Showing posts with label Health. Show all posts
Showing posts with label Health. Show all posts

‘Breakthrough’ Immunotherapy Method Cures Advanced Cancer





Killer T-Cell
A breakthrough therapy to modify T-cells into potent tumor-killing agents wiped out leukemia in three patients and allowed two of them to stay cancer-free for a year, US researchers said Wednesday.

The findings are the first to show how gene transfer therapy can create specialized T-cells, which guard the body from infection, that attack cancerous tumors in advanced cases of chronic lymphocytic leukemia (CLL).

The technique helped three elderly male patients who otherwise had little hope of survival, said the research published simultaneously in the New England Journal of Medicine and Science Translational Medicine.

Further studies are needed, but the advances offer hope to people who suffer from other cancer types such as ovarian, lung, myeloma and melanoma.

"Within three weeks, the tumors had been blown away, in a way that was much more violent than we ever expected," said senior author Carl June of the Abramson Cancer Center of the University of Pennsylvania.

"It worked much better than we thought it would."

Scientists removed a sample of the patients' T-cells and genetically modified them to attack all cells that express a certain kind of protein, CD19, which includes tumor cells.

They also engineered the T-cells to start triggering other T-cells to multiply as soon as they attached to a cancer cell, bringing on a faster death for the tumor but avoiding the side-effects of cancer drugs.

"We saw at least a 1,000-fold increase in the number of modified T-cells in each of the patients. Drugs don't do that," said June, describing the infused T-cells as "serial killers."

"On average, each infused T-cell led to the killing of thousands of tumor cells -- and overall, destroyed at least two pounds of tumor in each patient."

One patient's case, described in the New England Journal of Medicine, involved a 64-year-old man whose blood and marrow were "replete with tumor cells."

He saw little change for the first two weeks after treatment, but then started experiencing nausea, chills and fever. Test showed he was undergoing a huge rise in T-cell count. By day 28, his blood showed no evidence of leukemia.

A 65-year-old patient saw similar results, with no trace of tumor after a year, but the 77-year-old patient saw a slight recurrence of cancer after he was treated with steroids. However his tumor load remains far from what it was before the treatment.

"Most of what I do is treat patients with no other options, with a very, very risky therapy with the intent to cure them," said co-principal investigator David Porter.

"This approach has the potential to do the same thing, but in a safer manner."

Bone marrow transplants are typically the only treatment for leukemia patients, but they carry a minimum 20 percent risk of dying from the procedure and cure rates hover at around 50 percent.

It remains unknown how long the treatment may keep cancer at bay.

"The doctors have found evidence that months after infusion, the new cells had multiplied and were capable of continuing their seek-and-destroy mission against cancerous cells throughout the patients' bodies," said the study.

Chronic lymphocytic leukemia is the second most common type of adult leukemia after acute myeloid leukemia, according to the National Cancer Institute.


The researchers intend to study similar approaches in children whose leukemia has resisted standard treatment.


They are also looking to see if the approach could target non-Hodgkin's lymphoma and acute lymphocytic leukemia, mesothelioma cancer cells, ovarian and pancreatic cancer cells.

New Drug Can Treat Almost Any Viral Infection

In the left set, rhinovirus (the common cold virus) kills untreated human cells (lower left), whereas DRACO has no toxicity in uninfected cells (upper right) and cures an infected cell population (lower right). Similarly, in the right set, dengue hemorrhagic fever virus kills untreated monkey cells (lower left), whereas DRACO has no toxicity in uninfected cells (upper right) and cures an infected cell population (lower right). MIT

A new broad-spectrum treatment for viruses could be as effective as antibiotics fighting bacteria, MIT researchers report. The method uses cells’ own defense systems to induce invaded cells to commit suicide, preventing the spread of the virus. In lab tests, the new drug completely cured mice that had been infected with influenza.
Viruses work by inserting themselves into a cell and hijacking its machinery for its own use. The invaded cell then creates more copies of the virus, which involves creating long strings of double-stranded RNA — which contains the virus’ genetic material, like DNA contains ours.
When the virus is done copying itself, its hostage cell usually dies, from the virus bursting through its walls (lysis), changes to the cell’s outer membrane, and from apoptosis, or programmed cell death.
Human cells have plenty of defenses against viral invasion, including proteins that attach to the double-stranded RNA, preventing the virus from replicating itself after successful invasion.
This new drug therapy combines those dsRNA proteins with a protein that induces apoptosis. It’s called a DRACO, Double-stranded RNA Activated Caspase Oligomerizer.
When one end of the DRACO binds to dsRNA, it signals the other end of the DRACO to induce cell suicide, an MIT News article explains. In this way, the cell is killed before the virus can take over and eventually kill it anyway. If there is no dsRNA, the healthy cells are left alone.
“In theory, it should work against all viruses,” said Todd Rider, a senior staff scientist at MIT’s Lincoln Laboratory who invented the new technology.
A handful of drugs can target specific viruses by interfering with their replication process, through addition of modified DNA building blocks or the blocking of enzymes the viruses need to stimulate the replication process. But viruses are wily bugs, and they can evolve to resist these treatments.
The DRACO therapy could be effective because it targets the host cell, not just the virus.
Rider and colleagues are testing DRACO against more viruses in mice, according to MIT. Rider hopes to license the technology for trials in larger animals and for eventual human clinical trials, too.
Source: MIT News

Bioengineered spinal disc implants to combat Back Pain


Researchers have created a biologically based spinal implant they say could someday provide relief for the millions of people suffering lower back and neck pain. Instead of removing damaged spinal discs - a surgery known as a discectomy - and fusing the vertebrate bones to stabilize the spine in patients diagnosed with severe degenerative disc disease, or herniated discs, the artificial discs could be used to replace damaged discs, performing better than current implants that are made from a combination of metal and plastic.
Although discectomies prevent pain, the often limit mobility. Human discs look something like a tire, with the outer part, called the annulus, made of a stiff material, and the inner circle, the nucleus, made of a gel-like substance that gets pressurized and bears weight.
To mimic this structure, engineers at Cornell University in Ithaca and doctors at the Weill Cornell Medical College in New York City engineered artificial discs out of two polymers - collagen, which wraps around the outside, and a hydrogel called alginate in the middle. They seeded the implants with cells that repopulate the structures with new tissue. Compared to artificial implants that degrade over time, the researchers found that the new implants get better as they mature in the body, due to the growth of the cells.
"Our implants have maintained 70 to 80 percent of initial disc height. In fact, the mechanical properties get better with time," says Lawrence Bonassar, Ph.D., associate professor of biomedical engineering and mechanical engineering at Cornell.
A surgical procedure approved by the FDA in 2005 for treating the degeneration of the intervertebral disc involves removing the damaged disc completely and replacing it with an implant made from a combination of metal and plastic, with the aim of mimicking the normal movement of the lumbar and the spine.
"Bone or metal or plastic implants are complicated structures which come with a mechanical risk of the structures moving around, or debris from the metal or plastic particles accumulating in the body from wear and tear," says Roger Härtl, M.D., associate professor of neurosurgery at Weill Cornell Medical College and chief of spinal surgery at New York-Presbyterian Hospital/Weill Cornell Medical Center.
Because the new discs integrate and mature with the vertebrae they would have a huge advantage over traditional implants, says Härtl, who is also the neurosurgeon for the New York Giants. This major surgery would also become less invasive, safer and come with fewer long-term side effects, he adds.
Bonassar and Härtl began collaborating on the project in 2006 and have since moved into the animal testing stages. The project has received a US$325,000 grant from Switzerland's AO Spine foundation and $100,000 in support from NFL charities. The research appears online in the Proceedings of the National Academy of Sciences.

3D Displays Does Cause 'visual discomfort'


No, it's not just you. According to studies recently conducted by the University of California, Berkeley, the viewing of stereoscopic 3D displays does indeed cause visual discomfort, fatigue and headaches. The problem appears to come from the fact that the viewers' eyes are simultaneously trying to focus on the screen, and on objects that appear to be located either in front of or behind that screen.
The studies involved 24 adult subjects, who viewed 3D content both on small, consumer electronics-style screens, and on larger, theater-style screens. With the smaller screens, which are viewed at a closer distance, content that appeared to be located in front of the screen caused the most discomfort. Interestingly, however, viewing of the larger, more distant screens was most uncomfortable when content appeared to be located behind the screen.
"When watching stereo 3D displays, the eyes must focus - that is, accommodate - to the distance of the screen because that's where the light comes from," said Martin S. Banks, professor of optometry and vision science. "At the same time, the eyes must converge to the distance of the stereo content, which may be in front of or behind the screen."
Further studies are planned, which would include a larger number of test subjects, including children. The U Berkeley researchers hope that their findings could be used to establish guidelines for the positioning of viewers relative to 3D displays.
"Discomfort associated with viewing Stereo 3D is a major problem that may limit the use of technology," said Banks. "We hope that our findings will inspire more research in this area."
The research was recently published in The Association for Research and Vision in Ophthalmology's Journal of Vision.
Source: Gizmag

New Liquid Biomaterial Could Help Rebuild Faces Without Surgery





Doctors are testing a new liquid polymer that can be injected under the skin, molded and sculpted, then set in place with a LED array. Ultimately intended for use around the face, it sounds like a plastic surgeon's worst nightmare.
According to Technology Review, the compound is made of substances that are already used in cosmetic surgery, but has different properties than any before it.
It's a blend of hyaluronic acid-a biological material already used as a soft-tissue implant-and polyethylene glycol, a synthetic material. The blend is a liquid polymer that can be injected-thus avoiding the need for surgery. Once injected, the material can be sculpted into the necessary shape. When exposed to light of specific wavelengths, the messy tangle of polymer chains in the liquid implant rearrange into a stable, crosshatched form, stiffening the implant.
It only takes a few minutes in front of the LED light array before the material sets, and the procedure is generally pain-free once finished. Doctors recently completed a small trial in Canada, which was mostly successful (save for some unwanted inflammation), and they plan to launch a full-scale trial soon. 
Source: Gizmodo via Technology Review

Artificial Lung Created !


Researchers have created an artificial lung that uses air as a ventilating gas instead of pure oxygen - as is the case with current man-made lungs, which require heavy tanks of oxygen that limit their portability. The prototype device was built following the natural lung's design and tiny dimensions and the researchers say it has reached efficiencies akin to the genuine organ. With a volume roughly the same as a human lung, the device could be implanted into a person and even be driven by the heart.
The artificial lung is filled with breathable silicone rubber versions of the blood vessels that branch down to a diameter less than one-fourth of human hair. It was created by first building a mould with miniature features and then layering on a liquid silicone rubber that solidified into artificial capillaries and alveoli. They air and blood channels were then separated with a gas diffusion membrane.
By making the parts of the artificial lung on the same scale as the natural lung, the researchers say they were able to create a very large surface-area-to-volume ratio and shrink the distances for gas diffusion compared to the current state-of-the-art. In comparison to current artificial lung systems that require pure oxygen due to their inefficient oxygen exchange, tests of the new artificial lung using pig blood showed a three to five times improvement in oxygen exchange efficiency over current devices. It is this efficiency that enables the new artificial lung to use plain air instead of pure oxygen as the ventilating gas.
Blood is injected into the device's fluid inlet, while air is fed into the gas inlet. Oxygen molecules diffuse across the gas exchange membrane into the blood on the way to the blood outlet, while carbon dioxide in the blood fed into the device would diffuse across the membrane to be released through the air outlet.
"Based on current device performance, we estimate that a unit that could be used in humans would be about 6 inches by 6 inches by 4 inches tall, or about the volume of the human lung. In addition, the device could be driven by the heart and would not require a mechanical pump," said Joe Potkay, a research assistant professor in electrical engineering and computer science at Case Western Reserve University.
Potkay says the device is a major step towards an easily portable and implantable artificial lung and the team envisions patients using the technology while allowing their own diseased lungs to heal, or implanting one while awaiting a lung transplant.
Potkay's team, which includes Brian Cmolik, MD, an assistant clinical professor at Case Western Reserve School of Medicine, and Michael Magnetta and Abigail Vinson, biomedical engineers and third-year students at Case Western Reserve University School of Medicine, is now collaborating with researchers from Case Western Reserve's departments of biomedical engineering and chemical engineering to develop a coating to prevent clogging in the narrow artificial capillaries and on construction techniques needed to build a durable artificial lung large enough to test in rodent models of lung disease.
The Case Western Reserve University researchers expect to have human-scale artificial lungs in use in clinical trials within a decade.
Source: Gizmag

Researchers create vaccine against heroin high


Researchers at the Scripps Research Institute have created a vaccine that stops the high one gets from from heroin. Designed as a therapeutic option for those trying to break their addiction, the vaccine produces antibodies that stop heroin as well as other psychoactive compounds metabolized from heroin from reaching the brain to produce euphoric effects.
Previous efforts to create a clinically viable heroin vaccine have struggled because heroin is metabolized into multiple substances that each produce psychoactive effects. To overcome this problem the researchers, led by the study's principal investigator, Kim D. Janda, targeted not just the heroin itself, but also the chemical it quickly degrades into, 6-acetylmorphine (6AM), and morphine.
They linked a heroin-like hapten (a small molecule that elicits an immune response only when attached to a large carrier) to a generic carrier protein called keyhole limpet hemocyanin (KLH), and mixed it with Alum, a vaccine additive, to create a vaccine "cocktail." This mixture slowly degraded in the body, exposing the immune system to different psychoactive metabolites of heroin such as 6AM and morphine.
"Critically, the vaccine produces antibodies to a constantly changing drug target," said G. Neil Stowe, who is first author of the new study. "Such an approach has never before been engaged with drug-of-abuse vaccines."
Testing the vaccine on rats provided promising results. After several booster shots of the vaccine, heroin addicted rates were found to be less likely to self-administer heroin by pressing on a lever. Only three of the seven rats that received the vaccine self-administered heroin compared to all of the control rats, including those that had been given a vaccine that only targeted morphine.
The team also found that the heroin vaccine was highly specific, only producing an antibody response to heroin and 6AM and not to other opioid-related drugs tested, such as oxycodone, and drugs used to treat opioid dependence, such as methadone, naltrexone, and naloxone.
"The importance of this is that it indicates these vaccines could be used in combination with other heroin rehabilitation therapies," said Janda.
"In my 25 years of making drug-of-abuse vaccines, I haven't seen such a strong immune response as I have with what we term a dynamic anti-heroin vaccine," Janda added. "It is just extremely effective. The hope is that such a protective vaccine will be an effective therapeutic option for those trying to break their addiction to heroin."
The Scripps Research team has also recently begun collaborating with researchers at Walter Reed Army Institute of Research to see if it is feasible to develop a dual-purpose vaccine against HIV and for the treatment of heroin addiction in a single shot.
Source: Gizmag

Antiretrovirals Show Huge Promise for Halting HIV Spread in Two Major Studies


Big time news on the fight against AIDS out of Rome today, and it essentially boils down to this: antiretrovirals work (at least, an astoundingly high percentage of the time when they are used correctly). At the biggest forum on HIV and AIDS in the 30-year battle against the deadly epidemic (it still kills 5,000 people a day, FYI), two breakthrough findings show that antiretrovirals (ARVs) not only battle HIV in infected persons, but can stop the disease from spreading in two important ways: it helps prevent HIV-positive folk from transmitting the disease, and also helps prevent non-infected people from contracting it.
A handful of big-time findings were presented, but two stand out. The first major strategy under study, known as “Treatment as Prevention,” showed that when HIV-positive people were given an early start on HIV drugs, the chances of their transmitting the virus to their non-infected partners dropped by an astounding 96 percent.
The second major finding goes by the acronym PreP, for pre-exposure prophylaxis. PreP involves giving ARVs to non-infected partners of HIV-positive subjects as opposed to the infected partner. This also works with statistically significant frequency, cutting transmission by 73 percent.
PreP, however, raises ethical issues as well. When some nine million HIV-infected people the world over are in need of daily ARVs, it’s very tough to justify giving them to those who aren’t infected just to stem the spread. Which leads us to the crux of the matter: HIV/AIDS prevention needs cash to roll these ARVs out in the field, and right now free cash around the world is on the decline.
Western nations, the major source of this kind of funding, are cutting budgets. Organization like the WHO and the UN, normally the fundraisers for this kind of relief, are tightening the purse strings right at the point when it might be possible to turn back the tide on HIV, which added 2.6 million infected people to its rolls in 2009. Says the AFP: “Just to get 15 million badly-infected people on AIDS drugs by 2015, in line with the newly stated goal by UN members, will require between $22 billion and $24 billion annually.”
So as always it comes down to money. But there is hope: Just last week California-based Giliead Sciences inked a deal with the UN’s medical patent pool to allow Indian firms that specialize in generic pharmaceuticals to make cheap copies of four leading ARVs for sale in 100 poor countries. And some low doses of ARVs can be offered now in pill form for just 25 cents a day.
Source: Popsci,AFP, New Scientist

Porsche designs a Hookah Pipe


We have to admit being more than a little surprised that in this increasingly health-conscious world, Porsche Design has released a new luxury Shisha waterpipe. Also known as a hookah or narghile, Shisha is becoming increasingly trendy in Western markets for "social" tobacco smokers and is already deeply embedded in African and Middle Eastern cultures.
Porsche is one of the strongest, well respected brand names in the world, synonymous not only with uncompromising engineering and innovation, but with the deepest concern and respect for the safety of its customers.
Why then would a company with such an impeccable public image create a product which is known to be so injurious to its users?
Are Porsche's brand custodians asleep, or did they think that as no-one had bothered to complain about its long term sale of Porsche pipes and cigarette lighters, that Shisha was of the same ilk?
Although the Porsche (or any other brand of) Shisha pipe unquestionably absorbs some of the nasties in the smoke it filters, smoking shisha is VERY bad for one's health, and mounting evidence suggests it is far worse for one's health than smoking cigarettes.
In 2005, a World Health Organisation study group on Tobacco Product Regulation issued a scientific advisory note on waterpipe tobacco smoking which highlighted how little is known about waterpipes and the health risks they present, and called for more research on the subject - quite an irony given that the waterpipe has been around 700 years and entered mainstream usage at the same time that tobacco did.
The WHO scientific advisory note emphasised that the smoke that emerges from a waterpipe contains numerous toxicants known to cause lung cancer, heart disease, and a range of other diseases, just as cigarette smoke does.
One of the primary issues associated with hookah smoking is that because the smoke is much "smoother" than cigarette smoke, smokers can and do inhale much greater quantities of smoke.
According to the WHO scientific advisory note, a typical waterpipe smoking session will most likely expose the smoker to more smoke over a longer period of time than occurs when smoking a cigarette. That's because typical shisha smokers inhale more often and for longer periods than typical cigarette smokers.
Cigarette smokers typically take around eight to twelve 40-75ml puffs during the five to seven minutes it takes to smoke a cigarette, inhaling on average 0.5 to 0.6 liters of smoke per cigarette.
In contrast, waterpipe smoking sessions typically last 20-80 minutes, during which the smoker may take between 50 and 200 puffs which range from about 0.15 liters to one liter each. A shisha smoker might hence inhale as much smoke in one shisha sitting, as a cigarette smoker would inhale in smoking 100 cigarettes.
One of the other key factors associated with shisha smoking is that it is often done at a venue, where the quality of the substances placed inside the pipe, the putirty of the charcoal used, and the cleaning of the pipes will all vary considerably depending on the establishment. As narcotics, hashish and marijuana are also commonly used in waterpipes, it is not that uncommon for users of shisha pipes in coffee shops, bars and restaurants where there are illegal back room activities, to get a little bit more punch to their shisha than they bargained for.
One of the saddest things about the shisha culture prevalent in the Middle East and Africa is that waterpipe smoking is a family affair in many countries. Just two nights ago I witnessed a family in a restaurant share a shisha - the father, wife, and two pre-teen boys all smoked from the hookah over a half hour period.
Research indicates that the shisha does not filter out sufficient nicotine to prevent addiction, so the current perception of the waterpipe being a safe way of smoking is no doubt unwittingly addicting children to tobacco. Just how widespread this practice is cannot be established accurately, though anecdotally, it is quite commonplace.
It seems there is a very common misconception amongst those who use the Shisha pipe that it is far less injurious to one's health than cigarette smoking.
Which brings us back to the Porsche Shisha pipe. The 55 centimetre tall aluminium, stainless steel and glass waterpipe is now available exclusively at the recently opened Porsche Design shop in the Millionaires Gallery at Harrods Knightsbridge store in London.
The pipe will be available at Porsche Design stores worldwide from the end of the month at an undisclosed, though no doubt substantial price.
The Porsche Design Shisha shows only discreet branding on the aluminum top of the hookah and comes with a long flexible TecFlex tube, utilizing the same Porsche-designed material employed in its TecFlex writing tools.
I had not been aware until researching this article that Porsche has been making smoking accessories (such as cigarette cases, cigar cases, cigarette lighters and pipes) for many years, but even knowing that, I feel certain that the publicity surrounding this product will change the public's perceptions of the Porsche brand. Shisha smoking is very detrimental to your health.
Does Porsche Design's new Shisha pipe change your opinion of the brand?
We'd be interested to see your opinion in the comments.
Source: Gizmag

Skin cancer risk assessment made as easy as an iPhone app !

Despite years of health promotion campaigns advising us about the dangers of skin cancer, the incidence of the most dangerous type - melanoma - has been steadily rising since the 1970s with around 130,000 cases now diagnosed globally each year according to the World Health Organization. Even if we no longer spend hours sunning ourselves on the beach, extended time outdoors playing sport or socializing can still put us at risk of this deadly cancer. Developed by molecular diagnostics company Health Discovery Corporation (HDC), MelApp is an iPhone app designed help detect melanoma at an early - and likely curable - stage using mathematical algorithms and image based pattern recognition technology.


To use the app, you take a photo of an unusual mole or freckle with your iPhone's camera using the zoom feature to ensure it fills the green box on the screen. The photo is then uploaded and evaluated against a database licensed from Johns Hopkins University Medical Center.



If the risk is significant MelApp recommends you seek medical advice and can refer you to a nearby specialist for proper follow up.
It can also store images in albums so you can track changes in your freckles and moles over time. Sliding indicators are used to note information such as size, color and how fast it has developed.
MelApp is available from the iTunes store and costs $1.99 - which seems like a small investment in your health. An Android version is on the way.
Source: Gizmag

Synthetic Vocal Cord gel could restore function to damaged vocal chords


Whether caused by intubation during surgery, laryngeal cancer, lesion removal, or simply overuse, vocal cord scarring can limit or even eliminate some peoples' ability to speak. This is because the scar tissue is stiff, and doesn't allow the vocal cords to vibrate adequately. Some doctors have tried to soften the tissue using materials from the fields of plastic surgery and dermatology, but the treatment doesn't work in all cases, and the effects are said not to last very long. Researchers from the Massachusetts Institute of Technology (MIT) and Harvard Medical School, however, are developing a new approach - an injectable gel that mimics vocal cord tissue.

Rather than approaching the problem as a physiological one, they looked at the vocal cords as a mechanical issue. That is, they didn’t attack the scar tissue in the vocal cords but devised a fix for it. That fix came in the form of a material known as polyethylene glycol (PEG), which they chose because it is already FDA approved for other medical applications.

Lab tests have also shown that it can restore vibration to stiffened, scarred vocal cords. The MIT/Harvard project is attempting to restore vocal functions despite the presence of scar tissue, while other approaches (such as those involving drug treatments) have focused more on trying to get rid of that tissue.

Their PEG30 gel, should it receive its own FDA approval, would be categorized as an injectable medical device rather than a drug, which could further speed it to market. If approved, it would have to be re-injected every six months or so because it breaks down over time. But it could restore voice to many who have lost their primary means of expression.

The video below shows how the gel performs, as compared to actual vocal cords.

The First Trial of an Embryonic Stem Cell Treatment for Blindness Begins in California


Keeping in step with this week’s flood of awesome stem cell news, a development on the embryonic front: California surgeons have implanted lab-grown retinal cells into the eyes of two patients losing their vision to macular degeneration, Technology Review reports.

The retinal cells were grown from embryonic stem cells--those controversial (because of their source) biological building blocks with the ability to turn into any human tissue. This latest effort is among the first in the world to use embryonic stem cells as treatment. Last year another biotech company called Geron began a small trial using stem cells to treat spinal cord damage (the jury is still out on that one).
The retinal treatment is being carried out at the University of California but the science comes from Massachusetts-based Advanced Cell Technology, which recently received approval from the FDA to test a treatment aimed at replacing the retinal pigment epithelial cells destroyed by macular degeneration. That destruction eventually leads to blindness as photoreceptors die off.
To do this, Advanced Cell grows brand new retinal cells in the lab from embryonic stem cells and then implants them directly into the retina, where researchers hope they will take root and stop the degeneration process. If it works, Advanced Cell could be onto something big. Macular degeneration affects some 10 million people in the U.S. alone and is a prevalent cause of blindness in older people.
Source: Popsci via Technology Review