text:
Energy-related emissions of ...
Indicator Specification
Energy-related emissions of particulate matter
Indicator codes: ENER 007
Published 10 Aug 2011 Last modified 04 Sep 2015
Topics: Energy Air pollution
This page was archived on 12 Nov 2013 with reason: Content not regularly updated
Combination of primary PM 10 and PM 2.5 emission data. PM 10 definition: "PM 10 " shall mean particulate matter which passes through a size-selective inlet with a 50 % efficiency cut-off at 10 μm aerodynamic diameter (Air Quality Framework Directive, first Daughter Directive, article 2 (11) - (Council Directive 1999/30/EC of 22 April 1999 relating to limit values for sulphur dioxide, nitrogen dioxide and oxides of nitrogen, particulate matter and lead in ambient air, Official Journal L 163 , 29/06/1999 P. 0041 - 0060):
Maps and graphs
Data providers and partners
European data centres
Required information is not filled in: Information about the starting date of the publishing schedule is missing.
Assessment versions
Published (reviewed and quality assured)
No published assessments
Energy-related emissions of primary PM10 (i.e. particulate matter with a diameter of 10μm or less, emitted directly into the atmosphere), and secondary PM10 precursors (the fraction of NOx, SO2, and NH3 emissions which, as a result of photo-chemical reactions in the atmosphere, transform into particulate matter with a diameter of 10 μm or less), contribute to elevated levels of fine particles in the atmosphere. The inhalation of such particles has harmful effects on human health and may increase the frequency and severity of a number of respiratory problems, which may increase the risk of premature death.
Energy-related emissions of primary PM10 and PM2.5[1], contribute to elevated levels of fine particles in the atmosphere. The inhalation of such particles has harmful effects on human health and may increase the frequency and severity of a number of respiratory problems and increase the risk of premature deaths. Reducing emissions of particulate matter will therefore result in improved human health condition. In addition, some primary particulate matter such as black carbon contribute to increased radiative forcing, therefore reducing the emission levels of these particles will also contribute to climate change mitigation.
[1] PM10 definition according to article 2 (18) (DIRECTIVE 2008/50/EC OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 21 May 2008 on ambient air quality and cleaner air for Europe, Official Journal L 152 , 11/06/2008 P. 5 ): "PM10" shall mean particulate matter which passes through a size-selective inlet as defined in the reference method for the sampling and measurement of PM10, EN 12341, with a 50 % efficiency cut-off at 10 μm aerodynamic diameter;.
Combination of primary PM10 and PM2.5 emission data.
PM10 definition: "PM10" shall mean particulate matter which passes through a size-selective inlet with a 50 % efficiency cut-off at 10 μm aerodynamic diameter (Air Quality Framework Directive, first Daughter Directive, article 2 (11) - (Council Directive 1999/30/EC of 22 April 1999 relating to limit values for sulphur dioxide, nitrogen dioxide and oxides of nitrogen, particulate matter and lead in ambient air, Official Journal L 163 , 29/06/1999 P. 0041 - 0060):
PM10 emission in kt
Levels of fine particulate matter and precursor emissions are controlled in the European Union by 3 main types of regulation:
Air quality standards.
Emission standards for specific (mobile or stationary) sources.
National emission ceilings and transboundary air pollution standards for emission precursors.
There are no direct emission limits or targets for primary PM10 within the European Union, although there are limits on emissions of the precursor pollutants NOx, SO2 and NH3. Limit values for the concentration of PM10 are set under EU Directive 99/30/EC relating to ambient air quality assessment and management (European Commission 1999).
Several EU-wide limits and targets exist for the reduction of SO2, NOx and NH3 emissions, including the National Emissions Ceiling (NEC) Directive (2001/81/EC) and the Gothenburg Protocol of the UNECE LRTAP Convention (UNECE 1999). These are discussed further in factsheet EN06. As part of the review of the NEC Directive that is currently taking place, the feasibility of introducing national emission ceiling targets for particulate matter is being investigated. A proposal for the revised directive is expected in 2013.
There are no specific EU emission targets for primary PM10. However, emissions of the precursors NOx, SOx and NH3 are covered by the NECD and the Gothenburg Protocol to the UNECE LRTAP Convention. Both instruments contain emission ceilings (limits) that countries must meet by 2010.
See also indicators CSI 003: http://www.eea.europa.eu/data-and-maps/indicators/emissions-of-primary-particles-and-5
Directive 2001/81/EC, national emission ceilings
Directive 2001/81/EC, on nation al emissions ceilings (NECD) for certain atmospheric pollutants. Emission reduction targets for the new EU10 Member States have been specified in the Treaty of Accession to the European Union 2003 [The Treaty of Accession 2003 of the Czech Republic, Estonia, Cyprus, Latvia, Lithuania, Hungary, Malta, Poland, Slovenia and Slovakia. AA2003/ACT/Annex II/en 2072] in order that they can comply with the NECD.
UNECE Convention on Long-range Transboundary Air Pollution
UNECE Convention on Long-range Transboundary Air Pollution.
Key policy question
Are energy-related emissions of particulate matter decreasing?
Specific policy question
How rapidly are energy related (except transport) emissions of fine particulate matter declining in Europe?
How rapidly are transport related emissions of fine particulate matter declining in Europe?
Indicator is based on officially reported national total and sectoral emissions to UNECE/EMEP (United Nations Economic Commission for Europe/Co-operative programme for monitoring and evaluation of the long-range transmission of air pollutants in Europe) Convention on Long-range Transboundary Air Pollution (LRTAP Convention), submission 2010. Recommended methodologies for emission inventory estimation are compiled in the EMEP/CORINAIR Atmospheric Emission Inventory guidebook, EEA Copenhagen (EEA, 2009). Base data are available from the EEA Data Service (http://dataservice.eea.europa.eu/dataservice/metadetails.asp?id=1096) and the EMEP web site (http://www.ceip.at/). Where necessary, gaps in reported data are filled by ETC/ACC using simple interpolation techniques (see below). The final gap-filled data used in this indicator is available from the EEA Data Service (http://dataservice.eea.europa.eu/dataservice/metadetails.asp?id=1058).
Base data, reported in NFR are aggregated into the following EEA sector codes to obtain a common reporting format across all countries and pollutants:
Energy Industries: emissions from public heat and electricity generation, oil refining, production of solid fuels, extraction and distribution of solid fossil fuels and geothermal energy;
Industrial processes: emissions derived from non-combustion related processes such as the production of minerals, chemicals and metal production;
Road transport: light and heavy duty vehicles, passenger cars and motorcycles;
Non-road (other) transport: railways, domestic shipping, certain aircraft movements, and non-road mobile machinery used in agriculture & forestry;
Household and services: emissions principally occurring from fuel combustion in the services and household sectors;
Manufacturing and Constructions: emissions from combustion processes used in the manufacturing industry including boilers, gas turbines and stationary engines;
Other non-energy (Solvent and product use): non-combustion related emissions mainly in the services and households sectors including activities such as paint application, dry-cleaning and other use of solvents;
Agriculture: manure management, fertiliser application, field-burning of agricultural wastes
Waste: incineration, waste-water management;
The following table shows the conversion of Nomenclature for Reporting (NFR) sector codes used for reporting by countries into EEA sector codes:
EEA classification
Non-GHGs (NFR)
GHG (CRF)
National totals
National total
National totals without LUCF
Energy Industries
Fugitive emissions
1B1, 1B2
1A3b
Non-road transport (non-road mobile machinery)
1A3 (exl 1A3b)
1A3a, 1A3c, 1A3d, 1A3e
Other non-energy (Solvent and product use)
Household and services
1A4ai, 1A4aii, 1A4bi, 1A5a
1A4A, 1A4B
Manufacturing / Construction
No methodology for gap filling has been specified. Probably this info has been added together with indicator calculation.
Methodology Reference EMEP/CORINAIR Emission Inventory Guidebook - 2009 This 2009 update of the emission inventory guidebook prepared by the UNECE/EMEP Task Force on Emissions Inventories and Projections provides a comprehensive guide to state-of-the-art atmospheric emissions inventory methodology. Its intention is to support reporting under the UNECE Convention on Long-range Transboundary Air Pollution and the EU National Emission Ceilings Directive. EMEP (2010). Transboundary, acidification, eutrophication and ground level ozone in Europe in 2008
Data specifications
EEA data references
EEA aggregated and gap filled air pollutant data (discontinued) provided by European Environment Agency (EEA)
Data sources in latest figures
Officially reported data following agreed procedures and Emission Inventory Guidebook (EEA 2009) Primary PM10 data reported by countries remains uncertain in terms of quality for many countries. In many cases the available reported data does not include all years.
The reported primary PM10 data is likely to be very uncertain. Much of the uncertainty in the overall reported PM10 emissions comes from uncertainties associated with emission factors. For many countries there is little country-specific data available from which PM10 emission factors can be determined. Emission factors in the literature can be very variable due to the differences that occur between sector processes both within and between different countries. For many countries a complete time series of PM10 data is not available from 1990, and so significant interpolation and extrapolation has had to be performed to obtain a complete time series of data. Similarly not all countries report emissions from every sector. In contrast, the uncertainties of sulphur dioxide emission estimates in Europe are relatively low, as the sulphur emitted comes from the fuel burnt and therefore can be accurately estimated. However, because of the need for interpolation to account for missing data the complete dataset used here will have higher uncertainty. EMEP has compared modelled (which include emission data as one of the model parameters) and measured concentrations throughout Europe (EMEP 2005). From these studies the uncertainties associated with the modelled annual averages for a specific point in time have been estimated in the order of ±30 %. This is consistent with an inventory uncertainty of ±10 % (with additional uncertainties arising from the other model parameters, modelling methodologies, and the air quality measurement data etc). NOx emission estimates in Europe are thought to have higher uncertainty than pollutants such as SO2, as the NOx emitted comes both from the fuel burnt and the combustion air and so cannot be estimated accurately from fuel nitrogen alone. EMEP has compared modelled and measured concentrations throughout Europe (EMEP 2005). From these studies differences for individual monitoring stations of more than a factor of two have been found. This is consistent with an inventory of national annual emissions having an uncertainty of ±30% or greater (there are also uncertainties in the air quality measurements and especially the modelling). The trend is likely to be much more accurate than for individual absolute annual values; the annual values are not independent of each other. However it is not clear that all countries backdate changes to methodologies so early years may have been estimated on a different basis to later years.
Further work
Short term work
Work specified here requires to be completed within 1 year from now.
Long term work
Work specified here will require more than 1 year (from now) to be completed.
General metadata
Responsibility and ownership
EEA Contact Info
Anca-Diana Barbu
Indicator code
ENER 007
Link: energy-related-emissions-of-particulate-matter-2
Version id: 3
Primary theme: Energy
DPSIR: Pressure
Relevant policy documents
Policy Document Directive 2001/81/EC, national emission ceilings Directive 2001/81/EC, on nation al emissions ceilings (NECD) for certain atmospheric pollutants. Emission reduction targets for the new EU10 Member States have been specified in the Treaty of Accession to the European Union 2003 [The Treaty of Accession 2003 of the Czech Republic, Estonia, Cyprus, Latvia, Lithuania, Hungary, Malta, Poland, Slovenia and Slovakia. AA2003/ACT/Annex II/en 2072] in order that they can comply with the NECD.
Policy Document UNECE Convention on Long-range Transboundary Air Pollution UNECE Convention on Long-range Transboundary Air Pollution.
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12 Jan 2011 - Energy-related emissions of particulate matter
05 Jul 2010 - Energy-related emissions of particulate matter
For references, please go to https://www.eea.europa.eu/data-and-maps/indicators/energy-related-emissions-of-particulate-matter-2 or scan the QR code.


Premium Shop: Can't Stand The Heat?
The following offer will be available in the Premium Shop from 18 September at 07:10 until 25 September at 07:00 CEST (UTC+2).
This offer will definitely interest anyone in need of refilling their treasury for the battles to come.
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Welcome new and returning members to Fresno County Women Lawyers. We look forward to a year full of meaningful and fun events that will foster comradery and support in our legal community as well as give back to our local community. Fill out the FCWL Membership Application and pay your respective dues below. Please follow the steps below to ensure we receive your membership application and dues properly.
STEP 1: Fill out the membership application by clicking the link below. You can fill this application out electronically and submit it to fcwl.secretary@gmail.com or print it out and mail it to our address.
STEP 2: After submitting your application, submit your payment by selecting your membership level below.
California attorneys admitted to practice for more than three years.
California attorneys admitted to practice more than one year but less than three years.
Non-attorney professional who serve the legal profession.
California attorneys employed by a GOVERNMENT ENTITY or a non-profit organization, and JUDGES.
We want our members to enjoy the benefits of membership and are continually expanding our benefit offerings.
Members enjoy a $5 discount on monthly luncheons, most of which qualify for MCLE credits.
FCWL membership is free of charge for law students. Paying members can receive a $5 discount on membership fees if you are a member of the California Women Lawyers organization.
Members enjoy a 20% discount on a head shot package with Rees Photography.
Listing on our Public Members Page.
Referrals come from many sources, and our member page can be one of them. We will list your name, area of practice and contact information.
Members are encouraged to build their leadership skills by becoming a Board member. Board positions become available at the end of each year. You could be our next President!
We are a very supportive group of women and enjoy spending time with law students and judicial officers at our various events.


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Special One, Bring Spurs to the top of the Premier League standings.
pranandaputra in Sports Talk Social • 2 months ago
The controversial Tottenham Hotspurs coach, Jose Mourinho, managed to bring Spurs to the top of the English league standings for a while, Spurs managed to beat Manchester City 2-0 and were entitled to the ranking.
Improving the appearance of Harry Kane cs could not be separated from the cold-handed tactics of the Portuguese coach, he managed to form a team by relying on a fast game scheme. The Spurs players know very well what The Special One wants in every match, the players always appear compact and good during the match.
Jose Mourinho relies on some of his best players at Tottenham Hotspurs, Harry Kane, H. Son and Lucas Maura have always been a mainstay of the former Inter Milan coach on the front lines. While Moussa Sissoko and Pierre-Emile Hoejbjerg became the mainstay of managing the game in midfield, Mourinho's defensive position still entrusted the duo of Eric Deir and Toby Alderweirld while the goalkeeping position was still entrusted to Hugo Lloris.
Apart from the names of the players above, Jose Mourinho still has some ammunition ready to appear as a substitute, Gareth Bale, Giovani Lo Celso, Joe Rodon, Lamela, Vinicius and Joe Hart are names who have great instincts in playing.
Jose Mourinho's strategy was able to be carried out by the players, Mourinho played an important role in his team's current performance. Until the ninth week of the Premier League this season, Tottenham have collected 20 points on par with Liverpool. The two teams also compete closely at the top of the standings. The good results that have been achieved by Tottenham Hotspurs have made Spurs fans immediately dream of hoping that Tottenham will win the Premier League. The desire is very big, considering that it has been a long time since Tottenham have won the Premier League.
Tottenham Hotspurs is now one of the strong candidates to win the English Premier League this season, his experience is really needed by the team. Mourinho has tasted the English Premier League title with Chelsea three times. This was achieved by Mourinho with Chelsea in 2004-2005, 2005-2006 and 2013-2014. Jose Mourinho's presence at Spurs also made H. Son, Harry Kane, Eric Dier and Moussa Sissoko increasingly play, H. Son and Harry Kane scored goals for Spurs, meanwhile Moussa Sissoko and Eric Dier were getting better in their respective positions. .
Last week the Spurs managed to beat Manchester City by two goals, Jose Mourinho appreciated his players. They are considered to have executed the strategy nicely. Jose Mourinho's strategy in the match made coach Pep Guardiola unable to do anything about it.
#sports #football #premierleague #tottenham #marlians #dblog #sportstalk
2 months ago in Sports Talk Social by pranandaputra
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redpajama_set_name: RedPajamaCommonCrawl


We are excited to launch our new uniform guidelines with our new school and parish logo for the 2017-2018 school year! Students may wear the current uniform for one school year as we transition into these new guidelines. Shaheen's Department Store provides our school uniforms and has many items in stock. If items are not available, orders can be placed at any time.
Shorts may be worn under jumper/skirts but must not be visible.
Hemlines must fall between the student's fingertips and the knees.
Navy, white, or black socks are to be worn. Socks must cover the ankle and be solid in color.
Girls may wear solid colored navy or black ankle length leggings. Socks must be worn with leggings.
Girls may wear solid colored navy or black opaque tights (not translucent or sheer). Socks are optional with tights.
Navy Shorts may be purchased where ever uniforms are sold, but must have belt loops, pleat or flat front, hemline closely approaching the knee, and no cuffs. Hemlines must fall between the student's fingertips and the knees. Shorts are only allowed April 1st – October 31st.
Navy Pants may be purchased where ever uniforms are sold, but must have belt loops, pleated or flat front, no cuffs, length should break at the shoe top, and pants should fit at the waist. Pants are required to be worn November 1st – March 31st.
Solid navy, brown or black belts must be worn. Boy scouts may wear their boy scout belt.
8th grade only: plain white button down with tie and khaki uniform pants (only November 1st – March 31st). Khaki pants may only be worn with button down shirt and tie.
For additional information on specific guidelines pertaining to general appearance, including shoes, hair, cosmetics, jewelry, and accessories, please see the student handbook here.
Students may wear a St. Raphael spirit wear top with any bottoms. Bottoms must free from hole, rips, tears, etc.
Leggings may be worn, but tops must be long enough to cover the student's bottom.
Hats are not permitted for in-school uniform breaks unless a special announcement is made.
Drug, violence, gang related, or obscene logos are not permitted.
In summer, sleeveless blouses are acceptable, but thin-strapped tops, form fitting tops or tops which display the student's midriff are not appropriate.


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Q: Do I need dnsmasq? When I nmap localhost get this:
53/tcp open domain dnsmasq 2.59

What is it and do I really need it?
I tried to remove it with
sudo apt-get remove dnsmasq-base

but it said if I would continue it will remove network-manager and network-manager-gnome too.
So do I need it for network-manager and network-manager-gnome or if I don't can I just remove it because I don't want to have it listen on port 53.

A: As I understand , dnsmasq is some configurable DHCP server .
From Ubuntu
DNSmasq provides two services, either of which can be used independently.

*

*DNS service

*DHCP service (including features relating to network boot)

A local DNS cache can speed up internet browsing because the user's browser will not need to access a domain name server when it looks up a domain name the computer has visited before.
From Ubuntu The main point :Note that the package "dnsmasq" interferes with Network Manager which can use "dnsmasq-base" to provide DHCP services when sharing an internet connection.
Other Sources:
Dnsmasq is a lightweight, easy to configure DNS forwarder and DHCP server. It is designed to provide DNS and, optionally, DHCP, to a small network. It can serve the names of local machines which are not in the global DNS. The DHCP server integrates with the DNS server and allows machines with DHCP-allocated addresses to appear in the DNS with names configured either in each host or in a central configuration file. Dnsmasq supports static and dynamic DHCP leases and BOOTP/TFTP/PXE for network booting of diskless machines.
Source:www.thekelleys.org.uk

redpajama_set_name: RedPajamaStackExchange


You won't be able to interact with anyone if you never see or talk to anyone. Deciding how to start a dialogue is a lot simpler when you have a prearranged topic of conversation such as an activity, common interest, or even a support group. Learn about what your sober living community has to offer so you can get involved by finding new friends.
Choose something that makes you feel at ease. You'll be able to start conversations while you're in your comfort zone instead of dealing with a new situation on top of finding new friends.
Look for outdoor activities as well as things to do inside. You may find that moving around out in nature and getting some exercise releases endorphins that make you feel good about approaching new people.
Don't be afraid to try something new once you get settled. You may find that in finding new friends, you also find a new passion that you never imagined could be something you'd love.
No matter how many activities you try and how much you get involved, you won't be able to make any lasting connections unless you share with others. The best way to get involved is to talk about your experiences and open up in order to relate to the people around you. In the safe environment of your sober living community, you can share with people in a judgment-free zone and finding new friends you can relate to every day.


  Thus those animals who are the more deprived of intelligence, are clothed with hair all over their bodies, whereas man, inasmuch as his lot in life is more brilliant, is the most bare of this natural burden. But that he may not boast of having no taint of fellowship with what is mortal, he is covered with hair in a few places. He, therefore, who has no hair anywhere is to the normal man what man is to the brute.
 And just as man is the most intelligent, and at the same time the least hairy of earthly creatures, conversely it is admitted that of all domestic animals the sheep is the stupidest, and that this is why he puts forth his hair with no discrimination, but thickly bundled together. It would seem that there is a strife going on between hair and brains, for in no one body do they exist at the same time.
 And huntsmen also must needs contribute something to the argument, for these men are dear to me as also the art they pursue. The cleverest hounds are those whose ears and bellies are bare; the hairy ones are stupid and rash and are better kept away from the chase; and if Plato, the sage, speaks of the unjust soul, attached to the chariot driven by the soul, as being deaf and with ears covered with hair, how can he think any good of hair?note[Plato, Phaedrus 253E.] Of course, even if Plato did not tell us so, it would of necessity follow that he would be deaf who had hair in that organ by which we hear, as one would also be blind who had hair in the organ by which we see.
 That would be a monstrosity, if it ever came to pass. Already cases have occurred of the growth of a double row of eyelashes, and it seems the last of calamities that hair has made its home close to the eye, and against such hairs every violent means is set in motion lest they should precipitate the undermining of the eye. Nature does not permit the baser elements to grow with the nobler, and the noblest parts of the animal are his perceptive faculties, for in these parts of the body most of all resided the principle of life, and to these first the soul has distributed its own powers. Now sight is the most divine of all faculties,note[Plato, Phaedrus 250D] but at the same time the least hairy.
 Again, as in an individual the nobles parts are the baldest, so must the best elements of the race itself be related to the race itself. This was shown a little while ago to be the case throughout the human race, which is as far removed from the brutes as it is from hairs. Now if man is really the most sacred of all animals,note[Plato, Laws 766A.] of men who have had the good fortune to lose their hair, the bald man would be the most divine thing upon earth.


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Occupation in the Channel Islands - Hitler's 'impregnable fortress'
In-depth look at a fascinating and relatively unknown portion of WWII history.
Visits Jersey's and Guernsey's primary military sites including special appointments and talks by local experts.
Features walks along striking coastlines.
Excellent hotels on both islands.
Led by historian Dr Paul Sanders.
Please call us for availability Please call us for availability
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German military band marching past Lloyds Bank on The Pollet, St Peter Port ©IWM.
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The Channel Islands, the oldest possession of the British Crown, were the only part of the British Isles to be occupied by German forces during the Second World War. Following the fall of France in June 1940 the British government withdrew from the islands, their exposed position in the bay of Saint-Malo having rendered them strategically untenable. On 19 June 1940, the islands were demilitarised, and it was announced that those who wanted to be evacuated should register forthwith.
German forces landed in Guernsey on 30 June 1940 and in Jersey the next day. There was no organised resistance movement against German forces – only acts by individuals or small groups. The occupying forces enforced a number of restrictions such as a nightly curfew and censorship of the press. In 1942 the deportation began of about 2,000 British-born Channel Islanders to internment camps in Germany. Other residents were deported to concentration camps.
During the occupation the islands were heavily fortified as part of Hitler's 'Atlantic Wall'. Construction was overseen by the German Forces and the Organisation Todt – a paramilitary engineering outfit. Forced labourers were imported to build the fortifications. This included Spanish Republican refugees from France who had been surrendered by the Vichy government, and people rounded up in Eastern Europe who were treated as work-slaves. Visitors to the islands are often struck by the scale of construction; a staggering 10% of German resources spent on the Atlantic Wall were used to fortify the Channel Islands, much of which remains visible today. This has been deliberately preserved by local volunteers, as a reminder of this chapter in Channel Islands history.
The D-Day landings in June 1944 came as both a blessing and a curse. Whilst they marked the beginning of the end for the German occupiers who relied on supply lines from the continent, they also meant that food imports were cut. As supplies dwindled, islanders faced starvation. However, following trilateral negotiations involving the Foreign Office, the Germans and the Red Cross, the SS Vega was authorized to deliver food, saving the lives of many islanders.
The islands were finally liberated on 9 May 1945, the day after VE Day. HMS Beagle and HMS Bulldog arrived in Jersey and Guernsey respectively, with on board British officers who finalised the unconditional surrender of German forces in the islands.
This tour visits the two largest islands exploring a fascinating and little understood episode of Britain's WWII history.
London to Jersey. Fly at c. 11.05am (British Airways) from London Gatwick to Jersey. The vast complex of the Jersey War Tunnels provide an excellent introduction to the background of the Occupation of Jersey including individual wartime stories and award winning galleries. It also provides an idea of the scale and intent of the occupying forces in defending the Islands. First of two nights in Jersey.
Noirmont Point, St Ouen, St Brelades. The dramatic coastline on Jersey's western and northern fronts were some of the most heavily defended parts of the island. The coastal artillery batteries protected German shipping between Cherbourg and Brest as well as providing all-round defence from the air and sea. The location of these batteries provide the opportunity to look inside these impressive outposts while enjoying some of Britain's finest coastal scenery. St Ouen's Bay, one of the island's most picturesque bays, was one of the most vulnerable and is now the location of the privately owned Channel Islands Military Museum.
St Martin, St Helier, St Peter Port. In 2011 the Jersey Occupation Collections held at Jersey Archive were inscribed on the unesco UK Memory of the World Register. After a guided tour and lecture enjoy some free time in St Helier before a short flight to Guernsey for the first of two nights.
Fort Hommet, Pleinmont, St Peter Port. Guernsey, the first Channel Island to be occupied, has much in common with its sister Island but is distinctly different. The excellent German Occupation Museum displays an impressive collection of occupation memorabilia while Fort Hommet and Pleinmont Tower on the island's western coast reveal the scale of German defences that contributed to Hitler's Atlantic Wall. The afternoon is free to wander the charming streets of St Peter Port, considered one of the prettiest of Channel Island towns.
St Peter Port. The headquarters of the German Naval Commander Channel Islands handled all the important radio signals traffic for the German forces in the Channel with messages being transmitted and received by naval codes using the Enigma enciphering machines. Housed in the original bunker, the headquarters have been accurately restored providing a rare opportunity to see inside a German military operations centre. Fly c. 4.30pm (Aurigny) arriving Gatwick at approximately 5.30pm.
Price, per person
Two sharing: £2,130 or £1,890 without flights. Single occupancy: £2,430 or £2,190 without flights.
Flights (world traveller) with British Airways (Airbus A319) and Aurigny (Embraer 195), hotel accommodation; travel by private coach; breakfasts, 2 lunches, 4 dinners with wine, water and coffee; all admissions; all tips; the services of the lecturer and tour manager.
The Somerville Hotel, Jersey: located above the picturesque St Aubin's Bay, the hotel enjoys wonderful sea views and excellent facilities (4-stars). Old Government House, Guernsey: former Governor's residence, this historic hotel is considered the best on the island and is located in the heart of St Peter Port (5-stars). Single rooms are doubles for sole use.
How strenuous?
This tour would not be suitable for anyone who has difficulty with everyday walking. The location of some of the visited sites are on exposed cliff paths so a good level of fitness and surefootedness is essential. Our hotel in Jersey is located part way up a steep hill and is not accessible by coach. Military bunkers often have numerous steps and low ceilings; sufferers of claustrophobia might struggle in some of the inner chambers.
Are you fit enough to join the tour?
Between 10 and 22 participants.
Berry & Touraine Central France, Romanesque to Renaissance
'A terrible beauty' Ireland and the Troubles 1916–1998
09 - 14 Jul 2020 £1,860
Medieval Alsace Both sides of the Rhine in France & Germany
06 - 13 Oct 2020 £3,230
Patagonia: 'Uttermost Part of the Earth' History, legends, landscapes and wildlife in southern Argentina & Chile
26 Nov - 11 Dec 2020 £8,170
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03 - 08 Aug 2020 £1,680


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RAPIDLY DISINTEGRATING LYOPHILIZED ORAL FORMULATIONS OF A THROMBIN RECEPTOR ANTAGONIST
Disclosed is a lyophilized rapidly disintegrating solid dosage form, one embodiment of which comprises a thrombin receptor antagonist such as,
or a pharmaceutically acceptable salt or hydrate thereof, a polymer such as gelatin, and a matrix forming agent such as mannitol. Systems for effectively buffering the pre-lyophilized suspension are taught, along with methods of treating patients at risk for acute coronary syndrome by administering such a rapidly disintegrating solid dosage form.
Monteith, David (Pittstown, NJ, US)
Veltri, Enrico P. (Princeton, NJ, US)
Duggirala, Srinivas (Raritan, NJ, US)
Falvo, Michael Angelo (Chester, NJ, US)
Erbey, John R. (Flemington, NJ, US)
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PALENIK, JEFFREY T
MERCK (P O BOX 2000, RAHWAY, NJ, 07065-0907, US)
1. A lyophilized rapidly disintegrating solid dosage form comprising an effective amount of a thrombin receptor antagonist.
2. The rapidly disintegrating solid form according to claim 1 wherein the thrombin receptor antagonist is selected from the group consisting of: or a pharmaceutically acceptable salt or hydrate thereof.
3. The rapidly disintegrating solid dosage form according to claim 2, further comprising at least one polymer and at least one matrix forming agent.
4. The rapidly disintegrating solid dosage form according to claim 3, wherein the polymer is selected from the group consisting of gelatin, alginates, and modified starches.
5. The rapidly disintegrating dosage form according to claim 3, wherein the matrix forming agent is selected from the group consisting of mannitol, sorbitol, and dextrins.
6. The rapidly disintegrating dosage form according to claim 1, further comprising a buffering system.
7. The rapidly disintegrating dosage form according to claim 6 wherein said buffering system is selected from the group consisting of acetate, phosphate, and citrate buffer systems.
8. The rapidly disintegrating solid dosage form according to claim 1 wherein an average platelet inhibition of at least about 80% is achieved within 30 minutes of administration.
9. A lyophilized rapidly disintegrating solid dosage form comprising about 20 to about 120 mg of Compound A or a pharmaceutically acceptable salt or hydrate thereof.
10. The rapidly disintegrating solid dosage form according to claim 9 comprising about 40 mg of Compound A or a pharmaceutically acceptable salt or hydrate thereof.
11. The rapidly disintegrating solid dosage form according to claim 9, wherein Compound A is in the form of a bisulfate salt.
12. A lyophilized rapidly disintegrating solid dosage form comprising about 40 mg of Compound A or a pharmaceutically acceptable salt or hydrate thereof, a polymer, and a matrix forming agent.
13. The rapidly disintegrating solid dosage form according to claim 12, further comprising a buffer system.
14. A method of treating a patient at risk of acute coronary syndrome comprising administering to said patient a single lyophilized loading dose comprising an effective amount of a thrombin receptor antagonist and then a series of maintenance doses comprising said thrombin receptor antagonist.
15. The method according to claim 14 wherein said thrombin receptor antagonist is selected from the group consisting of: or a pharmaceutically acceptable salt or hydrate thereof.
16. The method according to claim 14 wherein said thrombin receptor antagonist is or a pharmaceutically acceptable salt or hydrate thereof.
17. The method according to claim 16 wherein said lyophilized loading dose comprises between about 20 and about 120 mg of said thrombin receptor antagonist.
18. The method according to claim 16 wherein said lyophilized loading dose comprises about 40 mg of said thrombin receptor antagonist.
19. The method according to claim 16, wherein said thrombin receptor antagonist is in the form of a bisulfate salt.
This application claims the benefit of U.S. provisional application No. 60/847,306, filed Sep. 26, 2006.
The present invention relates to rapidly disintegrating orally administered pharmaceutical compositions containing a thrombin receptor antagonist and their uses in the treatment of patients at risk of acute coronary syndrome.
Thrombin is known to have a variety of activities in different cell types and thrombin receptors are known to be present in such cell types as human platelets, vascular smooth muscle cells, endothelial cells and fibroblasts. It is believed that thrombin receptor antagonists ("TRAs"), also known as protease activated receptor (PAR) antagonists, are useful in the treatment of thrombotic, inflammatory, atherosclerotic and fibroproliferative disorders, as well as other disorders in which thrombin and its receptor play a pathological role. Acute coronary syndrome is one such disorder.
Acute coronary syndrome ("ACS") is an umbrella term used to cover any of a group of clinical symptoms compatible with acute myocardial ischemia, including unstable angina, and non-ST segment elevation myocardial infarction ("MI") and ST segment elevation MI. Acute myocardial ischemia is associated with chest pain due to insufficient blood supply to the heart muscle that results from coronary artery disease (also called coronary heart disease). These life-threatening disorders are a major cause of emergency medical care and hospitalization in the United States. Coronary heart disease is the leading cause of death in the United States. Unstable angina and non-ST-segment elevation myocardial infarction are very common manifestations of this disease.
It is not atypical for an ACS patient to arrive at a hospital emergency room unconscious or otherwise unresponsive or incapable of taking direction immediately following an acute cardiac episode. When it is determined that such a patient could benefit from administration of a thrombin receptor antagonist, it can be important to administer a loading dose sufficient to immediately raise the level of the medication in a patient's cardiovascular system to prevent further damage. However, an unresponsive patient may be incapable of swallowing a conventional orally administered, solid dosage form, such as a tablet or capsule. Thus, there exists the need for pharmaceutically acceptable formulations containing a thrombin receptor antagonist, to provide a loading dose of the thrombin receptor antagonist in such a dosage form that it can be quickly and conveniently administered to a patient who may be unresponsive. Such a dosage form could be administered without creating the need to swallow an essentially intact solid tablet, and without the need to administer concomitantly with water to assist in such swallowing of the intact dosage form. Such formulations may be useful in treating the immediate risks associated with ACS.
Rapidly disintegrating dosage forms which are designed to release the active ingredient in the oral cavity are well known and can be used to deliver a wide range of drugs.
Thrombin receptor antagonists have been suggested in the literature as being potentially useful in treating a variety of cardiovascular diseases or conditions including, for example, thrombosis, vascular restenosis, deep venous thrombosis, lung embolism, cerebral infarction, heart disease, disseminated intravascular coagulation syndrome, hypertension (Suzuki, Shuichi, PCT Int. Appls. WO 0288092, WO 0285850 and WO 0285855), arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions (Zhang, Han-cheng, PCT Int. Appl. WO 0100659, WO 0100657 and WO 0100656).
Thrombin receptor antagonists are disclosed in U.S. Pat. Nos. 6,063,847; 6,326,380; and 6,645,987 and U.S. publication nos. 03/0203927; 04/0216437A1; 04/0152736; and 03/0216437. The use of a small subset of thrombin receptor antagonists to treat a variety of conditions and diseases is disclosed in U.S. publication no. 04/0192753. A crystalline form of the bisulfate salt of a particular thrombin receptor antagonist is disclosed in U.S. Pat. No. 7,235,561. All of these patents and patent publications mentioned herein are incorporated by reference in their entirety.
In one embodiment, the invention is directed to a lyophilized rapidly disintegrating solid dosage form comprising an effective amount of a thrombin receptor antagonist. In some embodiments, the thrombin receptor antagonist is selected from the group consisting of:
or a pharmaceutically acceptable salt or hydrate thereof.
In some embodiments, the solid dosage form further comprises at least one polymer and at least one matrix forming agent. In some embodiments, the polymer is selected from the group consisting of gelatin, alginates, and modified starches. In some embodiments, the matrix forming agent is selected from the group consisting of mannitol, sorbitol, and dextrins. In some embodiments, the polymer is gelatin and the matrix forming agent is mannitol. In some embodiments, the weight ratio of thrombin receptor antagonist to gelatin is about 2.2 to about 2.3 and the weight ratio of gelatin to mannitol is about 1.0 to about 1.2. In some embodiments, the weight percent of gelatin is about 3.5 on a wet-weight basis. In some embodiments, the weight percent of mannitol is about 3 on a wet-weight basis.
In some embodiments, the rapidly disintegrating dosage form further comprises a buffering system. In some embodiments, the buffering system is selected from the group consisting of acetate, phosphate, and citrate systems.
In some embodiments, an average platelet inhibition of at least about 80% is achieved within 30 minutes of administration.
In some embodiments, the solid dosage form comprises about 20 to about 120 mg of Compound A
In some embodiments, the rapidly solid dosage form comprises about 40 mg of Compound A or a pharmaceutically acceptable salt or hydrate thereof. In some embodiments, Compound A is in the form of a bisulfate salt. In some embodiments, the solid dosage form further comprises a polymer, and a matrix forming agent. In some embodiments, the solid dosage form further comprises a buffer system.
In some embodiments, the solid dosage form further comprises gelatin and mannitol. In some embodiments, the solid dosage form comprises about 17.5 mg of gelatin and about 15 mg of mannitol, and a buffer system capable of achieving a pH of between about 3.5 and about 5.5 in the pre-lyophilized suspension as measured directly after addition of said Compound A bisulfate.
In some embodiments, the invention is directed to a lyophilized rapidly disintegrating solid dosage form comprising about 40 mg of Compound A or a pharmaceutically acceptable salt or hydrate thereof, about 18 mg of gelatin, about 15 mg of mannitol, about 19 mg of sodium citrate, and about 8 mg of citric acid.
In some embodiments, the invention is directed to a method of treating a patient at risk of acute coronary syndrome comprising administering any of the rapidly disintegrating solid dosage forms described above.
In some embodiments, the invention is directed to a method of treating a patient at risk of acute coronary syndrome comprising administering to said patient a single lyophilized loading dose comprising an effective amount of a thrombin receptor antagonist and then a series of maintenance doses comprising said thrombin receptor antagonist. In some embodiments, the thrombin receptor antagonist is selected from the group consisting of:
or a pharmaceutically acceptable salt or hydrate thereof. In some embodiments, the thrombin receptor antagonist is
or a pharmaceutically acceptable salt or hydrate thereof. In some embodiments, the thrombin receptor antagonist is in the form of a bisulfate salt. In some embodiments, the loading dose comprises between about 20 and about 120 mg of said thrombin receptor antagonist. In some embodiments, the loading dose comprises about 40 mg of said thrombin receptor antagonist.
A variety of compounds have been demonstrated as displaying activity as thrombin receptor antagonists, many being himbacine analogs. As disclosed in U.S. publication no. 04/0152736, a subset of particularly preferred compounds of Formula I is as follows:
and pharmaceutically acceptable salts thereof.
U.S. publication no. 03/0216437 discloses a subset of thrombin receptor antagonists of Formula II which are both particularly active and selective. These compounds are as follows:
and the pharmaceutically acceptable isomers, salts, solvates and polymorphs thereof.
The following compounds are particularly favored based on their pharmacokinetics and pharmacodynamic characteristics:
or a pharmaceutically acceptable isomer, salt, hydrate, solvate, polymorphs or co-crystal form thereof. The bisulfate salt of Compound A is currently in development as a thrombin receptor antagonist by Schering-Plough Corp. Its synthesis is disclosed in U.S. publication no. 03/0216437, which publication also discloses Compound C. Compound B is disclosed in U.S. Pat. No. 6,645,987.
Other compounds for use in the formulations of the present invention are disclosed in any of U.S. Pat. Nos. 6,063,847, 6,326,380, U.S. Patent Publications U.S. 03/0203927, U.S. 03/0216437, US 04/0192753, and U.S. 04/0176418, the compound-related disclosures of which are all incorporated by reference in their entirety. Combinations that include other agents that display activity as thrombin receptor antagonists are also within the scope of the present invention, including E5555 currently in development by Eisai, the structure of which is as follows:
In one embodiment of the present invention, the formulation is an oral solid dosage form that can be swallowed without water, because it disintegrates rapidly on the tongue, in some embodiments, in less than about 60 seconds, preferably, in less than about 30 seconds, more preferably, in less than about 10 seconds, and most preferably, in less than about 3 seconds. Such a rapid disintegration phenomenon may provide for enhanced dissolution of the active ingredient, and subsequent realization of an optimal, i.e., rapid, pharmacokinetic profile of such an ingredient. Preferably, essentially all of the thrombin receptor antagonist dissolves within about 15 minutes.
Dissolution rates of the active ingredients are typically measured in an in vitro setting using pharmaceutical compendial apparatus such as the USP Dissolution Apparatus 1 (basket) or Apparatus 2 (paddle). Alternate dissolution test methodologies may also be employed, e.g., flow-through dissolution cells, based upon the physical nature of the embodiment.
One of the ultimate purposes in providing a rapidly disintegrating solid dosage form is to provide a blood concentration profile of the thrombin receptor antagonist is sufficient to result in a rapid onset of blood platelet inhibition in the patient at risk for ACS. The formulations of the present invention are believed to result in an average platelet inhibition of at least about 80% within 30 minutes of administration. Platelet inhibition is discussed in U.S. Publication no. 03/0216437, which discussion is incorporated herein.
The solid dosage forms of the present invention are in the form of a lyophilized (or freeze-dried) matrix in the shape of a wafer suitable for placement on the tongue. The matrix confers sufficient strength to the dosage form to allow for routine handling during product packaging, storage, and shipment, and to prevent breakage during removal from the package. Once placed within the oral cavity, however, the matrix disintegrates rapidly and may provide for rapid dissolution of the active pharmaceutical agent. Various aspects of lyophilized formulations are disclosed in WO 00/44351.
The matrix is composed of any of one or more of a variety of materials designed to achieve a number of objectives. A polymer can be used to form a glassy amorphous structure which imparts strength and resilience during handling. A matrix forming agent can be used to impart crystallinity and hardness. Water can be used in the manufacturing process to ensure the production of porous units which disintegrate rapidly on the tongue. A preservative, such as a para-benzoic acid, at bacteriostatic concentration, can be used to prevent microbiological growth of the aqueous solution during the manufacturing process.
As used herein, the term "polymer" shall be understood to include the following: gelatins; modified starches; materials derived from animal or vegetable proteins; dextrins and soy; wheat and psyllium seed proteins; gums such as acacia, guar, agar, and xanthan; polysaccharides; alginates; carboxymethylcelluloses; carrageenans; dextrans; pectins; synthetic polymers such as polyvinylpyrrolidone; and polypeptide/protein or polysaccharide complexes such as gelatin-acacia complexes.
A range of modified starches are commercially available and useful in the present invention and include:
Pregelatinized starches, produced by drum drying or extrusion;
Low-viscosity starches, produced by controlled hydrolysis of glycosidic bonds;
Dextrins, produced by roasting dry starch in the presence of a small amount of acid;
Acid modified starches, produced by suspension in dilute acid until the required viscosity is reached;
Oxidized starches, in which oxidizing agents cause the introduction of carbonyl or carboxyl groups, wherein depolymerization occurs, leading to decreased retrogradation and gelling capacities;
Enzymatically modified starch, produced by controlled enzyme degradation to attain required physicochemical properties;
Crosslinked starches, generated by reacting bi- or polyfunctional reagents (e.g., phosphorus oxychloride, sodium trimetaphosphate and epichlorohydrin) with hydroxyl groups to form crosslinks; and,
Stabilized starches, produced by reacting a starch with etherifying or esterifying reagents in the presence of an alkaline catalyst to give a wide range of products.
As used herein, the term "matrix forming agent" shall be understood to include include sugars such as mannitol, dextrose, lactose, galactose and trehalose; cyclic sugars such as cyclodextrin; inorganic salts such as sodium phosphate, sodium chloride and aluminum silicates; and amino acids having from 2 to 12 carbon atoms such as a glycine, L-alanine, L-aspartic acid, L-glutamic acid, L-hydroxyproline, L-isoleucine, L-leucine and L-phenylalanine.
One or more matrix forming agents may be incorporated into the solution or suspension prior to solidification. The matrix forming agent may be present in addition to a surfactant or to the exclusion of a surfactant. In addition to forming the matrix, the matrix forming agent may aid in maintaining the dispersion of any active ingredient within the solution, suspension or mixture. This is especially helpful in the case of active agents that are not sufficiently soluble in water and must, therefore, be suspended rather than dissolved.
Suspending or flocculating agents, or both, for example various gums, can be used to prevent the sedimentation of dispersed drug particles in the manufacturing process. pH-adjusting excipients, such as citric acid and sodium hydroxide, can be used to optimize the chemical stability of the drug, to minimize the solubility of water-insoluble compounds or to optimize the extent of ionization of drugs which are absorbed into the blood stream through the pregastric membranes. Permeation enhancers such as sodium lauryl sulphate can be used to optimize the transmucosal delivery of drugs absorbed through pre-gastric tissues. Collapse protectants such as glycine can be used to prevent the shrinkage of the units during the freeze-drying process or during long term storage. Flavors and sweeteners can be used to optimize taste, and microencapsulation polymers, such as various celluloses, can be used to mask any bitterness. Coloring agents can be used to impart product differentiation.
An example of a lyophilized formulation using sodium hydroxide as a pH-adjusting excipient is shown as Example 1.
Concentration*
Ingredient % w/w mg/unit
Compound A Bisulfate 8 40
Gelatin 3.5 17.5
Mannitol 3 15
Flavor (spearmint or peppermint) 0.5 2.5
Aspartame 0.5 2.5
10% NaOH 4 20
Purified Water q.s. to 100 mL q.s. to 500 mL
*Expressed on a wet-weight, i.e., suspension basis, prior to lyophilization.
Prototypes of Example 1 displayed disintegration times of about 2 seconds and have acceptable stability. Essentially 100% of the Compound A Bisulfate dissolved within a 15-minute time frame when tested in an in vitro dissolution setting such as that referenced supra.
Buffering Systems
The prototype formulations first prepared included NaOH as a pH adjusting excipient. The use of NaOH may be acceptable for initial pH adjustment of suspensions, however pH can subsequently drift over time due to the dissociation of the bisulfate salt into the free base and the counterion. Such pH variations can impact the performance of the final product. In order to stabilize pH, it was recognized that a buffer system with the appropriate buffering capacity is required. The purpose of the buffering system is to maintain the suspension pH at a suitable value, typically a pH of between about 3.5 and about 5.5, within the production time frame.
Pharmaceutically acceptable buffer systems can be used in conjunction with, or as an alternative to, the above-described pH-adjusting excipients. The selection of the buffer system is based on the targeted pH range, which in this case is between about 3.5 and about 5.5, preferably, between about 4 and about 5. These pH ranges are required to meet the stability requirement of Compound A Bisulfate and the performance of the rapidly disintegrating solid dosage form. In particular, it was found that lower pHs can adversely impact on the dissolution rate of the final product. Pharmaceutically acceptable buffer systems capable of maintaining pH in these ranges include acetate, phosphate, and citrate buffer systems. Examples of such buffer systems include acetic acid/sodium acetate, phosphoric acid/sodium phosphate, and citric acid/sodium citrate systems. Additional buffer systems within the scope of the present invention include those based on the following water soluble acids and their salts:
(+)-L-Tartaric acid;
D-Glucuronic acid;
Glycolic Acid;
D-Glucoheptonic Acid;
(−)-L-Pyroglutamic Acid;
DL-Mandelic Acid;
(−)-L-Malic Acid;
Formic Acid;
D-Gluconic Acid;
DL-Lactic Acid;
L-Ascorbic Acid;
Succinic Acid; and,
Glutaric Acid.
In order to determine the concentrations of buffer system components for a specific pre-lyophilized TRA suspension, a series of citrate buffer systems for Compound A bisulfate suspensions was prepared for various target pHs according to Table 1A below:
Buffer Concentration [Citric Acid] [Sodium Citrate]
No. pH (mM) (g/L) (g/L)
1 3 50 8.98 2.13
2 3 100 17.96 4.26
5 4 100 13.12 11.05
8 5 100 7.69 18.64
Mt. of citric acid = 210.0
Mt. of sodium citrate = 291.4
To a 20 ml aliquot of each buffer solution of Table 1 was added 0.7 g of gelatin. The solutions were heated to 60° C. (via hotplate w/stirring) for approximately 30 minutes. Then, the solutions were cooled to ˜25° C. (via water bath) and pH was recorded. 1.6 g of Compound A bisulfate (the active pharmaceutical ingredient or "API") was added to solutions to prepare an 8 w/w % suspension. During sample preparation, about ⅓rd of the solution was added to prepare a survey. Each survey was homogenized to ensure homogeneity. The remaining ⅔rd of the solution was then added while stirring. Each suspension was held for 48 hours and pH was recorded. The results of the pH measurements are shown in Table 2/3.
Buffer Tar- Ac- pH after pH after after 48
Buffer Solution get tual Gelatin API Hour
No. Concentration pH pH Addition Addition Hold
1 50 mM 3 2.88 3.37 2.88 1.31
2 100 mM 3 2.87 3.12 2.79 1.16
The experimental data show that for a citrate buffer (in this case, a citric acid/sodium citrate buffer system) the systems that target pHs of 4 and 5 at any of the concentrations of 50, 100 and 200 mM (in this case, Buffer Nos. 4-9) are adequate to control Compound A Bisulfate suspension pH between 3.5 and 5.5, as measured after API addition. This will be adequate in most process scenarios, in which lyophilization is occurs directly after suspension preparation. However, in cases in which the suspension is stored for up to 48 hours prior to lyophilization, only the systems that target a pH of 5 at concentrations of 50, 100, and 200 mM (Buffer Nos. 7-9), and the system that targets a pH of 4 at a concentration of 200 mM (Buffer No. 6) are adequate to maintain the suspension pH within the range of 3.5-5.5.
To maintain a pH of 5, citric acid concentrations of 0.7 to 3.4% w/w and sodium citrate concentrations of 1.7 to 8.3% w/w were found to be effective. To maintain a pH of 4, citric acid concentrations of 1.2 to 5.8% w/w and sodium citrate concentrations of 1.0 to 4.9% w/w were found to be effective. Thus, to maintain a pH range of about 4 to about 5, a citric acid concentration range of about 0.7 to about 5.8% w/w and a sodium citrate concentration range of about 1.0 to about 8.2% w/w would be expected to be effective. The concentrations of citric acid and sodium citrate are expressed with respect to the pre-lyophilized suspension.
Based on the above results, a lyophilized formulation of Compound A Bisulfate can be buffered as shown in Example 2.
Sodium Citrate 3.73 18.65
Citric Acid 1.54 7.70
Based on the above, it is believed that useful lyophilized formulations of a 40 mg loading dose of Compound A, or its pharmaceutically acceptable salts and hydrates, include those comprising:
gelatin in an amount of about 16 to about 19 mg, preferably about 17.5 mg;
mannitol in an amount of about 14 to about 16 mg, preferably about 15 mg;
sodium citrate in an amount of about 18 to about 19 mg, preferably about 18.7 mg; and,
citric acid in an amount of about 7 to about 8 mg, preferably about 7.7 mg.
Alternate embodiments in which the excipient components recited in Examples 1 and 2 above are substituted with other components within the same functional class are within the scope of the present invention. Thus, embodiments in which gelatin is substituted with another polymer, e.g., starch, are encompassed in the present invention. Similarly, embodiments in which mannitol is substituted with another matrix forming agent, e.g., lactose, are encompassed in the present invention. Flavoring agents (e.g., spearmint) and sweetening agents (e.g., aspartame) are also substitutable within class. As discussed above, buffering systems can be substituted.
Furthermore, the wet-basis (i.e., pre-lyophilized) percent compositions (under the heading "% w/w") disclosed in Examples 1 and 2 are exemplary, but not limiting. For example, the applicable range of wet-basis compositions of polymer (e.g., gelatin) is from about 2 to about 5% w/w, and that of matrix forming agent is from about 2 to about 4% w/w. The concentrations of flavoring agents and of sweetening agents can be varied as required. As discussed above, concentrations of the components of the buffering systems can be varied to some degree, while maintaining desired pH.
Higher doses of Compound A can be incorporated into the inventive formulations. Loading doses of up to 150 mg are within the scope of the present invention. For example, loading doses of 80 and of 120 mg of Compound A, or of a pharmaceutically acceptable salt or hydrate thereof, are within the scope of the present invention.
Lyophilization Process
In essence, lyophilization (i.e., freeze-drying) consists of at least two steps: first, freezing a solution or suspension (almost invariably aqueous) of the material to be freeze-dried; and second, raising the temperature of the frozen material with a concomitant application of vacuum so that the frozen solvent (almost invariably ice) sublimes without melting. The term "lyophilized" as used herein will be understood to refer to a formulation that is the product of at least these two processing steps. The effects of freeze-drying temperature on formulation appearance and processing times are discussed in U.S. Pat. No. 5,044,091, which is herein incorporated in relevant part.
The production sequence typically begins with the bulk preparation of an aqueous drug solution or suspension and subsequent precise dosing into pre-formed blisters. It is the blister that actually forms the tablet shape and is, therefore, an integral component of the total product package. The second phase of manufacturing typically entails passing the filled blisters through a specially designed cryogenic freezing process to control the ultimate size of the ice crystals. This aids in ensuring that the tablet possesses a porous matrix to facilitate the rapid disintegration function. These frozen units are then transferred to large-scale freeze dryers for the sublimation process, whereby the majority of the remaining moisture is removed from the tablets. The final phase of production involves sealing the open blisters via a heat-seal process to ensure stability and to protect the product from varying environmental conditions. Procedures for preparing formulations in this aspect of the present invention are described in, for example, U.S. Pat. Nos. 6,509,040 and 6,709,669, both of which are hereby incorporated by reference.
An example of a commercially available freeze-drying technology applicable to such dosage forms is known by its trade name of Zydis®, and is available from Catalent, formerly Cardinal Health, of Somerset, N.J. See H. Sager, "Drug-delivery Products and the Zydis Fast-dissolving Dosage Form," J. Pharm. Pharmacol. 50:375-382 (1998). As an example of such a product, a freeze-dried formulation of olanzapine is marketed by Eli Lilly as Zyprexa® Zydis® orally disintegrating tablets. Inactive ingredients include gelatin, mannitol, asparatame, sodium methyl paraben and sodium propyl paraben. Claritin® RediTabs®, marketed by Schering-Plough Corp., provides another example of Zydis-based formulations, which are as follows:
Ingredient Amt (mg) Wt %** Amt (mg) Wt %**
Loratadine 5 23.2 10 37.6
Gelatin NF 8.985 41.7 8.985 33.8
Mannitol USP 7.188 33.3 7.188 27.1
Flavor Mint 51296 TP0551 0.150 0.7 0.150 0.6
Anhydrous Citric Acid 0.250 1.2 0.250 0.9
Purified Water (—)* (—)* (—)* (—)*
Theoretical Dry Tablet 21.573 100% 26.573 100%
*Sublimed during lyophilization.
**Dry Basis
The present invention further encompasses methods of treatment of a patient at risk of Acute Coronary Syndrome by administering an effective amount of a rapidly disintegrating formulation of a thrombin receptor antagonist as described above. As used herein, the term "effective amount" will be understood to describe an amount of a thrombin receptor antagonist effective to prevent further damage to the cardiovascular system after an acute cardiac event.
In the treatment of ACS, thrombin receptor antagonist dosing regimens will comprise one-time administration of a loading dose followed by regular administration of maintenance doses. The TRA concentration of the loading dose will be sufficient to very quickly achieve high levels of platelet aggregation inhibition. Following administration of the loading dose, platelet aggregation inhibition levels of at least 80-90% within no more than 1-2 hours are targeted. TRA concentrations in the loading dose formulation will be 20-120 mg. The TRA concentration of the maintenance dose will be sufficient to maintain the desired levels of platelet aggregation inhibition. TRA concentrations in the maintenance dose formulation will be 1-10 mg. A dosing regimen of the bisulfate salt of Compound A comprising a 40 mg loading dose followed by daily 2.5 mg maintenance doses is planned for evaluation in phase iii clinical trials. The rapidly disintegrating solid dosage forms of the present invention are intended for administration as loading doses within these dosing regimens. Such lyophilized loading dose formulations may be capable of attaining platelet aggregation inhibition of at least about 80% within 30 minutes of administration. They may allow essentially all of the thrombin receptor antagonist to dissolve within about 15 minutes.
The lyophilized TRA formulations of the present invention will also find utility in treating victims of acute stroke and patients who undergo percutaneous coronary intervention ("PCI").
While the present invention has been described in conjunction with the specific embodiments set forth above, many alternatives, modifications and variations thereof will be apparent to those of ordinary skill in the art. All such alternatives, modifications, and variations are intended to fall within the spirit and scope of the present invention.
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Sold-out Public Forum Explores Community Health
Posted by islandword | Dec 7, 2017 | Editorial, Featured, Latest News | 0 |
by Vanessa Scott
The Comox Valley is lucky to have a range of community groups, associations, coalitions and volunteer organizations working to make it a safer, healthier and more sustainable place to live.These initiatives help hold together the fabric of our community well-being. But every issue-specific group works in its own sector, such as education, health or the environment, and there is no one place for groups and citizens to pool their collective intelligence, explore shared priorities and address the big picture issues affecting us all.
That's why the planning committee behind the proposed Comox Valley Community Health Network (CVCHN ) hosted an all-day public forum on Thurs. Nov. 16 to explore how this collaborative network approach could bring people together to create more positive health outcomes. With financial support from the Association of Registered Nurses of BC (ARNBC), the Comox Valley Healthcare Foundation, Island Health and a private donor, the 150-person forum tapped into participants' knowledge to identify collective ways to help promote wellbeing.
"The only way we are going to solve challenges to our community is to work together in 'common unity' to plan and implement new approaches which have the full support of all our citizens," says CVCHN supporter Jack Stevens, a retired teacher, former principal and pioneer of the community school movement. "A Community Health Network offers us the best option for the road ahead."
The forum was structured around the social determinants of health. These are a dozen key factors that drive community health outcomes, such as economic status, social support, culture and lifestyles.
"It's exciting to see the potential Comox Valley Community Health Network exploring the power of more systemic and proactive collaborations," says Courtenay city councilor David Frisch. "Issues like development, neighbourhood planning and transportation all impact well-being. It's certainly time to look at public health from a holistic and preventative approach rather than the more costly approach of relying on medicine to fix our lifestyles."
Because social challenges and solutions are interconnected, organizers of the CVCHN forum sought participants with a wide range of perspectives from different backgrounds, including First Nations, social service providers, local officials and interested community members.
"When I heard about the Comox Valley Community Health Network, I thought it was important to be part of that healthy community dialogue," says Sue Vince, a member of the CV Cycling Coalition and advocate for safe cycling infrastructure. "Cities that build safe, accessible and convenient infrastructure that encourages active travel is key for personal health, community health and world health."
The Comox Valley Regional District (CVRD) is one of the last regions on Vancouver Island without a community health network. "I am very pleased to see the widespread support for this development in the Comox Valley," said Island Health Medical Health Officer Dr. Charmaine Enns. "Each community health network on Vancouver Island is unique, reflecting the values and priorities of the community. I look forward to learning how this community defines what health and wellness look like to them."
Most recently the Strathcona Community Health Network formed in 2015 to foster partnerships and leverage resources after a successful public forum, which focused on themes of shared understanding, community building and healing, the environment and the historical context of First Nations.
The environment is a key point of interest and common ground. In the most recent Vital Signs Report by the Comox Valley Community Foundation in 2016, survey respondents identified the environment as the top determinant of a healthy community, followed by arts, culture and recreation.
"The more we learn about the benefits to public health that we receive from green space, parks and natural areas, we see that in many ways our community can only be as healthy as the nature surrounding us," says Tim Ennis, Executive Director of the Comox Valley Land Trust. "When you add in benefits like cleaner air and cleaner water, wildlife habitat, enhancing biodiversity and potential flood protection, it's exciting to see how land restoration and conservation are recognized as key parts of building a healthier community."
The concept of a Comox Valley Community Health Network began as an initiative of ARNBC. With input from other Community Health Networks on Vancouver Island, a planning committee of community members and agency representatives formed to organize the Comox Valley forum. The CVCHN planning committee includes two fourth-year nursing students from North Island College (NIC) who are providing event support.
"I'm excited to be on the organizing committee," says Melissa Enamorado, NIC student in the Bachelor of Science in Nursing program. "I think convening a diverse group of people who all share a common interest in a healthier community is a powerful step toward positive social change and solving shared problems."
For more information, contact cvcommunityhealthnetwork@gmail.com or visit facebook.com/cvchealthnetwork.
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Hey John! I wanted to ask your opinion--I am working on trying to get into my cargo boxes. I have all but one of them open-the one that was too rusty. I ground off the rivets and pulled the handle assembly out. I cut it loose from the cable that goes to the latches on the sides. One of the latches opens fine, but the other one is rusted in place. I had this same problem in one of the other boxes, but it was one of the boxes that's divided in half, and I was able to crawl inside and unscrew the latch. When I looked at the latch, there was so much rust built up on the "bolt" part of the latch that it couldn't slide in the "housing channel" part of the latch.
This box is a single large box, and there's no way I can access the back of the latch. I'm REALLY loathe to destroy the door, but I'm not sure there's any other way to get the box open.


Before Rihanna got "edgy" (have you heard? Rihanna's "edgy." She rides on tanks in Mickey Mouse ears and poses for GQ and everything.), she actually was kind of edgy, we just didn't get to hear it much. Here's the proof.
Trivia: "Breakin' Dishes" was one of the two options for the - get this - EIGHTH single released from Rihanna's blockbuster third album Good Girl Gone Bad and its re-release, Good Girl Gone Bad: Reloaded, but Def Jam chose the other possibility, the Justin Timberlake-penned "Rehab," which peaked at number 18 on the Billboard Hot 100 two weeks after its October 7, 2008 release as a single. The term "blockbuster" for Good Girl Gone Bad is not hyperbole: it went 2x Platinum in the USA (meaning sales of at least two million) and has sold over 7.6 million copies worldwide. "Breakin' Dishes" was one of four tracks on the album written by Christopher "Tricky" Stewart (who also produced) and Terius Nash, aka The-Dream, only one of which was released as a single: the other of Stewart's two production efforts, and arguably Rihanna's biggest hit, "Umbrella."
Get Rihanna's latest album, the "edgy" (but intriguing) Rated R (seriously, you can download the whole thing for $5 on Amazon!).


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The original item was published from 4/3/2020 10:08:08 AM to 5/30/2020 5:05:02 PM.
[ARCHIVED] Mayor Rilling encourages Norwalkers to Ring Bells and Shine Lights for solidarity
As the Norwalk community continues to practice physical distancing, some may feel socially disconnected. Starting tonight, April 3, and every day moving forward, Mayor Rilling encourages residents to shine a light from their homes and for churches and houses of worship to ring their bells or chimes from 7 p.m. - 7:02 p.m. This is a way to offer thanks to first responders and other essential employees, and to show solidarity as a community.
"Times are tough, no doubt about it, but small acts, like shining a light or ringing a bell, could really make a difference for our neighbors, first responders, and essential employees," Mayor Rilling said. "Whether it's a church bell or a flashlight from the front porch, hearing the chimes and seeing the lights will hopefully create a sense of solidarity across the community. I encourage all of us to mark 7 p.m. on our calendars every day."
The best way to slow the spread of coronavirus is to stay home, if possible. However, that could create the feeling of being disconnected from the community and loved ones. Mayor Rilling hopes the sound of bells and chimes, or the visuals of lights and candles, will serve as a reminder that Norwalk stands together. Those who can leave a light on or in the window throughout the night are encouraged to do so, to reach those who may still be working at 7 p.m.
Additionally, anyone participating is encouraged to take videos or photos of their nightly routines and share on social media. That way, even neighborhoods that are far apart can be connected through the power of technology. Residents can also share photos and videos directly with Mayor Rilling by emailing Mayor@norwalkct.org. These submissions may also be used on City of Norwalk social media properties.
"Norwalk – even though we might be apart – we can still be together," Mayor Rilling said. "Let's make some noise each and every night for our friends, neighbors, and loved ones."


The former fashion director of Net-a-Porter is known for her eye-catching outfits and regular presence on street style blogs via the front row of international fashion weeks. However, she is also increasingly carving out a reputation at the helm of iconic London boutique Browns. Having joined the business mid-way through 2015, shortly after it was bought by Farfetch, Rogers has wasted no time in rebooting the business and turning around its fortunes.
Although figures were not released, Browns reported triple-digit growth over 2016 thanks to Rogers' new strategy. A rethink of its digital proposition, led by Rogers, has reportedly led its online sales to rocket to 70% of the total, from 30% over 2017.
In the biggest development of 2017, Rogers opened Browns' first bricks-and-mortar store in 20 years. The 4,000 sq ft Browns East opened in October in London's Shoreditch, and made a splash thanks to its innovative and experiential concept. Referred to as an "augmented retail environment", it is the first step in parent company Farfetch's 'store of the future' initiative.


SERVPRO of Tinley Park has experience restoring homes affected by storms and flooding. We can respond immediately with highly trained technicians who employ specialized equipment and techniques to restore your home or business back to pre-storm condition.
A fast response is crucial to flooding and storm damage, because it reduces secondary damage and restoration costs. Storms don't wait for regular business hours and neither do we. Our technicians will respond immediately, day or night, to help Tinley Park business owners and residents.
We live and work in this community too; we might even be neighbors. As a locally owned and operated business, SERVPRO of Tinley Park is close by and ready to respond to storm and disaster events. We are proud to be an active member of the Tinley Park community and want to do our part to make our community the best it can be.
Josh and the crew were so nice. I felt safe leaving my home in his hands.


"Audience development," "impact," "arts participation," are catch phrases of conversations I read and sometimes take part in in the social media universe of arts advocates, managers, and producers. I am blessed to be playing some small part in a project that is achieving significant impact through deep participation and co-creation. This project, At Home in the Desert, has taken me about as far from where I started in NYC commercial theatre as one can get without leaving the US. Thanks to this project, I have found myself in a south Phoenix high school observing a dance class or in a central city Boys and Girls club watching sixth graders move to a track of spoken word beats they created themselves.
Will this project result in increased audiences at the city's LORT theatre or its symphony? Unlikely. But for the 40 or so students involved, the impact on their lives is profound. At a recent showing of work in process (we decided recently that the co-creative process would BE the product), the spoken word performer/artist who works at the Boys and Girls Club said, "For most of these kids, this is their first experience doing something where people are watching them perform. The confidence this is building in them is awesome." Meanwhile, at the high school site, members of Dance Exchange (formerly Liz Lerman Dance Exchange) help 17 teens create a movement vocabulary that expresses their complicated perspectives on living in a city in the desert.
I don't know if any of these kids are going to make dance or music or theatre their career. What I do know is that they are learning to trust themselves and to trust the arts as a viable way of understanding and communicating about their world. The project is having a deep impact on them – and on me.
This entry was posted in Arts education, Culture and democracy and tagged Arts education, community arts, home in the desert, public practice. Bookmark the permalink.


Collect the free trail from FEAST HQ and find all our missing animals. Completed trails to be handed in at the Retro Village for a small prize.
The Community Choir aim to bring local communities together through a love of music. Absolutely everyone and anyone is welcome to contribute in any way you can.
The return of local favourites Jacob's Ladder, Chas & Momo, Great Pan, Fiendish & Cooke, Bunting & Pops, Flying Tapas and much more.
Community stalls at the Food Fair from Lambeth Community Youth Services and Community Cooperative Insurance Services.
Brixton and Norwood Foodbank will be accepting donations inside St. Lukes.
Collectibles, vintage and retro treasures and curiosities along with fabulous coffee from Tryencore Coffee, cakes from Lovesome Cake and music from our local Record Man.
Local artists and makers will be selling their jewellery, prints, toys, crocheted items, baby products and children's clothing.
Free ipad portraits from local artist Timothy Sutton.
From 11am onwards – Red Watch from the West Norwood Fire Station will be attending. Come and see the fire engine and learn about their community fire safety initiatives.
12.30pm – The Green Ravens, local acoustic folk group of students from Dunraven school will be performing their latest set.
We welcome new traders Hattie's Chocolate Treats and Mean Green Foods to Fresh 'n' Green, along with Drum and Kernel popcorn, Floral Hall, South London Botanical Institute, Giggly Pig, the Oliveria, Levain Bakery, Marsh Produce and Dulwich Tails.
Have a coffee and croissant at Beamish & McGlue with the Sunday newspapers or how about a game of connect 4 or chess?
Free children's activities at each market hub.
South Lambeth Play Partners will be in the St. Luke's memorial garden with children's outdoor games, arts and crafts and face painting.


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Mozilla is announcing the seven recipients of its Creative Media Awards — projects that use art and advocacy to highlight the unintended consequences of artificial intelligence
The artificial intelligence (AI) behind our screens has an outsized impact on our lives — it influences what news we read, who we date, and if we're hired for that dream job.
More than ever, it's essential for internet users to understand how this AI works — and how it can go awry, from radicalizing YouTube users to promoting bias to spreading misinformation.
Today, Mozilla is announcing funding for seven art and advocacy projects that shine a light on the AI at work in our everyday lives.
These seven projects are winners of Mozilla's latest $225,000 Creative Media Awards. They hail from five countries. And they make AI's impact on society understandable using science fiction, short documentaries, games, and more. These projects will launch to the public by June 2019.
Mozilla's Creative Media Awards are part of our mission to support a healthy internet. They fuel the people and projects on the front lines of the internet health movement — from digital artists in the Netherlands to computer scientists in the United Arab Emirates to science fiction writers in the U.S.
The winners:
[1] Stealing Ur Feelings | by Noah Levenson in the U.S. | $50,000 prize
Stealing Ur Feelings will be an interactive film that reveals how social networks and apps use your face to secretly collect data about your emotions. The documentary will explore how emotion recognition AI determines if you're happy or sad — and how companies use that information to influence your behavior.
An early version of Stealing Ur Feelings
[2] Do Not Draw a Penis | by Moniker in the Netherlands | $50,000 prize
Do Not Draw a Penis will address automated censorship and algorithmic content moderation. Users will visit a web page and will be met with a blank canvas. Users can draw whatever they like, and an AI voice will comment on their drawings (e.g. "nice landscape!"). But if the drawing resembles a penis or other "forbidden" content, the AI will scold the user, take control, and destroy the image.
[3] A Week With Wanda | by Joe Hall in the UK | $25,000 prize
A Week With Wanda will be a web-based simulation of the risks and rewards of artificial intelligence. Wanda — an AI assistant — will interact with users over the course of one week in an attempt to "improve" their lives. But she quickly go off the rails. Along the way, Wanda might send uncouth messages to Facebook friends, order you anti-depressants, or freeze your bank account. (Wanda's actions are simulated, not real.)
A potential conversation from A Week With Wanda
[4] Survival of the Best Fit | by Alia ElKattan in the United Arab Emirates | $25,000 prize
Survival of the Best Fit is a web simulation of how blind usage of AI in hiring can reinforce workforce inequality. Users will operate an algorithm and see first-hand how white-sounding names are often prioritized, among other biases.
[5] The Training Commission | by Ingrid Burrington in the U.S. | $25,000 prize
The Training Commission is a work of web-based speculative fiction that tells the stories of AI's unintended consequences and harms to public life. It unfolds from the perspective of a journalist who is reckoning with how deeply AI has scarred society.
[6] What Do You See? | by Suchana Seth in India | $25,000 prize
What Do You See? highlights how differently humans and algorithms "see" the same image, and how easily bias can take root. Humans will visit a website and describe an image in their own words, without prompts. Then, humans will see how an image captioning algorithm describes that same image.
[7] Mate Me or Eat Me | by Benjamin Berman in the U.S. | $25,000 prize
Mate Me or Eat Me is a dating simulator that examines how exclusionary real dating apps can be. Users create a monster and mingle with others, swiping right and left to either mate with or eat others. Along the way, users have insight into how their choices affect who they see next — and who is excluded from their pool of potential paramours.
A mock-up from Mate Me or Eat Me
These seven awardees were selected based on quantitative scoring of their applications by a review committee, and a qualitative discussion at a review committee meeting. Committee members include Mozilla staff, current and alumni Mozilla Fellows, and outside experts. Selection criteria is designed to evaluate the merits of the proposed approach. Diversity in applicant background, past work, and medium were also considered.
These awards are part of the NetGain Partnership, a collaboration between Mozilla, Ford Foundation, Knight Foundation, MacArthur Foundation, and the Open Society Foundation. The goal of this philanthropic collaboration is to advance the public interest in the digital age.
Also see: (June 4, 2018) Mozilla Announces $225,000 for Art and Advocacy Exploring Artificial Intelligence
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Robert Gray, Managing Partner
Mr. Gray has 30 years of experience as a principal in commercial real estate. Prior to co-founding the commercial real estate investing platform of TerraCap in March 2011, Mr. Gray was with Cantor Fitzgerald & Co from March 2010 to March 2011 in the role of Senior Managing Director and Global Head of Merchant Banking. His role encompassed establishing, capitalizing and acquiring real estate investing and operating companies globally.
Mr. Gray was a Managing Director at Morgan Stanley Real Estate Investing from August 2002 to March 2010, a $60 billion real estate investment business. As the head of Real Estate Capital Markets for the real estate private equity investing business for the Americas, Mr. Gray ran a team responsible for sourcing and executing the capital structure for substantially all real estate investments in the United States, Canada, Mexico and Brazil. Mr. Gray also was responsible as Chief Investment Officer for the Morgan Stanley Mezzanine Partners Fund, a $1.5 billion global debt fund raised in December 2007. Previously, Mr. Gray served from September 2002 to August 2007 in the capacity of head of Real Estate Capital Markets for real estate investing throughout Europe, and was responsible for capital structures in Morgan Stanley offices located in London, Frankfurt, Paris, Milan, Madrid, Moscow and Istanbul. Mr. Gray worked closely with the Morgan Stanley investment banking team on various international corporate acquisition advisory mandates. Mr. Gray was a voting member of the investment committee, and his vote was required for substantially all investment decisions.
Prior to joining Morgan Stanley, Mr. Gray worked at J.P. Morgan from March 1995 to March 2001. He was a senior member of the team that developed J.P. Morgan's Commercial Real Estate Lending and Securitization Program in the United States, and eventually Tokyo and London. The program originated loans across the United States, Europe and Asia and was integrated with investment banking and debt trading. Mr. Gray was a voting member of the global credit and capital allocation committee, and his vote was required for substantially all credit investment decisions. Mr. Gray had personal signature authority of $150 million.
From March 1991 to March 1995, Mr. Gray worked as Vice President for Creamer Realty Consultants with three Managing Directors who spun out of Citicorp Real Estate to represent borrowers on prominent commercial real estate projects in their debt restructure negotiations with lenders.
Mr. Gray worked in the loan restructuring group for Citicorp Real Estate as Associate, Commercial Real Estate Debt Restructuring from May 1990 to March 1991, and in commercial property equity acquisitions for Citicorp Real Estate Investment & Management from May 1988 to April 1990 as a Management Associate providing investment analysis on commercial real estate investments across the United States.
Mr. Gray graduated from Columbia Business School in January 1990 with an MBA in finance and from Lehigh University in June 1985 with a Bachelor of Science in engineering and minor in economics.
Mr. Gray owns an interest in TerraCap Management, LLC. Mr. Gray devotes a portion of his business time and attention to oversight of TerraCap Management, LLC's activities in respect of TerraCap II and TerraCap III. Mr. Gray will not devote any time or attention to TerraCap IV, or to the oversight of TerraCap Management, LLC's activities in respect of TerraCap IV, and he otherwise will not be involved with TerraCap IV.