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RHEUMATOID ARTHRITIS ADVISOR
Home » Rheumatoid Arthritis Advisor
Differences Identified in Serious Infection Risk Among Biologic Drugs for Rheumatoid Arthritis
Virginia Schad, PharmD
Respiratory infections accounted for 42% of all serious infections and were the most frequently reported.
Although antitumor necrosis factor therapy has been associated with an increased risk for infection compared with conventional synthetic disease-modifying antirheumatic drugs in patients with RA, the infection risk with other biologics has not been confirmed.2-4 Therefore, using data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis, researchers compared the incidence of SI.
SI was defined as an infectious event requiring admission to a hospital, needing intravenous antibiotics, or resulting in death across biologic drugs used to treat RA.1 The overall incidence of SI was found to be 5.51 events/100 patient years for a cohort of 19,282 patients with 46,771 years of follow-up. Etanercept was the largest cohort and was used as the reference for all other comparisons.
The only drugs that had significantly different rates of SI compared with etanercept were rituximab, tocilizumab, and certolizumab pegol. Tocilizumab and rituximab both had higher rates of infection (6.98 cases and 6.29 cases/100 patient years), whereas certolizumab pegol had the lowest crude incidence of infection (3.80 cases/100 patient years).
Respiratory infections accounted for 42% of all SI and were the most frequently reported, followed by soft tissue and skin infections. The overall 30-day mortality rate after a SI was 10.4%. Although sepsis was found to be a significant predictor of mortality, choice of biologic treatment was not.
Addressing the Increased Risk for Malignancy in Rheumatoid Arthritis
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Sirukumab Effective in Rheumatoid Arthritis Refractory to Methotrexate or Sulfasalazine
"For the majority of patients, biologic therapies remain a safe and efficacious treatment strategy. However, in a population of 'high-risk' individuals, differences in the relative risk of infection can have a significant impact on the absolute risk of SI," concluded the authors.1
Rutherford AI, Subesinghe S, Hyrich KL, et al. Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis [published online March 28, 2018]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2017-212825
Curtis JR, Patkar N, Xie A, et al. Risk of serious bacterial infections among rheumatoid arthritis patients exposed to tumor necrosis factor alpha antagonists. Arthritis Rheum. 2007;56:1125-1133.
Galloway JB, Hyrich KL, Mercer LK, et al. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the British Society for Rheumatology Biologics Register with special emphasis on risks in the elderly. Rheumatology 2011;50:124-131.
Askling J, Fored CM, Brandt L, et al. Time-dependent increase in risk of hospitalization with infection among Swedish RA patients treated with TNF antagonists. Ann Rheum Dis. 2007;66:1339-1344.
Next post in Rheumatoid Arthritis Advisor
Methotrexate Discontinuation Safe in Tocilizumab-Treated RA With Low Disease Activity
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Brandon Michael Butt
1468 St. Paul St., Kelowna , British Columbia, Canada V1Y2E6
1468 Saint Paul Street Kelowna British Columbia V1Y 2E6 CA
https://www.suncityphysiotherapy.com/
Brandon studied at Simon Fraser University and obtained his BSc in Kinesiology in 2001. The next year he began his physical therapy education at the University of Toronto. In 2003 he graduated with his MSc in Physical Therapy and began work in private practice at the Nanaimo Physiotherapy Clinic. After completing the second level of manual training through the Orthopedic Division, he traveled to Australia to study in the Master of Manipulative Therapy at Curtin University. During this time he worked as both a teaching assistant at the University and as a clinical instructor for students on clinical placement. In 2006 he graduated with a Masters of Manipulative Therapy and returned home to continue practice in the Nanaimo Physiotherapy Clinic. He is currently a co-owner in this clinic.
Throughout his career he has been involved in sports physiotherapy working with a variety of sports such as rugby, WLA Lacrosse, Senior A baseball, Junior A hockey, soccer, and the Canadian World Cup Ski Team (Alpine Canada). He currently holds an intermediate sport physiotherapist qualification and is studying for the Diploma level qualification.
Brandon has also pursued training in vestibular rehabilitation, intramuscular stimulation (IMS) and exercise management of osteoporosis. He enjoys putting all these skills to work to help his clients achieve their goals. Brandon believes that manual therapy used in conjunction with a specific and thoughtful exercise program is a powerful way to help his clients reach their functional goals.
Robert Ewanuk
1, 606 Christleton Avenue, Kelowna, BC, Canada, V1Y5J2 1.68 km
rob@newleafphysio.ca
https://www.newleafphysio.ca
Rob graduated from the University of Alberta in 2003. He has worked in private practice for 12 ye...
New Leaf Physiotherapy
Joan Russell
LifeMark Health Centre104-1634 Harvey Avenue, Kelowna, BC, Canada, V1Y 6G2 2.17 km
joan.russell@telus.net
Completed Part A of the Orthopedic Manual Therapy Exam in 1985 and Part B in 1988. Have worked in...
LifeMark Health
Jordan Ruder
2755 Tutt St #212, Kelowna, British Columbia, Canada V1Y 0G1 2.36 km
Jordan has been a physical therapist working in Private Practice since graduating with Distinctio...
Prime Physiotherapy and Performance
Greg Redman
110-2900 Pandosy Street, Kelowna , British Columbia, Canada V1Y 1V9 2.51 km
http://www.wavephysio.ca/
Wave Physiotherapy
Ross McKinnon
1934 Ambrosi Rd., Kelowna , British Columbia, Canada V1Y 4R9 3.15 km
rcmckinnon@hotmail.com
http://www.kmtc.ca
Ross is a 1995 graduate of the University of Manitoba. After graduation Ross continued to study a...
Kelowna Manual Therapy Centre
Amanda Nichol
310-1974 Kane Road, Kelowna, British Columbia, Canada V1V 3C4 4.82 km
amanda@neumovement.com
http://www.neumovement.com/
Vince Cunanan
3970 Lakeshore Rd, Kelowna , British Columbia, Canada V1W 1V5 5.24 km
vinnyrehab@gmail.com
http://suncityphysiotherapy.com
Vince is a Senior Physical Therapist, Clinic Director, and Clinical Education Coordinator at Sun ...
Manuel Villatoro
4105 Gordon Drive, Kelowna , British Columbia, Canada V1W4Z1 5.74 km
mannyv.pt@gmail.com
https://www.lifemark.ca/therapists/manuel/villa...
Lifemark Sport Medicine - CNC
Shari Brown
104 145 Asher Road, Kelowna, BC, Canada, V1V 1P3 7.24 km
Shari_Brown@shaw.ca
http://www.rutlandphysio.ca
Rutland Physical Therapy
Christine Campbell
353 Winnipeg St, Penticton , British Columbia, Canada V2A 5M4 43.95 km
ccampbellphysio@gmail.com
https://www.dalecharlesphysio.com/dale-charles-...
Dale Charles Physiotherapy
Anne Fleming
105 - 2504 Skaha Lake Rd., Penticton , British Columbia, Canada V2A6G1 48.15 km
250 3283321250 3283321
https://www.resolvept.ca/
Anne graduated from the University of Alberta with a Master's of Science in Physiotherapy in 2010...
Skaha Physiotherapy and Health Centre
Daniel Krebs
105-2504 Skaha Lake Rd, Penticton, British Columbia, Canada V2A 6G1 48.15 km
Graduated from the University of Alberta in 2010 and worked at various orthopaedic clinics from P...
Skaha Physiotherapy
#2 - 480 Harbourfront Drive, Salmon Arm, British Columbia, Canada V1E 3L4 91.97 km

redpajama_set_name: RedPajamaCommonCrawl


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Denny Roy
Senior Fellow and Supervisor of POSCO Fellowship Program Senior Fellow and Supervisor of POSCO Fellowship Program
Denny Roy Denny Roy
Staff office/program
Northeast Asian political and security issues
Denny Roy's work has focused mostly on Asia Pacific security issues, particularly those involving China. Recently Roy has written on Chinese foreign policy, the North Korea nuclear weapons crisis, China-Japan relations, and China-Taiwan relations. His interests include not only traditional military-strategic matters and foreign policy, but also international relations theory and human rights politics.
Before joining the East-West Center in 2007, Roy worked at the Asia-Pacific Center for Security Studies in Honolulu for seven years, rising to the rank of Professor after starting as a Research Fellow. In 1998--2000 Roy was a faculty member in the National Security Affairs Department at the Naval Postgraduate School in Monterey, California. There he taught courses on China, Asian history, and Southeast Asian politics. He also designed and taught an innovative course titled Human Rights and National Security in Asia.
From 1995 to 1998, Roy was a Research Fellow with the Strategic and Defence Studies Centre at the Australian National University in Canberra, where he studied and wrote on Northeast Asian security issues. He also participated in educational activities with the Australian armed forces and the Australian College of Defence and Security Studies. In January and February 1997 Roy was attached to the Singapore Armed Forces Training Institute as coordinator for Singaporean students enrolled in the SDSC's M.A. program.
From 1990 to 1995, Roy held faculty appointments in the Political Science Departments of the National University of Singapore (Lecturer) and Brigham Young University (Assistant Professor), teaching courses on international relations and Asian politics.
Roy has five years of work and residency experience in Taiwan, Korea and Singapore. He has made presentations at academic conferences in China, Thailand, Korea, Singapore, Taiwan, Japan, Australia and the USA. He is conversant in Mandarin Chinese and fulfilled his graduate school foreign language qualification in Korean.
Roy is the author of Return of the Dragon: Rising China and Regional Security (Columbia University Press, 2013), The Pacific War and its Political Legacies (Westport, CT: Praeger, 2009), Taiwan: A Political History (Cornell University Press, 2003), and China's Foreign Relations (Macmillan and Rowman & Littlefield, 1998), co-author of The Politics of Human Rights in Asia (Pluto Press, 2000) and editor of The New Security Agenda in the Asia-Pacific Region (Macmillan, 1997). He has also written many articles for scholarly journals such as International Security, Survival, Asian Survey, Security Dialogue, Contemporary Southeast Asia, Armed Forces & Society, and Issues & Studies.
The North Korea Crisis and Regional Responses, (co-editor with Utpal Vyas and Ching-Chang Chen), (Honolulu: East-West Center, 2015).
Return of the Dragon: Rising China and Regional Security (Columbia University Press, 2013).
The Pacific War and its Political Legacies (Westport, CT: Praeger, 2009).
Taiwan: A Political History (Ithaca, NY: Cornell University Press, 2003). Published in Chinese as Taiwan Zhengzhi Shi (Taipei, Taiwan: Commercial Press, 2004).
The Politics of Human Rights in Asia (co-author with Kenneth Christie), (London: Pluto Press, 2000).
China's Foreign Relations (London: Macmillan Press, 1998).
The New Security Agenda in the Asia-Pacific Region (editor), (London: Macmillan Press, 1997).
A Time to Kill: Reflections on War (co-editor with Grant Skabelund and Ray Hillam), (Salt Lake City, UT: Signature Books, 1990 and 1992).
Selected Journal Articles
"Parsing Pyongyang's Strategy," Survival, February-March 2010.
"China's Democratised Foreign Policy," Survival, April-May 2009.
"Taiwan Perilously Ponders its Strategic Missile Force," China Brief, Jamestown Foundation, Oct. 4, 2006.
"The Sources and Limits of Sino-Japanese Tensions," Survival, Summer 2005.
Rise of China and the Strategic Environment in Northeast Asia Analysis
Rise of China and the Strategic Environment in Northeast Asia
Taiwan's 2008 Legislative Elections: DPP's Pain is U.S. and PRC's Gain
Under Foreign Pressure, Chinese Support Their Government
The Pacific War and Its Political Legacies
Explore our Staff & Experts
A. Terry Rambo
Minja Kim Choe
Laura Brewington


No es un hotel, son apartamentos cutres y sucios. La comida, además de ser mala, tiene unos horarios extrañísimos, cierran la cocina muy, muy pronto y o comes/cenas a las horas de los alemanes, o te quedas sin comer/cenar.
Hi . Is there any night time entertainment at this hotel? If no what do people do?
Hello can you tell me how far away from the resort and beach this hotel is situated please. Are hairdryers provided in the rooms?
Hi, Hairdryers are in all Rooms. The hotel is approx 1,5km from a suitable beach, if you are thinking about bathing and sunbathing.


Perfect for families, the large family apartment features a queen bed in the master bedroom and two single beds in the second bedroom. Large open plan living area features lounge with TV and DVD player, fully self contained kitchen with cooktop (no oven), microwave, full size fridge/freezer and kitchen table. Bathroom with shower and toilet. Reverse cycle air conditioning will keep you comfortable all year round. Outside has a small deck area with outdoor setting. (Sleeps 4). NO PETS allowed in this accommodation.


Undaunted by the lack of evidence, US Secretary of State John Kerry has nevertheless declared that the US and its NATO allies will strike Syria. Any intervention by an new "coalition of the willing" will be against international law and must be opposed.
– NATO and its allies have and will continue to lie about the use of Weapons of Mass Destruction to justify "humanitarian" intervention.
– NATO-led attacks, justified as a "responsibility to protect" (R2P) civilians, have resulted in tens of thousands of civilian deaths. The death toll from military attacks in Afghanistan, Iraq and Libya can be counted in the hundreds of thousands.
– The geopolitical calculations of the NATO powers, and not the interests of ordinary people, are always the main considerations for any intervention.
During the Vietnam War, US officials described a situation where it became necessary to "destroy the village in order to save it." As with all the recent evocations of R2P, it appears that the goal of NATO is to bomb civilians in order to save them. We must, therefore, stand in opposition to the actions of the aggressor states in NATO and call on the government of Canada to keep its hands off Syria.
Many CPA member groups, as well as coalitions in other countries including the US, have devised emergency response plans in the event of an attack on Syria. These plans are often for a demonstration the day of, or one day following, such an attack. The CPA calls upon peace and social justice groups to devise such plans, whether or not an attack immediately involves Canada, and to continue to pressure the Government of Canada and NATO to keep their hands off Syria.
Please email details about local emergency actions to cpa@web.ca. All actions will be posted on www.acp-cpa.ca.


We all have that one thing happening in our lives that s occupying too much of our thoughts. Especially when you feel like there s nothing you can do. Or is there? Maybe you ve done everything you possibly and rationally can. If you have, then it s time to give good old intuition a chance. Sometimes the answer is within our reach, but we need help with being able to see it. That s where Call Psychic Now can help. Because we know how important trust is in our line of work, psychics online who approach us go through a strict evaluation and screening process before we feature them on our website. Their profiles can tell you more about how they conduct readings, and what other clients experiences with them are. Our hope, when you sign up, is that we help get the best psychic for you. A phone reading can be better than a face-to-face reading simply because your psychic can better read your pure energy. They won t be distracted by your gestures or facial expressions. It s usually much easier to talk openly over the phone than in person. Most importantly, both you and the psychic can choose the environments where you want to have your reading, leading to greater comfort and openness.


When your kidneys are no longer functioning properly, toxins and excess fluid build up in the body. Hemodialysis filters out the toxins and excess fluids while balancing electrolytes. This is done by connecting a dialysis machine to your blood vessels by vascular access. A common access is a fistula made by joining an artery and vein in your arm.
What is hemodialysis endovascular intervention?
Overtime, the fistula created to give vascular access for hemodialysis may become narrowed and stop working properly. An interventional radiologist can then directly insert a balloon device to widen the narrowed blood vessel. In rare cases, the fistula may start to narrow again and the interventional radiologist will insert a stent (metal mesh tube) into the fistula to keep the vessel permanently open.
What is the inferior vena cava (IVC)?
IVC is the large vein in the abdomen that returns blood from the lower body to the heart.
What is IVC filter placement and what are some common uses for the procedure?
Blood clots that form in the veins of the legs and pelvis (also called deep vein thrombosis) can break up and travel to the lungs and heart, which can cause a pulmonary embolism or blockage. An IVC filter (small metal device) is placed by an interventional radiologist using image guidance, which traps the fragments of the blood clots and prevents them from traveling to the lungs and heart. These filters can be permanent or removed later when the risk of the blood clot has diminished.
IVC filter placement is used for patients with a high risk of developing blood clots in the legs and for those who cannot be treated by traditional methods such as taking blood thinners.
Thrombolysis is a minimally invasive procedure that treats vascular blockages by dissolving abnormal blood clots in blood vessels, which improves blood flow and prevents damage to tissue and organs. When there is a blockage in a blood vessel, blood will clot and become gel like. If not treated, the blood clot will continue to grow and cut off blood supply to parts of the body causing serious damage and potentially the loss of an organ or extremity. In a catheter-directed thrombolysis procedure, an interventional radiologist uses x-ray imaging to help guide medication or a device to the site of the blood clot.


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Carriera

Club
Ayagwa ha vestito la maglia delle Lobi Stars, prima di accordarsi con il Plateau United.

Il 15 agosto 2018, i norvegesi del Lillestrøm hanno reso noto l'ingaggio di Ayagwa, che si è legato al nuovo club con un contratto valido fino al 31 dicembre 2022. Il trasferimento è stato reso possibile anche grazie all'intervento economico di privati.

Ha esordito in Eliteserien in data 24 settembre 2018, subentrando ad Arnór Smárason nella vittoria casalinga per 1-0 sul Tromsø.

Il 25 giugno 2019 ha rescisso il contratto che lo legava al Lillestrøm.

Tornato in forza alle Lobi Stars, il 3 novembre 2019 ha ricominciato a calcare i campi da calcio nigeriani: è stato schierato titolare nella partita persa per 3-1 sul campo della sua ex squadra del Plateau United.

L'11 gennaio 2020 è stato tesserato dagli statunitensi del Tulsa. L'11 febbraio 2021 ha firmato per una nuova stagione.

A partire da gennaio 2022, ha fatto ritorno ai Lobi Stars.

Nazionale
Ayagwa ha esordito per la  in data 19 agosto 2017, subentrando ad Ifeanyi Ifeanyi nella vittoria per 2-0 contro il , sfida valida per le qualificazioni al campionato delle Nazioni Africane 2018.

Statistiche

Presenze e reti nei club
Statistiche aggiornate al 27 febbraio 2023.

Cronologia presenze e reti in Nazionale

Note

Collegamenti esterni

Calciatori della Nazionale nigeriana

redpajama_set_name: RedPajamaWikipedia


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Development strategies for Pacific Island economies: is there a role for the cultural industries?
David Throsby
Amongst the range of possible strategies to deal with ongoing development challenges facing the Pacific Island economies, one that has some potential is a policy focus on stimulating the creative or cultural industries. This article reviews the rise in interest around the world in the concept of the so-called creative economy and its role in sustainable development. This interest has particular relevance at the present time in the light of international efforts to raise the profile of culture in development, especially with the replacement in 2015 of the Millennium Development Goals with a new set of sustainable development objectives. The article outlines the current state of the cultural industries' contribution to growth in the Pacific region, and discusses opportunities and obstacles affecting their further development. The article concludes by identifying some important considerations to be taken into account in the design of effective policy strategies in this area in the future.
Asia & the Pacific policy studies
https://doi.org/10.1002/app5.75
Pacific Island economies
10.1002/app5.75
Dive into the research topics of 'Development strategies for Pacific Island economies: is there a role for the cultural industries?'. Together they form a unique fingerprint.
Pacific Islands Business & Economics 100%
Cultural Industries Business & Economics 95%
Strategy Development Business & Economics 78%
development strategy Social Sciences 77%
economy Social Sciences 47%
industry Social Sciences 44%
Sustainable Development Business & Economics 37%
Creative Industries Business & Economics 34%
Throsby, D. (2015). Development strategies for Pacific Island economies: is there a role for the cultural industries? Asia & the Pacific policy studies, 2(2), 370-382. https://doi.org/10.1002/app5.75
Throsby, David. / Development strategies for Pacific Island economies : is there a role for the cultural industries?. In: Asia & the Pacific policy studies. 2015 ; Vol. 2, No. 2. pp. 370-382.
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In: Asia & the Pacific policy studies, Vol. 2, No. 2, 05.2015, p. 370-382.
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SHOOTING 200,000 volts of electricity through a customer's body, causing the hair to stand up on end as if in fright, is the somewhat unique though harmless, means employed by Charles Hawker, of Portland, Oregon, to increase his speed at his barber chair.
The chair in which Mr. Hawker performs this tonsorial stunt is mounted on insulators, as illustrated at the left. Current is sent through the customer's body by means of contact plates on the arms of the chair.
I am sorry, that man would never cut my hair. Too lazy to use a comb, he has to shock his customers.


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The Evening Express ePaper
The Aberdonian
Latest Dons News
Willie Miller
Cove Rangers FC
Sport / Local Sport
Inverurie swimmer Miley using fightback from injury as time to inspire others in north-east
by Ryan Cryle
09/11/2018, 10:32 am Updated: 09/11/2018, 10:42 am
Hannah Miley, left, and dad/coach Patrick. Picture by Kenny Elrick
North-east swimming hero Hannah Miley is using a period of injury recovery to inspire the next generation.
Inverurie's Miley, 29, is Scotland's most successful female swimmer with golds at world, Commonwealth and European championships.
However, the triple Olympian is three months into a potential 12-month spell out of elite competition after ankle ligament surgery.
Not content to rest on her laurels, the 400-metre individual medley specialist is continuing to train in and out of the pool, and last night lifted the lid on her success along with coach and dad Patrick in a talk at Aberdeen Sports Village Aquatics Centre.
Miley said: "The journey for my dad and I – swimming has been our whole career and the journey has been exciting. It's a great opportunity for us to reflect on what we've achieved and share with the public, for those who want to know.
"We started in a four-lane, 25-metre pool in Inverurie."
She added: "There was a phrase I heard: 'every young athlete doesn't start off as an elite athlete'. You develop through experience, skill and confidence.
"I'm not the tallest and biggest athlete – for me it's not about the size. It's about working with what you've got."
"I want to inspire the next generation, whether that's in swimming, in other sports or in business. I feel there's something in both our stories that is worthwhile."
ASV is preparing to host the LEN European Junior Swimming Championships in 2020 (July 6-12). For more information, visit http://www2.len.eu/?cat=54
Help support quality local journalism … become a digital subscriber to the Evening Express
Hannah Miley
Ross Graham open to Cove Rangers return after Dundee United recall
Aberdeen boss Derek McInnes says he will retain three-man defence, despite disarray in Dingwall
Missing Aberdeen man traced safe and well
Overnight road closures to accommodate rail bridge inspections
Number of homes across north-east affected by power cut
Snow gates closed on A939 due to adverse weather
Teenager arrested in connection with spate of thefts across north-east
Craig Stewart hoping for fan backing at Deveronvale
Peterhead's Jim McInally hopeful about completion of the season
Who are Aberdeen's most memorable January signings of recent times?
Anas Sarwar: 'I've changed, now so can Scottish Labour'
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The first and foremost type of firm are the firms that are based in the united States and are yet looking forward to opening a subsidiary as far as the international market is concerned. Out of the three types of firms to be discussed under the scope of this chapter, this one is perhaps the most common and as a result, you are certainly aware of this already.
The second type of firm that is concerned about the currency hedging process is the firm that is revolving around the exporters of the United States. These exporters predominantly deal with the exportation of good and as a result, eliminating the risk factor due to foreign currency referred to as currency hedging is one of their primary tasks. In the event that these exporters aren't able to carry out this task properly, it is for certain that they aren't going to make much of a profit exporting goods. However, in the event that they are actually able to eliminate the risk factors due to currency of various countries, it is for certain that they are going to be rich.
The third type of firms that ought to be concerned as far as currency hedging is concerned that of the importer, the European importer in this case. Just like the exporters, the importers also need to be well aware of the various factors that are associated with the currency of various countries. If they are not able to optimize their risk as a result of currency, they certainly will not be able to make much of a profit. In addition to this, if proper currency hedging is not done at a corporate level, then their company may face heavy losses. As a manager, you will certain not want this to happen. Hence, it is strongly recommended for you to eliminate the risk factor as far as foreign currencies are concerned. In the event that you aren't able to do so, it is strongly recommended that you seek the aid of experts in the field. That surely ought to suffice for the task.
As already mentioned under the earlier subhead, hedging is one of the many processes that are used to eliminate the risk of currency. In the event that this risk factor isn't eliminated various types of firms such as the ones discussed under the previous subhead ought to pay the price. Hence, in the event that you wish to invest in the foreign stock market, make you that you appoint professional for currency hedging in the event that you are not able to do it yourself. A hedge is often used in order to eliminate this factor that we are talking about. The question now is what this hedge actually is. Well, it can be thought of as an alternative form of investment whose probability is negative to that of the actual investment. In the event that your investment in the forward direction ought to fail, all you need to do is pick the ashes up and start all over again. In the event that you don't have this hedge, it is for certain that you would ended up close to bankruptcy. However, thanks to this hedge, you will have what it takes to get going once again. The following example takes into account an investment of about hundred and eight dollars.
In the event that the direction of the alteration of the currency rates move in a direction that ought to ruin you, this hedge amount will definitely come in handy. It more like a coin toss where in you place a considerable bet amount on the favorable outcome say heads and then just to ensure that you don't lose everything you place a lesser amount on tails. Hence, irrespective of what the outcome of the event turns out to be, you are the one who stands to gain. Hence, one thing is certain from this example, i.e. you are not going to lose everything.
Suppose a contract promised hundred euros I exchange of about hundred and seven dollars? Suppose the rate of depreciation of the euro is about a dollar per euro, event then you ought to receive an amount of about hundred and seven euros. These minute alterations in the value of currency has the capability of making individuals rich overnight. In the event that the value of euro depreciates, all you need to do is invest about seven dollars from your future invests, this ought to solve all the issues that you were facing.
If you consider the factor of volatility with respect to the Football League of German origin alone and if you consider it along with the hedge, the second option ought to be a lot less volatile as compared to the first option. In the event that you are willing to play it safe, then considering the hedge might as well be your last option.
Though the term hedge was coined a couple of years back as far as the field of finance is concerned. However, the idea has been around for thousands of years. It has been around ever since the idea of placing bets, i.e. gambling came into existence. Though the idea of gambling and investing in foreign projects is quite different, however, the term hedge conveys the same meaning for both.
As far as gambling is concerned, individuals often used place bets on more than one possibility in order to ensure that their chances of ending up with nothing is reduced to the maximum possible extent. If case of horse races that have been carried out for hundreds of years, bookies often tend to place bets on more than one horse, i.e. they always keep a second option. This second option often turned out to be extremely vital as far as the net profit made out of a particular bet is concerned. In the event that an individual isn't able to get anything right, then may GOD save thee.
L'O réal is a firm that is based in Europe, if it wishes to open a subsidiary as far as the US stock market is concerned, then it ought to be quite similar to a German based company such as NFL trying to doing the same in the European stock market. There parameters though neglected quite often are of utmost importance if you consider it from the perspective of the international stock market.
Firms concerned if importing affairs in the United States are another major example.
Boeing and Airbus are quite opposite to each other. It manufactures and sells airplanes in Europe and the United States respectively.
If a company is worth a million dollar, it certain won't be looking forward to investing about ten million dollars on hedging. Hence, the idea is to some extent eliminated as far as this context is concerned.
There are various implications that these hedges can provide as far as the field of accounting is concerned. In the event that a particular contractual hedge is marked on the basis of a country, then one thing is for certain that the losses with respect to that country are to be minimized.
Suppose a hundred years are to be hedged, predicting the flow of cash for the hundred years is certainly impossible.
Metallge sells chaft is an ancient large scale German company that is over a hundred years old. It had undergone a critical crisis as far as the year 1993 is concerned. Metallge sells chaft was the owner of a large number of gas plants. As a result, it decided on purchasing about two billion barrels of oil. The deal was promised at the rate of sixteen to eighteen dollars / barrel. The sole objective of this hedge was to neuritis the cost of input. Unfortunately for Metallg esells chaft, the price of the oil went way against the hedge and as a result the company faced heavy losses. In addition to this, the gas stations that they owned didn't perform as efficiently as they used to and as a result the consumption of oil was reduced as well. The fall of Metallge sells chaft till date is one of the most tragic cases as far as the international stock market is concerned. It went from about four billion to one and a half billion which is nothing but absolutely tragic.
When it comes to money supporting, the contracts in the forward direction are not by any means the only technique. To understand the concept better, let us consider a small scenario, we are aware of a firm that purchases bonds in other countries' currencies. We ought to realize that an organization that buys contributions to its home cash and has deals in the currency of an international market. In the event that it somehow contributes to a remote operation, which would then be able to likewise buy its contributions to the outside market in remote cash, at that point its money trade hazard will be a lot lesser—both expenses and incomes will happen in a similar cash. Under such circumstances, it is you who stands to benefit the most. If in the event that you are not being able to exploit the opportunities of the international stock market to the maximum possible limit, it is strongly recommended for you to take this option into consideration. It will without a doubt play a huge role as far as ensuring that you make the maximum possible profit is concerned.
However another technique for supporting for companies is to coordinate resources and liabilities: In the event that a company has an advantage, (for example, a remote task) whose net present estimation of 100 euros, at that point it can make a risk that is likewise a valuation of 100 euros. The least demanding approach that can be taken in order to carry this out is financing keeping in mind the benefit not in the currency of the U.S., i.e. dollars (the same has been demonstrated in diagram 25.2) yet in euros. In the event that a particular task is able to acquire 100 euros and has a valuation of 100 euros, the money hazard on the benefits itself practically vanishes: Currency chance stays just in the income execution of the euro auxiliary. In the event that we bring this capital up in the outside host nation itself, it might likewise relieve Host nation financing (remote bonds) can support political hazard: nationalized, odds state that the individuals involved will by no means be at risk to pay of the various spectaculars of the Russian origin and loan specialists. This kind of fence is frequently expert with remote bonds. These bonds without a doubt date way back, i.e. for no less than hundred years. These bonds are very often issued by companies remote to country that is issuing them and named in have nation cash. These bonds without a doubt are given distinct names as far as the various nations are concerned: Yankee bonds of US (These were issued by enterprises that weren't based in the US), Japan's samurai bond, Spain's bonds of bullfighter, and Britain's bonds of bulldog.
Before moving on any further with this chapter, it is a must that I provide you with the idea of Euro bonds at this junction. Let us take a small example, suppose you reside in Spain where you are the owner of a corporation and your corporation is looking forward to issuing a bond in the stock market of Germany. Such a bond is considered to be a euro bond where in the corporation or enterprise that is issuing the bond in a particular country isn't based in that country. In the event that it is actually able to get the bond issued, there are numerous conditions that need to be meet. The thing about these bonds is that neither their denominations are carried out in the host country nor is it traded there. The only place where these bonds can be traded is the country where they have been issued. Though these types of bonds may sound to be kind of absurd but in the real world, they do exist. Have you ever wondered why would a firm based in Spain wish to issue bond in Germany? Well, the answer to this is extremely simple. The valuation of currency exchange is something that needs to be taken into consideration here. In the event that it is carried out smoothly, then it is for certain that the bonds will be quite well off and will in turn bring in handsome revenues. This is something that gets most firms interested and perhaps the major reason as to why the idea of euro bonds came up in the first place. Bearer bond was the very first euro bond to have ever been issued. It was way back in 1822 when Russian firms issued bonds in Britain. There was a lot of chaos as far as the issue of this bond was concerned as it was the first of its type. However, as the public gradually began to realize the amount of revenue that these bonds were capable of bringing to both countries, the chaos eventually settled down. When it comes to these euro bonds, their face value may go as high as a trillion dollars. This is something that most investors and buyers of bonds often look out for as it very well as the capability of making them rich overnight.
Swap after issue. This is another term that individuals in the stock market will have definitely come across. This market is another large market as far as the financing market in the corporate field is concerned. In the event that an individual is looking forward to earning millions of dollars, he or she might as well try out his or her luck at this market. The thing about these bonds is that it is immediately swapped with its remaining portion as soon as it is issued. Sounds kind of absurd? Doesn't it? Well, definitely it does! However, if you have been in the field for about a year or so, you will definitely understand the true essence of these bonds and the manner in which they can bring revenue to your company. In the event that they are actually issued, then there's nothing that the one issuing the bond needs to worry about as it will definitely bring home handsome revenues.
25.4 D Should Firms Hedge?
If you are the owner of a firm or at the managerial level of a particular firm, then the next thing that ought to pop up in your mind is whether or not your firm should hedge as well. Well, this is quite debatable a topic. Over the years, there have been numerous arguments as far as the essence of hedging for a particular firm is concerned. Though the number of critics were huge but all of them were silenced thanks to the utility of these hedges. Without a doubt your firm must hedge as well. Irrespective of whether everything's going your way or not, one thing is for certain that you must also introduce the idea of hedging into the management team of your firm. This will play a huge role as far as your firm's success in the near future is concerned. As already discussed in the previous subheads, hedges are something that are an absolute must as far as any firm or company is concerned. In the event that a particular company isn't willing to adapt these strategies, it is for certain that the company isn't going to last long as far as the international stock market is concerned.
In the event that you come across currency fluctuations that are nowhere close to what you had expected, the loss that your firm may incur is tremendous. Hence, you might as well consider hedging to be your only option the next time around. The key factor as far as hedging is concerned is that it reduces the risk factor drastically. In the event that you are willing to make sure that the company or firm that you belong to excels, you must definitely try out his option as it will never fail you. It can also be considered to be a security clearance for you and your firm in the event that things don't go your way which may happen if you are in the foreign stock market.
In the event that your company is into the act of hedging, the task of evaluating your manager and the various other corporate staffs ought to become a hell lot easier. This is something that will definitely help your company prosper. In the event that there are certain staffs who don't add much of an input as far as the progress of your company is concerned, you can easily chuck them out in the event that you have considered the hedging option. Thus it has various added advantages as far as the owners of the various firms are concerned.
You at times may try this option out for the sole purpose of reducing the risk involved. In the event that you actually try this out, there may be instances where it doesn't have any impact on your company's revenue. However, in the event that any sort of adverse circumstances arise, it will definitely help.
Sadly enough, there are not always the reasons as to why the firms go for hedging in the first place. This is mostly due to the management team of such firms whose members believe that they can very well out class the others in the financial market but that is something that will seldom happen. Hence, if you are using the idea of hedging for such purposes, you will only end up getting disappointed. These are certain thing that the manager or the owner of a firm must deal with. Leaving these things in the hands of the employees may often turn out to be a devious task. Hence, it is strongly recommended that you look after you firm.


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Bobby Hayden, Oral History
Bobby Hayden (b.May 28, 1937) Born in Huntsville, Alabama, Bobby was very active with the sports program at Alabama A&M and worked closely with Paul White (who would become "Tall Paul" in Birmingham at WENN 1320 AM) who would broadcast A&M games on WEUP 1600 AM. Bobby also gave tours later on in life at the Underground Railroad safe house in Huntsville. In 1963, Hayden was one of the first African-American presidential honor guards. He served for Presidents Kennedy and Johnson, along with six other African-Americans who referred to themselves as "The Magnificent Seven.'' In this interview, Bobby talks about his relationship with Paul White and the overcoming of obstacles and racism while pioneering Black radio sports broadcasting. He also speaks of Paul White's relationship with Leroy Garrett, founder and owner of WEUP.
Also present: Dr. Roy McRay
Bobby Hayden
Roy McRay
Margo Monks
Bob Friedman: And where, and so the picture that people can see is a picture of Paul broadcasting at A&M, right?
Bobby Hayden: He was the man who developed, founded the program at Alabama A&M, which is the first of all historical Black colleges in the United States. In two years, Paul White had the largest broadcast hookup – other than Notre Dame – in the United States.
BF: Now that's quite a mouthful. So…
BH: He had eleven stations playing in two years.
BF: He had… You're saying that –
BH: The first year of broadcasting he broadcasted eight games, home and road. A&M was the first Black college to broadcast a football game – home, road, day, or night in 1959. It was Paul White who led the way, who gathered all the sponsors and all the production. The most unique thing about Paul was at that time he didn't drive.
BF: He didn't drive.
BH: He didn't own a car, nor could he drive. He's broadcasting the football at Alabama A&M over two-years span of time – cost him his job at WEUP. He and Garrett fell out over the broadcast about the second year. It was so successful the first year, Woody Anderson was one of his sponsors. Woody Anderson bought in with the idea of giving him an automobile to pay for his time on the air and that created a problem 'cause Garrett wanted Paul White to sell the car to give him the money. That was his pay for being one of the sponsors of A&M football. He gave Paul a car, then Paul had to learn how to drive.
BF: Now Bob, back in the day because I see that it's obvious that you're close to Paul from the picture – are you hearing all of these stories from Paul?
BH: No. I was part of all the show!
Transcript of Video:
Bobby Hayden: And one day's time I met the man who wrote the order. I met the man who refused to pass on the order. I met the man who passed the order on. I met the man who carried it out. Truman, Eisenhower, Kennedy, and Johnston. All in one lifetime, all in one day.
Video: 22 seconds
1950s, Alabama A&M, Bobby Hayden, Football, George McCalup, HBCU, Legion Field, Leroy Garrett, Magic City Classic, Paul "Tall Paul" White, Sports, WEUP
Bobby Hayden, Roy McRay, and Bob Friedman, "Bobby Hayden, Oral History," The Birmingham Black Radio Museum, accessed January 21, 2022, http://thebbrm.org/item/540.


Found out on Friday I lost the baby. The hospital made me wait 2 days before inducing me to have the baby. Finally they called me to come in for the induction. This was truely the worst thing I have ever gone through in my life. As if losing a baby at 5 months along wasn't enough, I had to give birth as well. I could not believe this when they told me, and thought there must be a better way! I cannot express the pain I feel for this loss.
No one was happy the first time I got pregnant. It was back in October of 2005. I was so alone and regretably made the terrible decision to end the pregnancy. I didn't feel like it was my choice. I didn't stand up for myself or my child.
Nothing could help the pain. I was traumatized. And it only got worse a few months later when I was diagnosed with high risk HPV. The pre-cancerous cells covered my cervix. Even though they caught it quickly enough to treat it, the damage was done. I was told I had a very slim chance of getting pregnant due to the trauma my cervix went thru. I was determined. I was still emotionally scarred from the abortion and wanted nothing but to have a child.
And then it happened. I was so nervous I couldn't even bring myself to look at the stick to see if the line was there. It was a dream. I had what I so desperatly wanted. Instantly the maternal instincts kicked in. I bought books, subscribed to magazines, told EVERYONE. I even kept the first home pregnancy test. I loved every minute.
My pregnancy was rough. The nausea was terrible. It was literally all day long. Even brushing my teeth set the vomiting off. And the father and I were going thru a break up at the time so I was really stressed. But I found my support group and lived up every moment. I bought pregnancy clothes that I wouldnt fit into for months. Thought of names. Everyone was happy.
Than it was time for my first doctors appointment. I went in and right off the bat wanted an US. I was a little early for one but they gave me one anyways....They couldn't find the baby. Something they played off as normal. They had every excuse. "Maybe its the machine, your bladder isn't full enough, it's too early, the baby is hiding." But I knew. I did. Something was deathly wrong. I didn't know how right I was.
They scheduled me for an US 2 weeks later in their Radiology department. Once I went home I shrugged it off and went back to my happy pregnant self. I remained so cautious of what I did and what I ate. Like nothing was bothering me at all.
I did start noticing things that just seemed a little off to me. The big one being I had no morning sickness. At all. And I was so used to having such intense morning sickness it was odd for me. I still had the breast tenderness and all that so I wrote it off as I was one of the lucky ones who just don't get sick.
Today was my second ultrasound... I made sure the father and my parents were there with me. And I'm so glad they were.
They started with just the standard US. The doctors were completely silent. I even said to them that it was eery how quiet they were being. Still nothing. Than they left to get another doctor. Than the 3 doctors left. And in came 6 more doctors. Count them 6 more doctors. I automatically started crying. Something was wrong. And these 6 doctors were just about to confirm it.
For the first time in the entire visit they let me see what they were whispering about. It looked like a deflated balloon. The sack had swollen 3x what it was suppose to be and instead of being the perfect circle it looked like it was popped.
My baby is gone. What has happened is so incredibly rare the doctors had never seen it before. And didn't know of a name for what happened. Everything but my baby is growing inside of me. The sack continues to swell. I will have to have it removed.
You hear so many reasons for miscarriage. Stress, Weight, Health, on and on and on. The doctors have no idea how this happened. I have nothing but guilt. Like I did something wrong but they don't know what I did. I blame myself.
How can crack addicts and prostitutes have children but I cant???? Why am I not good enough??? This baby was a living part of me. I was suppose to protect it from pain and suffering. But I didnt. I let him/her die. All I have left is the emptiness. Where my child and my heart used to be.
I'm numb. All out of tears. I cant stand the "well on the brighter side..." F that. There is no bright side to this. There is nothing but dark and hurt. I don't want to talk to anyone. Sympathy annoys me. They don't know what I'm going thru how dare they try to console me now. I want to be alone. But most of all I don't want it to be happening.
The doctor said there is a 1% chance the baby is there. 1%. What kind of beacan of hope is that suppose to be exactly? Theres nothing left. I know it.
I've been reading the stories at my home this 4th of July and wondering "Why me" just like the rest of these women on here. Why within a 1 year peroid did I have 2 failed attempts at pregnancy? I wish someone could provide me with the whys/and how comes? As I'm currently pregnant with a baby that has no heartbeat as of last Thursday, now come the questions of what to do/and how. I too find myself crying and feel like this is a cruel joke of some kind. I'm 36, no kids and thought once again this was it. I can't put into words the range of emotions I've been going through these past few days. My whole world right now turned upside down all in 1 morning. I'm tired of hearing this happened for a reason/or maybe it will happen next time, that's all fine until you go through something like this, it isn't fine. I'm sorry other women like myself have had to go though this same experience with no answers to their questions. It is frustrating, and hurtful. I just wish if I was to miscarry let it happen so I don't have to make the decision to take the medication to end this pregnancy, or to have the D&C. I just feel so alone.
I am 25 years old. In August of 2005 my husband and I started trying to get pregnant. It only took one try and I found out I was pregnant very early. I had an ultrasound at what I thought was my 7th week, but it showed nothing. I was devastated. I came back for another ultrasound one week later, and there was a fetal pole and gestational sac. I had just had my dates wrong. I had another ultrasound at what was my real 7th week, as well as a quantitative hCG test, and both tests were fine. The US showed a heartbeat of 138 and my hCG was at about 13,000.
For the next four weeks, I was the happiest I have ever been. My best friend started knitting me a baby blanket, my mother bought me a baby memories book and a toy and outfit, and my husband was very happy as well. I had no nausea, and my only true symptoms were fatigue and some breast tenderness, which started disappearing at 10 weeks.
I went to my 12 weeks appointment with my husband to hear the heartbeat. The midwife could not hear anything after trying for over 15 minutes and decided that perhaps I had a tilted uterus, though no one had mentioned this at any of the US appointments. She said I should come back in another month. Another month! I told her emphatically that I would not wait this long in case something was wrong. She begrudgingly said I could come in for another US two mornings later.
I had to go to that appointment alone. The US technician started working and before she even spoke I could see that something was wrong. She told me "It looks like you had a loss." I will never forget hearing that. The pregnancy had only progressed to 8 weeks by the size of the embryo. For an entire month I had been falsely planning for a new life that I would bring into the world. I felt cheated, angry, and completely dejected.
Over the next three days I learned that I had had a "missed miscarriage." I had never bled or had cramps or pain or a sign of any kind. I had to have a DNC on November 15 05. This was an extremely traumatic experience for me. I had never had surgery and was terrified of the anaesthesia. We had told all of our family and friends and co-workers about the pregnancy, which was a terrible mistake. I had to answer so many questions and receive so much information and advice and words of love. Believe it or not, this did not help in the least. It made me feel worse, small, and compromised. All I wanted was to be alone.
It is now July 4th of 2006 and I am 9 weeks pregnant. We started trying in April, and again it only took one try. While I feel very fortunate, I am terrified. I have been to have an US, and my husband and I saw the heartbeat at 6.5 weeks, but this means nothing to me. However, this pregnancy is very different. I have been nauseated almost every day, and on some days have had to literally sit completely still for hours to keep from vomiting. It has been quite difficult. I can only eat a few "staples" - chips, bread, yogurt, cereal, broccoli, and salmon (for some reason) - without feeling disgustingly queasy. Also, my breast changes have been much much more pronounced and I had to purchase two new bras in a larger cup size. I've also noticed that I'm having strange, vivid dreams that I can remember very clearly. This is unusual for me. My lower abdomen above my pubic bone is very firm and feels quite different.
I do not know what to hope for at this time. I cannot stop thinking that the child I am carrying could already be dead inside me. My husband and I have told _no one_ - and we have decided to keep holding off until the 15th week. This is difficult because, for all my fears, I am very excited and I feel that this time may be different. I just cannot wait to hear the baby's heartbeat and to see it move on an ultrasound. Until then I will continue to be afraid that my previous tragedy will repeat itself. With any luck this pregnancy will come to fruition and I will be able to post good news in a few weeks.
Best wishes to all of you and I am so sorry for the losses you have suffered.


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WHO is celebrating the 50th anniversary of its presence in Laos
Published on April 5, 2013
The World Health Organisation WHO in Laos is celebrating the 50th anniversary of its presence in the country. The Lao Health Minister Professor Dr Eksavang Vongvichit said the WHO is one of the most important development partners contributing to health sector development in Laos, working closely with the Ministry of Health.
A joint reception was organised with the Ministry of Health on Friday, attended by the Lao Health Minister Professor Dr Eksavang Vongvichit and WHO Regional Director for the Western Pacific, Dr Shin Young Soo who stated at the gathering that, The WHO has come a long way in Laos. This is an important milestone for us. While much has been achieved in the past years, we face new challenges brought about by economic developments and global health trends.
Prof. Dr Eksavang said, the Ministry of Health wants to continue the cooperation, working closely with the WHO and other development partners to achieve these goals. He said adding, "We are facing a high risk of not meeting the MDGs, especially MDG 1 regarding malnutrition and MDG5 concerning maternal mortality rate reduction. The ministry believes that health reform must be implemented to overcome these challenges."
Four key strategic priorities define WHO's work in the country. The first calls for better access to primary healthcare and reducing health inequalities by strengthening the health system and improving aid effectiveness.
More than 200 guests from government line ministries, ambassadors of foreign missions and embassies in Laos and the heads of United Nations agencies gathered for the celebration.
LNTV Lao News, broadcast on 1/04/2013
Category: Health & Beauty
Health System Development Project in Laos
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166 hotline launches


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NGC 7808 ist eine Spiralgalaxie mit aktivem Galaxienkern vom Hubble-Typ (R)SA0? im Sternbild Walfisch südlich der Ekliptik. Sie ist schätzungsweise 396 Millionen Lichtjahre von der Milchstraße entfernt und hat einen Durchmesser von etwa 150.000 Lj.
Im selben Himmelsareal befindet sich u. a. die Galaxie IC 1529.

Das Objekt wurde im Jahr 1886 vom US-amerikanischen Astronomen Frank Muller entdeckt.

Weblinks
 SIMBAD Astronomical Database

Einzelnachweise


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Tracks all across the subway system are littered with dangerous debris that could potentially injure riders and people on the street — and MTA brass has long ignored warnings that the messes could cause a tragedy, agency workers told The Post.
The clutter includes old pieces of wood, sections of metal rail, fiberglass and metal plates that could crash down and kill people.
MTA workers sounded the alarm once again Friday, a day after a piece of wood left unsecured on the elevated 7-train tracks in Queens plummeted and pierced the windshield of an SUV traveling along Roosevelt Avenue in Jackson Heights, missing the driver by inches and terrifying passersby.
Train conductor John Ferretti gave The Post several letters he sent to MTA bosses last summer warning them of the dangers.
He said some of the debris is left behind indefinitely when workers finish projects.
In the summer of 2017, a loose section of rail that workers had left on the track bounced up and derailed an A train heading through Harlem.
That derailment led to a chaotic evacuation where riders had to escape through the train tunnel as fires sprung up from the impact of the crash.
Ferretti claims he has brought up the issue to MTA management — including directly to New York City Transit Director Andy Byford — many times, but they have refused to follow up and find a better system than leaving the old material on the tracks.
"The managers are responsible for this," said Ferretti.
Pedestrians say they are now scared to walk underneath elevated-train tracks.
The wood that crashed through the SUV windshield Thursday had been left on the 7-train tracks for decades and was rotten, Byford said. It appeared to have been used in a painting project.
He said the agency would now scour all 168 miles of elevated tracks to look for other debris.
MTA officials declined to say why agency brass had not addressed the clutter before now.


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OSTI.GOV Journal Article: Computational strategy for quantifying human pesticide exposure based upon a saliva measurement
Title: Computational strategy for quantifying human pesticide exposure based upon a saliva measurement
The National Research Council of the National Academies report, Toxicity Testing in the 21st Century: A Vision and Strategy, highlighted the importance of quantitative exposure data for evaluating human toxicity risk and noted that biomonitoring is a critical tool for quantitatively evaluating exposure from both environmental and occupational settings. Direct measurement of chemical exposures using personal monitoring provides the most accurate estimation of a subject's true exposure, and non-invasive methods have also been advocated for quantifying the pharmacokinetics and bioavailability of drugs and xenobiotics. In this regard, there is a need to identify chemicals that are readily cleared in saliva at concentrations that can be quantified to support the implementation of this approach.. The current manuscript describes the use of computational modeling approaches that are closely coupled to in vivo and in vitro experiments to predict salivary uptake and clearance of xenobiotics. The primary mechanism by which xenobiotics leave the blood and enter saliva is thought to involve paracellular transport, passive transcellular diffusion, or trancellular active transport with the majority of drugs and xenobiotics cleared from plasma into saliva by passive diffusion. The transcellular or paracellular diffusion of unbound chemicals in plasma to saliva has been computational modeled using amore » combination of compartmental and physiologically based approaches. Of key importance for determining the plasma:saliva partitioning was the utilization of a modified Schmitt algorithm that calculates partitioning based upon the tissue composition, pH, chemical pKa and plasma protein-binding. Sensitivity analysis of key model parameters specifically identified that both protein-binding and pKa (for weak acids and bases) had the most significant impact on the determination of partitioning and that there were clear species dependent differences based upon physiological variance between rats and humans. Ongoing efforts are focused on extending this modeling strategy to an in vitro salivary acinar cell based system that will be utilized to experimentally determine and computationally predict salivary gland uptake and clearance for a broad range of xenobiotics. Hence, it is envisioned that a combination of salivary biomonitoring and computational modeling will enable the non-invasive measurement of both environmental and occupational exposure in human populations using saliva.« less
Timchalk, Charles; Weber, Thomas J.; Smith, Jordan N.
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
PNNL-SA-108384
Journal ID: ISSN 1663-9812; 400480000
AC05-76RL01830
Frontiers in Pharmacology
Journal Volume: 06; Journal ID: ISSN 1663-9812
Frontiers Research Foundation
compuational strategy; quantifying; human pesticide; saliva measurement
Timchalk, Charles, Weber, Thomas J., and Smith, Jordan N. Computational strategy for quantifying human pesticide exposure based upon a saliva measurement. United States: N. p., 2015. Web. doi:10.3389/fphar.2015.00115.
Timchalk, Charles, Weber, Thomas J., & Smith, Jordan N. Computational strategy for quantifying human pesticide exposure based upon a saliva measurement. United States. doi:10.3389/fphar.2015.00115.
Timchalk, Charles, Weber, Thomas J., and Smith, Jordan N. Wed . "Computational strategy for quantifying human pesticide exposure based upon a saliva measurement". United States. doi:10.3389/fphar.2015.00115.
title = {Computational strategy for quantifying human pesticide exposure based upon a saliva measurement},
author = {Timchalk, Charles and Weber, Thomas J. and Smith, Jordan N.},
abstractNote = {The National Research Council of the National Academies report, Toxicity Testing in the 21st Century: A Vision and Strategy, highlighted the importance of quantitative exposure data for evaluating human toxicity risk and noted that biomonitoring is a critical tool for quantitatively evaluating exposure from both environmental and occupational settings. Direct measurement of chemical exposures using personal monitoring provides the most accurate estimation of a subject's true exposure, and non-invasive methods have also been advocated for quantifying the pharmacokinetics and bioavailability of drugs and xenobiotics. In this regard, there is a need to identify chemicals that are readily cleared in saliva at concentrations that can be quantified to support the implementation of this approach.. The current manuscript describes the use of computational modeling approaches that are closely coupled to in vivo and in vitro experiments to predict salivary uptake and clearance of xenobiotics. The primary mechanism by which xenobiotics leave the blood and enter saliva is thought to involve paracellular transport, passive transcellular diffusion, or trancellular active transport with the majority of drugs and xenobiotics cleared from plasma into saliva by passive diffusion. The transcellular or paracellular diffusion of unbound chemicals in plasma to saliva has been computational modeled using a combination of compartmental and physiologically based approaches. Of key importance for determining the plasma:saliva partitioning was the utilization of a modified Schmitt algorithm that calculates partitioning based upon the tissue composition, pH, chemical pKa and plasma protein-binding. Sensitivity analysis of key model parameters specifically identified that both protein-binding and pKa (for weak acids and bases) had the most significant impact on the determination of partitioning and that there were clear species dependent differences based upon physiological variance between rats and humans. Ongoing efforts are focused on extending this modeling strategy to an in vitro salivary acinar cell based system that will be utilized to experimentally determine and computationally predict salivary gland uptake and clearance for a broad range of xenobiotics. Hence, it is envisioned that a combination of salivary biomonitoring and computational modeling will enable the non-invasive measurement of both environmental and occupational exposure in human populations using saliva.},
doi = {10.3389/fphar.2015.00115},
journal = {Frontiers in Pharmacology},
DOI: 10.3389/fphar.2015.00115
The need for non- or minimally-invasive biomonitoring strategies and the development of pharmacokinetic/pharmacodynamic models for quantification
Journal Article Timchalk, Charles ; Weber, Thomas J. ; Smith, Jordan N. - Current Opinion in Toxicology
Advancements in Exposure Science involving the development and deployment of biomarkers of exposure and biological response are anticipated to significantly (and positively) influence health outcomes associated with occupational, environmental and clinical exposure to chemicals/drugs. To achieve this vision, innovative strategies are needed to develop multiplex sensor platforms capable of quantifying individual and mixed exposures (i.e. systemic dose) by measuring biomarkers of dose and biological response in readily obtainable (non-invasive) biofluids. Secondly, the use of saliva (alternative to blood) for biomonitoring coupled with the ability to rapidly analyze multiple samples in real-time offers an innovative opportunity to revolutionize biomonitoring assessments. Inmore » this regard, the timing and number of samples taken for biomonitoring will not be limited as is currently the case. In addition, real-time analysis will facilitate identification of work practices or conditions that are contributing to increased exposures and will make possible a more rapid and successful intervention strategy. The initial development and application of computational models for evaluation of saliva/blood analyte concentration at anticipated exposure levels represents an important opportunity to establish the limits of quantification and robustness of multiplex sensor systems by exploiting a unique computational modeling framework. The use of these pharmacokinetic models will also enable prediction of an exposure dose based on the saliva/blood measurement. This novel strategy will result in a more accurate prediction of exposures and, once validated, can be employed to assess dosimetry to a broad range of chemicals in support of biomonitoring and epidemiology studies.« less
DOI: 10.1016/j.cotox.2017.03.003
Physiologically based pharmacokinetic modeling of salivary concentrations for noninvasive biomonitoring of 2,4-dichlorophenoxyacetic acid (2,4-D)
Journal Article Han, Alice ; Timchalk, Charles ; Carver, Zana A. ; ... - Toxicological Sciences
Saliva has become a favorable sample matrix for biomonitoring due to its non-invasive attributes and overall flexibility in collection. To ensure measured salivary concentrations reflect the exposure, a firm understanding of the salivary transport mechanism and relationships between salivary concentrations and other monitored matrices (i.e. blood, urine) is needed. Salivary transport of a commonly applied herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), was observed in vitro and in vivo and a physiologically based pharmacokinetic (PBPK) model was developed to translate observations from the cell culture model to those in animal models and further evaluate 2,4-D kinetics in humans. While apparent differences in experimentalmore » in vitro and in vivo saliva/plasma ratios (0.034 and 0.0079) were observed, simulations with the PBPK model demonstrated dynamic time and dose-dependent saliva/plasma ratios, elucidating key mechanisms affecting salivary transport. The model suggested that 2,4-D exhibited diffusion limited transport to saliva and was additionally impacted by protein binding saturation and permeability across the salivary gland. Consideration of sampling times post-exposure and potential saturation of transport mechanisms are then critical aspects for interpreting salivary 2,4-D biomonitoring observations. This work utilized PBPK modeling in in vitro to in vivo translation to explore benefits and limitations of salivary analysis for occupational biomonitoring.« less
DOI: 10.1093/toxsci/kfz206
Disposition of Lead (Pb) in Saliva and Blood of Sprague-Dawley Rats Following a Single or Repeated Oral Exposure to Pb-Acetate
Journal Article Timchalk, Chuck ; Lin, Yuehe ; Weitz, Karl K. ; ... - Toxicology
Biological monitoring for lead (Pb) is usually based upon a determination of blood Pb concentration; however, saliva has been suggested as a non-invasive biological matrix for assessing exposure. To further evaluate the potential utility of saliva for biomonitoring, the disposition of Pb was evaluated in whole blood (WB), red blood cells (RBC), plasma, parotid gland, bone, and saliva following either a single oral dose of 100 mg Pb-acetate/kg body weight in rats or {approx}1-week after 5 sequential daily oral gavage doses of 1, 10, or 100 mg Pb-acetate/kg/day. Saliva volume, pH, total saliva protein, and ?-amylase activity were also determined.more » At specified times post-dosing groups of animals were anethetized and administered pilocarpine to induce salivation. Saliva was collected, the animals were humanely sacrificed, and tissue samples were likewise collected, weighed, and processed for Pb analysis. Following a single dose exposure to PB-acetate, Pb was detectable in all samples by 30 min post-dosing. For both the single and repeated dose treatments the concentration of Pb was highest in WB and RBC relative to plasma and saliva. However, the Pb rapidly redistributed (within 5-days post-treatment) from the blood into the bone compartment based on the substantial decrease in WB and RBC Pb concentration, and the concurrent increase in bone Pb following repeated exposure at all dose levels. Although there is clear variability in the observed Pb concentrations in plasma and saliva, there was a reasonable correlation (r2=0.922) between the average Pb concentrations in these biological matrices which was consistent with previous observations. The single oral dose of Pb-acetate resulted in a decrease in salivary pH which recovered by 24 hr post-dosing and a decrease in ?-amylase enzyme activity which did recover within 5-days of ceasing exposure. It is currently unclear what impact these slight functional changes may or may not have on Pb salivary clearance rates. These results demonstrate a feasibility to rapidly detect Pb in saliva and suggest that saliva may correlate best with plasma Pb concentration.« less
DOI: 10.1016/j.tox.2006.01.030
Noninvasive Biomonitoring Approaches to Determine Dosimetry and Risk Following Acute Chemical Exposure: Analysis of Lead or Organophosphate Insecticide in Saliva
Journal Article Timchalk, Chuck ; Poet, Torka S. ; Kousba, Ahmed A. ; ... - Journal of Toxicology and Environmental Health Part A
There is a need to develop approaches for assessing risk associated with acute exposures to a broad-range of chemical agents and to rapidly determine the potential implications to human health. Non-invasive biomonitoring approaches are being developed using reliable portable analytical systems to quantitate dosimetry utilizing readily obtainable body fluids, such as saliva. Saliva has been used to evaluate a broad range of biomarkers, drugs, and environmental contaminants including heavy metals and pesticides. To advance the application of non-invasive biomonitoring a microfluidic/ electrochemical device has also been developed for the analysis of lead (Pb), using square wave anodic stripping voltammetry. Themore » system demonstrates a linear response over a broad concentration range (1 2000 ppb) and is capable of quantitating saliva Pb in rats orally administered acute doses of Pb-acetate. Appropriate pharmacokinetic analyses have been used to quantitate systemic dosimetry based on determination of saliva Pb concentrations. In addition, saliva has recently been used to quantitate dosimetry following exposure to the organophosphate insecticide chlorpyrifos in a rodent model system by measuring the major metabolite, trichloropyridinol, and saliva cholinesterase inhibition following acute exposures. These results suggest that technology developed for non-invasive biomonitoring can provide a sensitive, and portable analytical tool capable of assessing exposure and risk in real-time. By coupling these non-invasive technologies with pharmacokinetic modeling it is feasible to rapidly quantitate acute exposure to a broad range of chemical agents. In summary, it is envisioned that once fully developed, these monitoring and modeling approaches will be useful for accessing acute exposure and health risk.« less
DOI: 10.1080/15287390490428035
Negative Ion Chemical Ionization Mass Spectrometry for the Analysis of 3,5,6-trichloro-2-pyridinol in Saliva of Rats Exposed to Chlorpyrifos
Journal Article Campbell, James A. ; Timchalk, Chuck ; Kousba, Ahmed A. ; ... - Analytical Letters
Organophosphorus (OP) insecticides (e.g. chlorpyrifos) are widely used in a variety of applications, and the potential exists for significant occupational and environmental exposures. They have been associated with more occupational poisoning cases than any other class of insecticides. One of the best approaches for accurately assessing human dosimetry and determining risk from both occupational and environmental exposure is biomonitoring. Biological matrices such as blood and urine have been routinely used for biomonitoring; however, other matrices such as saliva represent a simple and readily obtainable fluid. As a result, saliva has been suggested as an alternative biological matrix for the evaluationmore » of a broad range of biomarkers such as environmental contaminants, drugs of abuse, hormones, chemotherapeutics, heavy metals, and pesticides. Chlorpyrifos (CPF), and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCP), have been quantified in urine and blood as a biomarker for exposure to OP insecticides. The purpose of this study was to develop an analytical approach for detecting and quantitating the levels of TCP in saliva obtained from rats exposed to CPF and to evaluate the potential of saliva as a non-invasive biomonitoring matrix. Adult male rats were administered CPF, and blood and saliva were humanely collected for analysis of TCP and CPF. TCP was detected and quantitated in saliva using negative ion chemical ionization mass spectrometry with selected ion monitoring. Initial results indicate that saliva may be potentially utilized as a non-invasive biomonitoring matrix to determine exposure to organophosphate insecticides.« less
DOI: 10.1081/AL-200054056


CREATE-NET is an international research consortium active in the telecommunications and networking field based in northern Italy. CREATE-NET was founded in 2003 by some of the most prestigious universities and research centers in Europe (Technion, Budapest University of Technology and Economics, University of Trento, Fondazione Bruno Kessler), and currently collaborates with around 100 researchers, coming from 13 countries worldwide. By bringing together major academic institutions, corporations and research actors from around the world, CREATE-NET is engaged in combining highest quality research, addressing telecommunications and advanced services challenges, with experimentation on a unique real life experimental facility in Trentino. CREATE-NET is a partner of the EIT-ICTLabs initiative. The center has also developed very strong collaborations with major industrial stakeholders (Cisco Systems, Orange-FT, Siemens, Ericsson), while recently it has spinned off three promising startups (U-Hopper, eXrade, Intelincs) that are now capitalising on previous research efforts. CREATE-NET is also supporting eMobility, NEM, NESSI, ISI, E2B and participates in standardization activities in ETSI. CREATE-NET has participated in 8 projects in FP6 and is currently involved in 25 European projects, for five of which under FP7 it acts as coordinator (NetIDE, MONARCA, iCORE, CONGAS, Social-IST and UBIHEALTH) and for three other ones as technical/scientific coordinator (XiFi, INFINITY and SUPERHUB). CREATE-NET is also a very active actor of the scientific community through the organization and sponsoring of several international events in collaboration with IEEE, ACM, EU, ICST, IFIP and NSF.
CREATE-NET will act as coordinator of NetIDE and contribute the the overall success of the project by: supporting integration activities in WP2 by coordinating the integration efforts; leading the Task 4.1, responsible for the development of IRF interpreter within the Network App Engine; supporting the development of OpenFlow controllers drivers, thanks to its deep knowledge of Floodlight and Trema; and leading the dissemination activities in Task 6.1.


The Texans defeated the Colts on Sunday, Dec. 16, 2012, in Houston.
Houston Texans defensive end J.J. Watt (99) reacts to one of his sacks during the second quarter of an NFL football game at Reliant Stadium, Sunday, Dec. 16, 2012, in Houston.
Houston Texans linebacker Bryan Braman (50) scores a touchdown on the live ball when he blocked a punt during the second quarter at Reliant Stadium on Sunday, Dec. 16, 2012, in Houston.
Houston Texans head coach Gary Kubiak on the sidelines during the first quarter of an NFL football game at Reliant Stadium, Sunday, Dec. 16, 2012, in Houston.
Houston Texans wide receiver Andre Johnson (80) easily gets intio the end zone against the Indianapolis Colts defense during the first quarter at Reliant Stadium on Sunday, Dec. 16, 2012, in Houston.
Indianapolis Colts quarterback Andrew Luck (12) is sacked by Houston Texans defensive end J.J. Watt (99) during the first quarter at Reliant Stadium on Sunday, Dec. 16, 2012, in Houston.
Houston Texans defensive end J.J. Watt (99) inspires his team before they play the Indianapolis Colts ina NFL football game, Sunday, Dec. 16, 2012, in Reliant Stadium in Houston.
Houston Texans linebacker Bryan Braman (50) celebrates his touchdown after he blocked the punt during the second quarter of an NFL football game at Reliant Stadium, Sunday, Dec. 16, 2012, in Houston.
Houston Texans defensive end J.J. Watt (99) runs off the field after beating the Indianapolis Colts, Sunday, Dec. 16, 2012, in Reliant Stadium in Houston.
Indianapolis Colts quarterback Andrew Luck (12) throws on the run from the Houston Texans defense during the second quarter of an NFL football game at Reliant Stadium, Sunday, Dec. 16, 2012, in Houston.
Houston Texans defensive end J.J. Watt (99) and other members of the defense celebrate a turnover during the second quarter of an NFL football game at Reliant Stadium, Sunday, Dec. 16, 2012, in Houston.
Houston Texans free safety Danieal Manning (38) tries to tackle Colts Mewelde Moore (37) during the second quarter of an NFL football game at Reliant Stadium, Sunday, Dec. 16, 2012, in Houston.
Houston Texans outside linebacker Connor Barwin (98) tries to get the crowd involved during the second quarter of an NFL football game at Reliant Stadium, Sunday, Dec. 16, 2012, in Houston.
Houston Texans defensive end J.J. Watt (99) is able to get to Indianapolis Colts for a second sack of the fourth quarter during a NFL football game, Sunday, Dec. 16, 2012, in Reliant Stadium in Houston.