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Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local

Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose.Nolvadex uses

We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ.

Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen (P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo.
Breast intraepithelial neoplasia, including atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), and ductal carcinoma in situ (DCIS), has a five to 10 times higher risk of developing into invasive breast cancer compared with the general population and accounts for 15% to 25% of breast neoplasms on the basis of screening mammography.1 The natural history of breast intraepithelial neoplasia is heterogeneous. Some forms remain indolent, whereas other forms can progress to life-threatening invasive disease, which has led to controversial issues with regard to its optimal approach.1,2


Low-Dose Tamoxifen Halves Breast Cancer Risk in Women With Preinvasive Breast Lesions

5 mg/d, given for 3 years rather than 5 years—halved the risk of breast cancer recurrence or new lesions over placebo in women with breast intraepithelial neoplasia, without producing the usual toxicities seen with the standard dose, Italian researchers reported at the 2018 San Antonio Breast Cancer Symposium.1
“We believe our results have external validity and—given their pragmatic nature and the easy accessibility of tamoxifen—are generalizable,” said Andrea De Censi, MD, of the National Hospital E.O. Ospedali Galliera–Division of Medical Oncology in Genoa, Italy. “Tamoxifen, 5 mg a day (splitting the tablet) or 10 mg every other day, is applicable in clinical practice tomorrow.”Nolvadex dosage

Breast cancer experts at the meeting said this is news they can use. “Looking at these data, I would definitely give lower doses of tamoxifen, especially in patients with atypical ductal hyperplasia and lobular carcinoma in situ,” said Virginia G. Kaklamani, MD, Professor of Medicine at The University of Texas at San Antonio and leader of the Breast Cancer Program at The University of Texas MD Anderson Cancer Center, Houston.
This information tells me I can perhaps cut back on the dose for patients who are not tolerating tamoxifen. This would help me keep them on the dose, rather than have them abandon therapy,” said John Cole, MD, of the Ochsner Health System in New Orleans.

ALTHOUGH TAMOXIFEN is effective in preventing breast cancer recurrence, its side effects—menopausal symptoms, endometrial cancer, deep-vein thrombosis, and pulmonary embolism— are barriers for its use as a preventive measure. The aim of this de-escalation study was to determine whether a lower dose and shorter duration of tamoxifen therapy would be as efficacious as and better tolerated than the standard dose.

Dr. De Censi and colleagues had previously shown that a dose as low as 1 mg/d is noninferior to 20 mg in decreasing Ki67 (a marker of proliferation), though less effective in modulating serum biomarkers.2 For the current study, the investigators decided 5 mg/d would be a reasonable compromise between activity and safety. He explained that the government- and charity-funded study could not afford to financially support the use of a very large noninferiority trial of tamoxifen at 20 mg/d for 5 years as the control arm.



Donepezil improves the function of nerve cells in the brain. It works by preventing the breakdown of a chemical called acetylcholine (ah SEET il KOE leen). People with dementia usually have lower levels of this chemical, which is important for the processes of memory, thinking, and reasoning. Donepezil is used to treat mild to moderate dementia caused by Alzheimer's disease.crl-40 940 powder buy
Donepezil Hydrochloride is a noncompetitive acetylcholinesterase inhibitor (IC50 = 11.6 nM. It is known that Donepezil Hydrochloride is a useful tool in the study of Alzheimer's disease. Studies indicate that Donepezil Hydrochloride protects the brain against diisopropylfluorophosphate-induced effects. Studies indicate that Donepezil Hydrochloride selectively inhibits acetylcholinesterase, whereas it has little effect on butyrylcholinesterase. Alternate studies suggest that Donepezil Hydrochloride increases the concentration of extracellular acetylcholine.

Donepezil HCl Application (indications)
Donepezil is approved for the symptomatic treatment of mild to moderate dementia of the Alzheimer's type. It can relieve the symptoms of dementia and slow the progression of symptoms for some time. Although the effect was statistically significantly demonstrated in scientific clinical trials using different measuring methods, it is very low. In severe Alzheimer's dementia, it is outside the drug approval in the form of a so-called off-label use as a second-line choice. Also without drug approval Donepezil is occasionally used in vascular dementia and is therefore the first choice. Its effectiveness in treating mild cognitive impairment, often heralding or showing signs of dementia, is considered minimal and poorly documented.
Contraindications (Contraindications)
Donepezil is contraindicated in a known hypersensitivity to this drug or other piperidine derivatives such as domperidone. In patients with gastric ulcers, arrhythmia (sick sinus syndrome, supraventricular conduction disorders), syncope, seizures, obstructive pulmonary disease (eg, bronchial asthma, chronic obstructive pulmonary disease), bladder obstruction or regular use of non-steroidal anti-inflammatory drugs, such as acetylsalicylic acid or naproxen, special Precautions and the use of donepezil are subject to a benefit-risk assessment.

Since donepezil may be ineffective for the individual and in this case should be discontinued after 15 to 20 weeks, the possible improvement in cognitive performance must be monitored. Patients should also be monitored for possible gastrointestinal complaints (which may indicate gastric ulcers or gastrointestinal bleeding) and for their ECG (which may indicate new cardiac arrhythmias). Therefore, a comparison ECG should be derived before starting therapy.
Due to its effect on acetylcholine metabolism, donepezil may show pharmacodynamic interactions with other drugs with effects on the acetylcholine system. These include in particular muscle relaxants, such as succinylcholine, anticholinergics and acetylcholine agonists. Pharmacodynamic interactions with beta-blockers are also possible.

Since donepezil is metabolised via the cytochrome P450 enzyme system, there is, at least in theory, the possibility of an interaction with substances that inhibit or induce this enzyme system. For example, CYP3A4 inhibitors, such as ketoconazole and erythromycin, and CYP2D6 inhibitors, such as fluoxetine, may inhibit the degradation of donepezil, leading to an increase in the blood plasma level of the drug. On the other hand, enzyme inducers such as rifampicin, phenytoin, carbamazepine and alcohol can accelerate the degradation of donepezil and thus lower its plasma levels. However, the extent of these interactions and their clinical relevance has not been sufficiently investigated.


The 5 Biggest Casino Gaming Stories of 2018

With 2018 almost over, it’s time to consider just what the biggest news-makers were for the casino industry in that year. 2018 did not lack for either headlines or significant changes in the gaming industry, which continues to adapt to changing social and economic software

Steve Wynn exits Wynn Resorts. He’s widely hailed as the man who created modern Las Vegas. Certainly without the resorts he built—Golden Nugget, Mirage, Treasure Island, Bellagio, Wynn, and Encore—Las Vegas would look much different today. The Mirage changed the paradigm of what a casino resort should be, paving the way for the mega-resort era of the 1990s. His leaving Wynn Resorts is unquestionably a big deal.
With or without Wynn, the Las Vegas Strip would have grown in the 1990s. Without him, though, new resorts would have tended more to the Excalibur than Caesars Palace. After all, Circus Circus Enterprises was wildly profitable, while Caesars was a takeover target of none other than Donald Trump (among others) before being acquired by ITT in 1995. Hence the skepticism, which was widespread, over the potential profitability of The Mirage. Without Wynn’s design sensibilities and financial savvy to prove it could be done, the concept of an integrated mass luxury resort with a non-gaming emphasis might not have caught on.

With or without Wynn, the Las Vegas Strip would have grown in the 1990s. Without him, though, new resorts would have tended more to the Excalibur than Caesars Palace. After all, Circus Circus Enterprises was wildly profitable, while Caesars was a takeover target of none other than Donald Trump (among others) before being acquired by ITT in 1995. Hence the skepticism, which was widespread, over the potential profitability of The Mirage. Without Wynn’s design sensibilities and financial savvy to prove it could be done, the concept of an integrated mass luxury resort with a non-gaming emphasis might not have caught on.

Sports betting comes to you! The second earth-shaking story of 2018 was the Supreme Court’s strikedown of PASPA, the 1992 legislation that had kept states outside of Nevada from legalizing new sports betting. Since May, Delaware has started offering straight-up sports wagering (it had previously been offering only multi-game parlays) and New Jersey, Pennsylvania, Mississippi, West Virginia, and Rhode Island have begun offering sports betting.


Hong Kong is China’s biggest economic success – and the mainland needs it more than ever

If the riots in Hong Kong are troubling to the world, as they jolly well should be, they are even more troubling to China.To get more china economy news, you can visit shine news official website.

Hong Kong is tiny, with 7.5 million people, but has been stunningly successful. It is China’s second richest city in terms of income per head, with only the gambling hub of Macau (also a former colony) a bit ahead. Its nominal GDP of $50,000 (£40,000) per capita means that it is wealthier than Germany, France and the UK.

But that is just the start. The success of Hong Kong was the beacon inspiring Deng Xiaoping to reform China’s economic system. Those reforms, from 1978 onwards, have set the country on its march to become the world’s largest economy within the next decade. In 1980 the special economic zone of Shenzhen, just across from Hong Kong, was the first such experiment. It has transformed a collection of fishing villages into a metropolis that is now larger than Hong Kong itself. The model was then extended to other special zones, which in turn formed the basis for other reforms throughout mainland China. 

It was the genius of Deng to change the system slowly and incrementally – I am in awe of what he achieved. But now China has become such an economic success story, does it still need the example of Hong Kong to point a way forward?

A political observation and an economic question. The observation is that the “one country, two systems” political accord under which Hong Kong was returned to China is an obvious model for the reintegration of Taiwan. So riots in Hong Kong have wider political resonance. And the question is: does China still need Hong Kong as a beacon for development?There are two views. One, popular within some sections of the Chinese elite, is to say not really. Anyone who has visited Shanghai will be aware of the might of the country’s great commercial capital. Hong Kong has more glitter, but lacks the raw power. A nation of 1.4 billion people versus a city of 7.5 million? No contest.

This view would maintain that Hong Kong continues to be useful to China, because it remains a gateway both into and out of the mainland. But whatever it might be able to teach the rest of China, the lessons are either unnecessary or inappropriate.The other view – which I admit I find more compelling – is that Hong Kong is as important as ever, for it points the way China might avoid “the middle-income trap”, in which a country reaches a middle-income level of economic development but fails to progress further. That is the core economic challenge China faces.

Many countries get stuck. In much of Latin America and in Russia, wealth per head rises to a certain level then fails to climb much further. Sometimes it goes backwards. Argentina being the sad example of that. The World Bank noted that only 13 of the 101 countries deemed to be middle-income countries in 1960 had achieved high-income levels in 2011.

Even Japan, certainly a high-income country and the third largest economy in the world, has slipped in the global league table. Some people in China are concerned that as the country ages it too will face the same challenges as Japan, the difference being that growth will top out at a much lower level of wealth per head. It will, as many commentators suggest, grow old before it becomes rich. 

What Hong Kong does is to show that it can indeed make that leap. It has done so, and continues, despite headwinds, to push forward.


Shanghai Rolex Masters Tickets on Sale Now

Wimbledon champ and world number one Novak Djokovic and 20-time Grand Slam winner Roger Federer are among a host of elite names heading to China for the illustrious Shanghai Rolex Masters in October.To get more shanghai rolex masters, you can visit shine news official website.

The eighth tournament of nine in the ATP World Tour Masters 1000 spans eight days, and will see 99 matches of jaw-dropping action and thrilling excitement played out.

The world’s top talents will battle it out for their share of the mouth-watering USD7,086,700 prize pot, as the Qizhong Forest Sports City Arena, retractable magnolia-inspired roof and all, will play host to Novak, Roger and co.Arguably the most exciting draw of the event will be to see what Australian star Nick Kyrgios manages to throw a tantrum about this time, as the controversial Aussie has had outbursts at his last four Shanghai Rolex Masters.

Djokovic was triumphant last time out on Shanghai’s hard court, after the Serb overcame Croatia’s Borna Coric in straight sets in 2018's final.

While Wimbledon may have already passed, don’t miss your chance to indulge on strawberries and cream, not to mention the quintessential tennis companion – Pimm’s.October 6-13, All Day; RMB60-RMB480. Qizhong Forest Sports City Arena. See event listing. Purchase tickets here.


Meeting the demand for smaller LED displays

The search for a breakthrough display technology that addresses the needs of next generation products could be over.

A growing number of emerging applications, such as Head Up Displays (HUDs), AR/VR headsets and general wearables, are looking at new display technologies to enable the development of next generation products that will meet growing global demand. According to research consultancy Yole Développement, the xafs could reach as many as 330million units by 2025.indoor fixed led display

Although augmented and virtual reality are probably being seen consumer technologies, they are increasingly used in industrial and manufacturing applications, providing skilled and semi-skilled workers with access to information that can assist them in a range of tasks. Examples may include showing a worker the correct sequence for fixing and tightening bolts in an engine, or rivets in a larger structure such as a fuselage. When tools are also connected, the process becomes altogether more integrated, delivering quality assurance as each fixing is recorded or highlighting those that haven’t yet been secured.

Head-mounted displays not only add a level of realism to the scene, they can further increase productivity by allowing workers to move around unencumbered by large handheld displays or tablets.

Display technology is evolving in order to meet demand for smaller, lighter headsets that can be worn for an entire shift without becoming a burden or potential health hazard. The drive for more efficient displays is pushing innovative manufacturers towards microLEDs; a technology that promises lighter, smaller and more efficient displays.Headsets are one important and emerging application area for smaller displays, but others include HUDs, which are now being integrated into road vehicles. Existing applications include general wearables such as smart watches and, of course, displays have always been part of the Human-Machine Interface. This will continue, as smaller displays will allow them to be embedded within a wider range of devices.

Displays generally fall into one of two categories; reflective or emissive. Reflective displays typically require a separate light source and mirror arrangement, while emissive displays, such as LEDs, generate their own light.

Today’s headsets are often based on reflective display technology due to the lack of available emissive displays, which is why they appear large and heavy and are generally power-intensive. Moving to an emissive display solution for headsets will reduce the overall size, weight and power consumption, leading to a significant change in xafs dynamics.

Like other forms of emissive display technology, microLEDs feature three LEDs per pixel – red, green and blue – in order to provide the full spectrum of visible light. The name reflects the small size of each LED, often 10μm or less, on a pixel pitch of less than 40μm. While this makes them suitable for HUD applications, they can, in theory, be applied to any display of any size; scalability is one of the technology’s many benefits.


Tiny MicroLED Display from Mojo Vision Features Highest-Yet Pixel Density

Tiny MicroLED Display from Mojo Vision Features Highest-Yet Pixel Density

Mojo Vision’s new microdisplay is just 480μm (or 0.48mm) across, smaller than a grain of sand. The display seems to be targeted at the virtual reality and or augmented reality xafss. But, maybe not.indoor full color led display screen

Mojo Vision is heavily involved in what it calls Invisible Computing, a somewhat nebulous concept. Mojo Vision’s website copy makes references to the technology allowing us to “focus on a world around us and give us access to immediate and relevant information wherever we go, without distraction.”

This would seem to suggest that the company’s goal is to allow consumers to access digital information at the same time that they view the real, physical world around them.

In any case, the company is being somewhat coy about its purpose. According to Steve Sinclair, the senior vice president of product and xafsing, the Mojo Vision LED display “is one piece of several building blocks that we have to have in place to build the product that we’re making,”The new display sports 14,000 pixels per inch. This is over two orders-of-magnitude greater than the pixel density of most smartphones.

The new display is 0.48 mm across, and according to Paul Martin, VP for displays, “The pixels are 1.3 [micrometers across], which means that the gap is only 0.5 µm. Smaller gaps creates harder and harder problems of fabrication.”GaN (gallium nitride) technology is well known to power engineers, and the material can also be used to fashion LEDs. Among their advantages over the now dominant OLED (organic light-emitting diodes) technology is that they consume about 10% of the power and shine almost ten times as bright.

This by itself makes them a great bet for smartphones—viewable in daylight and longer time between charges. And, it’s also quite relevant for devices like virtual reality headsets and heads up displays (HUDs).


Apple considering micro LED display for 2020 Apple Watch

Apple considering micro LED display for 2020 Apple Watch

According to sources in the supply chain, Apple is close to signing a deal with two Taiwanese manufacturers for Apple Watch micro LED displays in 2020. If correct, the move is the culmination of several years of Apple attempting to replace the current OLED displays. outdoor led digital display

The two manufacturers are believed to be Yu Chuang, which develops micro LED processors, and Sui Bao, which assembles displays. These two companies recently collaborated on microLED products for Samsung which are also expected to be released in 2020.

Yu Chuang would not comment, but Sui Bao told Economic Daily News that its production line is ready and that it is in discussions with what is described as the US smart watch industry.

Despite that, Economic Daily News says that it will take nine months to have that line mass-produce items, and that Sui Bao is not likely to start preparations until later this year. That would see micro LED Apple Watch displays being released around the fall of 2020.

If correct, that would make it six years since Apple was first revealed to be looking into micro LED displays for Apple Watch.

Apple acquired micro LED specialist LuxVue for this back in 2014. Then in 2017, the company was reported to be doing this in order to benefit from the lower power consumption of micro LED, but it quickly appeared to abandon its discussions with Taiwanese firms due to a lack of progress.

While apparently then doing more research in the US, Apple did reach back out to Taiwanese firms with it reportedly being close to signing a deal with PlayNitride in April 2018 and then meeting with other firms in August of that year too.


LED Display xxx Now Valued At More Than $5B: Futuresource

LED Display xxx Now Valued At More Than $5B: Futuresource

LED displays are now a $5 billion global xafs, with the Americas region reaching a key milestone of $1 billion for the first time in 2017.outdoor fixed led display

The data comes from the xafs research firm Futuresource Consulting, which makes displays one of a relatively short list of vertical xafss it studies. I note this because news searches on digital signage and displays are cluttered with pricey but mostly worthless reports from Indian research factories that produce encouraging reports on absolutely anything they can dream up.

“The introduction of MicroLED by Sony in 2016 caused a great stir of excitement in the industry, but it was thought to be a measure of what was possible, not what was viable in the near term,” says Chris McIntyre-Brown, Associate Director at Futuresource Consulting. “However, this year has seen far more buzz around new chip-on-boards (COB) solutions, MiniLED and glue-on-board. All offer different benefits, but it is really the potential of MiniLED that has the industry excited. Troublingly though, are the lack of standards around MiniLED, MicroLED and indeed the LED industry as a whole. This is creating confusion – and that certainly needs to be addressed.”
1000 percent agreed there. As someone trying to watch this emerging xafs, trying to put a finger on what really is micro LED, mini LED and so on is very, very tough.

I’ve not seen the report ($$$$) but a press release says it goes into the competitive landscape, which is very cluttered but as with most emerging businesses, sees consolidation: The LED xafs has also witnessed strong merger and acquisition activity in recent years, with display vendors looking to access new technologies, increase their geographical footprint or diversify their customer bases. Futuresource expects to see this activity continue in the coming years as the xafs matures.

“An area to watch will be the new entrants launching LED products, typically coming from other areas of the visual display xafs. Indeed, it is increasingly rare to find a professional display vendor without LED in its range – although there are still a number of heavyweights in adjacent display areas yet to enter,” adds McIntyre-Brown. That’s a polite way of saying integrators and end-users have had the painful experience and now know they don’t want to deal with 12-hour time zone differences and equally yawning language gaps between North America and China.

Futuresource expects big growth in LED through at least 2022. It is now almost impossible to find a vertical xafs or end application where LED displays haven’t been optimized for both indoor and outdoor applications and this is for good reason. “The industry is poised to take the next step in technological advancement and with that we see the LED display community beginning to wonder just how much share it can take from the giant that is the LCD industry.”

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