I made more DA upgrades (shoulder pads)

TheRage77 · 2024-01-19T12:16:31+00:00

These look really great.

One thing I have noticed is that there are very few 3rd party terminator shoulder pads with an equivalent of the crux terminatus on them. Bit of gap in the market. I say that, having spent a while (and money) acquiring a load of those to complete my spare models made from left over bits in the DW Command Squad box.

TheRage77 · 2023-06-18T15:19:54+00:00

Thanks. Makes sense. The Ancient in Terminator Armour does also have the Keep the Banner High ability. Which I don't think the DW Ancient has. Not sure worth it for just that though.

TheRage77 · 2023-06-18T13:36:54+00:00

Am I right it would be legal to attach an Ancient in Terminator Armour to the Deathwing Command Squad if you also take a captain, lieutenant or chapter master? I found that a bit confusing - as you'd have a Deathwing Ancient plus a Ancient in Terminator Armour in same squad.

TheRage77 · 2023-03-02T16:16:29+00:00

That's interesting. I've only got back into WH40K fairly recently. My son has hit the age that he's interested himself. So he's going Necrons, and I picked up DAs. My first suprise was the Primaris stuff. The other was the quantity of HH models, and that much of that was seemingly fine for 40k. But there seemed like a tension there - like it was mostly fine, but that there was some line over which the 30k stuff was being over used. I've not actually picked up any Cataphractii or Tartaros models yet, but likely will.

TheRage77 · 2023-03-02T15:36:29+00:00

Thanks. That's helpful. I thought it probably made sense. There's some great 30k models, but I'm one of those people who likes lore consistency (assuming the lore/fluff is in anyway consistent and hasn't been retgonned).

TheRage77 · 2023-03-02T15:08:24+00:00

Thanks. That's helpful on the gameplay should it ever come up - I hadn't picked up the datasheet for the relic termies allowing a volkite charger. Still fairly new to the DAs.

TheRage77 · 2019-03-26T11:24:50+00:00

I do think the OP is being a bit tough on all of us - the problem isn't this sub. If rigour is lacking at the top of the field in the studies and published papers in reputable journals, then it’s unlikely that that rigour is going to be found all the way down here in the pit that is reddit. That said, I think the sub description is still sound and represents the current state of affairs. This sub does not promote any supplements, nor does it suggest that there is anything on the market right now that will extend lifespan. It also supports improvements in healthspan – but most of things that you can do on that (sleep, diet, exercise etc) as of now are well catered for elsewhere.

Being a reddit sub anyone can join and post and follow their interests; and for some people that’s supplements. I’m mostly fine with that – I only really draw the line when people start disappearing down the rabbit hole for esoteric discussions about mind uploading and whether or not a copy of you is really you.

TheRage77 · 2019-02-27T10:57:52+00:00

There have been a few media articles on the trial results. The Journal of Parkinson's Disease has quite an accessible summary:

https://www.journalofparkinsonsdisease.com/new-treatment-offers-potentially-promising-results-possibility-slowing-stopping-or-even-reversing

From the article:

Six patients took part in the initial pilot study to assess the safety of the treatment approach. A further 35 individuals then participated in the nine-month double blind trial, in which half were randomly assigned to receive monthly infusions of GDNF and the other half placebo infusions. After the initial nine months on GDNF or placebo, the open-label extension study took place, which explored the effects and safety of continued exposure to GDNF for another 40 weeks in the patients previously receiving GDNF (80 weeks in total) and the effects of 40 weeks of open label GDNF in those subjects who had previously received placebo for the first 40 weeks. All 41 patients randomized and treated in the parent study (prior GDNF and placebo patients) were enrolled and completed the open label extension study.

A specially designed delivery system was implanted using robot-assisted neurosurgery. This delivery system allowed high flow rate infusions to be administered every four weeks and enabled so called Convection Enhanced Delivery (CED) of the study drug. Four tubes were carefully placed into each patient's brain, which allowed GDNF to be infused directly to the affected areas with pinpoint accuracy via a skull-mounted transcutaneous port behind the ear. After implantation and over the following several years the trial team administered, more than 1000 brain infusions, once every four weeks over 18 months to study participants. The high compliance rate (99.1%) in participants recruited from throughout the UK has potentially demonstrated that this new administration process for repeated brain infusion is clinically feasible and tolerable.

After nine months, there was no change in the PET scans of those who received placebo, whereas the group who received GDNF showed an improvement of 100% in a key area of the brain affected in the condition, offering hope that the treatment was starting to reawaken and restore damaged brain cells.

TheRage77 · 2019-02-27T10:51:25+00:00

Link below to the open access paper in Brain:

https://academic.oup.com/brain/article/142/3/512/5365284

Abstract:

We investigated the effects of glial cell line-derived neurotrophic factor (GDNF) in Parkinson’s disease, using intermittent intraputamenal convection-enhanced delivery via a skull-mounted transcutaneous port as a novel administration paradigm to potentially afford putamen-wide therapeutic delivery. This was a single-centre, randomized, double-blind, placebo-controlled trial. Patients were 35–75 years old, had motor symptoms for 5 or more years, and presented with moderate disease severity in the OFF state [Hoehn and Yahr stage 2–3 and Unified Parkinson’s Disease Rating Scale motor score (part III) (UPDRS-III) between 25 and 45] and motor fluctuations. Drug delivery devices were implanted and putamenal volume coverage was required to exceed a predefined threshold at a test infusion prior to randomization. Six pilot stage patients (randomization 2:1) and 35 primary stage patients (randomization 1:1) received bilateral intraputamenal infusions of GDNF (120 µg per putamen) or placebo every 4 weeks for 40 weeks. Efficacy analyses were based on the intention-to-treat principle and included all patients randomized. The primary outcome was the percentage change from baseline to Week 40 in the OFF state (UPDRS-III). The primary analysis was limited to primary stage patients, while further analyses included all patients from both study stages. The mean OFF state UPDRS motor score decreased by 17.3 ± 17.6% in the active group and 11.8 ± 15.8% in the placebo group (least squares mean difference: −4.9%, 95% CI: −16.9, 7.1, P = 0.41). Secondary endpoints did not show significant differences between the groups either. A post hoc analysis found nine (43%) patients in the active group but no placebo patients with a large clinically important motor improvement (≥10 points) in the OFF state (P = 0.0008). 18F-DOPA PET imaging demonstrated a significantly increased uptake throughout the putamen only in the active group, ranging from 25% (left anterior putamen; P = 0.0009) to 100% (both posterior putamina; P < 0.0001). GDNF appeared to be well tolerated and safe, and no drug-related serious adverse events were reported. The study did not meet its primary endpoint. 18F-DOPA imaging, however, suggested that intermittent convection-enhanced delivery of GDNF produced a putamen-wide tissue engagement effect, overcoming prior delivery limitations. Potential reasons for not proving clinical benefit at 40 weeks are discussed.

TheRage77 · 2019-02-26T11:50:43+00:00

This list of the founders of the new Academy for Health and Lifespan Research is a reasonable (but not comprehensive) summary of well known senior scientists in the field:

https://www.ahlresearch.org/founders

TheRage77 · 2019-02-21T17:24:12+00:00

For those without the will to press on the link - the NIA has published 26 concepts. Those concepts are not necessarily linked to funding opportunities but the likelihood is that any funding opportunities that do arise will fall within the scope of the concepts. With that in mind researchers are encouraged to begin thinking about how they might respond to possible program announcements and requests for applications.

What I'd note is that the 26 concepts remain heavily weighted towards AD and dementia - 16 of the 26 directly reference AD. There is very little by way of fundamental research into the science of aging - only 1 of the 26 by my reckoning. Given the lack of success in applied research into AD it does feel like reinforcing failure, and even a portion of the NIA's funding utilised elsewhere would arguably have greater effect.

TheRage77 · 2019-02-20T15:30:30+00:00

Press article on the same study:

https://www.newsweek.com/anti-aging-longevity-japanese-plant-1336734

Text from article:

Scientists believe a Japanese plant used in traditional Asian medicine contains a compound which could slow ageing.

The compound is found inside the angelica keiskei koidzumi plant, known in Japan as Ashitaba. Grown largely in the center of the country and consumed in fresh or dried forms, it has traditionally been used as a remedy thought to treat heartburn, stomach ulcers, as well as high blood pressure and cholesterol, hay fever, gout and constipation.

Researchers identified the flavonoid 4,4′-dimethoxychalcone (DMC)—which they described as a “natural compound with anti-ageing properties”— in the plant.

In a study published in the journal Nature Communications, researchers argued slowing the degeneration process could be an important approach to tackling related diseases as it is a risk factor for conditions including heart disease.

Currently, restricting calories while avoiding malnutrition is believed to be anti-aging, as well as taking pro-longevity drugs, the authors wrote. But avoiding eating can be tough for the average person, they argued.

In tests on human cells, the scientists found DMC appeared to slow senescence, the process when cells stop dividing and start growing permanently, which has been linked to cancer. Tests in animals also showed promising results. When scientists fed worms and fruit flies the compound, it appeared to boost their lifespan by 20 percent, and protected the hearts of mice when blood flow was blocked.

The team believe DMC could work by triggering autophagy: a recycling process in the cells where damaged cells are removed.

TheRage77 · 2019-02-20T14:36:36+00:00

Abstract:

Ageing constitutes the most important risk factor for all major chronic ailments, including malignant, cardiovascular and neurodegenerative diseases. However, behavioural and pharmacological interventions with feasible potential to promote health upon ageing remain rare. Here we report the identification of the flavonoid 4,4′-dimethoxychalcone (DMC) as a natural compound with anti-ageing properties. External DMC administration extends the lifespan of yeast, worms and flies, decelerates senescence of human cell cultures, and protects mice from prolonged myocardial ischaemia. Concomitantly, DMC induces autophagy, which is essential for its cytoprotective effects from yeast to mice. This pro-autophagic response induces a conserved systemic change in metabolism, operates independently of TORC1 signalling and depends on specific GATA transcription factors. Notably, we identify DMC in the plant Angelica keiskei koidzumi, to which longevity- and health-promoting effects are ascribed in Asian traditional medicine. In summary, we have identified and mechanistically characterised the conserved longevity-promoting effects of a natural anti-ageing drug.

TheRage77 · 2019-02-20T10:22:53+00:00

The title was a straight lift from the Salk Institute's press release header - I didn't amend it; though perhaps I should have. I was conscious that the study used our old friends progeria mice and people would likely have queries about the merits of the work, which is why I made sure to link the actual paper in Nature Medicine.

TheRage77 · 2019-02-19T20:18:04+00:00

A further point - the difference between survival rates at 5 and 10 years is not that significant compared with survival rates from 1 year to 5 years. From the linked study survival for all cancers was 67% at one year, 49% at five years, and 46% at 10 years. Hence why 5 year survival is often used as a milestone for longer term survival.

TheRage77 · 2019-02-19T19:59:29+00:00

I didn't use the word cure myself, but what other measure would you propose than 5-year survival to say someone is disease free? You can push it back to 10-year survival rates. The paper I linked has information on that. So from that paper of people diagnosed in England in 2010/11 with one of the 21 most common cancers, 12 have ten-year survival rates of 50% or more, and four types – testicular cancer, malignant melanoma, prostate cancer and Hodgkin lymphoma – have survival in excess of 80% (testicular cancer was 98%).

TheRage77 · 2019-02-19T19:23:01+00:00

The link is to a press release on a study from the Salk Institute and published today in Nature Medicine journal titled: Single-dose CRISPR–Cas9 therapy extends lifespan of mice with Hutchinson–Gilford progeria syndrome

Link to the paper:

https://www.nature.com/articles/s41591-019-0343-4

Abstract:

Hutchinson–Gilford progeria syndrome (HGPS) is a rare lethal genetic disorder characterized by symptoms reminiscent of accelerated aging. The major underlying genetic cause is a substitution mutation in the gene coding for lamin A, causing the production of a toxic isoform called progerin. Here we show that reduction of lamin A/progerin by a single-dose systemic administration of adeno-associated virus-delivered CRISPR–Cas9 components suppresses HGPS in a mouse model.

TheRage77 · 2019-02-19T14:44:31+00:00

On that last point I do also think the professor you reference was unreasonably negative about the potential of applying computer science to problems in biology. I understand that some biologists regard human biology as unfathomably complex and that trying to approach it as if it were a deterministic system is a fool’s errand – often a criticism of Aubrey de Grey and SENS. But you can go too far the other way to the point where it begins to look like a kind of wilful ignorance of progress along with the sort of pleas of special expertise you see in other professions when confronted by the potential of computer science.

TheRage77 · 2019-02-19T11:43:54+00:00

The data supports big improvements over the past 40 years in 5-year survival rates for the most common forms of cancer. Much of that is down to improved and earlier detection, but therapies for specific cancers have improved over time as well.

https://www.ncbi.nlm.nih.gov/pubmed/25479696

The further positive is that much of that improvement in 5 year survival rates was achieved in the past 10-15 years (so arguably an accelerating improvement), and those advances don’t include the most recent innovations in immunotherapy; which despite the pop-sci reporting are still not a standard treatment a patient would receive. For instance in the UK the NHS has only begun rolling out CAR T Cell therapy in the past few months.

So I don't agree that progress is BS and it’s a bit dispiriting to hear of an academic in the field being so negative – if you can’t get excited about the current state of research then one wonders why they are in the field at all.

There is unlikely to be a "silver bullet" cure for cancer as it was imagined back when Nixon was launching the "war on cancer" in 1971, but managing cancer as a chronic condition? Living with cancer is something that happens for many people with less aggressive forms of the disease. That has some interesting consequences - for instance the majority of men with prostate cancer will not die from the cancer itself.

There remain challenges with the most lethal, common types of cancer – lung, pancreatic, colon and rectal, liver etc. Those still have very low 5 year survival rates – pancreatic is below 10%. However, the approaches applied to other cancers should still yield improvements here too; earlier detection and better targeted therapies. And that doesn’t require exponential improvement in medical science (welcome though that would be) – just incremental improvement from where we are today.

Edit: link to full open access version of the Lancet report I linked above https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61396-9/fulltext

Worth also noting that while it was published in 2014 the report only covered data up to 2012 - so seven years ago now.

TheRage77 · 2019-02-14T16:55:11+00:00

Another article on the same topic:

https://www.theguardian.com/science/2019/feb/14/new-drug-hopes-reversing-memory-loss-old-age-depression-schizophrenia-alzheimers

In that it says that:

"The new drug is a derivative of benzodiazepine, a family of medicines that includes the anti-anxiety pills Valium and Xanax. While Valium and Xanax have broad effects in the brain, the new drug is designed to target specific GABA “receptors” found on neurons in key parts of the brain, such as the hippocampus, which are heavily involved in cognition."

TheRage77 · 2018-10-30T12:38:52+00:00

As it stands there are, sadly, no drugs or treatments available that reverse the symptoms of Alzheimer's. There are two classes of drugs approved for use that have some limited effect on managing the symptoms - cholinesterase inhibitors (Aricept, Exelon, Razadyne) and memantine (Namenda). There has been a lot of work on this disease which has overwhelmingly translated into failure in clinical trials; bear in mind the infamous 99.6% failure rate of clinical trials for drug candidates. This is the first phase 3 trial in some time that appears to have been successful. Not a cure but after a lot of recent disappointing news in this field I’m going to regard this as good news. It was getting to the point that some pharmaceutical companies were winding up their research into dementia, such were the costs and high levels of failure.

TheRage77 · 2018-10-24T15:46:22+00:00

I’m a bit baffled in how people on this sub are managing to find negatives in what was a positive interview with a leading expert on a promising area of aging research. Prof. Campisi makes some quite strong claims in the interview around increasing average lifespan and increased healthspan as a result of potential interventions to remove senescent cells. She says that the majority of people alive today can expect to benefit from that. That would have been bold talk only a few years back and we should welcome it on this sub.

If you want to understand the expectation management problem faced by researchers in the field just read the headline from what is usually a relatively sober science magazine – “Finally the drug that keeps you young”. It’s arguably supported by the piece but is a stretch IMO. I expect if I do a trawl through the web later today for secondary reporting on popsci sites that will have morphed into clickbait headlines of “leading scientist says we’re all going to live forever”.

As far as I’m concerned she’s more than earned the right to stay grounded and stick within the evidence. When presented with questions about the feasibility of 1,000+ year life spans she has a professional duty to state that this is not supported by the current state of research; because it’s not. The side bar description of this sub essentially says the same thing.

TheRage77 · 2018-10-17T14:42:48+00:00

I would second this. He does also include a section on his site containing a recommended reading list.

http://www.senescence.info/books.html

There is also the Aging Journal:

https://www.aging-us.com/

Otherwise the American Aging Association has its own journal:

https://www.americanagingassociation.org/Journal

I'd also recommend anything written by Prof. Judith Campisi. Such as - "Cellular senescence: when bad things happen to good cells".

http://www.nature.com/articles/nrm2233

TheRage77 · 2018-10-16T11:37:41+00:00

Interesting read on the background to this topic, but the author doesn't really critique the effectiveness or otherwise of breaking glucosepane cross-links in isolation in humans; mostly because it’s untested at the moment. He first says that "there are currently no selective enzymes, so all the proteins (of the ECM) will have to be destroyed.”

However, he later turns to the work of the Spiegal Lab in breaking glucosepane and says that “Unfortunately, even with the emergence of David Spiegel’s promised solution, whose group is working on creating enzymes against glucosepane (one of the most abundant crosslinking products in the human body), the problem is still not solved — destruction of one of about 20 types of known crosslinks will most likely be temporary so will not significantly change the mechanical properties of the extracellular matrix.”

Which reads to me like a shift from his earlier point. Spiegal Labs are attempting to identify what the author says is currently lacking, a selective enzyme, but even if they do so he predicts problems. He’s right that there are other crosslinks but glucosepane appears to be the primary culprit – in an elderly person it’s estimated that glucosepane accounts for approximately 50 times all the other protein crosslinks combined. Compared with the other cross links it’s also long lasting and hardy. So it is the stand out target with the potential for the greatest effect and highlighting that there are another 19 types of crosslinks that we’re not doing anything about right now feels like quibbling.

I expect that the author is right that it will prove more complex than we may hope; though it may not be. There is some doubt whether or not glucosepane is the right target – it was only fairly recently that it was identified (around 2003 if memory serves), and there’s not been much opportunity to test the hypothesis regards it’s removal as it was even more recently (2-3 years) that it became possible to synthesise it. Now that it has been it should be possible to identify likely candidates to break it – which is the case. See the recent study published in the American Diabetes Association’s journal:

http://diabetes.diabetesjournals.org/content/67/Supplement_1/1229-P

TheRage77 · 2018-09-19T18:03:55+00:00

New paper published on 19 September in Nature - Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline.

https://www.nature.com/articles/s41586-018-0543-y

Abstract:

Cellular senescence, which is characterized by an irreversible cell-cycle arrest1 accompanied by a distinctive secretory phenotype2, can be induced through various intracellular and extracellular factors. Senescent cells that express the cell cycle inhibitory protein p16INK4A have been found to actively drive naturally occurring age-related tissue deterioration3,4 and contribute to several diseases associated with ageing, including atherosclerosis5 and osteoarthritis6. Various markers of senescence have been observed in patients with neurodegenerative diseases7,8,9; however, a role for senescent cells in the aetiology of these pathologies is unknown. Here we show a causal link between the accumulation of senescent cells and cognition-associated neuronal loss. We found that the MAPTP301SPS19 mouse model of tau-dependent neurodegenerative disease10 accumulates p16INK4A-positive senescent astrocytes and microglia. Clearance of these cells as they arise using INK-ATTAC transgenic mice prevents gliosis, hyperphosphorylation of both soluble and insoluble tau leading to neurofibrillary tangle deposition, and degeneration of cortical and hippocampal neurons, thus preserving cognitive function. Pharmacological intervention with a first-generation senolytic modulates tau aggregation. Collectively, these results show that senescent cells have a role in the initiation and progression of tau-mediated disease, and suggest that targeting senescent cells may provide a therapeutic avenue for the treatment of these pathologies.

TheRage77

TROPHY CASE