instrument of Prednisolone for treating GVHD of the skin.

We were fortunate enough to tour the research labs at Peter Mac.  There are 650 researchers currently employed there – it’s a leader in its field throughout the world.  I certainly ended up at the right place for my treatment.

Jan with Steffi Chang from the Peter Mac Foundation.

Other things

We have enjoyed spending more time on the farm in Tasmania.

CASA have come good and returned my medical without any restrictions – which means I can go flying again solo once I am retested by an instructor.  This is good news and something I have been waiting on since the day I first got sick.

We are currently in Broome having joined Claire and her boyfriend Toby earlier in the week for a few days of outback camping and expolring at Cape Leveque.  Following that Claire, Jan and I will be joined by Michael and Fiona Sheridan to drive back across the desert from Marble Bar to Alice Springs (sadly Toby has to return to Victoria for work).  We will join up with the Thomson family from Wagga Wagga at Marble Bar.

Things have been tracking along well for the past few months (apart for the Lichen Planus on my hands) and I was quite buoyed by my progress.

However my latest blood tests this week showed a significant drop in all parameters.  Amit was not overly concerned but thought it may have been as a result of a virus or some other infection.  The problem is that I haven’t felt unwell in the past few weeks – so of course my mind is asking “what can it be?”.

Red blood cells have dropped from 143 to 125, Platelets from 216 to 100 (of greatest concern), white blood cells from 13.5 to 6.6 and neutrophils from 9.6 to 2.7.  Creatinine and Magnesium are both steady at 75 and 7.9.

Amit has suggested we wait for the next set of blood tests in a fortnight before jumping to conclusions.

The good news is the Lichen Planus has improved considerably, although is still evident.  It is treated with a steroid cream which seems to be doing the job.  Once again it is probably a condition that will come and go over the years and something that I will have to live with.

The other issue that has been under investigation is the evidence of blood in my urine.  I have had an ultrasound of my kidneys and prostate gland but this did not reveal anything (other than the prostate is quite small) so the next round of tests include a CT scan of my urinary tract and a cystoscopy (internal examination of the urinary tract) which should reveal more.  My urologist is investigating for evidence of cancer.  Stay tuned for more information!

Other things

We have managed to experience a few interesting things in the last few weeks including:

A visit from my Mum and Dad to Tasmania for a week.  We managed to install the ‘family swings’ that my father built in 1966 for us – which has been moved from house to house over the years.  A family heirloom!

A day out at the Campbell Town show – Australia’s longest running agricultural show established 181 years ago!  I even felt tempted to join up with the local pipe band.

Returning to my old Rotary Club in Wagga, Wollundry Rotary, to thank members for their well wishes and to co-ordinate a fund raiser for the Leukaemia Foundation where 11 members (and one wife, Kath Wallace) shaved their heads!  We raised close to $20,000 on the day! Thanks to all who shaved and gave!

A trip to Kununurra and Broome to catch up with business partners Michael and Kate McConachy.  There are many new faces in the business since we last visited about 2 years ago.  This pic is of Tim Heasman (Head of checking and training for Aviair) with one of our PC12s at our Broome base.

Some great weather on our farm in Tassie – even though we are seeing minus 2 and 3 some mornings!

And of course a few bike rides with Ross Williams and friends in the great Tassie bushland.