***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This pilot aims to better underst and the market for childcare in Saudi Arabia – both the supply and dem and sides – and to design a r and omized controlled experiment to test whether access to affordable day care ( in the form of subsidies , for example ) would incentivize Saudi mothers to search actively for employment and to remain employed once they are hired . In addition , the study seeks to underst and the degree to which employment early on in one ’s life impacts employment in later stages . The pilot will provide information on the groups of women the experiment should target , appropriate levels for the childcare subsidy , and the quality and current geographic locations of daycare sites . Expected Impact Determine the effects of facilitating childcare access on Saudi women ’s employment . PRINCIPAL INVESTIGATORS  Boston University Patricia Cortes  Harvard University Claudia Goldin  Swarthmore College Jennifer Objective To find out whether changes within the hemostatic system are related to the severity of illness and organ failure in patients at the onset of clinical ly defined sepsis and to find some indications for the contribution of endothelial cell activation or perturbation to the patient 's status . The following measurements were undertaken : Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , multiple organ failure ( MOF ) score , plasma levels of thrombin — antithrombin III complexes ( TAT ) , antithrombin III ( AT III ) , protein C antigen , factor XII , and plasminogen activator inhibitor type 1 antigen ( PAI-1 ) , neopterin , and interleukin 6 ( IL-6 ) . Design A prospect i ve case series study . Setting Intensive care unit ( ICU ) of the Department of Internal Medicine , Justus Liebig University , Giessen , Germany . Patients 28 consecutive patients ( 11 females , 17 males ; mean age 58 years ) with clinical ly defined sepsis . Eleven patients were admitted from the surgical ICU ( 9 after elective surgery  , 2 after trauma surgery )  . The operations were done 1–26 days ( mean 14 days ) prior to the onset of sepsis . Main results At the onset of sepsis we found elevated plasma levels of TAT , PAI-1 , neopterin , and IL-6 , and lowered plasma levels of AT III , factor XII , and protein Cantigen . Neopterin , PAI-1 , IL-6 , and factor XII showed a statistically significant correlation with the APACHE II score . The MOF score is significantly correlated with IL-6 and neopterin . The extent of hemostatic abnormalities was related to increasing levels of IL-6 . Conclusions Clinical evidence of a septic process is most likely to be preceded by activation of the hemostatic system , the vascular endothelium , and the monocyte/macrophage system . IL-6 may have a regulatory function for hemostasis in inflammation . Laboratory monitoring could be helpful in deciding whether to start early intensive therapy in patients at risk for sepsis Variables of the fibrinolytic system were prospect ively studied in patients with haematologic malignancies in chemotherapy-induced leukocytopenia at onset and during the course of septicemia to evaluate their prognostic value . This group of patients was chosen because of their high risk of developing severe septic complications , thus allowing serial prospect i ve testing of fibrinolytic variables prior to and during evolving sepsis or septic shock . 62 patients with febrile infectious events were accrued to the study . Of these , 13 patients progressed to severe sepsis and an additional 13 patients to septic shock as defined according to st and ard diagnostic criteria . At onset of fever , plasminogen activator inhibitor ( PAI ) activity and PAI-1 antigen levels increased from normal baseline levels and were significantly higher in the group of patients who developed septic shock compared to those with severe sepsis ( medians : 10.6 versus 1.3 U/ml , p = 0.0001 ; 50.0 versus 5.0 ng/ml , p = 0.0002 ) . The increase in PAI activity and antigen in septic shock was accompanied by an increase in tissue-type plasminogen activator antigen and total fibrin(ogen ) degradation products and a decrease in alpha(2)-antiplasmin activity ( p < 0.006 ) . In contrast , in the group of patients that developed severe sepsis the variables of the fibrinolytic system remained unchanged at onset of fever . These differences between septic shock and severe sepsis were sustained throughout the septic episode for all variables ( p < 0.0001 ) . PAI activity of > 5 U/ml at onset of fever predicted a lethal outcome with a sensitivity of 92 % and a specificity of 100 % . Thus , septic shock in leukocytopenia is associated with significant activation of the fibrinolytic system presumably as a response of the vascular endothelium to inflammatory injury . Furthermore , PAI activity measurements are sensitive markers of an unfavourable prognosis Circulating levels of thrombin-antithrombin III complex ( TAT ) and plasmin-α2 plasmin inhibitor complex ( PIC )  in 49 septic patients ( 23 patients with organ dysfunction ( OD ) , 26 without OD ) and 11 postgastrectomy patients were measured to determine the significance of the coagulation-fibrinolytic systems in the development of OD . Tissue plasminogen activator ( t-PA ) , plasminogen activator inhibitor 1 ( PAI-1 ) , and thrombomodulin  were also measured . The mean level of TAT on the day when OD occurred was significantly higher compared with the maximum level of TAT in septic patients without OD ( P < .01 ) or postoperative patients ( P < .01 ) . There was no difference in PIC levels between the three groups . The TAT/PIC ratio was significantly higher in septic patients with OD compared with the other groups ( P < .001 ) . Septic patients with OD showed higher levels of PAI-1 ( P < .001 ) but not of t-PA . Thrombomodulin levels were significantly higher in the septic patients with OD compared with the others ( P < .001 ) . We conclude that suppression of the fibrinolytic system contributes to the imbalance between coagulation and fibrinolysis , and that this hypercoagulabe millieu on the endothelial surface leads to the onset of OD Introduction Impairment of fibrinolysis during sepsis is associated with worse outcome . Early identification of this condition could be of interest . The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality . Methods This single center observational prospect i ve pilot study was performed in an adult Intensive Care Unit ( ICU ) of a tertiary academic hospital . Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included . Forty healthy individuals served as controls . We modified conventional kaolin activated thromboelastography ( TEG ) adding urokinase to improve assessment of fibrinolysis in real time ( UK-TEG ) .  TEG , UK-TEG , plasminogen activator inhibitor (PAI)-1 , thrombin-activatable fibrinolysis inhibitor ( TAFI ) , d-dimer , DIC scores and morbidity ( rated with the SOFA score ) were measured upon ICU admission . Logistic regression was used to calculate odds ratios ( ORs ) and 95 % confidence intervals ( 95 % CIs ) of mortality at ICU discharge . Results UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1 . TAFI was not different between sepsis patients and healthy individuals . 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score ( 8 ( 6–13 ) vs 5 ( 4–7 ) , p = 0.03 ) , higher mortality ( 39 % vs 5 % , p = 0.01 ) and greater markers of cellular damage ( lactate levels , LDH and bilirubin ) . Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 ( % ) parameter ( OR 0.95 , 95 % CI 0.93–0.98 , p = 0.003 ) . Conclusions Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage , morbidity and mortality Introduction Current criteria for early diagnosis of coagulopathy in sepsis are limited . We postulated that coagulopathy is already complicated with sepsis in the initial phase , and severe coagulopathy or disseminated intravascular coagulation ( DIC ) becomes overt after progressive consumption of platelet and coagulation factors . To determine early diagnostic markers for severe coagulopathy , we evaluated plasma biomarkers for association with subsequent development of overt DIC in patients with sepsis . Methods A single-center , prospect i ve observational study was conducted in an adult ICU at a university hospital .  Plasma sample s were obtained from patients with sepsis at ICU admission . Fourteen biomarkers including global markers ( platelet count , prothrombin time , activated partial thromboplastin time , fibrinogen and fibrin degradation product ( FDP ) ) ; markers of thrombin generation ( thrombin-antithrombin complex ( TAT ) and soluble fibrin ) ; markers of anticoagulants ( protein C ( PC ) and antithrombin ) ; markers of fibrinolysis ( plasminogen , α2-plasmin inhibitor ( PI ) , plasmin-α2-PI complex , and plasminogen activator inhibitor (PAI)-1 ) ; and a marker of endothelial activation ( soluble E-selectin ) were assayed . Patients who had overt DIC at baseline were excluded , and the remaining patients were followed for development of overt DIC in 5 days , and for mortality in 28 days . Results A total of 77 patients were enrolled , and 37 developed overt DIC within the following 5 days . Most patients demonstrated hemostatic abnormalities at baseline with 98.7 % TAT , 97.4 % FDP and 88.3 % PC . Most hemostatic biomarkers at baseline were significantly associated with subsequent development of overt DIC . Notably , TAT , PAI-1 and PC discriminated well between patients with and without developing overt DIC ( area under the receiver operating characteristic curve ( AUROC ) , 0.77 ( 95 % confidence interval , 0.64 to 0.86 ) ; 0.87 ( 0.78 to 0.92 ) ; 0.85 ( 0.76 to 0.91 ) , respectively ) , and using the three together , significantly improved the AUROC up to 0.95 ( vs. TAT , PAI-1 , and PC ) . Among the significant diagnostic markers for overt DIC , TAT and PAI-1 were also good predictors of 28-day mortality ( AUROC , 0.77 and 0.81 , respectively ) . Conclusions Severe coagulation and fibrinolytic abnormalities on ICU admission were associated with subsequent development of overt DIC . A single measurement of TAT , PAI-1 , and PC activity could identify patients with ongoing severe coagulopathy , early in the course of sepsis Introduction Previous reports suggest that endothelial activation is an important process in sepsis pathogenesis . We investigated the association between biomarkers of endothelial cell activation and sepsis severity , organ dysfunction sequential organ failure assessment ( SOFA ) score , and death . Methods This is a prospect i ve , observational study including adult patients ( age 18 years or older ) presenting with clinical suspicion of infection to the emergency department ( ED ) of an urban , academic medical center between February 2005 and November 2008 .  Blood was sample d during the ED visit and biomarkers of endothelial cell activation , namely soluble fms-like tyrosine kinase-1 ( sFlt-1 ) , plasminogen activator inhibitors -1 ( PAI-1 ) , sE-selectin , soluble intercellular adhesion molecule ( sICAM-1 ) , and soluble vascular cell adhesion molecule ( sVCAM-1 ) , were assayed . The association between biomarkers and the outcomes of sepsis severity , organ dysfunction , and in-hospital mortality were analyzed . Results A total of 221 patients were included : sepsis without organ dysfunction was present in 32 % , severe sepsis without shock in 30 % , septic shock in 32 % , and 6 % were non-infected control ED patients . There was a relationship between all target biomarkers ( sFlt-1 , PAI-1 , sE-selectin , sICAM-1 , and sVCAM-1 ) and sepsis severity , P < 0.05 . We found a significant inter-correlation between all biomarkers , including the strongest correlations between sFlt-1 and sE-selectin ( r = 0.55 , P < 0.001 ) , and between sFlt-1 and PAI-1 ( 0.56 , P < 0.001 ) . Among the endothelial cell activation biomarkers , sFlt-1 had the strongest association with SOFA score ( r = 0.66 , P < 0.001 ) , the highest area under the receiver operator characteristic curve for severe sepsis of 0.82 , and for mortality of 0.91 . Conclusions Markers of endothel 
    Output:
    
Conclusion PAI-1 is a significant predictor of disease severity and all-cause mortality in sepsis .