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- 07-28-2014, 02:31 AM Thread Author #1
Galaxy s4 yellow screen
Please help, for the past 3 weeks in the morning, the screen on my galaxy s4 goes yellow, even after i restart the phone, pull out the battery, the screen still stays yellow when i switch it on again, the only way i can seem to get rid of it is to plug in the charger for a few seconds until it disappears and goes back to normal....is this a fairly common issue or is my phone just f#*Ked.
Thank you
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Re: Galaxy s4 yellow screen
Does it turn solid yellow without anything else showing, or is it just a yellowish tint? Is the phone rooted or unrooted?
Try booting into Recovery and wiping the cache partition: Reset: Samsung Galaxy S 4 | T-Mobile Support
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New County Hotel
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How has this hotel rated in the past?
- Meeting rooms/conference facilities
- Airport Transportation
- Wireless internet connection in room (free)
- Room service
- Wireless internet connection in public areas
- Non-smoking rooms
Photos of New County Hotel
Travelers also looked at:
- Restaurant
- Bar/lounge
- Wireless internet connection in room (free)
- Wireless internet connection in public areas
- Non-smoking rooms
- Non-smoking hotel
- High-speed internet in room
- Breakfast Available
- Free High-Speed Internet
- Family rooms
- Meeting rooms/conference facilities
- Airport Transportation
- Room service
- Conference facilities
- Meal plan
- Laundry
TripAdvisor Reviews New County Hotel Perth
Travel Blogs from Perth
Visiting the OTHER Perth
... toss was my favourite. I hand't realised that it wasn't actually about chucking it as far as you can, but about making sure it flips end over end and then falls as straight as possible. Points are given if it goes end over end and more points the straighter, or 'closer to the hour' it falls. It was a fantastic day out and we were really lucky that we happened to catch it. We seem to have a knack for running into festivals in this ...
Scotland visits
... production to try and fast track material to market. They very kindly gave us lunch and we looked at some potatoes in the field. After this we meet with a grower that works with saltire seeds. The operation was 1,000 ac growing 300 ac of seed for saltire but also the farm owner has more land in England and is growing seed for him self. We ran out of time here a bit and had to head back to perth. Caught up with Keith and Greame, a grower the team met on ...
Where we are at so far
... and many beers later we came up with a plan.
Dee researched the Visas. I sorted the Travel side of things.
Many weeks later we had moved a little bit forward but it seemed to be issue after issue with the Visas and what was the best way to travel. We approached a company called Real Russia which turned out to be the best move so far, although they did cause all the issues we had.
They have ...
The icy road to Isle of Man
... in the door felt more like I was walking into a furnace rather than into a coffee shop.
As I sat down in the heat and placed my order my body begins to start to shiver from being so cold. It's a strange fact but while on the bike one does not seem to feel the cold so much but after getting off the bike and sitting down is when the extreme cold really seems to start biting.
After a wonderful hot chocolate and breakfast it's time to head on. Outside the ...
Shopping in Perth
... was lovely and filling. More wandering of shops followed lunch including looking at a cute little bead shop before we headed back to the hotel bar where we had a relaxing drink while watching the Olympics. Afew hours later dad arrived back from his hard days fishing and we loaded up the car and went on our one hour drive to Edinburgh. Arriving in Edinburgh we found our hotel, checked in and went to grab some dinner before heading to ...

subset: commoncrawl


text:
As today's workforce becomes increasingly connected and mobile at the same time, communicating simply via email or a phone call doesn't always cut it. Therefore, it is now crucial for businesses to equip their employees with a solution that seamlessly integrates a broad range of communication methods to allow businesses to communicate and collaborate more efficiently. And a Unified Communications (UC) solution is the answer.Sponsored Listing
Dynamic Content Software
- Message Boards
- CGI Tools/Libraries
Hot topics in Dynamic Content Softwarecds/isis library software reactor server phpdev arduino simulator reactor iptv web server php apache mysql cds-isis dating script accounting
The Malete database core is the new basis of OpenIsis, which has its roots in the UNESCO CDS/ISIS database. Traditionaly used in libraries; now a general purpose highspeed database.180 weekly downloads
FoxServ Win32 & Linux Edition
FoxServ is an Apache / mySQL / PHP installer package for Windows and Linux. Unlike NuShpere or PHPTriad, FoxServ features the latest version of all included pacakges, user defined configuration during installation, PHP as a module, PEAR, and the Zend Opt25 weekly downloads
phpdev is a bundle of PHP/Apache/MySQL/PERL/phpMyAdmin/PHP-GTK preconfigured to run \\\'out of the box\\\' on the win32 platform. phpdev is constantly upgraded to the latest versions of its components, and grows in functionality with each release, phpdev20 weekly downloads
You're probably paying too much for cell phone service. Wirefly compares hundreds of plans to help you save. Enter what you need (minutes, data, texts) into Wirefly's innovative plan comparison tools and see your savings instantly.Sponsored Listing
Reactor Server
The Reactor Server is an easy to install Apache distribution for Windows - MySQL, PHP, Perl, phpMyAdmin, PHP-Nuke and Zina. Begin operating a web portal with a streaming music interface in only minutes.12 weekly downloads
getmyip - command-line utility showing IP address of the computer. Download executables from http://getmyip.sourceforge.net and http://aleant.com4 weekly downloads
Open Business Accounting (OBA)
OBA is a web based business accounting software modified from sql-ledger to suit accountants ,auditors and who required massive data entry. it comes with some new modules such as quick-entry, sales summary, unique transaction number for managing indivi3 weekly downloads
eXtensible PERl scripTable MUD client
A MUD-Client for Windows (Win32) and KDE, featuring perl, python and ruby scripting, as well as multi-window output. The main focus is a very strong scripting engine (nearly everything is accessible from a script) while trying to stay user friendly.1 weekly downloads
Perl Web Objects ADE
Compiles a file of reusable, context-overridable html/perl chunks into straight perl CGI. Project file can survive being edited in a wysiwyg html editor (eg Frontpage or Dreamweaver) for artistic polish. Tracks session data. MySQL integration optional.1 weekly downloads
Domesu Wiki
A variant of the popular UseModWiki software, updated with new features including per-user language support and anti-spam features.
DreamPage lets you create dynamic web sites with PHP and is perfect for skinned websites, multiple languages, multiple sites (hosting), large sites, HTML, WML and pretty much anything.
Empire Land
Empire Land Game of world rule! A realtime, multiplayer, medieval, web-game with a moduler architecture. Capable of running on multiple servers.
Etree Automation Tools (EAT)
Server and client tools to reduce stress for etree siteops and downloaders. Command line python based ftp client - very simple; just gets music. Server Tools: Fully automates user management for etree servers.
Gorilla Software
Gorilla Software is a company which makes games and web applications in PHP, Perl, C, and C++. We are all open source and are always looking for people to join come check out some of our projects in development.
LiveTamil NetPals
Have you ever used Yahoo personals? or Lava Life? If then you know what Net-Pals mean. LiveTamil Networks develops a similar system using CGI/PERL. Run your own personal or dating webpage using our secure Net-Pals script.
PHP World Portal
PHP World Portal is being developed as the framework for JLS Web Development's site. After each module is completed it will be released as open source for the public. The core framework will be released by 1/23/04.
PlayerGraph is a game information tool. It can collect information like player count, frags, kills, ping, current map, server name and more. This all works from a template system either live or as a cron job! Supports 30+ games.
The purpose of this project is to collect and provide snippets often needed by developers to translate the TLD code to the more readable names in various languages. The snippets will be made available as associative arrays for PHP and Perl.
The SAFARI Project
The goal of SAFARI is to create an advanced newsletter management tool that is both powerful and easy to use. The first release will have all the basic features needed for content management.
This simple Skript is a small solution for web-aplications to upload pictures.The features: - CGI-parser in Perl for simultaneously upload of formdatas and pictures (jpg and gif) - running on Win-, Unix- or Linux-Servers - no compellingly need for Per
Web IDE / Command Line interface
An Web IDE that enables you to edit, compile, cvs in/out, do file release and produce documentation from a single friendly user web page or out of a Makefile!
ples is a set of ReSTful HTTP interfaces to commonly used Open Source databases for the Perl, Python and PHP (PPP) scripting languages. ples-utils is an assortment of some useful PPP server scripts that can not be found *anywhere* else.


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British Engineering Manufacturers Association
Welcome to the BEMA website.
As a well established trade association we feel that not only should our members be informed but the world at large should have the opportunity to see what is happening in the industry that we support. The vast majority of this site is open to the public for information that not only helps the employer but also the employee. Please feel free to use the contact area to inform us of any ideas that can help to improve this site.
If you are looking for an Apprenticeship and would like further information then please click here.
BEMA apprentices win regional awards.
EEF (Engineering Employers' Federation) have just held their South West regional awards ceremony, held at @Bristol, where local engineering companies propose candidates for the Intermediate/advanced award for First year apprentice of the year.
Out of the many companies that put forward their nominated apprentices BEMA are proud to announce that both the first and second award winners were trained in our Training Centre in Yate.
Chris Edwards who came first is from Broadway (Bristol) Engineering Co. Ltd. and will be going up to London to take part in the National awards competing against the other regional winners, and Tyler Couzens who came a very close second is from Avon Valley Precision Engineering. Both companies' representatives who were at the awards ceremony were delighted with the results.


text:
Northern Arizona University Reviews
Student & Graduate Reviews (25)
The program has gone from a total enrollment of ten students to SEVENTY. Beware. As with any business that experiences too-rapid growth, the quality of the instruction and the quality of the instructors has plummeted. Most in the program now will clearly tell you to run...not walk..., to a different choice, for your advanced practice studies. The professors are adjunct, with no teaching ability, no passion for their students, and no commitment to truly mentor and guide. In reality, there is no true teaching happening; your learning is dependent upon self-teaching in the textbooks and through your private purchase of FNP review courses. Clinical sites for students are scarce, and many in our program were left with substandard practice sites that were detrimental to their learning. There have also been numerous staffing and faculty "departures" that have been costly in continuity of information and program values.
I chose it because I wanted to stay in state. It wasn't as large as the other options but still allowed me to get the college experience. The campus was beautiful, had great campus life and offered a different cultural than I was used to. I enjoyed the liberal atmosphere that it was.
I, like so many others, was hesitant about this school's online program as I have been burned before. I did all of my research about this school's program and only read good things and I also made sure it is regionally accredited. It's really the tuition that clinched it for me. It is absolutely the most affordable way to complete a degree online and I love the fact that it's a subscription and not credit based because they give you six months to complete as many lessons as you can so it's really up to the individual as to how much you complete. Also, if you can pass a pretest you don't have to do the lessons at all and you receive the credit. The tests are challenging and aside from the math are mostly essay based, with one long essay and up to 20 other short essay questions. However, you are allowed to use the resources from the lessons as long as you cite your sources. I learned so much through my program and I would do it again in a second. I wish they offered the Master's degree I need because I would definitely sign up! You are assigned a personal mentor that always answered my question either the same day or the next depending on the time difference (I live on the east coast). Professors are more than willing to help and all of my questions were always answered within a day. I highly recommend this school if you are after either a B.A. or B.S. in Liberal Arts, Information Technology or Small Business Administration however they are actively developing new degrees. I check back often just in case.
NAU is an excellent school because of the community, the city, the resources and the professors. The finance professors really cared about my education and even supported me in finding jobs and making big purchases. I felt that they wanted me to really succeed and were honest with the class. They recommended that we take more math classes than what was actually required because it would be necessary in life, and it proved to be true! The only con: Unfortunately, NAU doesn't have a great reputation despite its obvious good reviews so when it comes to getting jobs, any place that says 'only graduates from top universities' won't hire you. The college of business has a stronger reputation and provides job placement assistance, but still most people don't think NAU is good because they don't spend as much money as ASU on marketing :/
I was originally very excited to be able to attend NAU's Nursing Program. However, my experience turned out to be awful. This program is a joke. Many of the teachers have no education background and (while smart) lack the ability to truly teach. I have had to commute up to 4 hours in 1 day for "clinical." The school has no desire to actually work with their students and place them where they want. For clinical placements, I have been told by a professor to "suck it up" and she will put us wherever she feels like it. This is in spite of family obligations, marries, children. etc. Flagstaff is not large enough to accommodate their nursing students. Be prepared to travel and commute. For our public health rotation, there were many times where I felt unsafe going into someone's home BY MYSELF. There were also dangerous situations the school put us in during our mental health rotation. The staff is unorganized and many clinical rotations consist of our poor professors trying desperately just to find a place for us to go. I would not recommend this program to any future students.
This School is a Joke ,don't waste your time! I couldn't get a job any better than if I had gone to work right after high school with just a HS degree. I even worked for Labor Ready for a while! It's a Ski and Party School the only thing I learned was how to use a Beer Bong! Just a bunch of Stoners and Partiers like right out of the Movie "Fast Times From Ridgemont High". The "professors" are a bunch of losers who couldn't get a job anywhere else.
I loved this college for the college experience, however when actually applying to medical schools this did not make the list for impressive colleges.
I love the campus and Flagstaff. I enjoyed my time there. I wish I'd lived on campus though. I feel like i would have been more involved and made more friends. I'm still good friends with my roommates and several friends from NAU.
NAU was a great college to attend! Lots of resources for students, beautiful campus, and wonderful Faculty.
My Educational Technology program was outstanding. Great professors and students who wanted to learn. I went back to school after 30 years away from education. I now work at a University in Academic Technology. Great people, great program! Instructors were knowledgeable and engaged students in learning. It was a challenging program but I only took two courses at a time so it was manageable.


text:
Police asking public's help to find man missing since December 2014
Morgan City police are asking for the public's help to locate Ronald Brady Breaux, 52, who was last seen in December 2014 by family members in the area. Anyone with any information on Breaux's possible whereabouts should contact the Morgan City Police Department Detectives Division at 985-380-4605. (Submitted)
Morgan City police asking the public's assistance in an ongoing investigation to locate a missing man last seen by his family in the Morgan City area over two years ago.


text:
Lulu City
No prices found through our partners. Please contact the business directly or check some of our recommended alternatives.
TripAdvisor Reviews Lulu City Telluride
Travel Blogs from Telluride
"They Hide it up in Telluride"
... click here. Local residents and visitors have included Bob Dylan, Daryl Hannah, Jerry Seinfeld, Ed Helms, Sean Penn, Oprah Winfrey and Tom Cruise. All rich and famous. Just like in Aspen. *** Feeling somewhat rich and famous ourselves, if only by association, we hop on our bikes and continue south on CO-145 for 60 miles, to the town of Dolores. For you etymology fans, Dolores is Spanish for "sorrows" and is named for the river ...
World Travel Highlights
... font-style: normal;">Pide and halvah in Turkey
The Final Count Down
... br>
Day 11 Zadar
Day 12 This is a surprise!
Day 13 & 14 Dubrovnik
Day 15 Split
Day 16 Frankfurt
Day 17 Houston
Top of the Rockies from Ouray
... feet above sea level, things warmed back.
Tomorrow, we drive the Million Dollar Highway to Silverton, where Scott hitches a ride on the Durango & Silverton Narrow Gauge ...
Telluride - Colorado's Most Beautiful Town
... mountain town after Aspen.
Telluride is so far from Denver that I've never gone there as a destination in its own right. I stopped in the town once for lunch with my parents on the way back from a 1994 trip to California and spent a few hours in it with my brother on a short trip to Utah in 2009. So this time around I've decided to give myself a full and relaxing day after yesterday's long hike to wander around town ...
Other places to stay in Telluride
Riverside Condominiums460 South Pine Street, Telluride | 3 star condofrom $185
ResortQuest Etta Place666 West Colorado Avenue, Telluride | Condofrom $189
Viking Lodge651 W. Pacific Ave., Telluride | 2 star condofrom $239
Double Diamond350 South Mahoney, Telluride | Condofrom $159
ResortQuest Spiral Stairs666 West Colorado Avenue, Telluride | Condofrom $139
Bear Creek Lodge135 San Joaquin Rd, Telluride | 4 star condofrom $153
ResortQuest Boomerang Village666 West Colorado Avenue, Telluride | Condofrom $99
Ghost Riders700 W Colorado Ave, Telluride | Condofrom $119
The Peaks See Forever Rentals145 Sunny Ridge, Telluride | 4 star condofrom $634
Muscatel Flats200 S. Willow, Telluride | Condofrom $135
Cimarron Lodge300 South Mahoney, Telluride | 3 star condofrom $103
Blue Mesa Lodge117 Lost Creek Ln, Telluride | Condofrom $109
ResortQuest Ore Station666 West Colorado Avenue, Telluride | Condofrom $119
Westermere Condominiums646 Mountain Village Blvd, Telluride | Condofrom $229
The River Club Condos550 West Depot Avenue, Telluride | 4 star condofrom $400
Le Chamonix135 San Joaquin - Bear Creek Lodge, Telluride | Condofrom $129
ResortQuest Bachman Village 26763 West Smuggler Avenue 26, Telluride | Condofrom $269
Auberge Residences at Element 52398 South Davis Street, Telluride | Condofrom $395


text:
|Publication number
|Publication type
|Application number
|Publication date
|Mar 21, 2006
|Filing date
|Jan 18, 2000
|Priority date
|Jan 18, 2000
|Fee status
|Also published as
|Publication number
|Alain Mayer, Avishai Wool, Elisha Ziskind
|Original Assignee
|Lucent Technologies Inc.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (9), Non-Patent Citations (2), Referenced by (60), Classifications (18), Legal Events (6)
|External Links: USPTO, USPTO Assignment, Espacenet
The present invention relates generally to firewalls, and more particularly, to a method and apparatus for analyzing the security policy of a firewall.
Network firewalls provide important safeguards for any network connected to the Internet. Firewalls are not simple applications that can be activated "out of the box." A firewall must be configured and managed to realize an important security policy for the particular needs of a given company or entity. It has been said that the most important factor affecting the security of a firewall is the firewall configuration. While firewalls have seen impressive technical advances, there have been few, if any, advances in firewall configuration and management.
A firewall is a network gateway that filters packets and separates a proprietary corporate network, such as an Intranet, from a public network, such as the Internet. Most of today's firewalls are configured by means of a rule-base or firewall configuration file. In the case of a firewall guarding a single, homogeneous Intranet, such as the local area network (LAN) of a small company, a single rule-base instructs the firewall which inbound sessions (packets) to permit to pass, and which should be blocked. Similarly, the rule-base specifies which outbound sessions (packets) are permitted. The firewall administrator needs to implement the high-level corporate security policy using this low-level rule-base.
The firewall's configuration interface typically allows the security administrator to define various host-groups (ranges of IP addresses) and service-groups (groups of protocols and corresponding port-numbers at the hosts that form the endpoints). A single rule typically includes a source, a destination, a service-group and an appropriate action. The source and destination are host-groups, and the action is generally either an indication to "pass" or "drop" the packets of the corresponding session.
In many firewalls, the rule-base is order sensitive. In other words, the firewall checks if the first rule in the rule-base applies to a new session. If the first rule applies, the packets are either passed or dropped according to the action specified by the first rule. Otherwise, the firewall checks if the second rule applies, and so forth until a rule applies. This scheme often leads to misconfiguration due to redundant rules in the rule-base, and the desired security policy is realized only after re-ordering some of the rules.
The problems of administering a firewall are even worse for a larger company, which may use more than a single firewall. Multiple firewalls divide a company's Intranets into multiple zones, and the security policy is typically realized by multiple rule-bases, located on multiple gateways that connect the different zones to each other. Thus, the interplay between the various rule-bases must be carefully examined so as not to introduce security holes. The complexity of designing and managing the rule-bases grows, as the Intranets get more complex.
Today, even a moderately sized corporate intranet contains multiple firewalls and routers, which are all used to enforce various aspects of the global corporate security policy. Configuring these devices to work in unison is difficult, especially if the devices are made by different vendors. Even testing or reverse engineering an existing configuration, for example, when a new security administrator takes over, is hard. Firewall configuration files are written in low-level formalisms, whose readability is comparable to assembly code, and the global policy is spread over all the firewalls that are involved.
Currently, firewall administrators do not have an easy way to determine the security permissions that are applicable to various classes of machines or services in a corporate environment. Thus, it can be difficult, if not impossible, for the administrator to answer routine questions regarding the corporate security policy, such as whether one or more given services are permitted between one or more given machines. There are several reasons why evaluation of the corporate security policy can be difficult. First, packets may have multiple paths between a source and destination, with each path crossing several filtering devices. To answer a query, the administrator would need to check the rules on all of these. In addition, typical vendor configuration tools deal with a single device at a time, which may lead to inconsistent global behavior. If packet-filtering devices made by different vendors are involved, the situation quickly becomes much worse. Furthermore, even understanding the policy on a single interface of a single packet-filtering device is problematic. As previously indicated, firewall configuration languages tend to be arcane, very low level, sensitive to rule order, and highly vendor specific.
Currently, a number of vulnerability testing tools are commercially available. For example, Satan™, described, for example, in M. Freiss, Protecting Networks with SATAN, O'Reilly & Associates, Inc. (1998), attempts to exploit known flaws in widely deployed protocols and operating systems, some of which can be blocked by appropriate firewall policies. In this manner, Satan™ can be used to test the firewall policy. In addition, NetSonar 2.0™, commercially available from Cisco Systems Inc. of San Jose, Calif., connects to a corporate intranet and probes the network, thereby testing the deployed routing and firewall policies.
Currently available vulnerability testing tools are active. In other words, they send and receive packets on the network. As such, they suffer from several limitations, which if overcome, could greatly expand the utility and efficiency of such vulnerability testing tools. For example, if the intranet is large, with many thousands of machines, current vulnerability testing tools are either slow (if they test every single IP address against every possible port), or statistical (if they do random testing). Certainly, they cannot test every possible IP address on the Internet.
In addition, current vulnerability testing tools can only catch one type of firewall configuration error: allowing unauthorized packets through. They do not catch the second type of error: inadvertently blocking authorized packets. This second type of error is typically detected by a "deploy and wait for complaints" strategy, which is disruptive to the network users and may cut off critical business applications. Active testing is always after-the-fact. Detecting a problem after the new policy has been deployed, however, is (a) dangerous (since the network is vulnerable until the problem is detected and a safe policy is deployed), (b) costly (since deploying a security policy in a large network is a time consuming and error prone job), and (c) disruptive to users. Furthermore, an active tool can only test from its physical location in the network topology. A problem that is specific to a path through the network that does not involve the host on which the active tool is running will go undetected.
A need therefore exists for a firewall analysis tool that allows an administrator to discover and test a global firewall policy. A further need exists for a firewall analysis tool that uses a minimal description of the network topology, and directly parses the various vendor-specific low-level configuration files. Yet another need exists for a firewall analysis tool that interacts with the user through a query-and-answer session, which is conducted at an appropriate level of abstraction.
Generally, a method and apparatus are disclosed for analyzing the operation of one or more firewalls or other network gateways, such as routers, that perform a packet filtering function in a network environment. The security policy for a particular network environment is typically implemented by defining a packet filtering configuration file (a rule-base) for each firewall. The packet filtering configuration file instructs a given firewall whether to pass or drop certain inbound and outbound packets. Given a user query, the disclosed firewall analysis tool simulates the behavior of the various firewalls, taking into account the topology of the network environment, and determines which portions of the services or machines specified in the original query would manage to reach from the source to the destination.
The disclosed firewall analysis tool collects and reads the relevant packet filtering configuration files and builds an internal representation of the implied security policy. In addition, the firewall analysis tool utilizes a graph data structure to represent the network topology. A gateway-zone graph is comprised of a number of nodes interconnected by edges. Each node corresponds to either a gateway (firewall or router) or a zone created by a gateway. Generally, the present invention assumes that a given packet can travel along any physical path, even if not allowed according to the route scheme. The gateway-zone graph contains a node for each device containing a packet-filtering rule-base, and for each zone defined by such devices. The firewall analysis tool does not need to be aware of every router and switch in the network, and is indifferent to the routing scheme that is used.
The gateway-zone graph permits the firewall analysis tool to determine where given packets will travel in the network, and which gateways will be encountered along those paths. In this manner, the firewall analysis tool can evaluate a query object against each rule-base object, for each gateway node in the gateway-zone graph that is encountered along each path between the source and destination.
According to a further aspect of the invention, the firewall analysis tool provides a graphical user interface for receiving and evaluating simple queries, such as whether one or more given services are permitted between one or more given machines. The present invention permits a user to aggregate queries where a given service may be a set of services (up to a wildcard "all possible services"), and given machines may be arbitrary sets of IP addresses (up to a wildcard "all possible addresses"). According to a further feature of the present invention, the firewall analysis tool can simulate a spoofing attack by altering the source IP address. The firewall analysis tool allows the user to specify where the packets are to be injected into the network, which may not be the true location of the source host-group. The firewall analysis tool can also take into account firewall rules that perform network-address-translation (NAT).
A more complete understanding of the present invention, as well as further features and advantages of the present invention, will be obtained by reference to the following detailed description and drawings.
Behind the server zone 130 is an internal firewall 150 that guards the corporation's proprietary or internal network, such as an Intranet. The internal firewall 150 has three interfaces. A first interface is to the server zone 130, a second interface connects the internal firewall 150 to the corporate network zone 160, and a third interface connects the internal firewall 150 to the firewall administration zone 140. Securing the firewall administration host is critical to the network's integrity and should be separated from the other corporate hosts. Within the corporate network zone there is generally one distinguished host, referred to as the control host (not shown), that provides the administration for the servers in the server zone 130. In the illustrative embodiment, each firewall 120, 150 has a packet filtering configuration file 125, 155, discussed below, associated with it.
Generally, the packet filtering configuration files 125, 155 are firewall-specific rule-bases. In the multiple firewall environment of
The illustrative corporate network environment of
As shown in
According to a further feature of the present invention, the firewall analysis tool 200 can simulate spoofing attacks that alter the source IP address. The firewall analysis tool 200 allows the user to specify where the packets are to be injected into the network, which may not be the true location of the source host-group. The firewall analysis tool 200 can also take into account firewall rules that perform network-address-translation (NAT).
Firewall Terminology and Modeling Concepts Typically, a firewall configuration tool allows the security administrator to define various host-groups (collections of IP addresses) and service-groups (groups of protocols and corresponding port-numbers at the hosts which form the endpoints). A single rule typically includes a source, a destination, a service-group, and an appropriate action. The source and destination are host-groups, and the action is typically to either "pass" or "drop" the packets of the corresponding session. In addition, the action may specify the writing of a log record or the performance of a network-address-translation (NAT).
As previously indicated, the rule-base is often order-sensitive. Generally, the firewall checks if the first rule in the rule-base applies to a new session. If so, the packets are either dropped or permitted to pass according to the action of the first rule. Otherwise, the firewall checks if the second rule applies, and so forth.
As used herein, gateways are the packet filtering machines and can be either firewalls or routers. Normally, a gateway is multi-homed, since a gateway has at least two Internet connections. Typically, a gateway has multiple network connections. Each connection goes through an interface, which has its own unique IP address. It is assumed that each interface has a packet filtering configuration file 125, 155 associated with it. The gateways partition the IP address space into disjoint zones, as shown in
A service is the combination of a protocol-base, such as tcp or udp, and the port numbers on both the source and destination sides. For example, the service telnet is defined as tcp with destination port 23 and any source port. A service-group is simply a set of services.
As shown in
As shown in
According to one feature of the present invention, the firewall analysis tool 200 does not need to be aware of every router and switch in the network, and is indifferent to the routing scheme that is used. Generally, the present invention assumes that a given packet can travel along any physical path, even if not allowed according to the route scheme. The present invention considers those devices that have packet-filtering rule-bases installed on them, and the zones these devices define. At this level of granularity, the topology is quite stable. Thus, the topology file 210 only needs to be modified if firewalls 120, 150 are added or replaced in the network 100.
As part of the topology definition file 210, the user 220 specifies the names of the packet filtering configuration files 125, 155 (hereinafter, collectively referred to as firewall configuration files 230) that contain the rule-bases for all of the gateway interfaces 120, 150 in the network environment 100. After reading the topology definition file 210, the firewall analysis tool 200 parses each of these configuration files 230 in turn (using a separate "front-end" module for each supported firewall variation), and populates its internal rule-base data structures for each device. It is again noted that these firewall configuration files 230 are vendor-specific, and are created by whatever tools are used to configure the devices in question.
The user forms a query by choosing each element of the query triple (service, source, destination), for example, from a drop-down menu offering the choice of all the host-groups or service-groups that were defined in the configuration files.
The network topology is modeled by partitioning the network 100 into zones 130, 140, 160, which are connected through gateways. A gateway 120, 150 has an interface for each adjacent zone 130, 140, 160. Each interface either has its own IP address (and is considered a host for some purposes), or is declared to be invisible (for example, using an INVIS keyword) if the firewall 120, 150 operates as a bridge. Packets leaving and entering a zone 130, 140, 160 can be filtered by the gateway 120, 150 on the corresponding interface. Packets sent and received within the same zone 130, 140, 160 cannot be filtered by a gateway 120, 150, simply because the packets do not pass through any gateway 120, 150. Therefore, from the perspective of the firewall analysis tool 200, there exists a path between any two hosts in the same zone, with any and all filtering being performed by the interfaces. Zones consist of host-groups. Host-groups are typically further subdivided into a hierarchy of smaller host-groups or single hosts.
In this section we give a complete listing of the topology file, written in MDL, used to describe the network environment 100. The topology file provides an input mechanism for building the gateway-zone graph 300, discussed further below. First, the host-groups are defined.
# the zones
Z_dmz = [126.96.36.199/24]
Z_corp = [184.108.40.206/24]
Z_admin = [18.104.22.168/24]
Z_internet = [0.0.0.0 − 126.96.36.199,
188.8.131.52 − 255.255.255.255]
# the (visible) gateway interfaces
I_dmz_in = [18.104.22.168]
I_admin = [18.104.22.168]
It is noted that an IP address range can be specified in different ways.
The slash notation defines a range by indicating how many of the most
significant bits are fixed.
Next, the interfaces are defined.
I_internet_dmz = {INVIS, NO_GEN}
I_dmz_in = {file="~/fw/analyzer/data/dmz_in"}
I_dmz_corp = {INVIS, NO_GEN}
I_corp_in = {INVIS,
I_admin = {file="~/fw/analyzer/data/admin"}
Interfaces with the NO_GEN attribute do not perform any filtering.
Interfaces with the INVIS attribute do not have an IP address since they
belong to a firewall that works as a bridge.
Finally, the gateways and zones are defined.
dmz_gw = {I_internet_dmz, I_dmz_in} : LMF
corp_gw = {I_dmz_corp, I_corp_in, I_admin} : LMF
Z_internet = {I_internet_dmz}
Z_dmz = {I_dmz_in, I_dmz_corp}
Z_corp = {I_corp_in}
Z_admin = {I_admin}
Naming In the model used by the present invention, all the objects (hosts, host-groups, service-groups) generally have names. This provides a high level of abstraction when interacting with the user. Meaningful names are more expressive than raw IP addresses and port numbers. To the extent possible, the firewall analysis tool 200 obtains these names from the vendor-specific configuration files. However, since each device and interface is assumed to have been configured independently, there may be name conflicts. For example, the administrator may have defined the name http to signify tcp on port 80 on one gateway, while on another gateway the administrator may use the same name to mean tcp on ports 80, 8000, and 8080. To support this level of naming, the firewall analysis tool 200 maintains a separate symbol table context per interface (i.e., per rule-base). If the same name appears in different contexts with different meanings, the firewall analysis tool 200 can optionally show all the variants in its drop-down menus, prefixed with the interface name. Otherwise, if all the variants are identical, the name will appear only once with no prefix.
The implicit security policy in place within the corporate network environment 100 is derived from the vendor specific packet filtering configuration files 125, 155. The firewall analysis tool 200 transforms each of these packet filtering configuration files 125, 155, associated with an interface, into a table of logical rules containing the following record structure (simplified for ease of explanation):
struct rule {
struct hostgrp
struct hostgrp
struct servicegrp
The actual semantics differ among different vendors. In the illustrative embodiment, the following exemplary semantics are utilized. When packets are filtered, the rules in the list are examined in their order until a match occurs. The source, destination and service_grp fields are compared to the corresponding fields in the packet. The direction specifies whether the rule applies to packets entering (IN) or leaving (OUT) the gateway 120, 150 on which this interface sits (i.e., the rules are gateway-centric). The wildcard direction (BOTH) indicates that the rule applies to both directions. If a match occurs, the corresponding action (DROP or PASS) is performed. The internal rule-base table also supports rules that perform NAT, and hence, the rule structure has some additional fields.
A central object in the firewall analysis tool 200 is a query. A query is a triple, consisting of a source host-group, a destination host-group, and a service group. The semantics of such a query are "which IP addresses within the source host-group can send services from the service-group to which IP addresses in the destination host-group?" The query is described by the following data structure:
struct query {
struct hostgrp *src;
struct hostgrp *dst;
struct servicegrp *service;
It is again noted that host-groups and service-groups may be wildcards, i.e., any element of the query triple can be the "*" wildcard, meaning "any." So the question "which machines can use the company's web-servers?" can be expressed by the query triple having the form (*, web_servers, http_services), assuming that the host-group web_servers and the service-group http_services are defined.
Typically, not all the packets described by a query can reach the destination. Through the operations of the various rule-bases 125, 155, some packets may be dropped. Therefore, the firewall analysis tool 200 will answer such a query with a refined list of "sub-queries", i.e., a list of query triples where each element is a subset of the corresponding element in the query triple.
The semantics of the answer are that for each subset triple, the corresponding source host-group can indeed send the service to the destination host-group.
The firewall analysis tool 200 utilizes a graph data structure, to represent the network topology.
For this purpose, the internal model contains the following auxiliary graph. As used herein, the gateway-zone graph 300 is defined as a bi-partite graph H=((G ∪ Z), I) whose vertices consist of the set of gateways G and the set of zones Z. The set of interfaces I forms the edges: H contains an edge i=(g,z) connecting a gateway g ∈ G to a zone z ∈ Z, if and only if g has an interface i whose adjacent-zone is z.
The vertices of the gateway-zone graph 300 are implemented using the following structure:
struct node {
union {
struct zone *z;
struct gateway *gw;
} zg;
struct hostgrp *hg;
node_ty type;
struct query *q;
There is a node for each gateway and zone. The type field indicates whether a gateway or zone is represented by a given node. The hg field keeps the IP range contained in the node. For zone nodes, hg is the host-group of the zone minus the IP addresses of the interfaces adjacent to this zone. For gateway nodes, hg is the set of IP addresses of the interfaces attached to the gateway. The q field in the node structure is used for processing the query, as discussed below.
The query engine of the firewall analysis tool 200 uses a combination of the graph data structure discussed above in conjunction with
Then, the algorithm attempts to propagate the query over all the edges that connect the current node during step 440. The algorithm continues in the same manner, propagating the query further until it searches the entire graph. All triples satisfying the query are identified during step 450 before program control terminates during step 460.
The basic step of the algorithm 400 is propagating a query over an edge in the gateway-zone graph 300, which represents a firewall interface. This models the effect of the rule-base that is attached to the interface on the packets described by the query. Typically, only portions of the query can cross any given edge, since some of the packets would be dropped by the interface. Therefore, after crossing an edge, the query may need to be broken up into a set of more refined queries, that represent only those packets that would have been allowed through. For instance, the original query may have been (corporate_net, internet, *), but the rule-base only allows outgoing http and smtp services so the set of queries that reaches the other side of the edge is now (corporate_net, internet, tcp), (corporate_net, internet, smtp).
It is noted that some nodes may be visited more than once, while other nodes will not be visited at all, since the algorithm 400 backtracks over all possible paths the query can take through the network 100, and continues as long as some portion of the query remains un-dropped. If the query can reach a node v (whether a zone or a gateway) via different paths, the new query that is attached to v is the union of the query results reaching v on each of the possible paths. In one variation, the search can be optimized to not perform a traversal if it is clear that no new packets will be allowed through that have not been already by other paths.
The final stage in processing a query is to collect the results during step 450. This simply involves looking at the node or nodes that contain the destination host-group and picking out those queries that have reached their correct destination.
In the worst case, the complexity of the algorithm 400 is exponential in the size of the gateway-zone graph 300. However, this worst case can only occur in very dense graphs. Typical gateway-zone graphs 300 are very sparse, since firewalls 120, 150 are normally placed at strategic choke points in the network, and the most common case gateway-zone graph topology is a tree. On a tree topology, the algorithm is essentially a depth-first-search, i.e., it is linear in the size of the graph. Furthermore, since only zones that are separated by firewalls are modeled, the gateway-zone graphs tend to be quite small.
A small extension to the basic algorithm 400 allows testing for spoofing attacks. In addition to the source, destination and service parameters that define a query, an optional fourth parameter is added which specifies the true source from which the packets originate. When this fourth parameter is defined, the original source host-group is then understood to be the fake source address in the packet. The query can then be processed in the manner described above, except that instead of starting from the nodes that contain the fake source host-group, the algorithm starts at those nodes that contain the true source.
Consider the query: "What services are allowed between the corporate zone and the DMZ?" The results, shown in
In another example, consider the query: "How much access does the Internet 110 have to the internal network 130, 140, 150?" The results are shown in
Another example illustrates how to check for spoofing. The most sensitive host is probably the firewall administrator 140, so no Internet host should be able to reach it, even with spoofing. To do this, the real source is set to be the Internet zone 110, and the given source (the spoofed address) is arbitrary. The results are shown in
In a further extension of the query-answer mechanism of the present invention, additional information about a query is provided. For example, the query results can indicate which rule in which interface is responsible for passing or dropping a particular packet. Such information can displayed graphically to show the path packets take from source to destination. Another extension is to enhance the firewall analysis tool 200 to enable topology independent queries via, e.g., defining zones as being "internal" or "external." If the firewall analysis tool 200 can read in queries from a file, the user would then be in a position to use expert-generated queries to test the network for some basic insecurities. The expert queries might cover well-known insecure ports or services and test accessibility of such ports from the external zones. As new vulnerabilities become known, organizations such as CERT could make updated query files available on their web-site for downloading.
As described in U.S. patent application Ser. No. 09/240,934, filed Jan. 29, 1999, assigned to the assignee of the present invention and incorporated by reference herein, a model definition language (MDL) is used to instantiate the security policy, and to map the policy onto the topology. A parser translates an MDL program into an instance of the entity-relationship model. The model is expressed by a corresponding data structure.
MDL for Security Policy Description
A service is defined by means of a statement in the form: <service-name>=<protocol-base>[<dest-port-no-range>, <src-port-no-range>].
For example, the following code fragment defines the widely used services smtp, ssh, ping, https and a service denoting all tcp-based packets:
smtp =
Services can be grouped into a service-group, ServiceGrp, by a statement of the following form:
The following code fragment defines the two service-groups, admin-to-gtwy and gtwy-to-admin:
A role is defined by a statement of the following form, where the arrow defines the direction attribute in an obvious way, the role-grp-name points to peers, and the srv-grp-name points to a service-group:
The following code fragment defines the roles mail_server and internal_mail_server, discussed above. The roles gateway-in and gateway-out model the capabilities of gateway interfaces in each direction. This example is continued in the next code fragment:
gateway_in ← fw_admin : admin_to_gtwy
gateway_out → fw_admin : gtwy_to_admin
intranet_machine → all_tcp : *
Roles are grouped into open (by default) role-groups 325 by the following statement:
Roles are grouped into closed role-groups by the following statement:
The following code fragment defines the role-group, gateway, bundling the unidirectional gateway roles into one role-group. It is noted that the gateway role-group is closed, thus effectively "stealthing" hosts which assume this role-group.
MDL for Topology Description and Policy Mapping
Hosts and host-groups are defined by the following statements:
The following code fragment defines the hosts, dirty (presumably outside the intranet) and dusty, assigning them roles of external and internal mail servers, respectively:
dirty =
: mail_server
dusty =
Gateways are defined by the following statement:
The following code fragment defines payroll_gw_interface1/2 as hosts and specifies their IP-addresses, and then defines the gateway payroll_gw as having payroll_gw_interface1/2 as its two interfaces. The code fragment also assigns the role-group, gateway, to the interfaces.
payroll_gw_interface1 = [22.214.171.124] : gateway
payroll_gw_interface2 = [184.108.40.206] : gateway
payroll_gw = {payroll_gw_interface1, payroll_gw_interface2}
Zones are defined by means of the following statement:
The following code fragment first defines the zones payroll_zone and corp_zone (parts of the intranet manhattan_office) as host-groups, specifies their IP-ranges and then defines parts of the network topology by specifying the payroll_zone to be connected to the payroll_gw by means of the payroll_gw_interface1, and the second interface of the payroll_gw to be connected to the corp_zone.
= [22.214.171.124–18.104.22.168] : intranet_machine
= [220.127.116.11–126.96.36.199] : payroll_machine
= [18.104.22.168–220.127.116.11] : non_payroll_machine
= {payroll_gw_interface1 }
= { payroll_gw_interface2, ...}
It is to be understood that the embodiments and variations shown and described herein are merely illustrative of the principles of this invention and that various modifications may be implemented by those skilled in the art without departing from the scope and spirit of the invention.
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text:
Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women
© Lind et al; licensee BioMed Central Ltd. 2012
Received: 14 December 2011
Accepted: 2 April 2012
Published: 2 April 2012
Phthalates, commonly used to soften plastic goods, are known PPAR-agonists affecting lipid metabolism and adipocytes in the experimental setting. We evaluated if circulating concentrations of phthalates were related to different indices of obesity using data from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Data from both dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) were used.
1,016 subjects aged 70 years were investigated in the PIVUS study. Four phthalate metabolites were detected in the serum of almost all subjects (> 96%) by an API 4000 liquid chromatograph/tandem mass spectrometer. Abdominal MRI was performed in a representative subsample of 287 subjects (28%), and a dual-energy X-ray absorptiometry (DXA)-scan was obtained in 890 (88%) of the subjects two year following the phthalate measurements.
In women, circulating concentrations of mono-isobutyl phthalate (MiBP) were positively related to waist circumference, total fat mass and trunk fat mass by DXA, as well as to subcutaneous adipose tissue by MRI following adjustment for serum cholesterol and triglycerides, education, smoking and exercise habits (all p < 0.008). Mono-methyl phthalate (MMP) concentrations were related to trunk fat mass and the trunk/leg-ratio by DXA, but less powerful than MiBP. However, no such statistically significant relationships were seen in men.
The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.
KeywordsPhthalates Obesity Mono-isobutyl phthalate DXA Abdominal MRI PIVUS Fat distribution PPAR agonist
Phthalates (phthalate diesters) are commonly used as plasticisers in e.g. polyvinylchloride (PVC) plastics, and are therefore found in numerous household products such as food packaging, furniture, and toys; and in medical devices such as tubing and intravenous bags. In addition, phthalates are used in personal care products and pharmaceuticals. Since phthalates are additives and as such not covalently bound to the plastic, they can easily leach and transfer to e.g. air and food. Humans are exposed to phthalates through inhalation, ingestion, and dermal exposure, and exposure is ubiquitous due to the abundance of plastic in our society and in our homes. Phthalates are rapidly degraded into the respective phthalate monoesters in phase I reactions catalysed by lipases and esterases. The respective monoesters are eliminated in the urine as glucuronide conjugates or are further metabolised, and it is in fact the monoester metabolites that have been claimed to be responsible for adverse health effects [1–4].
Phthalates have been identified as endocrine-disrupting compounds (EDCs) with anti-androgenic effects on the developing male reproductive system through decreased testosterone biosynthesis [5, 6]. Besides effects on reproduction, increasing attention is now being focused on the metabolic effects of phthalates and other EDCs, e.g. in the development of obesity [7–12]. The prevalence of obesity and associated diseases such as type 2 diabetes and cardiovascular diseases have risen dramatically worldwide during the last decades [13], and the search is on for explanations to complement the main causes of high caloric intake combined with low caloric expenditure, such as EDC exposure [11, 14].
Several phthalate monoesters indeed bind to and activate the human peroxisome proliferator-activated receptors (PPARs) [15, 16]. PPAR gamma is involved in fat storage by promoting adipocyte maturation and survival, and also controls insulin sensitivity [17]. PPAR gamma is targeted by the anti-diabetic thiazolidinedione drugs, whose agonistic actions not only improve insulin sensitivity but also promote weight gain [17, 18]. Accordingly, PPARs activation by MEHP and other phthalate monoesters promotes the differentiation of both mouse and human preadipocytes into adipocytes [15, 16, 19].
In the present study, we evaluated if human serum phthalate monoester concentrations were related to different indices of obesity as determined using dual-energy X-ray absorptiometry (DXA) combined with abdominal magnetic resonance imaging (MRI). DXA provides estimates of lean and fat mass from a frontal whole-body scan, while the abdominal MRI employed determines visceral and subcutaneous adipose tissue areas in a single transversal section. Two previous studies have investigated the associations between urinary phthalate monoester concentrations and obesity using body mass index (BMI) and waist circumference (WC) in US citizens [9, 10]. However, this is to our knowledge the first study on phthalate concentrations and obesity using advanced technology measures, allowing analyses of fat content in different body compartments (DXA), as well as comparisons between visceral and subcutaneous fat amount (MRI). We evaluated the hypothesis that phthalates could alter the adipose tissue distribution using measurements of fat distribution at MRI as our primary measurement. We also supply data on more commonly used obesity measures and DXA derived data.
The study base for the PIVUS study (Prospective investigation of the vasculature in Uppsala seniors) were all subjects aged 70 (standard deviation for age 1 month, investigated 2001-2003) living in the community of Uppsala, Sweden. The subjects were randomly chosen from the register of community living. A total of 1,016 subjects participated, giving a participation rate of 50.1%. All women were postmenopausal. The study was approved by the Ethics Committee of Uppsala University.
Basic characteristics of subjects
Mean (SD)
Median (25th and 75th percentile)
Mean (SD)
Median (25th and 75th percentile)
BMI (kg/m2)
27.1 (4.9)
26.5 (23.7, 30.1)
27 (3.7)
26.8 (24.4, 29.1)
Waist (cm)
87.6 (11.6)
87.0 (79.0, 94.0)
94.7 (10.4)
94.0 (87.0, 101.0)
Waist/hip ratio
0.90 (0.10)
0.90 (0.80, 0.90)
0.90 (0.10)
0.9 (0.9, 1.0)
DXA total fat (kg)
27.7 (9.2)
27.1 (21.1, 33.7)
23.5 (8.2)
22.5 (17.6, 28.4)
DXA leg fat (kg)
9.7 (3.4)
9.4 (7.2, 11.8)
6.3 (2.6)
5.9 (4.7, 7.5)
DXA trunk fat (kg)
13.9 (5.0)
13.8 (10.2, 17.4)
14.1 (5.1)
13.8 (10.5, 17.5)
DXA trunk/leg ratio
1.5 (0.4)
1.4 (1.2, 1.7)
2.3 (0.6)
2.3 (1.9, 2.6)
MRI SAT (cm2)
262.1 (108.9)
257.4 (190.9, 313.9)
189.0 (80.3)
172.8 (131.3, 231.7)
MRI VAT (cm2)
94.3 (49.1)
87.5 (58.5, 119.2)
119.3 (63.0)
102.4 (79.2, 151.9)
MRI VAT/SAT ratio
0.4 (0.2)
0.3 (0.2, 0.5)
0.6 (0.3)
0.6 (0.5, 0.8)
MEHP (ng/ml)
18.9 (42.5)
4.7 (2.0, 14.5)
20.3 (45.0)
4.3 (2.1, 17.4)
MEP (ng/ml)
14.0 (10.3)
11.6 (7.2, 16.8)
18.0 (21.1)
11.6 (7.2, 18.5)
MiBP (ng(ml)
44.6 (116)
13.4 (9.5, 24.5)
53.6 (146.1)
13.5 (9.1, 33.3)
MMP (ng/ml)
3.4 (5.1)
1.5 (0.9, 3.0)
3.3 (4.5)
1.5 (0.8, 3.2)
Current smoking (%)
Serum cholesterol (mmol/l)
5.7 (1.0)
5.7 (5.0, 6.3)
5.1 (1.0)
5.1 (4.5, 5.8)
Serum triglycerides (mmol/l)
1.3 (0.6)
1.1 (0.9, 1.5)
1.3 (0.6)
1.2 (0.9, 1.5)
Phthalate analysis
Human serum (0.5 ml) was analysed for concentrations of ten phthalate metabolites by an API 4000 liquid chromatograph/tandem mass spectrometer at ALS Canada following the general procedures presented by the Centers for Disease Control and Prevention and as previously described [20]. Briefly, quality control of the analyses was maintained by analysing a method blank (calf serum) and two spiked calf serum samples (20 ng/ml, all analytes) along with every 17 samples. The detection limits (LOD), was 0.2 ng/ml. Four out of the ten phthalate metabolites, namely mono-(2-ethylhexyl) phthalate (MEHP); mono-ethyl phthalate (MEP); mono-isobutyl phthalate (MiBP); and mono-methyl phthalate (MMP), were detectable in all but 5-12 subjects (at least 96% of subjects). The fact that some subjects showed undetectable concentrations rules out a general contamination of these compounds. Only the four metabolites with detectable concentrations were used in the statistical analysis. For the rest of the metabolites, 31-100% of the observations were below the detection limit. The measured serum concentrations of MEHP, MEP, MiBP, and MMP are given in Table 1. The analysis of the phthalates took place 5-8 years following collection of the samples.
Fat mass analysis by DXA
On average two years after the investigation at age 70 when data on phthalate metabolites were collected all subjects were invited to an investigation with dual-energy X-ray absorptiometry (DXA) (DPX, Lunar Prodigy, Lunar Corp., Madison, WI, USA), with the primary outcome total body fat mass. Of the original sample, 890 subjects (88% of subjects investigated at baseline) participated in this part of the study. Since abdominal fat repeatedly has been shown to be more harmful than fat located in the periphery [21] we also explored, as a secondary outcome, whether concentrations of phthalate metabolites were more closely related to trunk fat mass, defined as fat between the groins and the shoulders, or to leg fat mass, defined as fat below the groins.
In order to evaluate the reproducibility, fifteen subjects were scanned three times. The precision error of the DXA measurements was calculated to be 1.5% for total fat mass and 1.0% for total lean mass [22]. The bias associated with DXA fat measurement is systematic, with an underestimation of fat content for leaner subjects and an overestimation of fat content among obese subjects, but these inaccuracies amount to less than 2% [23].
Abdominal MRI
Also magnetic resonance imaging (MRI) of the abdominal region was performed in 287 randomly selected subjects from the PIVUS cohort on average two years after the investigation at age 70 when data on phthalate metabolites were collected. Only a restricted sample could be offered this examination for financial reasons. Visceral and subcutaneous adipose tissue areas (cm2) (VAT and SAT, respectively) were manually segmented from a single 10 mm thick axial steady-state-free precession slice as previously described [24]. Based on repeated measurements of VAT and SAT in 22 subjects, the reproducibility/coefficients of variation (CVs) were found to be 5.9 and 3.4%, respectively.
Since the DXA and MRI scan measurements are not affected by a single over-night fast, these investigations were performed in the non-fasted state.
Statistical analysis
All variables were evaluated regarding non-normality, and variables with a skewed distribution, such as plasma triglycerides and phthalate metabolite concentrations, were ln-transformed. In separate linear regression models for each phthalate metabolite and each gender, the phthalate metabolite concentrations (as ln-transformed continuous variables) were related to indices of obesity, as well as to fat mass measurements by DXA and abdominal MRI. In each model we adjusted for serum cholesterol and triglycerides, education, exercise, and smoking. In order to use the full power of the study, all subjects who had an obesity outcome measured were included in that particular model. The phthalate metabolites were also divided into quintiles to evaluate potential non-linear relationships, using both a linear and a quadratic term. For our primary hypothesis that the 4 phthalates were related to the two MRI measurements in both men and women, we adjusted the p-value for 16 tests (Bonferroni-adjusted p-value: 0.05/16 = 0.003125).
STATA 11 (College Station, TX, USA) was used for calculations.
Basic characteristics
The basic characteristics of subjects and the serum concentrations of the four phthalate metabolites are presented in Table 1 as mean values (standard deviations), and as median concentrations (25th and 75th percentiles) in the total sample. No significant differences were seen in the subsample with DXA measurements, or in the subsample with MRI scans, when compared with the total sample.
Linear regression analysis with continuous variable
Relationships between four phthalate metabolites and markers of obesity in women
Beta (95% CI)
Beta (95% CI)
Beta (95% CI)
Beta (95% CI)
BMI (kg/m2)
0.10 (-0.20-0.41)
0.008 (-0.67-0.69)
0.39 (0.002-0.79)
0.28 (-0.095-0.66)
Waist (cm)
0.34 (-0.39-1.1)
-0.80 (-2.4-0.81)
1.3 (0.425-2.3)
0.98 (0.090-1.9)
Waist/hip ratio
0.002 (-0.002-0.006)
-0.008 (-0.016-0.001)
0.004 (0.000-0.009)
0.005 (0.000-0.009)
DXA total fat (kg)
468 (-159-1096)
-469 (-1877-938)
1079 (283-1875)
705 (-74-1484)
DXA leg fat (kg)
163 (-73-399)
-165 (-694-363)
275 (-25-576)
115 (-179-409)
DXA trunk fat (kg)
206 (-127-539)
-187 (-934-559)
699 (279-1120)
546 (135-958)
DXA trunk/leg ratio
-0.007 (-0.033-0.019)
-0.004 (-0.062-0.054)
0.039 (0.006-0.072)
0.043 (0.011-0.075)
MRI SAT (cm2)
4.8 (-10-20)
12 (-24-48)
52 (24-81)
27 (3.1-52)
MRI VAT (cm2)
4.1 (-2.2-10)
3.6 (-11-19)
14 (1.4-26)
6.9 (-3.4-17)
MRI VAT/SAT ratio
0.005 (-0.018-0.028)
-0.001 (-0.056-0.054)
-0.018 (-0.064-0.028)
-0.019 (-0.057-0.019)
Relationships between four phthalate metabolites and markers of obesity in men
Beta(95% CI)
Beta (95% CI)
Beta (95% CI)
Beta (95% CI)
BMI (kg/m2)
-0.034 (-0.26-0.19)
0.31 (-0.097-0.72)
-0.083 (-0.35-0.19)
0.33 (0.051-0.61)
Waist (cm)
-0.27 (-0.91-0.37)
0.73 (-0.45-1.9)
-0.025 (-0.80-0.75)
0.97 (0.17-1.78)
Waist/hip ratio
-0.004 (-0.008-0.0)
0.005 (-0.003-0.012)
0.001 (-0.004-0.005)
0.006 (0.001-0.011)
DXA total fat (kg)
12 (-527-552)
269 (-776-1315)
-73 (-754-608)
365 (-340-1071)
DXA leg fat (kg)
-24 (-200-152)
46 (-296-388)
-44 (-266-179)
37 (-194-268)
DXA trunk fat (kg)
0.56 (-332-333)
347 (-297-991)
-23 (-443-398)
235 (-201-670)
DXA trunk/leg ratio
-0.008 (-0.048-0.033)
0.095 (0.018-0.17)
0.007 (-0.044-0.058)
0.021 (-0.031-0.074)
MRI SAT (cm2)
0.44 (-9.6-10)
9.2 (-10-29)
-11 (-34-12)
5.4 (-7.9-19)
MRI VAT (cm2)
3.3 (-4.9-11)
16 (0.49-32)
-5.9 (-24-13)
5.2 (-5.7-16)
MRI VAT/SAT ratio
0.002 (-0.032-0.036)
0.052 (-0.013-0.12)
0.001 (-0.076-0.079)
0.003 (-0.043-0.048)
The relationship between MiBP and SAT at MRI shows a p-value below the critical p-value obtained after correction for multiple testing. MMP concentrations in women were positively related to trunk fat mass and to trunk/leg-ratio by DXA (Table 2 both p < 0.01). However, no such significant relationships were seen in women for MEHP or MEP (Table 2), and no significant relationships were found in men for either metabolite (Table 3).
According to the regression models, a doubling of the MiBP concentrations corresponded to an increase of 45 cm2 in SAT at MRI, 0.8 kg in trunk fat mass at DXA, and 1.5 cm in waist circumference in women. The corresponding effects of a doubling of MMP were 35 cm2 in SAT at MRI, 0.4 kg in trunk fat at DXA, and 0.8 cm in waist circumference in women.
Quintile analysis
The results from the quintile analysis approach are presented in Additional file 1: Tables S1-S8. Quintile analysis showed the same linear relationships for MiBP in women as described above using continuous data. In addition, positive linear relations were found between MEP and DXA trunk/leg ratio, as well as between MMP and WC and waist/hip ratio, all in men. Furthermore, the quintile analysis showed U-shaped relationships between MEP and SAT by MRI in women (p = 0.0098), as well as between MiBP and waist/hip-ratio in men (p = 0.0011).
Since there is some bias in the DXA estimations regarding fat mass (see methods section), we performed a secondary analysis in which the fat mass values for the lean subjects (BMI < 25 kg/m2) were multiplied by 1.02, and by 0.98 in the obese (BMI > 30 kg/m2). This attempt to compensate for the bias introduced by the DXA technique did however only have marginally effects on the analysis presented above.
The present study showed that serum concentrations of the phthalate metabolites MiBP and MMP were positively correlated to several obesity indices in women. In particular, a strong positive relation was found between MiBP concentrations and the amount of abdominal subcutaneous adipose tissue measured by DXA and MRI two years following the phthalate measurements were performed.
Strengths of the study
Our study employed a hitherto unique combination of dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI), while previous studies of the relationship between phthalate concentrations and obesity have been limited to the use of body mass index (BMI) and waist circumference (WC) [9, 10]. Our approach combining DXA and abdominal MRI offers a whole new level of resolution and specificity to different aspects of obesity, in particular the distinction between visceral and subcutaneous adipose tissue, both as an MRI VAT/SAT ratio and as a DXA trunk/leg fat ratio. Furthermore, if we find a relationship between a phthalate metabolite and similar obesity measurements both at DXA and MRI, that will reduce the chance of false positive findings.
Both previous studies of phthalate concentrations in relation to obesity were based on data from the US National Health and Nutrition Examination Survey (NHANES) [9, 10]. Neither study included MiBP or MMP. Stahlhut et al found positive associations between MEP concentrations and WC in men over 18 years of age [10], while Hatch et al found mixed associations between MEP/MEHP and BMI in women and men of different age groups [9]. Hatch et al also found negative relations between MEHP urine concentrations and BMI in both women and men aged 60-80 years [9], which was not observed in our subjects. The advantage with the PIVUS study compared to NHANES is that we could characterize obesity in more detail by regional distribution of fat mass by DXA and MRI.
Limitations of the study
Two limitations in the present study related to the DXA and MRI measurements are that these examinations were performed two years following the measurements of the phthalates, and the fact that not all subjects investigated at baseline were investigated with the two imaging techniques. Regarding the time lag between the phthalate measurements and the imaging, this could lead to false negative results since both changes in phthalates and obesity measures could have occurred during the two year period that might have influenced the investigated relationships. However, it is very unlikely that the reported main finding that MiBP concentrations are related to trunk fat at DXA and to SAT at MRI could be created by a time lag. The fact that MiBP concentrations also were related to waist circumference, measured at the same day as MiBP, further strengthens the case that the main findings in the present study are not erroneously created by this time lag. However, only a true longitudinal study with serial evaluations with DXA and MRI will clarify this issue.
The fact that a time lag of two years will create a selection of survivors and a drop-out of subjects not willing to be reinvestigated is undisputed. We do not think that this selection of subjects attending the imaging procedures will introduce any major bias that will influence the results since all basic characteristics were essentially the same in the total sample and the subsamples attending the DXA and MRI scans.
In the present study we used serum measurements of phthalate metabolites. It is more common to use urinary measurements. The advantage of urinary measurements is that usually higher concentrations are found compared to serum and thereby more phthalate metabolites could be quantified above the lower detection limit. Therefore we can only report associations regarding four metabolites, although in fact 10 metabolites were evaluated. Serum concentrations might also change more rapidly than urinary concentrations, and therefore repeated measurements would be desirable for a more precise measure of exposure.
The participating subjects were all elderly (aged 70) Caucasians, which obviously confers limitations as to the applicability of the results with respect to the general population. For example, Hatch et al found large differences in associations between urine concentrations of phthalate metabolites and obesity depending on age group [9], and Stahlhut et al observed differences between ethnic groups [10]. On the other hand, the relative homogeneity and large number of subjects permit the detection of more subtle effects. Moreover, the age of our subjects isolates the effects of adult exposure and precludes any effects from gestational and perinatal phthalate exposure since these chemicals were not in use when the subjects were born. Furthermore, the populations in Europe and US are steadily increasing in age and therefore it is of importance to study the effect of exposure to environmental contaminants not only in the newborn, but also in the aged population.
Gender differences and possible mechanisms
In this study, circulating concentrations of MiBP were positively related to several obesity indices in women, most notably trunk fat by DXA and SAT by MRI, while no such associations were seen in men. This gender difference is particularly interesting since no significant differences in phthalate metabolite concentrations were found between men and women in this material [25]. The differences in effects thus cannot be attributed to differences in phthalate concentrations, but may instead reflect gender-specific regulation of adipose tissue distribution. Using BMI and WC, Hatch et al found no gender differences in subjects aged 60-80 years [9], reflecting the higher precision of our DXA/MRI approach.
Several studies have described a cross-talk between estrogen or estrogen receptors and activation of PPAR receptors, the most well characterized target for the phthalates [26–28]. Ovariectomized rats treated with a PPAR alpha agonist showed a less pronounced increase in fat mass. This condition was reversed by estrogen treatment, which also reduced PPAR alpha expression [28]. Similarly, overiectomized mice treated with a PPAR gamma agonist showed a less pronounced increase in fat mass. Also this condition was reversed by estrogen treatment, which also reduced PPAR gamma expression [26]. Ovariectomy increased fat tissue in mice compared to sham-operated controls. This effect was inhibited in mice lacking the PPAR alpha gene [16]. Thus, if these experimental data suggesting a cross-talk between PPAR receptor activation and estrogen are similar in humans they may explain why activators of PPARs, such as phthalates, could have different effects in men and women.
As noted in the introduction, several phthalate monoesters have been identified as PPAR gamma agonists and capable of promoting adipocyte maturation, providing a plausible mechanistic link to phthalate effects on obesity development and adipose tissue distribution [8, 15, 16, 19]. To our knowledge, MiBP has not been tested for PPAR activation, however MMP was found not to activate either PPAR alpha or PPAR gamma [16].
Statistical considerations
Some non-linear relationships were noted in the quintile analysis, including some relationships in men. Non-monotonic relationships have been previously described for endocrine disruptors [29, 30], however in this case the non-linear relationships were seen only for certain phthalates and certain obesity phenotypes, while MiBP was related to many obesity phenotypes in women in a consistent manner. The non-linear relationships described in the present study must thus be interpreted with caution.
In the present study, several statistical tests were performed and this could lead to false positive results due to multiple testing. However, regarding our primary hypothesis that the four phthalates were related to fat distribution measures at MRI a strict Bonferroni correction was used and when applying this MiBP was found to be related to SAT in women. All other tests were performed to seek for consistency between different obesity measures and are therefore not subjected to any adjustment for multiple testing. These results must therefore be taken with caution, but as could be seen these results fits well with findings regarding the primary hypothesis.
In the study we had outcome measures with variable number of observations, only one third as many MRI scans as DXA scans. Thus, when interpreting the p-values it must be kept in mind that an association has to be considerable stronger for a phthalate metabolite vs an obesity measured at MRI than vs an obesity measure at DXA to obtain a significant p-value. It is however not reasonable to delete two thirds of the entire sample from the calculations in order to make the p-values comparable, since that approach will induce false negative findings regarding the relationships between phthalate concentrations and obesity measurements at DXA.
The present evaluation shows that especially the phthalate metabolite MiBP was related to increased fat amount in the subcutaneous abdominal region in women measured by DXA and MRI two years later.
Body mass index
Di-ethylhexyl phthalate
Dual-energy X-ray absorptiometry
Endocrine-disrupting compound
Mono-(2-ethylhexyl) phthalate
Mono-ethyl phthalate
- MiBP:
Mono-isobutyl phthalate
Mono-methyl phthalate
Magnetic resonance imaging
Prospective Investigation of the Vasculature in Uppsala seniors
Peroxisome proliferator-activated receptor
Subcutaneous adipose tissue
Visceral adipose tissue
Waist circumference.
This study was financially supported by the Swedish Research Council (VR) and the Swedish Research Council for Environment, Agricultural Sciences, and Spatial Planning (Formas).
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