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Home|Blogs|Cross-Platform Game Development: What You Need and How It Works
Cross-Platform Game Development: What You Need and How It Works
April 26, 2022
A game’s commercial success depends on a variety of reasons. Among them is whether your title is engaging and catching enough to make users return and continue playing. The gameplay should be a reason to buy or download the game, too.
But one of the most important factors of game popularity, leading to successful monetization and high revenue, is availability. If you are aiming to release your game on many devices and platforms, you should learn how to create a cross-platform game.
87% of multiplayer gamers are constantly seeking more cross-platform titles to play.
43% of players wish for more cross-platform game options.
Taking your game cross-platform can increase revenue by 20% to 40% (VB Live).
So, if you are really interested in how to reach more engaged players, succeed in the gaming industry, and gain more profits, we’ll shed some light on how to develop cross-platform games, what challenges you may come across, and which cross-platform game development services are helpful.
Why Start with Cross-Platform Game Development?
Experienced developers usually know about the following “trap” in game development: they have designed a game that’s compatible with one or two platforms and succeeded greatly, but they still need a long time to adapt it to the new platforms.
The mobile game segment is fast-growing. Players downloaded 82.98 billion mobile games in 2021. SensorTower, a provider of the app’s marketplace performance monitoring, calculated in its whitepaper “Mobile Market Forecast” (2021 – 2025) that 71% of Google Play’s revenue would come from mobile games by 2025.
And the mainstream gaming solution is to meet players’ expectations to have access to their favorite mobile games on PC or console as well as vice versa. Creating a cross-platform game takes longer, but it prevents you from spending too much time and effort after game release to make it available on multiple platforms.
Game monetization is dependent on the users’ engagement level and readiness to make in-game purchases, which is connected to a social phenomenon of being committed to a group of players.
“I’m playing with my friends the same engaging game with no need to worry about which devices each of us has got,” Corey Davis, co-studio head of Psyonix, specified the idea in his talk for Epic Games blog. He continues: “Cross-play has a direct and meaningful impact on matchmaking speed and quality for online games.”
How to Develop a Cross-Platform Game?
Developing a single game for many platforms seems to be an efficient solution to reach a vast audience. Programmers are matching numerous operating systems, screen sizes, and power capabilities of the devices with the users’ expectations to play on a variety of platforms.
Steve Peterson, CEO at StoryPHORCE Entertainment, said: “We think of a game platform first while developing the title. But still more reasonable to think of customers and how their usage of platforms is changing.”
A developer willing to create a cross-platform game faces a set of challenges we are going to speak about below. They vary depending on the game you are working on (e.g., console players do not tolerate poor game flow or high device load as well as playing an adventure meditative game on a desktop demands smooth gameplay).
No matter whether you’re working with a pre-developed build of your project partner or designing an initial build, among the “must-do” issues are the following:
Learning more about the desired game performance
Outlining the possible bottlenecks
Prioritizing the order of certain optimization tasks
Main Challenges in Releasing a Cross-Platform Game
Developing a cross-platform game without proper analysis of game performance can lead to time wasted later while testing. You can miss something important concerning FPS, game thread, CPU, and GPU load if you do not apply a systematic approach to game performance analysis.
Under-developing a cross-platform game, the team usually faces a lot of repetitive monotonous tasks of finding performance/visual quality balance (e.g. to satisfy the owners of each console type) as well as manual tests and code reviews. To find and move away from all the unnecessary content loading CPU and GPU takes a lot of time. But as a result, you obtain odds detection to improve game performance.
Thus, for example, due to proper testing, you find out infinite looped actor spawn or unnecessary amount of meshes leading to the PC or console freezes.
Benefits of a Cross-Platform Game Design
Once you’ve faced a lot of challenges but are still ready to overcome them, it will lead to the release of a cross-platform title with manybenefits:
The developers’ team has no need to establish separate and specific codebases for each platform.
A unified single codebase makes the gameplay more stable and smooth.
You reach more players with the new title.
Users are grateful that they buy one title and are granted access to many other platforms.
A vast reach to the target audience contributes greatly to efficient monetization.
It’s easier to issue updates with no need to make changes in a lot of codebases.
We can continue this list of advantages, but one thing is obvious: a cross-platform game can have cross-play, which has a powerful impact on matchmaking speed and online games’ quality. And these features grant engaging gameplay to the users, making them interact with no need to think about who has which device or console.
So, by developing a cross-platform game, you have a chance to unite gamers together and make them committed much to the game playing, hence, easing game promotion and monetization.
Popular Cross-Platform Game Development Engines
Cross-platform game engines have the following benefits, proving that cross-platform game development is a reasonable endeavor:
They provide a single code base with no need to establish specific code for each platform.
Quicker upgrade: one change leads to an upgrade throughout all platforms.
Wide and quicker reach to the target audience: a player buys a single title and obtains access to the rest of the device’s gameplay.
Faster promotion: the cross-platform game covers a variety of players segments;
Better profitability via a reach to the users playing on different OS and devices (it increases the retention rates of the players).
CB Insights reported Unity and Unreal engines as those “providing everything a developer needs to design the next big cross-platform title (mobile, PC, or console game).”
Unity provides an efficient visual Blueprint tool for coders to create visual game elements compatible with a variety of platforms. This is a nice solution for those who are not willing to dive deeply into C++ code.
Moreover, Unity delivers a lot of 2D-ready elements optimized for mobile development. Once you installed the engine, you simply choose targeted platforms, and the required SDKs are downloaded automatically.
Unreal Engine is also an option.
To deal with Unreal Engine, you may need some setup: separately install SDKs for each intended platform.
Unreal and Unity game engines deliver efficient environments and tools for the development of mobile, console, AR/VR, and PC games. Developers can find many plugins for cross-platform game development on their marketplace or GitHub, including scripts, 2D/3D assets, animations, audio, and more.
We can, of course, talk about other engines with nice features for cross-platform game development. In this article, they are just for understanding that a cross-platform title may take more time to design, but at the same time, perfect out-of-the-box tools come in handy for the developers:
CryEngine, with its stunning, ready-made visuals.
GameMaker Studio is described as an extremely user-friendly tool with the possibility of creating customized game elements.
LibGDX is an open-source Java game development library.
Godot engine, a free option to generate 2D and 3D game development.
It may be hard to choose which engine will produce a game release perfectly matching your monetization and promotion strategy. But surely, after reading this blog, you’ve got a basic vision: cross-platform games demand more time for development, but less time for testing and upgrading, leading your titles to quicker and more powerful monetization.
Conclusion: Cross-Platform Game Is a Smart Technical Choice
Everybody wants a piece of the video game market (e.g. Tencent or Activision Blizzard) or hardware incumbents like Sony (PlayStation) and Microsoft (Xbox).
Unity and Unreal engines provide powerful digital infrastructure for a variety of the world’s popular games: Pokemon Go (Unity engine) or Fortnite (made with Unreal Engine).
In spite of the fact that while developing cross-platform games, the team may face a lot of challenges such as game performance evaluation, desired benchmarks outlining concerning FPS, GPU, and CPU load, as well as a smooth engaging experience for the players on any platform. But surely, after spending time and effort on namely cross-platform title design, they are to gain a lot of benefits in comparison with titles for a single platform.
If, after reading the article, you’re interested in cross-platform game development, but still you have a variety of questions concerning:
Which platforms to consider for wider title spread and better monetization
Which engine to choose for smoother code building and a more efficient QA testing process
Which measurements tools will assist better in systematic game performance evaluation
You are welcome to contact Innovecs because we cover all the aspects of cross-platform game development. And, moreover, we have gained more than ten years of hands-on experience delivering award-winning cross-platform titles worldwide.

domain: game


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domain: entertainment


all InfoSec news
Would you trust an AI to be your eyes?
Web: https://stackoverflow.blog/podcast/ Audio: https://chrt.fm/track/G8F1AF/cdn.simplecast.com/audio/6fa1d34c-502b-4abf-bd82-483804006e0b/episodes/745814da-5dd0-40ff-bb9c-43bb1d932fe0/audio/ba2de43b-c3d6-40d6-b057-bcececcd4dca/default_tc.mp3?aid=rss_feed&feed=XA_851k3
The Stack Overflow Podcast stackoverflow.blog
The crew has complicated feelings about products like Apple’s augmented reality glasses and Google Glass. Ceora put it best: “I'm very cautious about any big tech company having any more access to my perception of reality.”
On the other hand, products like Envision smart glasses that help visually-impaired people navigate their environments exemplify how AR technology can enable accessibility and empower users.
Speaking of different perceptions of reality, New York mayor Eric Adams dusts off that old chestnut about …


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Год издания: 2003
Количество страниц: 408
В продаже с 18.01.2012
Как только книга Albert Durer: His Life and Work, Part 1 станет доступна для заказа в одном из интернет-магазинов, Вам на e-mail будет отправлено уведомление.Укажите e-mail для связи:
Book Description1882. Volume 1 of 2. No exhaustive and critical account of the life and works of Albert Durer had been previously placed before the English reading public. This is a careful translation of the German original. Durer, the German painter and engraver, was considered the foremost artist of the Renaissance. He was strongly influenced by spending several years in Italy and worked with equal mastery in painting, woodblock, copper and iron engraving. These volumes tell the story of his life and work, with many, many gorgeous illustrations. Volume 2 ISBN 0766155102.

domain: library


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Three main building blocks make up the foundation of a good sound system for worship. They are:
A. The acoustics of the room, building or facility
B. Thoughtful electronic systems design and integration
C. The people who operate the systems
A. THE ROOM AND ITS ACOUSTICS
Providing quality sound reinforcement for the spoken word and for varying musical styles is an ongoing challenge -- a challenge with a catch. There are factors relating to room acoustics that significantly influence, and often limit the impact of messages and musical presentations, regardless of what microphone, loudspeaker or amplifier is connected.
Music directors, worship leaders, musicians and sound operators seldom have control over the acoustics of a sanctuary. Yet, the geometry, building size and the materials used to finish the interior are the primary factors controlling the room's specific tonality or reverberant "signature". Look at it this way; design a room with good acoustics for the application, and everything seems to work well. Design a room with no thought to the acoustics and watch as an endless parade of consultants, music directors, sound operators and worship leaders struggle to find ways to provide consistent sound coverage.
You may not have thought of it this way, but most, if not all worship centers are used as performing arts auditoriums. As such, the building and its sound system must accommodate a wide variety of applications; be they sermons, solo, ensemble, choral, orchestral or dramatic performances. Unfortunately, few architects are trained to design with a mind toward architectural acoustics. Therefore, they too often design worship spaces that acoustically resemble gymnasiums, classrooms or office structures, when in fact they should be designing performing arts-style facilities.
Providing even, natural-sounding sound reinforcement, coupled with the highest possible speech intelligibility is the goal of the acoustician and the sound system designer.
B. THE ELECTRONIC SYSTEMS
Once the room geometry and acoustics have been worked out, the system designer can select and install appropriate equipment to meet the goals and requirements of the client. The following outlines our priorities when designing a sound system.
Intelligibility and reliability. Most importantly, a good sound reinforcement system must provide maximum intelligibility and reliability. This is primarily accomplished through the careful selection, integration and installation of loudspeakers, power amps and digital system processing.
Proper coverage. Proper coverage means that the room receives an even distribution of sound energy at all frequencies. It also means the system distributes the greatest percentage of it's sound in areas where it is wanted and, therefore, is capable of operating without feedback. Room acoustics, and loudspeaker selection and placement are keys here too.
Headroom is the reserve capacity of the system to handle momentary peak demands without distortion, overload or failure. Thoughtful hardware selections and proper gain structuring will insure maximum headroom and signal-to-noise ratios for any given system. Gain structuring is the process of adjusting each electronic device in a system so that it can operate within its optimum range.
Proper wiring. If the equipment is not wired right, it won't perform the way it was designed to perform. Reliability suffers too. There are easily a half dozen different ways that two devices can be wired together. There is a reason and technique for each. If the right wiring scheme is employed throughout, the system will perform cleanly and consistently for years. But, if you've ever heard complaints of "gremlins" in the system (problems that seem to come and go, from week to week), you can generally point to poor wiring as a likely cause.
C. THE PEOPLE
Probably the aspect most overlooked when evaluating the overall performance of an existing or new sound system is the people who operate the system. For most churches, the duties and responsibilities of the sound operators are demanding and continually changing. Expectations are generally high, while training and experience are often minimal.
It takes a unique blend of talents and personality traits to serve in areas of technical support. Doing a consistently good job as a sound operator is much like singing or playing a musical instrument with virtuosity; it takes knowledge, experience, practice, patience and wisdom well beyond that which may be perceived as the basic skill required to "push a few buttons and flip a few switches".
Even if a great deal of money has been spent on the design and development of a wonderful acoustic space and sound system, the human interaction with these systems is equally vital. We encourage investing in these people with equal passion.
Copyright - Michael Fay 2015 - All Rights Reserved

domain: design


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domain: psychology


GoFundMe set up for Rhea Co. teen killed in car wreck
DAYTON, Tennessee (WDEF) – A “go fund me” account has been started to raise money for the funeral of a Rhea county girl killed in a car crash Wednesday night .
15 year old Chelsea Gunter died following a wreck about 8:15 pm on “White Flats Road” in Dayton.
She was a student at Rhea county High School .
T-H-P says the vehicle she was in ran off the roadway and into a ditch.
It rolled over several times, throwing the girl out. She was not wearing a seat belt.
The juvenile driver faces charges.
Another passenger was also injured.
Counselors were at Rhea county high school yesterday and today.
The funeral will be Saturday.


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Having made your mind up that you would like to start playing slot games online or on a mobile device, you will then need to spend a little bit of time looking around and discovering just which slot games have been designed in such a way that you will get the maximum fun and entertainment value out of playing them.
With there now being thousands upon thousands of different slots available to online and mobile players, the amount of time you could spend researching and comparing all of them could be huge!
However, we have spent weeks playing the vast majority of online slots and have put together this website to introduce to you the very best playing and paying ones, and one slot that certainly did tick all of the right boxes in regards to what we look for is the Zuma slot which is a colourful looking yet very unique video slot game.
The Zuma slot has both base game features that can be triggered at any time and also a main bonus game which is where you have the chance of winning some enormous amounts of cash if everything falls into place when that bonus game has been triggered and awarded to you.
Please do have a good look through this guide on the bonus games offered by the Zuma slot, for we are more than convinced when you do so it will become a slot you have listed high up on your list of slots to get stuck into playing when you are next logged into an online or mobile casino or even one of the many different bingo sites that have it available!
Bonus Games and Bonus Features
It is the bonus games and bonus features that we found made the Zuma slot such a highly playable game, and with that in mind here is an overview of the bonus games and features that you may just end up being awarded with if you choose to play it!
Pick and Win Bonus Games – The bonus game on offer on the Zuma slot machine is a three stage one and you will get to play off each stage every single time you have triggered the bonus round.
The way in which you trigger the bonus round is fairly straight forward and that is by you spinning in at eats three of the scatter symbols anywhere in view. It is at that moment in time you play off the first picking game which sees you picking one Tiki Boss on the screen to shoot and when shot it will then reveal a set of free spins.
At the end of the free spins bonus game all winnings you achieve can be boosted in value possibly quite significantly as you then have to play off another picking game much like the first but the Tiki Boss when shot reveals a multiplier which is then used to boost the value of our free spins winning payout.
Free Spins Bonus Games – The free spins bonus game which is awarded as described above is going to be playing out with the same paylines and the same stakes a you have in play on the triggering base game spin.
Gamble Game – Unlike many other slots which offer you a gamble game, the one gamble game attached to the Zuma game is completely random and not a predetermine one! So if you do like taking the occasional gamble and trying to increase the value of any base game spun in winning payout then you do have a very fair and reasonable chance of winning!
How this bonus game works is very unique, for when you have spun in a winning combination and then have clicked on the gamble button you will be presented with four reels. The aim is to pick the reel which will spin in with a win symbol as opposed to a losing one on its payline, and by doing so your base game winning payout will be boosted in value instantly.
However, the payout odds on each of those four reels is different, and as such you have the chance of picking a reel which if it does spin in the winning symbol will boost your payout by x2, x4, x5 or x10. So do make sure you think long and hard which reel you do spin, as each of them does come with their own unique level of risk.
You will also be able to gamble just a percentage of your base game winning payout if you do not fancy putting it all at risk via the gamble game. Plus, you can continue to gamble if you do have a winning outcome!
Zuma Slot Stakes and Prizes
As you have such an enormous and in fact ever growing range of different slot games all offering a range of different bonus games and bonus features, picking out the slots that appeal to you the most to play is of course important.
We really can guarantee you are going to be in for a roller coaster of a ride if you decide to play the Zuma slot game, and as such let us now take a look at some of the option settings that are available to you if and when you do decide to get stuck into playing this must play video slot!
Payline Options – The very first thing you will need to do if you do decide to play the Zuma slot is to choose just how many paylines you wish to activate and have in live play. You can put into play a minimum of one single payline or opt to have every single payline activated and by doing the latter you will have 20 paylines in total in live play.
Keep in mind however that the more pay lines you do decide to play the more chances you will then have on each spin of forming one of the many different winning combinations as listed on the pay table!
High Certified RTP – One thing that is bound to grab your attention about the Zuma slot game is that it is designed as a high paying slot by virtue of its long term expected payout percentage. It goes without saying the higher the RTP of any slot game the more winning payouts you will achieve over your long term play.
If you are wondering just how high that payout percentage is then we are happy to let you know the Zuma slot has been set to return a payout percentage of a huge 95% and is also a certified random slot too!
Staking Options – You can play this slot for very low stake levels as low as just one penny per spin or if you want to throw caution to the wind and play it for some much higher stake levels then you are going to be able to increase the coin values to ones you wish to play for.
Just keep in mind that being a multi-stake slot you can also chop and change the stakes you are playing the Zuma slot game for, so if you do have a run of good luck you can increase the coin values slowly but surely!
Auto Play – An auto play setting is also available to you should you fancy playing the Zuma slot for free to enable you to test it out or when playing it in a real money playing environment.
The things you will have to keep in mind when using the auto play option setting is just how many payline you wish to have in play on each spin and also what coin values and stake you wish to have in play. Then simply select the number of spins you want to play off and the slot will play them off for you!
Speed Settings – You will also find that if you are in a hurry and do not have much time to play the Zuma slot you will be able to configure the slot in such a way that you will be able to play off a lot of spins in a very short space of time.
To do so you will need to activate and turn on the speed play option setting which will then ensure the reels spin and stop very quickly and a lot of the animated graphics will be tuned off to enable you to play lots of spins quickly!
Sound and Screen Size – As you are going to be playing the Zuma slot on possibly a range of different devices, one additional set of option settings that you are going to be able to make use of and configure are the screen size and audio settings.
One tip for you getting the best playing experience will be for you to play this slot in the full screen size version of the game and do also make sure that you have the volume settings set as high as they can be!


Draft Regional ATP Funding Recommendation Released
$11,773,000 towards more biking and walking
The draft Regional ATP funding recommendation is now available. All SACOG Committees will review and discuss the funding recommendation in April, starting with the SACOG Transportation Committee on April 1.
- Staff report
- Regional ATP Funding Recommendations and Contingency List
- Resolution Approving Regional ATP Recommendations
- 2021 Regional Active Transportation Program Project Scopes and Scoring Breakdown
- Working Group Roster
- 2021 Regional Active Transportation Program Policy Framework
- Regional ATP Evaluation Process
A multidisciplinary working group evaluated and scored all competing Regional ATP projects to develop the funding recommendation. This recommendation is presented by staff for approval at the April 15 SACOG Board of Directors meeting.


Replica of the Colt M1911A1 pistol (1924-present) with trademarks
Ft/Sec: 270-280 with a .12gr bb
Sights: static ironsights: notch-type
Mag Capacity: up to 50bbs in the mag tank
Weight: about 1.4 lbs
Length: about 8.5 inches
Availability: Pyramyd Air, $27.95 as of Jan. 2009.
You get: pistol, 1 magazine, some .12gr 6mm bbs, instructions
Background: The M1911 was the US Armed Forces' mainstay sidearm for many years. It was adopted in 1911 as the Colt M1911 pistol. It fired a .45 ACP round, with the magazine holding 7 rounds maximum. The total load could be increased to 8 if a round was retained in the chamber along with a full magazine. The M1911 was modified slightly after WWI in response to ergonomic concerns that came out of the war. The refinements did not reach the core inner workings of the gun. The slightly modified gun was designated the M1911A1 and went into mass production in the 1920s. During the latter part of the 1920s and into the 1930s, the gun M1911 and M1911A1 were popular as self-defense weapons as well as with gangsters and certain lawmen. During the WWII it was the standard issue sidearm for most U.S. forces and served with distinction. The gun would continue to serve with the U.S. Army and other forces through the 1980s, when it was phased out. It continues to serve with certain special forces units right up through today, however. The gun remains popular today with collectors and enthusiasts. Licensed versions and copies have been produced by a variety of companies over the years.
The pistol comes in a small box with a styro-cutout form inside the box. The box includes the gun, a small bag of bb ammunition (6mm .12gr), a magazine, and an anti-moisture packing packet. The outside of the box has is glossy and has a picture of the gun, the specs, and a WWII image in the background. The packaging is adequate, though impractical for regular use. The styro-cutout form is tightly fitted, but tends to shred a bit when taking the gun in and out. A decent case is a good idea here. The box isn't bad and the packaging should protect the gun well enough to get to you intact. Rating: 8/10
The pistol matches the basic M1911A1 configuration. The only special addition to the standard is that this particular gun represents a Parkerized finish (as opposed to the usual blued). The finish looks alright and is, as you would expect, a dull medium gray. The checked grips are plastic and basic brown. They look fine. The trades are spaghetti-type lettering in a lighter shade of gray. The Colt logo is depicted, along with the patent dates. They look respectable, but nothing special. The orange tip mandated by federal law is present, and is held in place only by the mated halves of the frame. It could be removed easily, but is present here as out of the box. I only wish they'd done a blued gun rather than a Parkerized one. Rating: 8.5/10
The Parkerized finish appears to be basic factory spray paint. It can, and will chip and wear with age and use. The finish, however, is even and has some durability. It does the job and looks the part. I was not overly impressed with it, but not disappointed either. The grips actually look nice and approximate the real thing nicely. I had feared it would have very cheap, slippery plastic grips, but the plastic used is actually pretty good. The finish can be touched up somewhat effectively by mixing roughly even proportions of flat black and white. It wouldn't be hard to touch up bare spots if you wanted to do so. The gun has a fair degree of heft, as it's metal.
The halves of the gun are mated via basic metal screws. However there are no screws near the hollow handle (where the magazine goes in). The gun displays a fair degree of play and separation of halves there. This aspect was quite disappointing-- it would have been nice of them to sink a couple small screws into this area just to sure up the halves. It wouldn't have taken much, but the manufacturer failed in this regard. Rating: 8/10 (decent finish and quality, but the play in the handle is disappointing)
Function, the safety:
The gun has a basic thumb safety on the left side of the gun. The safety is pointed and mates to a notch in the slide. When the safety is on, the hammer and slide cannot move. The safety is similar to the real M1911/M1911A1, but has the annoying habit of slipping into the "safe" position if you're not careful. This is especially true for a lefty shooter, since the larger part of the hand will bump up against the thumb safety when firing. The real gun has it, and it is simulated well here. My only wish is that they had made the thumb safety a bit harder to move.
The gun also has a palm spring safety. The top of the grip is has a large, rounded grip. When in the unused position, the trigger cannot be pulled, even if the thumb safety is off. I find this safety mechanism more helpful than the thumb. If functioning, you can only fire the gun if you squeeze the palm safety. I like this system, and it is fairly effective and realistic. Rating 8.5/10 (the palm safety is great, the thumb safety o.k. I guess).
A single magazine comes with the gun. The front of the magazine has the usual slot/hole for the bb to transfer to the chamber. It also has a slide spring and edge for moving the spring. The back of the mag has a sliding door where bbs can be poured in. The mag can be loaded two ways: by loading the bbs individually into the mouth of the mag. The other method is to fill the tank and close the trap door, then to move the magazine slide to the bottom position and then to shake the bbs from the tank into the active part of the magazine. I prefer the former method, as I usually load only 7 rounds at a time. The magazine slides up into the handle smoothly and "clicks" down into position well. A small button on the left side of the gun by the trigger releases the magazine. Rating: 9/10
Function, Cocking the Spring:
Cocking the slide is fairly smooth and gives a definite "click". I've not had the slide jam. However, the slide must be fully pulled back. It is possible if pulled back most, but not all of the way, that the gun will chamber the bb and set the hammer, but not actually :censored2: the spring. The result is a firing malfunction where the hammer falls, but the bb doesn't go anywhere. Cocking the slide again ejects the first bb from the barrel (it just rolls out) and chambers a second bb. This happens every so often, but is not too common. Cocking the gun produces a nice metallic sound similar to the real M1911/M1911A1. It isn't too hard to :censored2:, but it does put up fair resistance. The knurled slide side sections help. Rating: 8.5/10
Function, Firing and Accuracy:
The firing operation is simple enough: make sure you squeeze the handle to depress the palm safety and then aim and pull the trigger. The ironsights are functional and basic; I like them. The trigger pull is definite and crisp. The gun has the added bonus of a functioning hammer: cocking the slide also :censored2: the hammer. When the trigger is pulled, the hammer falls and the gun fires a bb. This was a pleasant surprise, even if it is just a secondary addition to the gun. As an aside, the hammer can be "dry dropped" by squeezing the palm safety with the thumb safety off and then cocking just the hammer (without cocking the slide). When the trigger is pulled the hammer falls but the gun does not fire. It makes the familiar click you'd get when you try to fire a gun that is out of ammo. The functioning hammer simulates the real Colt. The accuracy isn't bad, even with .12gr bbs. The hop up does add a fair degree of spin up. The groupings are fairly tight, considering the gun's price. It's not great, but it passes muster from close range with .12gr bbs (under 30 feet). Of course the accuracy is better with .20gr. Rating: 9/10
This is one of those guns that is fun to operate and does a decent job simulating the real thing, but I think falls short of being a full-on battle gun. It makes a great practice partner and a fun historical addition to any collection, and for a good price. But the trade off is that it really can't compete with full gas blow back pistols. Cybergun does make a gas version of the M1911A1, but it sells for significantly more money. I would gladly recommend this gun as a practice vehicle or a fun plinking gun, but I wouldn't rely on it as a primary battle weapon in any situation. If you're particularly good with spring action pistols, it might make a workable secondary sidearm, but if you haven't totally mastered spring pistols, I would avoid battle use.
Overall Grade: B+
It does its job, it's fairly solid, but it does have its issues. It's far from perfect, but it makes a nice addition to a WWII or a "Gangster Era" collection and makes a fun practice partner.
Edited by Ray-Vigo, 26 January 2009 - 01:49 AM.


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Sheer and lace front and back.
Amount of waistband stretch:
⭐⭐⭐⭐★ Founded in 2002 in NYC with the idea to produce, import, and distribute luxury corsetry from Italy to the United States. Pfiff is crafted in the finest factories in the world with the fashion forward eye of Italy and the practical sensibility of New York
Warehouse ID: Pfiff-LBQP26-mauve (# 477)
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domain: geography


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6 Main Factors That Affect How You Feel When High On Weed
It’s very difficult to describe how being high on weed feels without resorting to videos and giggly movie depictions of people who are spaced out. But with cannabis use becoming widespread, new consumers are always asking how being high on weed actually feels like.
Cannabis is very individualized. Some people claim that their high makes them feel creative and inspired to go about activities like painting, writing, or even reading. Some people have the opposite experience. They may have a good time, but their memory is impaired, and they cannot commit to any activities that require any amount of engagement.
So what does being high feel like? Is there an ideal high?
Every person taking marijuana has an ideal high, which typically depends on why you are consuming weed. For some people, the goal of taking marijuana is to experience some relief from conditions that cause pain or symptoms like anxiety.
If your goal is relief, then your ideal high causes relaxation, euphoria, creativity, amusement etc. If you are getting high as a recreational activity or unwinding, you may want euphoria, amusement, relaxation, and creativity. There are a lot of strains that can cause all those effects.
THC (delta-9-tetrahydrocannabinol) is the primary active cannabinoid in the cannabis plant, and it’s responsible for the high feeling along with some of the physical and emotional benefits that you experience when consuming weed.
By choosing weed strains with more or less THC content, you can alter how your high will feel. But as we have mentioned, the cannabis experience is very individualized, and many factors influence the high.
That said, there are several things that you are likely to experience after consuming marijuana. Here is what being high feels like.
Cannabis may alter your sensory perceptions. While smoking weed will not produce real hallucinations as other drugs do, you may experience places, objects, sounds, flavours and scents differently.
Faces and familiar objects may look strange, usually, in an amusing way, colours can appear brighter, sounds and music become more powerful experiences, and you can appreciate aesthetics more.
This is why you may find a stoner staring at something that’s usually uninteresting, like a ballpoint pen, but they seem amused by it.
Another example of how marijuana can affect your sensory perception is the munchies. Cannabis can enhance your sense of taste resulting in “the munchies,” which causes you to consume more food than normal.
Experts believe an individual’s mood is projected onto their environment when high. As a result, being high in an environment you perceive positively can be enjoyable, but the opposite can also happen, causing the world to appear grim and harsh. This is called a “bad trip.”
Marijuana use can change your mood and mental state. When high, emotions are usually exaggerated such that normal emotionally neutral situations become amusing or ridiculous. The ability of weed to alter emotions makes it a potential remedy for mood disorders like anxiety and depression.
However, the effects of marijuana on mood vary from one person to another. This may be due to the differences in body chemistry, strains, age, among others. As a result, some people may experience higher anxiety levels or become upset by normal situations when high.
Many great artists produce some of their best work when high. There is even some evidence that weed use is associated with producing a greater number of novel ideas.
Getting high may spark some sort of creativity. Stoned people typically come up with bizarre, sometimes unfeasible ideas that sober people wouldn’t think of. However, we are not saying that smoking weed is a shortcut to artistic success. We are only saying that some strains may spark creative energy that may help develop new ideas.
On the other hand, weed may make it more difficult to use creative thoughts productively. One study suggests that low potency cannabis doesn’t impact creativity and that potent weed may actually impair divergent thinking.
You probably have come across scary tales of bad trips or getting too high on the internet. So yes, it is possible to get too high if you are not careful with the dosage or if your body is prone to these less-than-pleasant experiences.
Edibles are usually the culprits as their effects are delayed, which may tempt you to consume more.
Bad trips are characterized by increased anxiety, panic, paranoia, delusions, confusion, hallucinations, racing heartbeat, vomiting, nausea etc.
A fatal marijuana overdose is unlikely. So if you get too high, just find an activity you enjoy, and wait for the high to come down.
6 Factors That Affect A Cannabis High
As we stated earlier, individuals experience weed high differently. Here are some of the factors that affect a weed high
There are numerous strains with different effects to choose from. Sativa strains, for example, are known for their cerebral stimulation and energizing effects while indicas are famous for their heavy, relaxing body high that often results in a couch-lock.
On the other hand, Hybrids bring you the best of both worlds—a little of cerebral effect and a little of physical effects.
For example, this AA Blue Afghani strain from West Coast Cannabis is known for its powerful full-body effects that leave you anchored in relaxation while providing pain, anxiety relief. On the other hand, Sour Diesel is known for its invigorating cerebral high that opens up doors of creativity.
While many cannabis consumers depend on the sativa/indica/hybrid classification to predict the type of high a bud will provide, people now realize the effects terpenes can have on a high. Terpenes have health benefits, including anti-anxiety benefits and can modulate the effects of THC, affecting the high.
Your tolerance is essential to how you feel when high on weed. If you are new to cannabis, your tolerance is low, and you should start with less potent cannabis strains and lower dosages to avoid being overwhelmed.
How much THC or CBD is in the product? Strains with very high THC and low CBD can produce very intense highs compared to less potent strains with high CBD levels.
To have an enjoyable high, you have to figure out the exact amount of weed to take. Too little and you don’t get high, too much and you have a bad trip.
6. Other Cannabinoids Present
The cannabis plant has over 100 cannabinoids that may affect how the high feels. CBD, CBN, and THCV are some of the cannabinoids that could influence your experience by either supporting the effects of THC or decreasing them.
The Quality Of Your Cannabis Product Will Affect How Being High On Weed Feel Like
It’s almost impossible to describe what being high feels because THC, like most cannabinoids, affects everyone differently. So, your experience may differ from the others as a wide range of factors, including genes, the strain you are using, mood, tolerance, potency etc., may have a hand in shaping your high.
For the best experience, start with a low dose, examine how you feel, and take it slow to avoid overconsumption. It’s also best to start with a high-quality product like this AAAA Hawaiian Snow from West Coast Cannabis to ensure you have an effective product when getting high for the first time.

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PfFP Lecture 29: Quantum Physics I
14 Apr 2011 | | Contributor(s):: Jerry M. Woodall
PfFP Lecture 30: Quantum Physics II
27 Apr 2011 | | Contributor(s):: Jerry M. Woodall
PfFP Lecture 31: Quantum Physics III


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This study investigates differences in expression of clock and clock-controlled genes (CCGs) between human breast epithelial and breast cancer cells and breast tumor xenografts in circadian intact rats and examines if the pineal hormone melatonin influences clock gene and CCG expression. Oscillation of clock gene expression was not observed under standard growth conditions in vitro, however, serum shock (50% horse serum for 2 h) induced oscillation of clock gene and CCG expression in MCF-10A cells, which was repressed or disrupted in MCF-7 cells. Melatonin administration following serum shock differentially suppressed or induced clock gene (Bmal1 and Per2) and CCG expression in MCF10A and MCF-7 cells. These studies demonstrate the lack of rhythmic expression of clock genes and CCGs of cells in vitro and that transplantation of breast cancer cells as xenografts into circadian competent hosts re-establishes a circadian rhythm in the peripheral clock genes of tumor cells.
melatonin; clock genes; circadian; serum shock; breast cancer
Stroke thrombolysis may have a differential effect by sex. We sought to examine the relationship between sex and outcome after thrombolysis.
This is a retrospective cohort study of stroke patients from the Registry of Canadian Stroke Network phase 1 (June 2001-February 2002) and phase 2 (June 2002-December 2002). Variables including demographics, history, clinical data, process measures, and outcome were analyzed. The primary outcomes were the Stroke Impact Scale-16 score (SIS-16) and mortality at 6 months. We compared the outcomes of the thrombolyzed and nonthrombolyzed cohorts and examined the data for a tissue plasminogen activator (tPA)-by-sex interaction on the 2 primary outcomes.
The overall proportion of patients who achieved an excellent outcome (SIS-16 >75) was not different by gender. However, the proportion of patients achieving an excellent outcome in the non-tPA cohort was much greater in males, with an absolute risk difference of 11.8%. A multiplicative treatment by sex interaction was evident (p = 0.054). This interaction was not present for stroke case fatality.
Women fared poorly compared to men in the placebo groups, but this negative prognostic sex effect was neutralized by thrombolysis.
= modified Rankin Score;
= Registry of the Canadian Stroke Network;
= Stroke Impact Scale-16 score;
= tissue plasminogen activator.
Neoplastic events are marked by uncontrolled cell proliferation. One major focus of cancer research has been to identify treatments that reduce or inhibit cell growth. Over the years, various compounds, both naturally occurring and chemically synthesized, have been used to inhibit neoplastic cell proliferation. Two such oncostatic agents, melatonin and retinoic acid, have been shown to suppress the growth of hormone-responsive breast cancer. Currently, separate clinical protocols exist for the administration of retinoids and melatonin as adjuvant therapies for cancer. Using the oestrogen receptor (ER)-positive MCF-7 human breast tumour cell line, our laboratory has studied the effects of a sequential treatment regimen of melatonin followed by all-trans retinoic acid (atRA) on breast tumour cell proliferation in vitro. Incubation of hormonally responsive MCF-7 and T47D cells with melatonin (10(-9) M) followed 24 h later by atRA (10(-9) M) resulted in the complete cessation of cell growth as well as a reduction in the number of cells to below the initial plating density. This cytocidal effect is in contrast to the growth-suppressive effects seen with either hormone alone. This regimen of melatonin followed by atRA induced cytocidal effects on MCF-7 cells by activating pathways leading to apoptosis (programmed cell death) as evidenced by decreased ER and Bcl-2 and increased Bax and transforming growth factor beta 1 (TGF-beta1) expression. Apoptosis was reflected morphologically by an increase in the number of lysosomal bodies and perinuclear chromatin condensation, cytoplasmic blebbing and the presence of apoptotic bodies. The apoptotic effect of this sequential treatment with melatonin and atRA appears to be both cell and regimen specific as (a) ER-negative MDA-MB-231 and BT-20 breast tumour cells were unaffected, and (b) the simultaneous administration of melatonin and atRA was not associated with apoptosis in any of the breast cancer cell lines studied. Taken together, the results suggest that use of an appropriate regimen of melatonin and atRA should be considered for preclinical and clinical evaluation against ER-positive human breast cancer.
Falling in older age is a serious and costly problem. At least one in three older people fall annually. Although exercise is recognised as an effective fall prevention intervention, low numbers of older people engage in suitable programmes. Health and exercise professionals play a crucial role in addressing fall risk in older adults. This trial aims to evaluate the effect of participation in a fall prevention educational programme, compared with a wait-list control group, on health and exercise professionals’ knowledge about fall prevention and the effect on fall prevention exercise prescription behaviour and confidence to prescribe the exercises to older people.
Methods and analysis
A randomised controlled trial involving 220 consenting health and exercise professionals will be conducted. Participants will be individually randomised to an intervention group (n=110) to receive an educational workshop plus access to internet-based support resources, or a wait-list control group (n=110). The two primary outcomes, measured 3 months after randomisation, are: (1) knowledge about fall prevention and (2) self-perceived change in fall prevention exercise prescription behaviour. Secondary outcomes include: (1) participants’ confidence to prescribe fall prevention exercises; (2) the proportion of people aged 60+ years seen by trial participants in the past month who were prescribed fall prevention exercise; and (3) the proportion of fall prevention exercises prescribed by participants to older people in the past month that comply with evidence-based guidelines. Outcomes will be measured with a self-report questionnaire designed specifically for the trial.
Ethics and dissemination
The trial protocol was approved by the Human Research Ethics Committee, The University of Sydney, Australia. Trial results will be disseminated via peer reviewed journals, presentations at international conferences and participants’ newsletters.
Trial registration number
Trial protocol was registered with the Australian and New Zealand Clinical Trials Registry (Number ACTRN12614000224628) on 3 March 2014.
EDUCATION & TRAINING (see Medical Education & Training); GERIATRIC MEDICINE; PREVENTIVE MEDICINE
Delirium is a common cause and complication of hospitalization in older people, being associated with higher risk of future dementia and progression of existing dementia. However relatively little data are available on which biochemical pathways are dysregulated in the brain during delirium episodes, whether there are protein expression changes common among delirium subjects and whether there are any changes which correlate with the severity of delirium. We now present the first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few studies exploring protein expression changes in delirium. More than 270 proteins were identified in two delirium cohorts, 16 of which were dysregulated in at least 8 of 17 delirium subjects compared with a mild Alzheimer's disease neurological control group, and 31 proteins were significantly correlated with cognitive scores (mini-mental state exam and acute physiology and chronic health evaluation III). Bioinformatics analyses revealed expression changes in several protein family groups, including apolipoproteins, secretogranins/chromogranins, clotting/fibrinolysis factors, serine protease inhibitors and acute-phase response elements. These data not only provide confirmatory evidence that the inflammatory response is a component of delirium, but also reveal dysregulation of protein expression in a number of novel and unexpected clusters of proteins, in particular the granins. Another surprising outcome of this work is the level of similarity of CSF protein profiles in delirium patients, given the diversity of causes of this syndrome. These data provide additional elements for consideration in the pathophysiology of delirium as well as potential biomarker candidates for delirium diagnosis.
The simian-human immunodeficiency virus (SHIV)/macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of accessory genes in lentiviral pathogenesis. In this study, we introduced two amino acid changes in the highly conserved SLQYLA domain (to AAQYLA) of the SIV Vif protein. The resulting virus, SHIVVifAAQYLA, was used to infect three macaques, which were followed for over six months. Plasma viral loads and circulating CD4+ T cell levels were assessed during the course of infection. The three macaques inoculated with SHIVVifAAQYLA did not develop significant CD4+ T cell loss over the course of their infection, had plasma viral RNA loads that were over 100-fold lower than macaques inoculated with parental SHIVKU-1bMC33, and developed no histological lesions in lymphoid tissues. DNA and RT-PCR analysis revealed that only a select number of tissues were infected with this virus. Sequence analysis indicates that the site-directed changes were stable during the first three weeks after inoculation but thereafter the S147A amino acid substitution changed to a threonine in two of three macaques. The L148A substitution remained stable in the vif amplified from the PBMC of all three macaques. Sequence analysis of vif, vpu, env and nef genes revealed G-to-A mutations in the genes amplified from macaques inoculated with SHIVVifAAQYLA, which were higher than in a macaque inoculated with parental SHIVKU-1bMC33. We found that the majority (>85%) of the G-to-A mutations were in the context of 5′-TC (minus strand) and not 5′-CC, suggestive that one or more of the rhesus APOBEC3 proteins may be responsible for the observed mutational patterns with rhesus APOBEC3G for a minority of the mutations since its GG-to-AG mutational pattern was infrequently detected. Finally, macaques inoculated with SHIVVifAAQYLA developed immunoprecipitating antibody responses against the virus. The results from this study provide the first in vivo evidence of the importance of the SLQYLA domain in viral pathogenesis and show that targeted mutations in vif can lead to a persistent infection with G-to-A changes accumulating in the viral genome.
Pathogenic simian-human immunodeficiency viruses (SHIV)contain HIV-1 Vpu and SIV Nef, both shown to counteract BST-2 (HM1.24; CD317; tetherin) inhibition of virus release in a species-specific manner. We show that human and pig-tailed BST-2 (ptBST-2) restrict SHIV. We found that sequential “humanize” of the transmembrane domain (TMD) of the pig-tailed BST-2 (ptBST-2) protein resulted in a fluctuation in sensitivity to HIV-1 Vpu. Our results also show that the length of the TMD in human and ptBST-2 proteins is important for BST-2 restriction and susceptibility to Vpu. Taken together, our results emphasize the importance of tertiary structure in BST-2 antagonism and suggests that the HIV-1 Vpu transmembrane domain may have additional functions in vivo unrelated to BST-2 antagonism.
The Vpu protein of human immunodeficiency virus type 1 (HIV-1) is known to enhance virion release from certain cell types. To accomplish this function, Vpu interacts with the restriction factor known as bone marrow stromal cell antigen 2 (BST-2)/tetherin. In this study, we analyzed whether the Vpu protein is associated with microdomains known as lipid or membrane rafts. Our results indicate that Vpu partially partitions into detergent resistant membrane (DRM) fractions when expressed alone or in the context of simian-human immunodeficiency virus (SHIV) infection. The ability to be partitioned into rafts was observed with both subtype B and C Vpu proteins. The use of cholesterol lowering lovastatin/M-β-cyclodextrin and co-patching experiments confirmed that Vpu can be detected in cholesterol rich regions of membranes. Finally, we present data showing that raft association-defective transmembrane mutants of Vpu have impaired enhanced virus release function, but still maintain the ability to down-regulate CD4.
Human immunodeficiency virus type 1 (HIV-1) encodes for a Vpu protein, which interacts with CD4 resulting in its degradation. In this study, we examined the role of the ten amino acids within the predicted second α-helical domain of the subtype B Vpu cytoplasmic tail in CD4 down-modulation using a VpuEGFP reporter system. Our findings indicate that the invariant leucine at position 63 and, to a lesser extent, the valine at position 68 were required for CD4 down-modulation. Mutation of analogous L63 in Vpu proteins subtypes A2, B, C, D, and H also abolished CD4 down-modulation from the cell surface. Co-immunoprecipitation analysis revealed that L63A and V68A mutants were capable of binding CD4 and still retained the ability to interact with h-β-TrCP1. Taken together, these results indicate that amino acid substitutions in the second α-helical domain that retain the predicted structure and binding to h-β-TrCP1 can influence Vpu-mediated CD4 degradation.
Previously, we showed that the Vpu protein from HIV-1 subtype C is more efficiently transported to the cell surface than the well studied subtype B Vpu (Pacyniak et al., 2005) and that a SHIV expressing the subtype C Vpu exhibited a decreased rate of CD4+ T-cell loss following inoculation in macaques (Hill et al., 2007). In this study, we examined the role of overlapping tyrosine-based (YXXM) and dileucine-based ([D/E]XXXL[L/I]) motifs in the membrane proximal region of the subtype C Vpu (EYRKLL) in Vpu intracellular transport, CD4 surface expression and virus release from the cell surface. We constructed three site-directed mutants of the subtype C vpu and fused these genes to the gene for enhanced green fluorescent protein (EGFP). The first mutation made altered the tyrosine (EARKLL; VpuSCEGFPY35A), the second altered the dileucine motif (EYRKLG; VpuSCEGFPL39G), and the third contained both amino acid substitutions (EARKLG; VpuSCEGFPYL35,39AG) in this region of the Vpu protein. The VpuSCEGFPY35A protein was transported to the cell surface similar to the unmodified VpuSCEGFP1 while VpuSCEGFPL39G was expressed at the cell surface at significantly reduced levels. The VpuSCEGFPYL35,39AG was found to have an intermediate level of cell surface expression. All three mutant Vpu proteins were analyzed for the ability to prevent cell surface expression of CD4. We found that both single mutants did not significantly effect at CD4 surface expression while the double mutant (VpuSCEGFPYL35,39AG) was significantly less efficient at preventing cell surface CD4 expression. Chimeric simian-human immunodeficiency viruses were constructed with theses mutations in vpu (SHIVSCVpuY35A, SHIVSCVpuL39G and SHIVSCVpuYL35,39AG). Our results indicate that SHIVSCVpuL39G replicated much more efficiently and was much more cytopathic than SHIVSCVpu. In contrast, SHIVSCVpuY35A and SHIVSCVpuYL35,39AG replicated less efficiently when compared to the parental SHIVSCVpu. Taken together, these results show for the first time that the tyrosine-based sorting motif in the cytoplasmic domain of Vpu is essential for efficient virus release. These results also indicate that the dileucine-based sorting motif affects the intracellular trafficking of clade C Vpu proteins, virus replication, and release.
Accumulating evidence has revealed that dysregulation of the endocannabinoid system could contribute to the development of major depression. Studies carried out post-mortem in depressed suicide victims have revealed increased CB1 receptor binding site density in the prefrontal cortex (PFC). Accordingly, exposure of rodents to chronic unpredictable stress (CUS) results in phenotypic changes that mirror those of human depression, including increased CB1 receptor binding site density in the PFC. Our goal in these studies was to examine the effects of CUS on the density of CB1 receptor binding sites in the rodent medial PFC and to explore the role of this alteration in the behavioral changes invoked by CUS. Rodents exposed to CUS exhibited increased CB1 receptor maximal binding site density (Bmax) within the ventromedial PFC, but not the dorsomedial PFC. To determine whether this change in the ventromedial PFC is an adaptive response, or alternatively, a consequence of chronic stress that contributes to the adoption of passive coping, we examined whether local CB1 receptor blockade within the ventromedial PFC following CUS would significantly alter behaviors in the forced swim test (FST). CUS exposure significantly increased passive coping in the FST, and this was further augmented by discrete ventromedial PFC microinfusions of the CB1 receptor antagonist AM251 prior to swim stress. Moreover, local CB1 receptor blockade reduced active coping responses in CUS-exposed rats. These findings suggest that the increase in CB1 receptor Bmax observed in the ventromedial PFC of rodents exposed to CUS maintains proactive coping strategies following chronic stress exposure.
CB1 receptor; ventromedial prefrontal cortex; chronic unpredictable stress; forced swim test; microinfusion
To reinvestigate ultra-high dose rate radiation (UHDRR) radiobiology and consider potential implications for hadrontherapy.
A literature search of cellular UHDRR exposures was performed. Standard oxygen diffusion equations were used to estimate the time taken to replace UHDRR-related oxygen depletion. Dose rates from conventional and novel methods of hadrontherapy accelerators were considered, including spot scanning beam delivery, which intensifies dose rate.
The literature findings were that, for X-ray and electron dose rates of around 109 Gy s–1, 5–10 Gy depletes cellular oxygen, significantly changing the radiosensitivity of cells already in low oxygen tension (around 3 mmHg or 0.4 kPa). The time taken to reverse the oxygen depletion of such cells is estimated to be over 20–30 s at distances of over 100 μm from a tumour blood vessel. In this time window, tumours have a higher hypoxic fraction (capable of reducing tumour control), so the next application of radiation within the same fraction should be at a time that exceeds these estimates in the case of scanned beams or with ultra-fast laser-generated particles.
This study has potential implications for particle therapy, including laser-generated particles, where dose rate is greatly increased. Conventional accelerators probably do not achieve the critical UHDRR conditions. However, specific UHDRR oxygen depletion experiments using proton and ion beams are indicated.
Fragile X syndrome (FXS) is the leading cause of inherited intellectual and developmental disability. Policy development relating to carrier screening programmes for FXS requires input from large studies examining not only test uptake but also psychosocial aspects. This study will compare carrier screening in pregnant and non-pregnant populations, examining informed decision-making, psychosocial issues and health economics.
Methods and Analysis
Pregnant and non-pregnant women are being recruited from general practices and obstetric services. Women receive study information either in person or through clinic mail outs. Women are provided pretest counselling by a genetic counsellor and make a decision about testing in their own time. Data are being collected from two questionnaires: one completed at the time of making the decision about testing and the second 1 month later. Additional data are gathered through qualitative interviews conducted at several time points with a subset of participating women, including all women with a positive test result, and with staff from recruiting clinics. A minimum sample size of 500 women/group has been calculated to give us 88% power to detect a 10% difference in test uptake and 87% power to detect a 10% difference in informed choice between the pregnant and non-pregnant groups. Questionnaire data will be analysed using descriptive statistics and multivariate logistic regression models. Interview data will be thematically analysed. Willingness-to-pay and cost effectiveness analyses will also be performed. Recruitment started in July 2009 and data collection will be completed by December 2013.
Ethics and Dissemination
Ethics approval has been granted by the Universities of Melbourne and Western Australia and by recruiting clinics, where required. Results will be reported in peer-reviewed publications, conference presentations and through a website http://www.fragilexscreening.net.au. The results of this study will make a significant contribution to discussions about the wider introduction of population carrier screening for FXS.
Genetics; Public Health
Pyridoxine is frequently used to treat capecitabine-induced hand–foot syndrome (HFS), although the evidence of benefit is lacking. We performed a randomised placebo-controlled trial to determine whether pyridoxine could avoid the need for capecitabine dose modifications and improve outcomes.
A total of 106 patients planned for palliative single-agent capecitabine (53 in each arm, 65%/ 35% colorectal/breast cancer) were randomised to receive either concomitant pyridoxine (50 mg po) or matching placebo three times daily.
Compared with placebo, pyridoxine use was associated with an increased rate of avoiding capecitabine dose modifications (37% vs 23%, relative risk 0.59, 95% CI 0.29, 1.20, P=0.15) and fewer grade 3/4 HFS-related adverse events (9% vs 17%, odds ratio 0.51, 95% CI 0.15–1.6, P=0.26). Use of pyridoxine did not improve response rate or progression-free survival.
Pyridoxine may reduce the need for capecitabine dose modifications and the incidence of severe HFS, but does not impact on antitumour effect.
capecitabine; pyridoxine; hand–foot syndrome; randomised trial
Limbic endocannabinoid signaling is known to be sensitive to chronic stress; however, studies investigating the impact of prolonged exposure to glucocorticoid hormones have been limited by the concurrent exposure to the stress of daily injections. The present study was designed to examine the effects of a noninvasive approach to alter plasma corticosterone (CORT) on the endocannabinoid system. More precisely, we explored the effects of a 4-week exposure to CORT dissolved in the drinking water of mice (100 μg/ml) and measured cannabinoid CB1 receptor binding, endocannabinoid content, activity of the endocannabinoid degrading enzyme free fatty acid amide hydrolase (FAAH), and mRNA expression of both the CB1 receptor and FAAH in both the hippocampus and amygdala. Our data demonstrate that CORT decreases CB1 receptor binding site density in both the hippocampus and amygdala and also reduced anandamide (AEA) content and increased FAAH activity within both structures. These changes in both CB1 receptor binding and FAAH activity were not accompanied by changes in mRNA expression of either the CB1 receptor or FAAH in either brain region. Interestingly, our CORT delivery regimen significantly increased 2-AG concentrations within the hippocampus, but not the amygdala. Collectively, these data demonstrate that the confounder of injection stress is sufficient to conceal the ability of protracted exposure to glucocorticoids to reduce CB1 receptor density and augment AEA metabolism within limbic structures.
BACKGROUND AND AIMS:
Fatty acids are important cellular constituents that may affect many metabolic processes relevant for the development of diabetes and its complications. We showed previously that vegetarian diet leads to greater increase in metabolic clearance rate of glucose (MCR) than conventional hypocaloric diet. The aim of this secondary analysis was to explore the role of changes in fatty acid composition of serum phospholipids in diet- and exercise-induced changes in MCR in subjects with type 2 diabetes (T2D).
Subjects with T2D (n=74) were randomly assigned into a vegetarian group (VG, n=37) following vegetarian diet or a control group (CG, n=37) following a conventional diet. Both diets were calorie restricted (−500 kcal day–1). Participants were examined at baseline, 12 weeks of diet intervention and 24 weeks (subsequent 12 weeks of diet were combined with aerobic exercise). The fatty acid composition of serum phospholipids was measured by gas liquid chromatography. MCR was measured by hyperinsulinemic isoglycemic clamp. Visceral fat (VF) was measured by magnetic resonance imaging.
Linoleic acid (LA; 18:2n6) increased in VG (P=0.04), whereas it decreased in CG (P=0.04) in response to dietary interventions. It did not change significantly after the addition of exercise in either group (group × time P<0.001). In VG, changes in 18:2n6 correlated positively with changes in MCR (r=+0.22; P=0.04) and negatively with changes in VF (r=−0.43; P=0.01). After adjustment for changes in body mass index, the association between 18:2n6 and MCR was no longer significant. The addition of exercise resulted in greater changes of phospholipid fatty acids composition in VG than in CG.
We demonstrated that the insulin-sensitizing effect of a vegetarian diet might be related to the increased proportion of LA in serum phospholipids.
fatty acid composition of serum phospholipids; insulin resistance; linoleic acid; type 2 diabetes; vegetarian diet; visceral fat
Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors.
Diet; Palmitoleic acid; Fatty acids; Adipose tissue; Obesity management
The hypothalamic-pituitary-adrenal (HPA) axis regulates the outflow of glucocorticoid hormones under basal conditions and in response to stress. Within the last decade, a large body of evidence has mounted indicating that the endocannabinoid system is involved in the central regulation of the stress response; however, the specific role endocannabinoid signalling plays in phases of HPA axis regulation, or the neural sites of action mediating this regulation, was not mapped out until recently. This review aims to collapse the current state of knowledge regarding the role of the endocannabinoid system in the regulation of the HPA axis to put together a working model of how and where endocannabinoids act within the brain to regulate outflow of the HPA axis. Specifically, we discuss the role of the endocannabinoid system in the regulation of the HPA axis under basal conditions, activation in response to acute stress and glucocorticoid-mediated negative feedback. Interestingly, there appears to be some anatomical specificity to the role of the endocannabinoid system in each phase of HPA axis regulation, as well as distinct roles of both anandamide and 2-arachidonoylglycerol in these phases. Ultimately, the current level of information indicates that endocannabinoid signalling acts to suppress HPA axis activity through concerted actions within the prefrontal cortex, amygdala and hypothalamus.
Aged individuals with Down syndrome (DS) develop Alzheimer's disease (AD) neuropathology by the age of 40 years. The purpose of the current study was to measure age-associated changes in APP processing in 36 individuals with DS (5 months–69 years) and in 26 controls (5 months–100 years). Alpha-secretase significantly decreased with age in DS, particularly in cases over the age of 40 years and was stable in controls. The levels of C-terminal fragments of APP reflecting alpha-secretase processing (CTF-alpha) decreased with age in both groups. In both groups, there was significant increase in beta-secretase activity with age. CTF-beta remained constant with age in controls suggesting compensatory increases in turnover/clearance mechanisms. In DS, young individuals had the lowest CTF-beta levels that may reflect rapid conversion of beta-amyloid (Aβ) to soluble pools or efficient CTF-beta clearance mechanisms. Treatments to slow or prevent AD in the general population targeting secretase activity may be more efficacious in adults with DS if combined with approaches that enhance Aβ degradation and clearance.
Alzheimer's disease; Beta-amyloid; Oldest old; Trisomy 21
Faster recanalization correlates with better outcomes in acute ischemic stroke. We analyzed times from arrival in ER to end of treatment in patients undergoing endovascular treatment for acute ischemic stroke at our institution.
We retrospectively studied patients who underwent IA procedures for stroke from 2005 to 2009 noting the times of arrival to ER, CT scan, arrival to DSA, arterial puncture and recanalization from our endovascular database. A subgroup analysis was performed based on administration of GA, use of mechanical devices and whether the procedure was performed during regular hours or after hours.
Of 101 patients, 53 were male, with a median age of 66 years (range 18-87). There were 81 anterior circulation strokes. Median ER to CT time was 22 min (2-1025), CT to DSA arrival time 80 min (range 4-990), DSA arrival to puncture time 24 min (range 0-75) and puncture to recanalization time 84 min (range 11-206). 23.3% of patients had an ER to CT time interval of > 60 min and 71.3 % had a CT to DSA time interval of > 60 min contributing to significant in-hospital delays. For subgroup analysis the Mann-Whitney test was used. No significant differences in CT to DSA arrival (p=0.8), DSA arrival to puncture (p=0.1) and puncture to recanalization (p=0.59) times were noted between patients with and without GA. No significant difference was noted in puncture to recanalization times with or without device (p=0.78). 39 cases were done during regular (R) hours and 62 after (A) hours. Median ER to CT time (R=18 min, A = 27 min, p 0.02), CT to DSA arrival time (R=64 min, A=90 min, p 0.004) and DSA arrival to puncture time (R=18 min, A=25 min, p 0.003) was significantly higher after hours.
ER to CT and CT to DSA arrival times in patients undergoing endovascular stroke therapy show wide variability and therefore, considerable scope for reduction. Time differences during regular and after hours should serve as a reminder to make efforts to reduce overall ischemic times in spite of staffing patterns and resource availability.
stroke, thrombolysis, recanalization, tPA
Combining several methods for contact free micro-manipulation of small particles such as cells or micro-organisms provides the advantages of each method in a single setup. Optical tweezers, which employ focused laser beams, offer very precise and selective handling of single particles. On the other hand, acoustic trapping with wavelengths of about 1 mm allows the simultaneous trapping of many, comparatively large particles. With conventional approaches it is difficult to fully employ the strengths of each method due to the different experimental requirements. Here we present the combined optical and acoustic trapping of motile micro-organisms in a microfluidic environment, utilizing optical macro-tweezers, which offer a large field of view and working distance of several millimeters and therefore match the typical range of acoustic trapping. We characterize the acoustic trapping forces with the help of optically trapped particles and present several applications of the combined optical and acoustic trapping, such as manipulation of large (75 μm) particles and active particle sorting.
(140.7010) Laser trapping; (170.4520) Optical confinement and manipulation; (350.4855) Optical tweezers or optical manipulation; (110.7170) Ultrasound
The Vif protein of primate lentiviruses interacts with APOBEC3 proteins, which results in shunting of the APOBEC3-Vif complex to the proteosome for degradation. Using the simian-human immunodeficiency virus (SHIV)/macaque model, we compared the replication and pathogenicity of SHIVs that express a Vif protein in which the entire SLQ(Y/F)LA (SHIVVif5A) or HCCH (SHIVVifHCCH(−)) domains were substituted with alanine residues. Each virus was inoculated into three macaques and various viral and immunological parameters followed for six months. All macaques maintained stable circulating CD4+ T cells, developed low viral loads, maintained the engineered mutations, yielded no histological lesions, and developed immunoprecipitating antibodies early post-inoculation. Sequence analysis of nef and vpu from three lymphoid tissues revealed a high percentage of G-to-A-substitutions. Our results show that while the presence of HCCH and SLQ(Y/F)LA domains are critical in vivo, there may exist APOBEC3 negative reservoirs that allow for low levels of viral replication and persistence but not disease.

domain: medical


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People who are claustrophobic, or fear being in enclosed spaces, have a new option when it comes to receiving prescribed magnetic resonance imaging, or MRIs.
Open Upright MRI of Missouri recently opened at 11737 Olive Blvd. in Creve Coeur. It offers Missouri's only Open Upright MRI scanner. St. Luke's Hospital owns the center in partnership with Center for Diagnostic Imaging and ProSight Radiology Group.
Open Upright MRI scanners offer claustrophobic patients the best alternative to high-field MRI. They are different from traditional and other open scanners because patients who choose Open Upright MRI can be seated with nothing in front of their faces for most exams, and they can even watch television. The scanner also accommodates patients who weigh up to 500 pounds.
"Open Upright MRI of Missouri offers patients a high-quality imaging option, which is available nowhere else in the state," said Kishan Yalavarthi, M.D., Open Upright MRI of Missouri medical director. "For patients who are claustrophobic or who otherwise would not fit, the ability to sit comfortably during most MRI exams and relax by watching television makes all the difference in helping them get through the exams so their physicians have all the diagnostic information they need to provide the best care possible."
The scanner also offers unique positional imaging capabilities. Patients can be scanned sitting, standing or in other positions if they feel pain.
Appointments at Open Upright MRI of Missouri are available Monday through Friday during the day and evening and on Saturdays. Patients with physician referrals may schedule appointments by calling 314-291-6736 or 885-200-6736 (toll free). Visit stlukescdi-stl.com for more information.
St. Luke's Hospital is a regional healthcare provider committed to improving the quality of life for patients and the community. It offers care in more than 60 specialty areas and was the only St. Louis hospital named an America's 50 Best Hospital™ by Healthgrades® in 2007 through 2014 based on quality.


Integrated IgG Fragmentation and Fragment Purification Using a Reactant Adsorptive Membrane Bioreactor Separator System
Deqiang Yu and Raja Ghosh. Department of Chemical Engineering, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada
Immunoglobulin G fragments are widely used for different diagnostic and therapeutic applications. Fragmentation of immunoglobulin G is useful for characterizing antibodies. The enzymatic fragmentation of IgG is traditionally carried out by homogeneous liquid phase reaction and followed multi-step purification to remove the enzyme and byproducts. These processes tend to be complex with low overall productivity. The current work deals with use of a membrane chromatography system as a bioreactor and separator. In conventional bioreactors, the biocatalyst is immobilized within the reactor and the reactant is passed through it for carrying out the enzymatic reaction. In our bioreactor system the reactant i.e. IgG is reversibly immobilized and the enzyme is allowed to flow through the system. This approach allows the reaction to be carried out and multiple components i.e. reactant, impurities, enzyme, product and byproduct to be separated using a single device. In the present work hydrophobic interaction membrane chromatography (HIMC) was utilized to obtain F(ab')2 and Fab fragments directly from human serum using enzymes pepsin and papain. The reactant adsorptive HIMC system was able to selectively adsorb IgG from serum. When the bound IgG was pulsed with the enzyme under optimized condition, different fragments were obtained and these could be fractionated based on their different interactions with the membrane adsorber. The main advantage of our approach is the great process simplification by efficient integration of IgG purification, reaction and separation. Other advantages include high conversion, low process time and scalability.


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Former president of Americanas testifies to CVM – 03/16/2023 – Market
The former president of Americanas Miguel Gutierrez testified this Thursday (16) to the CVM (Securities and Exchange Commission), which has a series of lawsuits open to investigate responsibilities of the company’s management in the crisis that led to the request for judicial recovery.
Gutierrez stayed for about four hours at the autarchy’s headquarters, in downtown Rio de Janeiro, but came and went without speaking to the press. The CVM does not confirm for which of the processes the testimony was given. The content of the executive’s speeches was also not disclosed.
He spent 20 years in charge of Americanas, accumulating the role with the director of investor relations. He left the company in 2021 to be replaced by Sergio Rial, who announced the discovery of accounting inconsistencies and his balance sheets.
Rial, who has also since left the retailer, said the problem that resulted in the inconsistencies had dragged on for at least seven to nine years, during which Gutierrez ran the company. Other directors of the company during that term were removed at the beginning of the year.
Among the processes opened by the CVM, there are investigations into accounting practices, compliance with disclosure rules, the performance of audits and even the possible use of privileged information in the sale of shares by executives, who won the roles as a bonus for performance.
In addition to Americanas’ management, the CVM is also investigating the company’s main shareholders, the trio of billionaires Jorge Paulo Lemann, Beto Sicupira and Marcel Telles. They are the target of a process that investigates the steps taken after the announcement of the accounting scandal.
In all, the CVM has eight processes and two administrative inquiries to investigate the Americanas crisis. The inquiries are evolutions of the processes, a sign that the municipality already has more elements of irregularities.
Reserved, Gutierrez was very close to Sicupira, who held the presidency of the board of Americanas for many years and is today one of the reference shareholders and director of the retailer, alongside Lemann and Telles.
He was a member of the trio of partners from the former GP Investimentos (cradle of 3G Capital) responsible for developing the company, while Marcel Telles did the same at Ambev.

domain: news


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Analyze drawing on facts within the Netherlands is the first to point out how admissions to treatment centres increase and tumble in keeping with cannabis energy
There are 2 routes that should be applied to cognitively deal with compound abuse persons; keep track of the views that pulled them to addictions and monitor the feelings that avoid them from relapsing. Nevertheless, psychologist must also incorporate the theory of functionalism while in the equation of managing material related dysfunction. As make a difference of simple fact behavioral tactics have the biggest extensive share of software in managing substance relevant Issues. Behavioral psychologists would make use of the strategies of “aversion therapy”. This kind of therapy is based on the principles of classical conditioning of Ivan Pavlov. It is actually when pairing substance abuse with uncomfortable stimulus or issue, such as, pairing soreness, electrical shock, or nausea with Alcoholic beverages use.
Drowsiness, sedation, slumber; amnesia, blackout; lowered stress and anxiety; muscle mass rest, impaired reaction time and motor coordination; impaired psychological functioning and judgment; confusion; aggression; excitability; slurred speech; headache; slowed respiratory and heart fee.
Minimal doses: slight increase in breathing amount; improved blood pressure and heart amount; shallow breathing; encounter redness and sweating; numbness with the palms or feet; issues with motion.
Uncover details about addiction and mental health solutions close to you. You can research by point out or zip code on line or simply call the selection.
Next, the time period material dependence implies that dependence is the key pharmacologic phenomenon fundamental addiction, which is probably going not legitimate, as tolerance, sensitization, and Mastering and memory also Engage in central roles. It Bob Menendez is actually ironic and unlucky the Guide avoids use in the expression addiction, which gives the very best description on the medical syndrome.
Treatment can be pharmacologic, working with drugs; surgical, involving operative strategies; or supportive, developing the client's strength. It may be distinct for the disorder, or symptomatic To alleviate symptoms with out effecting a get rid of.
A lot more investigate is required to understand if behavioral therapies may be used to take care of addiction to dissociative drugs.
Drug-linked mental health admissions in NHS hit document significant Kid slavery victim to plead to stay in British isles with assistance of thousands
In search of and having the drug becomes compulsive. This is mostly as a result of the results of very long-time period drug publicity on brain functionality. Addiction affects portions of the Mind involved with reward and motivation, Understanding and memory, and Command in excess of habits.
Together with CREB, it is actually hypothesized that tension mechanisms play a role in dependence. Koob and Kreek have hypothesized that in the course of drug use, CRF activates the hypothalamic–pituitary–adrenal axis (HPA axis) together with other strain systems within the prolonged amygdala. This activation influences the dysregulated psychological point out linked to psychological dependence. They located that as drug use escalates, so does the presence of CRF in human cerebrospinal fluid.
The three most commonly encountered drugs existing through exams were cannabis, cocaine and opiates, and Many of us examined good for several drugs.
Nonetheless, frequent or for a longer time-time period use of opioids may lead to addiction. Misuse of such drugs or getting another person’s medication might have harmful—even fatal—effects.
Many of Brian Schatz us don't understand why or how Others grow to be hooked on drugs. They could mistakenly feel that those that use drugs absence ethical principles or willpower and that they may prevent their drug use simply by selecting to. In fact, drug addiction is a fancy ailment, and quitting commonly usually takes much more than good intentions or a strong will.