text:
Pre-eclampsia | |
Classification and external resources | |
Micrograph showing hypertrophic decidual vasculopathy, a histomorphologic finding seen in gestational hypertension - a component of pre-eclampsia. H&E stain.
DiseasesDB | 10494 |
MedlinePlus | 000898 |
eMedicine | med/1905 ped/1885 |
MeSH | D011225 |
Pre-eclampsia or preeclampsia is a medical condition characterized by high blood pressure and significant amounts of protein in the urine of a pregnant woman. If left untreated, it can develop into eclampsia, the life-threatening occurrence of seizures during pregnancy.
There are many different causes for the condition. It appears likely that there are substances from the placenta that can cause endothelial dysfunction in the maternal blood vessels of susceptible women.[1] While blood pressure elevation is the most visible sign of the disease, it involves generalised damage to the maternal endothelium, kidneys, and liver, with the release of vasoconstrictive factors being a consequence of the original damage.
An outdated medical term for pre-eclampsia is toxemia of pregnancy, since it was thought that the condition was caused by toxins.[2]
Pre-eclampsia may develop at any time after 20 weeks of gestation. Pre-eclampsia before 32 weeks is considered early onset, and is associated with increased morbidity. Its progress differs among patients; most cases are diagnosed before labor typically would begin. Pre-eclampsia may also occur up to six weeks after delivery. Apart from Caesarean section and induction of labor (and therefore delivery of the placenta), there is no known cure. It is the most common of the dangerous pregnancy complications; it may affect both the mother and fetus.[1]
The pre-eclampsia syndrome is thought in many cases to be caused by a shallowly implanted placenta which becomes hypoxic, leading to an immune reaction characterized by secretion of upregulated inflammatory mediators from the placenta, and acting on the vascular endothelium. The shallow implantation is thought to stem from the maternal immune system's response to the placenta and refers to evidence suggesting a lack of established immunological tolerance in pregnancy. This results in an immune response against paternal antigens from the fetus and its placenta.[3] In some cases of pre-eclampsia it is thought that the mother lacks the receptors for the proteins the placenta is using to downregulate the maternal immune system's response to it.[4] This view is also consistent with evidence showing many miscarriages to be an immunological disorder where the mother's immune system "unleashes a destructive attack on the tissues of the developing child".[5]
In many cases of the pre-eclampsia syndrome, however, the maternal response to the placenta appears to have allowed for normal implantation. It is possible that women with higher baseline levels of inflammation stemming from underlying conditions such as chronic hypertension or autoimmune disease may have less tolerance for the inflammatory burden of pregnancy.
If severe, pre-eclampsia progresses to fulminant pre-eclampsia, with headaches, visual disturbances, and epigastric pain, and further to the HELLP syndrome and eclampsia. HELLP syndrome itself is considered subtype of preeclampsia.[6] Placental abruption is associated with hypertensive pregnancies. These are life-threatening conditions for both the developing baby and the mother.
Many theories have attempted to explain why pre-eclampsia arises, and have linked the syndrome to the presence of the following:
- endothelial cell injury
- immune rejection of the placenta
- compromised placental perfusion
- altered vascular reactivity
- imbalance between prostacyclin and thromboxane
- decreased glomerular filtration rate with retention of salt and water
- decreased intravascular volume
- increased central nervous system irritability
- disseminated intravascular coagulation
- uterine muscle stretch (ischemia)
- dietary factors, including vitamin deficiency
- Hughes syndrome
- genetic factors[7] - There is an association between pre-eclampsia and certain variants of the genes coding for angiotensin-converting enzyme, CTLA-4, thrombin, factor V, lipoprotein lipase and plasminogen activator inhibitor-1.[8] These genetic risk factors are generally shared with those of cardiovascular diseases in general.[8]
- air pollution[9]
- obesity[10][11][12]
- Thyroid dysfunction: Subclinical hypothyroidism in early pregnancy, compared with normal thyroid function, has been estimated to increase the risk of pre-eclampsia with an odds ratio of 1.7.[13]
The current understanding of the syndrome is as a two-stage process, with a highly variable first stage which predisposes the placenta to hypoxia, followed by the release of soluble factors which result in many of the other events in pathogenesis.
Risk factors[edit]
Known risk factors for preeclampsia include:[6]
- Nulliparity
- Diabetes mellitus
- Renal disease
- Chronic hypertension
- Prior history of preeclampsia
- Age (>35 or <15)
- Obesity
- Antiphospholipid antibody syndrome
- Multiple gestation
Although much research into the cause and mechanism of pre-eclampsia has taken place, its exact pathogenesis remains uncertain. Some studies support notions of inadequate blood supply to the placenta making it release particular hormones or chemical agents that, in mothers predisposed to the condition, leads to damage of the endothelium (lining of blood vessels), alterations in metabolism, inflammation, and other possible reactions.[1]
Abnormalities in the maternal immune system and insufficiency of gestational immune tolerance seem to play major roles in pre-eclampsia. One of the main differences found in pre-eclampsia is a shift toward Th1 responses and the production of IFN-γ. The origin of IFN-γ is not clearly identified and could be the natural killer cells of the uterus, the placental dendritic cells modulating responses of T helper cells, alterations in synthesis of or response to regulatory molecules, or changes in the function of regulatory T cells in pregnancy.[14] Aberrant immune responses promoting pre-eclampsia may also be due to an altered fetal allorecognition or to inflammatory triggers.[14] It has been documented that fetal cells such as fetal erythroblasts as well as cell-free fetal DNA are increased in the maternal circulation in women who develop pre-eclampsia. These findings have given rise to the hypothesis that pre-eclampsia is a disease process by which a placental lesion such as hypoxia allows increased fetal material into maternal circulation that leads to an immune response and endothelial damage ultimately resulting in pre-eclampsia and eclampsia.
Some studies suggest that hypoxia resulting from inadequate perfusion upregulates sFlt-1, a VEGF and PlGF antagonist, leading to a damaged maternal endothelium and restriction of placental growth.[15] In addition, endoglin, a TGF-beta antagonist, is elevated in pregnant women who develop pre-eclampsia.[16] Soluble endoglin is likely upregulated by the placenta in response to an upregulation of cell-surface endoglin produced by the maternal immune system, although there is also the potential that sEng is produced by the maternal endothelium. Levels of both sFlt-1 and sEng increase as severity of disease increases, with levels of sEng surpassing levels of sFlt-1 in HELLP syndrome cases. Recent data indicate that Gadd45a stress signaling regulates elevated sFlt-1 expression in pre-eclampsia.[17] Another VEGF antagonist implicated in pathogenesis of preeclampsia is soluble fms-like tyrosine kinase-1.[6]
Both sFlt-1 and sEng are upregulated in all pregnant women to some extent, supporting the idea that hypertensive disease in pregnancy is a normal pregnancy adaptation gone awry. As natural killer cells are intimately involved in placentation and as placentation involves a degree of maternal immune tolerance for a foreign placenta which requires maternal resources for its support, it is not surprising that the maternal immune system might respond more negatively to the arrival of some placentae under certain circumstances, such as a placenta which is more invasive than normal. Initial maternal rejection of the placental cytotrophoblasts may be the cause of the inadequately remodeled spiral arteries in those cases of pre-eclampsia associated with shallow implantation, leading to downstream hypoxia and the appearance of maternal symptoms in response to upregulated sFlt-1 and sEng.
One hypothesis for vulnerability to preeclampsia is the maternal-fetal conflict between the maternal organism and fetus.[18] After the first trimester trophoblasts enter the spiral arteries of the mother to alter the spiral arteries and thereby gain more access to maternal nutrients.[18] However, occasionally there is impaired trophoblast invasion that results in inadequate alterations to the uterine spiral arteries.[18] It is hypothesized that the developing embryo releases biochemical signals that result in the woman developing hypertension and preeclampsia so that the fetus can benefit from a greater amount of maternal circulation of nutrients due to increased blood flow to the impaired placenta.[18] This results in a conflict between the maternal organism's Darwinian fitness and survival and the developing fetus because the fetus is invested in only its survival and fitness while the mother is invested in this pregnancy and subsequent potential pregnancies.[18]
Another evolutionary hypothesis for vulnerability to preeclampsia is the idea of ensuring pair-bonding between the mother and father and paternal investment in the fetus.[19] Researchers posit the idea that preeclampsia serves as an adaptation for the mother to terminate investment in a fetus that might have an unavailable paternal donor, as determined by repeated semen exposure of the paternal donor to the mother.[19] Various studies have shown that women who frequently had exposure to partners' semen before conception had a reduced risk of preeclampsia.[19] Also, subsequent pregnancies by the same paternal donor had a reduced risk of preeclampsia while subsequent pregnancies by a different paternal donor had a higher risk of developing preeclampsia.[19]
Pre-eclampsia is well diagnosed when a pregnant woman develops both:[6]
- blood pressure >140 systolic and/or >90 diastolic (two separate readings taken at least six hours apart)
- 0.3 grams or more of protein in a 24-hour urine sample (proteinuria).
A rise in baseline blood pressure (BP) of 30 mmHg systolic or 15 mmHg diastolic, while not meeting the absolute criteria of 140/90, is still considered important to note, but is not considered diagnostic.
"Severe pre-eclampsia" involves a BP over 160/110,[20][21] proteinuria more than 1 g / 24 h and signs of end organ damage (CNS) dysfunction with symptoms like headache; pulmonary edema; renal dysfunction with oliguria or creatinine over 1.5 mg/dL; hepatocellular injury with ALT more than two-fold upper normal limit; hematologic dysfunction with platelet count less than 100,000/μL or DIC; placental dysfunction with IUGR or oligohydramnios etc.)[6]
Other symptoms[edit]
Swelling or edema (especially in the hands and face) was originally considered an important sign for a diagnosis of pre-eclampsia, but in current medical practice only hypertension[22] and proteinuria are necessary for a diagnosis. Pitting edema (unusual swelling, particularly of the hands, feet, or face, notable by leaving an indentation when pressed on) can be significant, and should be reported to a health care provider.
Although eclampsia is potentially fatal (2% of cases), pre-eclampsia is often asymptomatic, and so its detection depends on signs or investigations. Nonetheless, one symptom is crucially important because it is often misinterpreted: epigastric pain may be confused with heartburn, a common problem of pregnancy. In general, none of the signs of pre-eclampsia are specific, and even convulsions in pregnancy are more likely to have causes other than eclampsia in modern practice. Diagnosis, therefore, depends on finding a coincidence of several pre-eclamptic features, the final proof being their regression after delivery.
Some women develop high blood pressure without proteinuria (protein in urine), which is called pregnancy-induced hypertension (PIH) or gestational hypertension. Both pre-eclampsia and PIH are regarded as very serious conditions and require careful monitoring of mother and baby.
Emerging predictive tests[edit]
Emerging tests aimed at predicting or at least quantifying the risk of pre-eclampsia include the following blood tests taken by venipuncture on the mother:
- Placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) levels in late first or second trimester appear to predict early-onset pre-eclampsia with a high sensitivity and specificity.[23]
- Vascular endothelial growth factor (VEGF) family proteins do not have sufficient statistical power to accurately predict late-onset pre-eclampsia, but may be useful in detection of early-onset pre-eclampsia.[23]
- Placental protein 13 (PP13) levels that are low in the first trimester of pregnancy confer a higher risk of developing pre-eclampsia later in pregnancy.[24]
In November 2011, a new test was announced that involves checking patients' urine for specific cells called podocytes. Out of the 300 women tested, all the women who went on to have pre-eclampsia were found to have podocytes in their urine, whilst none of the women who had a normal pregnancy, or who suffered from pregnancy-induced hypertension, tested positive for podocytes.[25][26]
Differential diagnosis[edit]
Pre-eclampsia can mimic and be confused with many other diseases, including chronic hypertension, chronic renal disease, primary seizure disorders, gallbladder and pancreatic disease, immune or thrombotic thrombocytopenic purpura, antiphospholipid syndrome and hemolytic-uremic syndrome. It must always be considered a possibility in any pregnant woman beyond 20 weeks of gestation. It is particularly difficult to diagnose when preexisting disease such as hypertension is present.[27] Women with acute fatty liver of pregnancy may also present with elevated blood pressure and protein in the urine, but differs by the extent of liver damage.
Thrombophilias may be weakly linked to pre-eclampsia. There are no high quality studies to suggest that blood thinners will prevent pre-eclampsia in thrombophilic women.[28]
Smoking cessation[edit]
In low-risk pregnancies the association between cigarette smoking and a reduced risk of pre-eclampsia has been consistent and reproducible across epidemiologic studies. High-risk pregnancies (those with pregestational diabetes, chronic hypertension, history of pre-eclampsia in a previous pregnancy, or multifetal gestation) showed no significant protective effect. The reason for this discrepancy is not definitively known; research supports speculation that the underlying pathology increases the risk of pre-eclampsia to such a degree that any measurable reduction of risk due to smoking is swamped.[29] A study into the effects of smoking on the incidence of pre-eclampsia in African-American women found a significantly lower incidence of pre-eclampsia with higher measured levels of nicotine. When adjusted for age, parity, and medical comorbidities the association was still observable, but no longer significant.[30] Medical authorities and anti-smoking advocates discourage smoking in general during pregnancy.
Protein or calorie supplementation have no effect on pre-eclampsia rates, and dietary protein restriction does not appear to increase pre-eclampsia rates.[31] Supplementation with antioxidants such as vitamin C and E have no effect.[32] There is no evidence that changing salt intake has an effect.[33]
Calcium supplementation in women with low-calcium diets found no change in pre-eclampsia rates but did find a decrease in the rate of severe preeclamptic complications.[34] Low selenium status is associated with higher incidence of pre-eclampsia.[35]
Low dose aspirin has moderate benefits when used for the prevention of pre-eclampsia.[36] Start of supplementation at or before 16th week of pregnancy resulted in a substantial reduction of preterm pre-eclampsia without any effect on term pre-eclampsia.[37]
There is insufficient evidence to recommend either exercise[38] or bedrest[39] as preventative measures of pre-eclampsia.
The only known definitive treatment for eclampsia or advancing pre-eclampsia is delivery, either by labor induction or Caesarean section of both fetus and placenta.[6] However, post-partum pre-eclampsia may occur up to six weeks following delivery even if symptoms were not present during the pregnancy. Post-partum pre-eclampsia is dangerous to the health of the mother since she may ignore or dismiss symptoms as simple post-delivery headaches and edema. Hypertension can sometimes be controlled with anti-hypertensive medication, but any effect this might have on the progress of the underlying disease is unknown.
Blood pressure medication[edit]
Antihypertensives reduce maternal and fetal mortality among pregnancy patients with hypertension as compared to placebo according to a randomized controlled trial.[40] Overall, after three weeks of treatment, mean arterial pressure was lower in the isradipine group, but when compared with the placebo group, the difference in mean arterial pressure did not have statistical significance. After treatment with isradipine, those patients with no proteinuria experienced a decrease of between 8.5 and 11.3 mmHg, whereas those with proteinuria experienced about only 1 mmHg difference in systolic blood pressure. Those treated with placebo in both groups did not experience much change in systolic blood pressure, regardless of proteinuria being present or not. Therefore, the authors concluded proteinuric patients may respond differently from nonproteinuric patients to this treatment, where the nonproteinuric patients responded the most to treatment with isradipine.
Labetolol, Hydralazine and Nifedipine are often the antihypertensives of choice for eclampsia or pre-eclampsia, especially Labetolol as it has little placental transfer. ACE inhibitors and angiotensin receptor blockers are contraindicated as they affect fetal development.[6]
The target blood pressure has been proposed to be 140-160 mmHg systolic and 90-105 mmHg diastolic, although some sources recommend lower values.[41]
Magnesium sulfate[edit]
In some cases, women with pre-eclampsia or eclampsia can be stabilized temporarily with magnesium sulfate intravenously to forestall seizures while steroid injections are administered to promote fetal lung maturation. Magnesium sulfate acts by interacting with NMDA receptors.[6] Magnesium sulfate as a possible treatment was considered at least as far back as 1955,[42] but only in recent years did its use in the UK replace the use of diazepam or phenytoin.[43] Evidence for the use of magnesium sulfate came from the international MAGPIE study.[44] When induced delivery needs to take place before 37 weeks gestation, it is accepted that there are additional risks to the baby from premature birth that will require additional monitoring and care.
Pre-eclampsia affects approximately 6-8% of all pregnancies worldwide,[45] with onset of symptoms in the late second or third trimester, most commonly after the 32nd week. Some women will experience pre-eclampsia as early as 20 weeks, though this is rare. It is much more common in women who are pregnant for the first time,[46] and its frequency drops significantly in second pregnancies. Change of paternity in a subsequent pregnancy has been implicated as affecting risk, except in those with a family history of hypertensive pregnancy[47] since increasing maternal age raises risk,.[48] It has been difficult to evaluate how significant paternity change actually is and studies are providing conflicting data on this point.
Pre-eclampsia is also more common in women who have preexisting hypertension, diabetes, autoimmune diseases such as lupus, various inherited thrombophilias such as Factor V Leiden, renal disease, women with a family history of pre-eclampsia, obese women, and women with a multiple gestation (twins or multiple birth). The single most significant risk for developing pre-eclampsia is having had pre-eclampsia in a previous pregnancy.[citation needed]
Pre-eclampsia may also occur in the immediate post-partum period. This is referred to as "postpartum pre-eclampsia". The most dangerous time for the mother is the 24–48 hours postpartum and careful attention should be paid to pre-eclampsia signs and symptoms.[49]
Eclampsia can occur after the onset of pre-eclampsia. Eclampsia, which is a more serious condition, complicates 1 in 2000 maternities in the United Kingdom and carries a maternal mortality of 1.8 percent.[50] The HELLP syndrome is more common, probably about 1 in 500 maternities, but may be as dangerous as eclampsia itself. These two major maternal crises can present unheralded by prodromal signs of pre-eclampsia.
Cerebral autoregulation is disturbed in preeclampsia leading to increased risk of stroke.[6] Cerebral hemorrhage is a lesion that can kill with pre-eclampsia or eclampsia. In that cerebral hemorrhage is a known complication of severe hypertension in other contexts, it must be assumed that this is a major predisposing factor in this situation, although this has not been proven. Adult respiratory distress syndrome appears to have become more common, it is not known whether this is a consequence of modern methods of respiratory support rather than of the disease itself.
Uric acid levels may help to predict maternal complications among patients with pre-eclampsia according to a systematic review and decision analysis.[51] In this study, the sensitivity was 68% and specificity was 68%. In this study which assumed a prevalence of maternal complications was 5%, the positive predictive value of 6.2% and negative predictive value of 98.6% (click here to adjust these results for patients at higher or lower risk of maternal complications). In their clinical decision analysis, they presumed initially a distress ratio of 10 (defined as being the expected distress of severe complications valued as 10 times worse than the expected distress of a caesarean section), and under these assumptions, they concluded that there would be the least expected distress from using serum uric acid for clinical decision making. The writers of this study acknowledged that there were significant limitations to their review due to heterogeneity of the individual studies they examined with regards to several variables.
In very rare cases, temporary vision loss can occur due to partial or complete cortical blindness by petechial hemorrhages and focal vasogenic edema in the occipital cortex.[52][53]
Women with preeclampsia are at higher risk of cardiovascular and renal disorders later in life.[6]
Many studies have also suggested the importance of a woman's immunological tolerance to her baby's father, whose genes are present in the young fetus and its placenta and which may pose a challenge to her immune system.[3][54] As the theory is further investigated,[55] researchers are increasingly studying the importance of a woman's continued exposure to her partner's semen as early as several years before conception. One study published in the American Journal of Obstetrics and Gynecology involved several hundreds of women and found that "women with a short period of cohabitation (less than 4 months) who used barrier methods for contraception had a substantially elevated risk for the development of pre-eclampsia compared with women with more than 12 months of cohabitation before conception".[56] However, the results from a study conducted in 2004 show that the theory is still not conclusive. In that study, the researchers found that after adjustment and stratification, the effect of barrier contraceptive use on the development of pre-eclampsia had disappeared, with both arms having identical rates of pre-eclampsia.[57] Although the study has since been criticized for its subjective adjustment of data, it remains important because it demonstrates that there is still some contention over the degree to which failure of tolerance induction can be attributed to prior exposure to the partner's sperm.
Continued exposure to a partner's semen has a strong protective effect against pre-eclampsia, largely due to the absorption of several immune modulating factors present in seminal fluid.[58][59]
Long periods of sexual cohabitation with the same partner fathering a woman's child significantly decreased her chances of suffering pre-eclampsia.[56][59] As one early study described, "although pre-eclampsia is a disease of first pregnancies, the protective effect of multiparity is lost with change of partner".[60] The study also concluded that although women with changing partners are strongly advised to use condoms to prevent sexually transmitted diseases, "a certain period of sperm exposure within a stable relation, when pregnancy is aimed for, is associated with protection against pre-eclampsia".[60]
Several other studies have since investigated the strongly decreased incidence of pre-eclampsia in women who had received blood transfusions from their partner, those with long, preceding histories of sex without barrier contraceptives, and in women who had been regularly performing oral sex,[61][62] with one study concluding "induction of allogeneic tolerance to the paternal human leukocyte antigen (HLA) molecules of the fetus may be crucial. Data collected strongly suggest that exposure, and especially oral exposure to soluble HLA from semen can lead to transplantation tolerance."[62]
According to the theory, the fetus and placenta both contain "foreign" proteins from paternal genes, but regular, preceding and coincident exposure to the father's semen may promote immune acceptance and subsequent implantation, a process which is significantly supported by as many as 93 currently identified immune regulating factors in seminal fluid.[3][54]
Having already noted the importance of a woman's immunological tolerance to her baby's paternal genes, several Dutch reproductive biologists decided to take their research a step further. Consistent with the fact that human immune systems tolerate things better when they enter the body via the mouth, the Dutch researchers conducted a series of studies that confirmed a surprisingly strong correlation between a diminished incidence of pre-eclampsia and a woman's practice of oral sex, and noted that the protective effects were strongest if she swallowed her partner's semen.[61][62][63][64][65][66] The researchers concluded that while any exposure to a partner's semen during sexual activity appears to decrease a woman's chances for the various immunological disorders that can occur during pregnancy, immunological tolerance could be most quickly established through oral introduction and gastrointestinal absorption of semen.[62][63] Recognizing that some of the studies potentially included the presence of confounding factors, such as the possibility that women who regularly perform oral sex and swallow semen also engage in more frequent intercourse, the researchers also noted that, either way, "the data still overwhelmingly supports the main theory" behind all their studies—that repeated exposure to semen establishes the maternal immunological tolerance necessary for a safe and successful pregnancy.[59][63]
A team from the University of Adelaide has also investigated to see if men who have fathered pregnancies which have ended in miscarriage or pre-eclampsia had low seminal levels of critical immune modulating factors such as TGF-Beta. The team has found that certain men, dubbed "dangerous males", are several times more likely to father pregnancies that would end in either pre-eclampsia or miscarriage.[59] Among other things, most of the "dangerous males" seemed to lack sufficient levels of the seminal immune factors necessary to induce immunological tolerance in their partners.[67]
As the theory of immune intolerance as a cause of pre-eclampsia has become accepted, women who with repeated pre-eclampsia, miscarriages, or In Vitro Fertilization failures could potentially be administered key immune factors such as TGF-beta along with the father's foreign proteins, possibly either orally, as a sublingual spray, or as a vaginal gel to be applied onto the vaginal wall before intercourse.[59]
It was reported that patients with pre-eclampsia have higher levels of endothelial microparticles than healthy controls. Concentration of endothelial microparticles has been proposed as a biomarker for pre-eclampsia severity.[68]
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- ^ Duley, L.; Henderson-Smart, D. J.; Meher, S.; King, J. F. (2007). Antiplatelet agents for preventing pre-eclampsia and its complications. In Duley, Lelia. "Cochrane Database of Systematic Reviews". Cochrane database of systematic reviews (Online) (2): CD004659. doi:10.1002/14651858.CD004659.pub2. PMID 17443552.
- ^ Roberge, S. P.; Villa, P.; Nicolaides, K.; Giguère, Y.; Vainio, M.; Bakthi, A.; Ebrashy, A.; Bujold, E. (2012). "Early Administration of Low-Dose Aspirin for the Prevention of Preterm and Term Preeclampsia: A Systematic Review and Meta-Analysis". Fetal Diagnosis and Therapy 31 (3): 141–146. doi:10.1159/000336662. PMID 22441437.
- ^ Meher S, Duley L (2006). "Exercise or other physical activity for preventing pre-eclampsia and its complications". In Meher, Shireen. Cochrane Database of Systematic Reviews (2): CD005942. doi:10.1002/14651858.CD005942. PMID 16625645.
- ^ Meher S, Duley L (2006). "Rest during pregnancy for preventing pre-eclampsia and its complications in women with normal blood pressure". In Meher, Shireen. Cochrane Database of Systematic Reviews (2): CD005939. doi:10.1002/14651858.CD005939. PMID 16625644.
- ^ Wide-Swensson, DH; Ingemarsson, I; Lunell, NO; Forman, A; Skajaa, K; Lindberg, B; Lindeberg, S; Marsàl, K; Andersson, KE (1995). "Calcium channel blockade (isradipine) in treatment of hypertension in pregnancy: a randomized placebo-controlled study". American journal of obstetrics and gynecology 173 (3 Pt 1): 872–8. doi:10.1016/0002-9378(95)90357-7. PMID 7573260.
- ^ Hypertensive Disorders in Pregnancy. Version 2.0. at Nederlandse Vereniging voor Obstetrie en Gynaecologie. Date of approval: 20-05-2005
- ^ PRITCHARD JA (February 1955). "The use of the magnesium ion in the management of eclamptogenic toxemias". Surgery, Gynecology & Obstetrics 100 (2): 131–40. PMID 13238166.
- ^ Compare descriptions in 1977 between a British and American paper.
* Hibbard BM, Rosen M (January 1977). "The management of severe pre-eclampsia and eclampsia". British Journal of Anaesthesia 49 (1): 3–9. doi:10.1093/bja/49.1.3. PMID 831744.
* Andersen WA, Harbert GM (October 1977). "Conservative management of pre-eclamptic and eclamptic patients: a re-evaluation". American Journal of Obstetrics and Gynecology 129 (3): 260–7. PMID 900196. - ^ The Magpie Trial Follow Up Study Management Group; The Magpie Trial Follow Up Study Collaborative Group (March 2004). "The Magpie Trial follow up study: outcome after discharge from hospital for women and children recruited to a trial comparing magnesium sulphate with placebo for pre-eclampsia ISRCTN86938761". BMC Pregnancy and Childbirth 4: 5. doi:10.1186/1471-2393-4-5. PMC 416479. PMID 15113445.
- ^ World Health Organization (WHO). World health report 2005: make every mother and child count. Geneva: WHO; 2005, page 63
- ^ Robbins and Cotran, Pathological Basis of Disease, 7th ed.
- ^ Hjartardottir S, Leifsson BG, Geirsson RT, Steinthorsdottir V (2004). "Paternity change and the recurrence risk in familial hypertensive disorder in pregnancy". Hypertension in Pregnancy 23 (2): 219–25. doi:10.1081/PRG-120037889. PMID 15369654.
- ^ Zhang J (July 2007). "Partner change, birth interval and risk of pre-eclampsia: a paradoxical triangle". Paediatric and Perinatal Epidemiology 21 (Suppl 1): 31–5. doi:10.1111/j.1365-3016.2007.00835.x. PMID 17593195.
- ^ Munjuluri N, Lipman M, Valentine A, Hardiman P, Maclean AB (November 2005). "Postpartum eclampsia of late onset". BMJ 331 (7524): 1070–1. doi:10.1136/bmj.331.7524.1070. PMC 1283194. PMID 16269495.
- ^ Douglas KA, Redman CW (November 1994). "Eclampsia in the United Kingdom". BMJ 309 (6966): 1395–400. doi:10.1136/bmj.309.6966.1395. PMC 2541348. PMID 7819845.
- ^ Koopmans, CM; Van Pampus, MG; Groen, H; Aarnoudse, JG; Van Den Berg, PP; Mol, BW (2009). "Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia: bivariate meta-analysis and decision analysis". European journal of obstetrics, gynecology, and reproductive biology 146 (1): 8–14. doi:10.1016/j.ejogrb.2009.05.014. PMID 19540647.
- ^ Cunningham, F. G.; Fernandez, C. O.; Hernandez, C. (1995). "Blindness associated with preeclampsia and eclampsia". American journal of obstetrics and gynecology 172 (4 Pt 1): 1291–1298. doi:10.1016/0002-9378(95)91495-1. PMID 7726272.
- ^ Do, D. V.; Rismondo, V.; Nguyen, Q. D. (2002). "Reversible cortical blindness in preeclampsia". American journal of ophthalmology 134 (6): 916–918. doi:10.1016/S0002-9394(02)01753-1. PMID 12470768.
- ^ a b "Sex Primes Women for Sperm". BBC News. 2002-02-06. Retrieved 2007-11-19.
- ^ Waite LL, Atwood AK, Taylor RN (May 2002). "Pre-eclampsia, an implantation disorder". Reviews in Endocrine & Metabolic Disorders 3 (2): 151–8. doi:10.1023/A:1015411113468. PMID 12007292.
- ^ a b Einarsson JI, Sangi-Haghpeykar H, Gardner MO (May 2003). "Sperm exposure and development of pre-eclampsia". American Journal of Obstetrics and Gynecology 188 (5): 1241–3. doi:10.1067/mob.2003.401. PMID 12748491.
- ^ Ness RB, Markovic N, Harger G, Day R (2004). "Barrier methods, length of preconception intercourse, and pre-eclampsia". Hypertension in Pregnancy 23 (3): 227–35. doi:10.1081/PRG-200030293. PMID 15617622.
- ^ Sarah Robertson. "Research Goals --> Role of seminal fluid signalling in the female reproductive tract".
- ^ a b c d e Robertson SA, Bromfield JJ, Tremellen KP (August 2003). "Seminal 'priming' for protection from pre-eclampsia-a unifying hypothesis". Journal of Reproductive Immunology 59 (2): 253–65. doi:10.1016/S0165-0378(03)00052-4. PMID 12896827.
- ^ a b Dekker GA, Robillard PY, Hulsey TC (June 1998). "Immune maladaptation in the etiology of pre-eclampsia: a review of corroborative epidemiologic studies". Obstetrical & Gynecological Survey 53 (6): 377–82. doi:10.1097/00006254-199806000-00023. PMID 9618714.
- ^ a b Bonney EA (December 2007). "Preeclampsia: A view through the danger model". Journal of Reproductive Immunology 76 (1–2): 68–74. doi:10.1016/j.jri.2007.03.006. PMC 2246056. PMID 17482268.
- ^ a b c d Koelman CA, Coumans AB, Nijman HW, Doxiadis II, Dekker GA, Claas FH (March 2000). "Correlation between oral sex and a low incidence of pre-eclampsia: a role for soluble HLA in seminal fluid?". Journal of Reproductive Immunology 46 (2): 155–66. doi:10.1016/S0165-0378(99)00062-5. PMID 10706945.
- ^ a b c Fox, Douglas (2002-02-09). "Gentle Persuasion". The New Scientist. Retrieved 2007-06-17.
- ^ Mattar R, Soares RV, Daher S (February 2005). "Sexual behavior and recurrent spontaneous abortion". International Journal of Gynaecology and Obstetrics 88 (2): 154–5. doi:10.1016/j.ijgo.2004.11.006. PMID 15694097.
- ^ Danielle Cavallucci, and Yvonne K. Fulbright (2008). Your Orgasmic Pregnancy. Alameda, CA: Hunter House Inc. Publishers. p. 90. ISBN 0897935012. http://books.google.com/books?id=othN_A1w2BYC&pg=PA90&lpg=PA90
- ^ Jelto Drenth (2005). The Origin of the World. London: Reaktion Books. pp. 114–115. ISBN 1861892101.
- ^ Dekker G (2002). "The partner's role in the etiology of pre-eclampsia". Journal of Reproductive Immunology 57 (1–2): 203–15. doi:10.1016/S0165-0378(02)00039-6. PMID 12385843.
- ^ Ling L (Feb 2014). "Evaluation of plasma endothelial microparticles in pre-eclampsia.". J Int Med Res 42 (1): 42–51. PMID 24319051.
External links[edit]
- MedlinePlus entry on high blood pressure in pregnancy
- Mayo Clinic fact sheet on pre-eclampsia
- "Preeclampsia Research at the NICHD". NICHD : US Department of Health and Human Services & National Institutes of Health.


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1st java try yuck Manga (Original)
Artist description:
totally experimental- 1 layer dont know how 2 use em lol- was gunna delete then was like o y not :p looks blurry i know :O
Created Dec 09, 2012. Unless noted Copyright 2012
anim3luver .
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Lions, Tigers and Bears Oh MY! love the expression,,, the eyes are sweet,,, a nice job for a first time,,, I love it
it is so good for you to experiment..I always use one layer, but this tool is fantastic, it's for fantasy to expand...lovely...5/5..
Takes a while to get the hang of it. Did you used layers? When you have lineart it's much easy to colour when you have the lineart above the colouring. Check out some of these: http://www.ratemydrawings.com/tutorials/manga/
You'll learn how to use java and, then, u'll love it. Search tutorials around here and you'll find some about how to use java, layers and etc.
i knew it was your drawing :p wait - what do you mean by 'yuck'? this is awesome! the shadings, the colours - all nicely done :3
looks great and the first draw never looks like you want... keep trying i love java i rarely use any other tool... I just hate the flash... cant so it not talented enough
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Sick of campus jobs, two Texas college girls turn to monster porn.
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Women can have it all. Hillary Clinton in particular.
Marissa Mayer returns to work next week. Are working moms overcompensating?
Hate your day job? This'll make you feel worse.


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This was definitely a good recipe. I couldn't find skin on breasts, so I used thighs. There is a video on this recipe and I would recommend watching it if you need help. Next time I make this though I will be making extra seasoning.
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We spoke very recently at length to a trusty source within BMW who is familiar with the development of the upcoming F80 M3 sedan / F82 M4 coupe and we were able to learn the following bits of news:
Regarding power output, the previously estimated 450HP figure is an overestimate. Instead, expect the horsepower output to be in ballpark of the current E90/E92 M3.
What will be increased greatly however, is the torque figure. The F80/F82′s multi turbo inline 6 cylinder engine [recently exposed] will add approximately 100 lb-ft more torque over the current M3 (which outputs 295 lb-ft torque). This would put the new M3/M4 in the range of 395 lb-ft torque. There's nothing like forced induction for thrust!
We were also glad to learn that … CONTINUED
We have been reporting and referring to the upcoming F32 and F82 models as the 4 Series Coupe and M4 Coupe for months now, and Automobile now comes in with their ruminations on what the M4 and 4 series lineup will bring. Although much of this is not new information, it provides a good review of what to expect for the upcoming 4 Series and M4:
4 Series Coupe (F32), 4 Series Convertible (F33), and Gran Coupe (F36)
• Coupe variant of F30 3 Series to be called 4 Series (positioned and priced in lineup just as the 6 Series Coupe is positioned in the 5/6 Series lineup)
• Four door "coupe" styled variant to be called 4 Series Gran Coupe … CONTINUED
Back in May we first confirmed that the F80 M3 and F82 M4 would be powered by an inline 6 cylinder turbo engine and indeed we've just received these first photos of the next gen M3/M4 engine, with visual proof of the inline cylinder setup.
The F80 M3 / F82 M4 will have some good cooling of the the heated air pumping from its turbos, via components such as the air-to-water/liquid intercooler unit (to the right of the engine cover) feeding the cylinders with cooled air. If this setup is anything like in the M5/M6 S63Tu engine, the air is cooled by this unit right before it reaches the cylinders. There appears to be twin intake boxes and the oil cooler bracket looks to be the same … CONTINUED
The 2014 F80 M3 continues prototype testing on the road and track on and around the Nurburgring. We've compiled this 3 minute video featuring plenty of new sights and sounds of the F80 M3 in various settings performing different maneuvers and driving action.
With its planted ride and suspension, together with plenty of power from its turbo inline 6 cylinder, the new M3 flies around the track with little body roll and suspension travel.
To reiterate our oft repeated details on the upcoming F80 M3 / F82 M4:
The F80 M3 / F82 M4 will be powered by an inline 6 cylinder engine with multiple turbochargers, pushing approximately 450 horsepower. The engine has been rumored to be an extensively reworked and reinforced N55 6-cylinder engine with a strengthened aluminium … CONTINUED
Watch and listen as the 2014 BMW M3 (F80) slings around the famous Karussell at the Nurburgring track, sounding thunderous as it accelerates out of the hairpin turn.
Here is a summary of the most up to date facts regarding the F80 M3 / F82 M4:
Lighter than current M3
Faster than current M3
More powerful than current M3
More efficient than current M3
Powered by an inline 6 cylinder turbo engine
Offered with optional or standard manual transmission
Electric Power Steering (completely reworked for precision for M3/M4)
Tires (from prototype) – Michelin Pilot Super Sport: … CONTINUED
Some updated F82 M4 coupe renders from Jerry Alvarez. The white M4 coupe render now incorporates the M6/1M styled front bumper with air curtain vents recently spied on the F80 M3 sedan. Not reflected in the renders however, is an expected sleeker front fascia and headlights (compared to the F30 3 series). The F82 M4 coupe is also expected to feature a carbon fiber roof.
The F80 M3 / F82 M4 will not be constructed extensively from carbon fiber (CFRP) as some earlier reports had speculated. Because this next generation M3/M4 began development two years ago, it's said to have been too early to take advantage of BMW's CFRP developments with the later introduction of the BMW i cars/project. The first model (besides the i cars) … CONTINUED
Resident digital artist Jerry Alvarez has put together this speculative side render of the F82 M4 coupe.
Although not visible in these renders, you can expect the F82 M4 coupe to receive the same (or very similar) hood lip/bulge that we recently spotted for the first time on the F80 M3 sedan.
Also not reflected in the renders is an expected sleeker front fascia and headlights (compared to the F30 3 series). The F82 M4 coupe is also expected to feature a carbon fiber roof.
The F80 M3 / F82 M4 will not be constructed extensively from carbon fiber (CFRP) as some earlier reports had speculated. Because this next generation M3/M4 began development two years ago, it's said to have been too early to take advantage of BMW's CFRP … CONTINUED
A 2014 M3 test prototype resumed testing at the Nurburgring yesterday and the strip tease continued by way of a possible (or intended) camouflage malfunction. Here's what we see.
Air Curtains
By coincidence (?), the passenger side lower front bumper camouflage was flapped open during the test runs, revealing and confirming the air curtain vents on the F80. Whether the camouflage was peeled back to feed air to the air curtains for testing purposes, resulted from a camouflage malfunction, or was purposely peeled back to tease us, matters not. What's important is that we get the first clear look at the air curtain vent, which appears very large judging by the amount of space between the air curtain vent outline and the outer edge of the still camouflaged … CONTINUED
Many of you requested to see a white version of our latest F80 M3 renders, so by popular demand, we've added a couple of white versions to the batch.
If you've been tracking our homepage or our M3 forum section, you've surely seen the flurry of F80 M3 test mule sightings in the past two weeks or so.
Not only have the sightings become more frequent, but they've also been more revealing. With the latest rounds of spy photos, we now have a fairly good idea of what to expect from the 2014 M3 sedan's front end styling.
The F80 will feature a hood bump and a very aggressive front bumper/apron with a what looks to be a mix of elements from the M6 and 1M's styling – M6 … CONTINUED


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Conceptually Accurate Signed English (CASE)
Conceptually Accurate Signed English (CASE) — sometimes called Pidgin Signed English (PSE) — is a building block that has developed between people who use American Sign Language (ASL), and people who use Manually Coded English (MCE), using signs based on ASL and MCE. This helps them understand each other better.
In CASE, American Sign Language (ASL) and Manually Coded English (MCE) are blended together. CASE is flexible, and can be changed depending on the people using it.
Other building blocks can be used with CASE. Often, finger spelling is used in combination with CASE. Finger spelling is used to spell out words that don't have a sign — such as names of people and places.
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On the way of Nathdwara to Ajmer
Albums: Colourful rajasthan
Pravin Bagga ji Thnx
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RIPLEY -A Bemus Point man was taken into custody after allegedly fleeing the scene of an automobile accident Friday night.
At 10:58 p.m., the Chautauqua County Sheriff's patrol located a vehicle crashed at the intersection of Route 76 and County Route 6 in the town of Ripley. The driver had fled the scene on foot. Deputies searched the area and spoke to neighbors to develop information on the operator's description.
Kamal K. Korkonda, 29, was determined to be the owner and operator of the vehicle, and was located not far from the accident scene at around 12:10 a.m.
Following the investigation, Korkonda was charged for driving while intoxicated, at unreasonable and imprudent speeds, and failure to stop at a stop sign.
After processing, Korkonda was later released. He is scheduled to appear in Ripley Court.


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New york woman sentenced to federal prison for selling contraband cigarettes in new jersey
January 6, 2010 |
CAMDEN, N.J. – A New York woman was sentenced today to nine months in federal prison and nine months in a halfway house for selling untaxed cigarettes through the Internet to restaurants and individuals in New Jersey, resulting in a $3.9 million revenue loss to the state, U.S. Attorney Paul J. Fishman announced.
Rita Roosa, 47, of Allegany, N.Y., pleaded guilty on July 7, 2009, to an Information charging her with one count each of conspiracy to traffic and trafficking in contraband cigarettes. Roosa entered her guilty plea before United States District Judge Joseph E. Irenas, who also imposed the sentence today in Camden federal court. Judge Irenas ordered the defendant's immediate surrender.
According to documents filed in this case and statements made in court:
Roosa admitted that from 2003 through September 2008, she owned and operated a contraband cigarette business, All-American Tobacco, from a Native American reservation located near her home in the Buffalo, N.Y., area. Roosa, who has never been a member of a Native American tribe, used the Native American status of the business to buy untaxed cigarettes. She then sold at least $4.9 million worth of untaxed cigarettes through the Internet to buyers in New Jersey, resulting in a $3.9 million tax revenue loss.
In addition to the prison term, Judge Irenas sentenced Roosa to three years of supervised release and ordered her to pay $3.9 million in restitution. The Court also granted the government's motion for the forfeiture of four pieces of commercial real estate located in nearby states, which were recently appraised at $2.5 million, as partial satisfaction of the restitution.
Roosa is the seventh defendant to be sentenced in this matter. In addition to the term of incarceration, Roosa was sentenced to three years of supervised release. To date, the government has recovered just over $2.85 million of the $3.9 million loss from the defendants.
U.S. Attorney Fishman credited inspectors of the United States Postal Inspection Service, under the direction of Acting Inspector in Charge Thomas Boyle; special agents of the Internal Revenue Service, under the direction of Special Agent in Charge Victor W. Lessoff; special agents of the United States Bureau of Alcohol, Tobacco, Firearms & Explosives, under the direction of Special Agent in Charge Matthew Horace; and special agents of the New Jersey Department of the Treasury, Division of Taxation, Office of Criminal Investigation, under the direction of Special Agent in Charge Charles Giblin, with the investigation leading to today's sentence.
The government is represented by Assistant U.S. Attorney Ronald Chillemi of the U.S.
Attorney's Office Health Care and Government Fraud Unit in Newark.
Defense counsel: Thomas J. Eoannou, Esq., Buffalo, N.Y.
Federal Emergency Management Agency (FEMA) announced that federal disaster aid has been made available to the State of New Jersey.
FEMA is now accepting applications from residents and business owners who sustained losses in Atlantic County, Cape May County, Essex County, Hudson County, Middlesex County, Monmouth County, Ocean County and Union County.
Register online at
www.disasterassistance.gov , by web-enabled mobile device atm.fema.gov or by calling 1-800-621-FEMA(3362) or 1-800-462-7585 (TTY) for the hearing and speech impaired. The toll-free telephone numbers will operate from 7 a.m. to 10 p.m. EDT seven days a week until further notice.


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"Aaah :/ I know that stage! I had it in the beguinning of the year... now I'm crushing. Hard! And hating myself for it xD
Its like a drug. Nearly impossible to stop."
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Easton Youth Instigator Training Pant
These practice pants are constructed with an elastic waist band with draw cord for a comfortable fit. The side pockets and leg hems both come with a zip opening and the pants are lined for moisture resistance.
Material: 100% High Count Polyester
Youth Sizes: XS, L - XL
Colors: Black, Dark Green, Maroon, Navy, Red, Royal Blue
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Nice warm ups, love the zippers on bottom of legs. The zippers are very long for ease of slipping on and off over shoes.
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- Feels half size too big
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The pants are great quality, just a bit too big for the size.
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Peoria's history, population, vision/mission statements, sustainability efforts, redistricting, and construction projects. Info on schools, the Peoria Leadership Institute seminar, and the Sister Cities program.
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A listing of links to directories of city services, including all online e-services.
The city of Peoria Municipal Complex is home to City Hall, the Council Chambers, the Main Library, the Development and Community Services Building, the Public Safety Administration Building, and the Municipal Court.
A listing of links to maps available on the city of Peoria Website.
The City of Peoria budget is managed by the Management and Budget Division. Find copies of the latest Program Budget and the CIP here.
The City Code and Zoning Ordinace, with updates are located here. Also, find the City Charter, and legal statements related to the website, including our Privacy Notice.
City Manager's Message on Diversity and Inclusion
How to pay bills you may have with the city, including water, sewer and trash collection fees, recreation program and class fees, traffic fines and more. Setup water and sewer service.
Home and Property Resources includes information on trash pickup,water conservation, swimming pool issues and recycling, along with other relevant information for homeowners.
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Use this page to find information on the city of Peoria website of interest to builders and developers.Included are inspections, zoning and zoning ordinance, the city code, general plan, permitting, and impact fees.
How to get a business license, tax license, sales tax schedules/forms, register to use the online eTax system, pay taxes and fees. Bidding on contracts with the city and auctions, trash collection, recycling, traffic counts.
Business and Real EstateDevelopment, and other assistance for businesses and developers finding sites, understanding the area, and growing their businesses. Links to the Building Development Division and PeoriaED.Com.
Information on Building Permits. Find out about permits for signs, temporary use of property, filming, and alarms. Download forms and track applications for development, building, planning and engineering permits.
The city's main document portal for development related documents including planning and zoning, building, engineering and fire prevention.
The Seattle Mariners and the San Diego Padres conduct spring training at the Peoria Sports Complex each February and March. Everything you need to know is at PeoriaSpringTraining.com.
A listing of area hotels, motels and RV Parks, listed by distance from the Peoria Sports Complex.
The city of Peoria, Arizona is proud to be the "Gateway to Lake Pleasant," one of the finest water recreation areas in Arizona.
Links to Items of interest to tourists, including VisitPeoriaaz.com, our official tourism website.
The Peoria Center for the Performing Arts consists of a 280 seat main stage auditorium and an 80+ seat black box theater, designed to bring award winning community theater to downtown Peoria.
City of Peoria hiking trails information, directions and maps.
Special Events, sponsored and hosted by the city, held throughout the year at the Peoria Sports Complex, Oldtown Peoria and other areas.
The Peoria Sports Complex is home to the San Diego Padres and Seattle Mariners during spring training, and many other events throughout the year.
Board Member Bios
Anthony IrbyMr. Irby has served in the United States Army and is a war veteran of both the Persian Gulf War and the Iraq War. Mr. Irby is actively engage on social issues that surround homeless and at-risk homeless veterans as the Homeless Veteran Outreach Coordinator for the Department of Veterans Affairs. Mr. Irby holds a Bachelor's in Human Services from the University of Phoenix. Anthony is married to his lovely wife Karen and has two adorable daughters Azuriah and Aurorah.
Chuck StrangeChuck Strange was born in Denver Colorado. He grew up as an army brat and traveled most of his young life. He joined the army in November 1958, and did tours in Germany, France, Vietnam, and Alaska. Chuck retired in June 1980; he worked in Public Safety along with his own endeavors, and he moved to Arizona in July 1999. He lives here with his wife Rosie. He has two sons, a daughter and five grandchildren scattered all over the globe. He serves on the Veterans Memorial Board, Peoria Chamber of Commerce, Diamond Club, and Sun City Visitor's Center. Chuck enjoys working with military affiliations and giving back to the community.
Lisa WakefieldLisa Wakefield is currently attached to the 56th Medical Group, Luke AFB, AZ. She is an Individual Mobilization Augmentee (IMA) and works as a Medical Service Corp Officer (MSC).
Lisa has been in the Air Force Reserves for 28 years, and was prior enlisted for six years. She has spent most of her time at Luke Air Force Base; with some time spend in England, Texas and the Pentagon. Lisa was activated during Operation Iraqi Freedom and Desert Storm. She has graduated from Squadron Officers School, Air Command and Staff College, and Air War College.
Lisa has a B.S. Degree in Business and a Masters in Education. She currently teaches English Language Learners (ELL) at Greenway High School. She started her service to the Veterans Board in Oct 2011.She lives in Peoria, AZ with her husband and their two children.
Ben GeigerBen Geiger was born and raised in Minneapolis, Minnesota. In 1999, Ben joined the Army Reserve. In 2003, while in college at Winona State University, Ben was deployed to Operation Iraqi Freedom. After returning from Iraq, Ben completed his Bachelor's of Science in Secondary Education Social Studies. Ben also met his lovely wife Kacey in college. Upon graduation, Ben and Kacey moved to the Phoenix area for better job opportunities. In 2009, Ben was called to Active Duty for Operation Iraqi Freedom once again. In his second tour, Ben worked in the logistics field to plan a successful drawdown. Ben's daughter was born shortly after his return from Iraq. Ben is a social studies teacher at Westview High School. Ben is a member of Iraq and Afghanistan Veterans of America and is proud to serve as a member of the Peoria Veterans Memorial Board.
City of Peoria 8401 W. Monroe Street Peoria, Arizona 85345 623-773-7000


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Leopard lizards are alert, capable of Mach-1 speed and bipedal during evasive maneuvers. Opportunistic in habit, they are predators of the highest esteem and cannibalistic when hunger dictates. In a nutshell, they are replicas directly out of Jurassic Park.
As the common name implies, and with a bit of colorful imagination thrown in, members of the genus Gambelia somewhat resemble real leopards. But some, such as blunt-nosed (G. sila) and to a lesser degree Cope's leopard lizards (G. copeii), definitely do not resemble their namesakes where pattern and color are concerned. However, they all practice similar leopardlike habits of stalking prey by "jumping" into the air to secure a worthwhile morsel. And when cornered and/or handled they show considerable malevolence — a well-placed bite by an adult leopard lizard is a painful encounter.
Range and Habitat
Four species of Gambelia (formerly Crotaphytus) have been described: Cope's (Gambelia copeii), blunt-nosed (G. sila), long-nosed (G. wislizenii) and Lahontan Basin leopard lizards (G. w. maculosa). The latter is not mentioned as such by Stebbins (2003), but referred to by St. John (2002), who puts it perfectly when he writes: "Depending on the authority consulted …. "
Leopard lizards range over a large area of the United States, northern Mexico, much of the Baja Peninsula, plus several Pacific islands and Isla Tiburón (a large island in the northern part of Mexico's Gulf of California). More specifically, they occur in all four major North American deserts (Great Basin, Mojave, Sonoran and Chihuahuan) ranging from central Idaho in the north to Zacatecas, Mexico, in the south.
Stebbins (2003) states that they range from near sea level to around 6,000 feet. However, any specimens that may be roaming near the Salton Sea in California, or points farther south and southeast, would in fact be doing so below sea level. I found a specimen east of El Centro, California, which is 40 feet below sea level, in the early 1960s. It was more than likely living at or just below sea level. Pickwell (1972) pictures a long-nosed leopard lizard found in Death Valley (most of the valley floor is below sea level). So it is possible that Pickwell's specimen was found at or below sea level too.
Because of this enormous range in elevation, leopard lizards frequent many different microhabitats. They avoid densely vegetated regions, however, because it interferes with their ability to give chase and efficiently subdue prey. Some of the plants found in Gambelia domain include creosote, sagebrush, greasewood, alkali bush, bunch grass, manzanita, live oak and flat-top buckwheat.
Captive Care
I don't recommend Gambelia for the beginning hobbyist. But if you are interested, you shou...


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Book List: Children's Books About the Environment
Looking for children's books about the environment? Here's a list of fiction and non-fiction books (for ages 4-16) to get you started. Let us know if we've missed your favorite book and we'll add it!
Guided Reading: The Wump World
Suggestions for teachers to guide students during a "read aloud" of Bill Peet's popular environmental book, with pages for students to fill in their own before, during, and after reading questions; this unit includes art prompts.
Book: Just a Dream (elem/upper elem)
Rather than focusing on text, this lesson addresses Chris Van Allsburg's use of light and shadow to tell a dystopian fairy tale... but it was surely just a dream. This is a great art appreciation lesson.
Book: Mighty Tree (primary)
Open-ended comprehension questions and prompts to go with Dick Gackenbach's tale of three trees: one used for material, one a Christmas tree, and one left in the forest. A great Earth Day tie-in.
Book: Something from Nothing (primary)
Reviews Phoebe Gilman's retelling of this Jewish folktale, with questions tying the story moral to the three Rs: reduce, reuse, recycle.
Book: Dr. Seuss' The Lorax (primary/elem)
Imagine yourself in the Truffula forest... Wonder what the Once-ler thinks of all his money... Finish verses with your own Seussian nonsense names... Enjoy the Lorax word find. You'll find these activities and more in this accompaniment to Dr. Seuss's cautionary classic, "The Lorax"!
Book List: Children's Books About the Environment
Guided Reading: The Wump World
Book: Just a Dream (elem/upper elem)
Book: Mighty Tree (primary)
Book: Something from Nothing (primary)
Book: Dr. Seuss' The Lorax (primary/elem)
* March is National Reading Month
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"Revealed: The 7-Steps to an Effective Presentation. A Proven System For Creating Massive Income From Speaking That Allows You to Profit From Your Passion & Build An Audience Of Raving Fans!
(No Experience Required)"
Here's A Taste Of What You'll Learn Inside This Amazing Chapter from my "Presentation Profits Blueprint":
The difference between a "good talk" and an "Effective Presentation" and why you must have at least 1 Effective Presentation as your "keynote"… | p. 14 | |
The 5 Questions you must ask yourself BEFORE you design any presentation so that you can be assured it will get the result you're looking for… | p. 19 | |
How I stumbled across the 7 steps to an effective presentation, and how it turned upside down almost everything I knew about speaking… | p. 14 | |
How to create a magnetic and attractive offer that has people leaping out of their seats to buy from you, without ever looking or feeling "sales-y"… | p. 22 |
The importance of intention in sales, and how to find the right intention for you so you are not "repellant" to your crowd… | p. 13 | |
The two key elements you need to Create Connection with your audience so they feel like "old friends", even if it's the first time they've met you… | p. 15 |
Why you should only sell one product per presentation. One speaker increased his conversions from 5% to 30% just by applying this simple strategy… | p. 23 | |
Discover what to do in the first 30 seconds and last 30 seconds on stage and why these two moments are the difference between the success and failure of your presentation… | p. 24 | |
The one simple mistake I made, that is made by most speakers, which caused me to absolutely bomb, and how you can avoid my costly mistake | p. 18 | |
And much MUCH more... |


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To view this page ensure that Adobe Flash Player version 10.0.0 or greater is installed.
During the AstraZeneca Nobel Medicine Initiative Lecture Event, held on 1-2 December 2010, at Alderley Park, United Kingdom, Dr. Tim Hunt gave his lecture 'Switches and Latches: Surprising New Elements in Control of Mitosis'.
Credits: Verri Media (production)
Copyright © Nobel Media AB 2010
The Nobel Prize in Physiology or Medicine 2001


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Master of Science in Athletic Administration
Course Descriptions
RSA 501 – (3 hrs.) – Research Methods in REC Sport: Research terminology, design, methods, data analysis, and manuscript preparation in recreation and sport.
RSA 513 – (3 hrs.) – Recreation and Sport Admin: Leadership and management of recreation and sport agencies with emphases on strategic planning, policy, human resources, programming, governance, and organizational behavior and culture.
RSA 517 (3 hrs.) - Legal Issues in REC and Sport: Legal systems, legal concepts, and landmark cases influencing the recreation and sport industry.
RSA 519 (3 hrs.) - Fiscal Practices in REC Sport: Financial principles and practices relevant in recreation settings. Topics include economic principles, financial management and organization, income sources, fundraising, pricing, and budgeting.
RSA 515 (3 hrs.) - REC Sport Facility Development: Facility development process with emphasis on the unique features of many different types of facilities. Field experience required. Students are responsible for their own transportation to off campus meetings. University transportation provided when possible.
RSA 543 – (3 hrs.) - Sports Medicine Admin. For Interscholastic Athletics: An in-depth study of the many issues administrators and coaches face in supporting and developing an interscholastic sports medicine program within a school or school district. Does not count toward certification or rank change in Kentucky.
RSA 542 – (3 hrs.) – Investigation of Current Interscholastic Athletics Issues: A capstone experience for the concentration in IAA that will involve an in depth investigation of the various issues addressed throughout this program of study. Does not count toward certification or rank change in Kentucky.
RSA 544 – (3 hrs.) – Championship Events (Practicum): Study of the Organization and Administration of interscholastic championship events. Does not count toward certification or rank change in Kentucky.
RSA 530 – (1 – 3 hrs.) – Indep Investigation/PE: Research problems or projects in the organizational, administrative, or supervisory areas of physical education.
RSA 523 – (3 hrs.) - Theory of Recreation and Sport: Philosophy, theory, and ethics of recreation and sport, including current professional trends in the field.
RSA 521 – (3 hrs.) - Public Relations in Rec/Sport: Specialized application of effective communication techniques for building relationships with internal and external constituencies that support marketing from the general practice of public relations.


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IKKε-Mediated Tumorigenesis Requires K63-Linked Polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 Ubiquitin Ligase Complex
IKKε-Mediated Tumorigenesis Requires K63-Linked Polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 Ubiquitin Ligase ComplexCrystal Structure and Mechanism of Activation of TANK-Binding Kinase 1Structure and Ubiquitination-Dependent Activation of TANK-Binding Kinase 1
Cell Reports, Volume 3, Issue 3,
Pages 724-733,
Publication Date 28 February 2013
Copyright © 2013 The Authors All rights reserved.
DOI: 10.1016/j.celrep.2013.01.031
Alicia Y. Zhou
Rhine R. Shen
Eejung Kim
Ying J. Lock
Ming Xu
Zhijian J. Chen
William C. Hahn
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA
Corresponding author
► K63-linked ubiquitination regulates IKKε innate immune and oncogenic functions ► IKKε is ubiquitinated on K30, K401, and K416 ► Ubiquitination of K30 and K401 is essential for IKKε activity and oncogene function ► A cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex binds to and modifies IKKε
IκB kinase ε (IKKε, IKBKE) is a key regulator of innate immunity and a breast cancer oncogene, amplified in ∼30% of breast cancers, that promotes malignant transformation through NF-κB activation. Here, we show that IKKε is modified and regulated by K63-linked polyubiquitination at lysine 30 and lysine 401. Tumor necrosis factor alpha and interleukin-1β stimulation induces IKKε K63-linked polyubiquitination over baseline levels in both macrophages and breast cancer cell lines, and this modification is essential for IKKε kinase activity, IKKε-mediated NF-κB activation, and IKKε-induced malignant transformation. Disruption of K63-linked ubiquitination of IKKε does not affect its overall structure but impairs the recruitment of canonical NF-κB proteins. A cIAP1/cIAP2/TRAF2 E3 ligase complex binds to and ubiquitinates IKKε. Altogether, these observations demonstrate that K63-linked polyubiquitination regulates IKKε activity in both inflammatory and oncogenic contexts and suggests an alternative approach to targeting this breast cancer oncogene.


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Tuesday, August 13, 2013
© Copyright 2014
Newton Citizen
Salem softball coach Ronnie Miller thinks Peyton Mitchell is primed for a breakout junior season. If the first two games are any indication, Miller may be on to something.
Mitchell hit a first inning home run for the second consecutive day, setting the tone for the Seminoles in an 8-0 victory in five innings over Rockdale Tuesday.
Salem evened its record at 1-1, while slumping rockdale remained winless at 0-6.
Mitchell went 3-for-3 with a three-run home run in Monday's loss to Loganville, then ripped a two-run home run to center field, part of a three-run first inning against Rockdale starter Miasia Mayer. Mitchell roped an RBI-double in a three-run second against reliever Sidney Driver, and that was more than enough for Whitney Lester. The senior right-hander retired the first eight batters she faced before Tyzia Roberts reached on a two-out error in the second. Rockdale got its first and only hits of the game when Keishaun Drake blooped an opposite field double and Driver followed with an infield single. Lester got a fielder's choice and a pop out, then escaped the jam when Kaila Gabaree was called for runner's interference after striking out and trying to advance to first.
Kennedy Lester got the Salem offense going all night. reaching base three times - a single and two walks - stealing four bases and scoring three runs. Knarhine Bailey added a run-scoring single in the second.
Lester threw just 53 pitches in her abbreviated complete game. In the bottom of the fifth, Mariah Briney singled and went to second on a throwing error by right fielder Doran Johnson. Alexis Chisman's ground ball was thrown away by shortstop India Davis and Briney raced home to end the game by mercy rule.
Rockdale will try to pick up its first win when it travels to another county rival, Heritage today at 4:30 p.m. Salem hosts Newton Thursday at 5:30 p.m.
More like this story
- Lester no-hits Gainesville again, 'Noles head to region quarters ( September 30, 2013 )
- Green, Loganville top Salem on the diamond ( August 27, 2013 )
- Salem softball routs Clarke Central ( September 5, 2013 )
- Salem beats Rockdale in softball for 5th straight time ( September 9, 2013 )
- Heritage sweeps Region 8 softball awards ( November 5, 2013 )


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21 Apr 2009 8:35 PM #1
Forum Search Using XML Reader
Forum Search Using XML Reader
Am new to xml. In forum search example, it uses json method to retrieve the data. How can i retrieve data from my own xml file. I dont know how to use xmlreader also.
22 Apr 2009 3:03 AM #2
- Join Date
- Mar 2007
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- Frederick MD, NYC, DC
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There is an XML grid example. have you seen it?
Jay Garcia @ModusJesus || Modus Create co-founder
Ext JS in Action author
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22 Apr 2009 3:21 AM #3
Thanks - But wants like forum Search
Thanks - But wants like forum Search
Yes but i want to display only the searched items lik forum-search.


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Stories Tagged with "international commerce"
2008 - 1 story
NJIT Features New Online Master of Science in Management Plus 5 New Online Graduate Certificates
July 31, 2008
It's not easy these days attending school, working, plus worrying about increased commuting costs. That's why NJIT is pleased to announce a new online master's degree program in management as well as five new online business-related certificate programs starting Sept. 2, 2008. Registration is currently underway. >>


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Everyone is always looking to make some extra gold, so here are 5 quick gold making tips to make some extra gold with your professions.
Find out how to defeat all the bosses in the Terrace of Endless Springs raid in the LFR version.
Find out all about the new scenario "A Little Patience" being launched in patch 5.1.
Learn how to defeat the bosses in the second half of the Heart of Fear, called the Nightmare of Shek'zeer in the LFR system.
Check out the new scenario launching with patch 5.1 called Assault on Zan'vess.
Learn how to defeat the bosses in the LFR version of the Heart of Fear raid in Mists of Pandaria.
A look at the new Patch 5.1 scenario for Alliance players called Lion's Landing.
Find out how to make gold easily and quickly in World of Warcraft: Mists of Pandaria.


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The Surprising 'Alpha' from Malkiel's Monkey and Upside-Down StrategiesRobert D. ArnottResearch Affiliates, LLC Jason C. HsuResearch Affiliates, LLC; University of California, Los Angeles - Anderson School of Business Vitali KalesnikResearch Affiliates LLC Phil TindallTowers Watson Limited March 17, 2013 Journal of Portfolio Management, Summer 2013, Vol. 39, No. 4: pp. 91-105 Abstract: The latest index literature is bursting with new innovations based on quantitative strategies that are predicated on sensible investment beliefs. Empirical studies confirm that these strategies do indeed deliver economically large and statistically significant excess returns over the cap-weighted market benchmarks in nearly all geographical and country studies. To the casual observer, it will be shocking to learn that inverting the portfolio construction algorithms does not reverse the alphas. Embarrassingly, the inverted strategies often outperform the originals. This paradoxical result is driven by the phenomenon that seemingly unrelated and non-value-based strategies and their inverse strategies often have unintended and almost unavoidable value and small-cap tilts. Even Burt Malkiel's blind-folded monkey, throwing darts at the Wall Street Journal, would produce a portfolio strategy with a significant value and small-cap bias that would have outperformed historically. The value and small tilts stem from the fact that these new weighting schemes sever the link between a company's share price/capitalization and its weight in the portfolio. Generally, an investment thesis where price does not drive the weight in the portfolio will have a value tilt and an investment thesis where company size/capitalization does not drive portfolio weights will have a small-cap tilt. As a result, these strategies produce outperformance against the cap-weighted benchmark due to the often unintended value and small cap tilts and independent of the investment philosophies that drive the product design. Number of Pages in PDF File: 23 Keywords: smart betas, alternative betas, Fundamental Index, rebalancing premium, value premium JEL Classification: G10, G11, G12 Accepted Paper SeriesDate posted: October 22, 2012 ; Last revised: August 11, 2013Suggested CitationContact Information
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