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Comparison of Serum Nucleosomes and Tissue Inhibitor of Metalloproteinase1 (TIMP1) in Predicting Mortality in Adult Critically Ill Patients in Sepsis: Prospective Observational Study
Corresponding Author: Lokesh Kashyap, Department of Anesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India, Phone: +91 9873531192, e-mail: firstname.lastname@example.org
How to cite this article: Rai N, Khanna P, Kashyap S, Kashyap L, Anand RK, Kumar S. Comparison of Serum Nucleosomes and Tissue Inhibitor of Metalloproteinase1 (TIMP1) in Predicting Mortality in Adult Critically Ill Patients in Sepsis: Prospective Observational Study. Indian J Crit Care Med 2022;26(7):804–810.
Source of support: This study received a financial assistance from ICMR (India Council of Medical Research, New Delhi, No. 3/2/Jan. 20 I S/PG-Thesis-HRD (25) Dated: 07.09.2018).
Conflict of interest: None
Background: Sepsis is a life-threatening organ dysfunction due to dysregulated host response to infection. Timely identification is important for risk reduction and better outcomes in critically ill patients. Nucleosomes and tissue inhibitors of metalloproteinase1 (TIMP1) are the biomarkers whose validity and utility in predicting organ dysfunction and mortality in sepsis have been proven. However, which biomarker among these two has better predictive value in elucidating disease severity, organ dysfunction, and mortality in sepsis is yet to be answered, and further studies are needed.
Methods: Eighty patients with sepsis/septic shock, aged between 18 and 75 years admitted in intensive care unit (ICU) were recruited in this prospective observational trial. Quantification of serum nucleosomes and TIMP1 was done using enzyme linked immunosorbent assay (ELISA) within 24 hours of diagnosis of sepsis/septic shock. The primary outcome was to compare the predictability of nucleosomes and TIMP1 in estimating sepsis mortality.
Results: The area under the receiver operating characteristic curve (AUROC) for TIMP1 and nucleosomes to discriminate between survivors and non-survivors were 0.70 [95% Confidence interval (CI), 0.58–0.81] and 0.68 (0.56–0.80), respectively. Although independent, TIMP1 and nucleosomes have statistically significant capacity to discriminate between survivors and non-survivors (p = 0.002 and p = 0.004, respectively), superiority of one biomarker over the other in discriminating between survivors and non-survivors was not observed.
Conclusion: The median values of each biomarker showed statistically significant differences between survivors and non-survivors, superiority of one biomarker over other in predicting mortality was not observed. However, this was an observational study and larger studies are needed in the future to validate the findings of this study.
Keywords: Mortality, Nucleosomes, Sepsis, Septic shock, Tissue inhibitor of metalloproteinase1.
Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. A septic shock is characterized by hypotension despite an adequate volume resuscitation and requiring vasopressors for maintaining mean arterial pressure (MAP) more than or 65 mm Hg along with a serum lactate level more than 2 mmol/L (18 mg/dL). The hospital mortality for septic shock is approximately 40%.1 It is one of the leading etiologies of morbidity and mortality throughout the world.2
The recent statistics show that the actual prevalence of sepsis is as high as 6% in hospitalized adults, while the reliable predictions suggest that its future incidence may nearly double in the next 30 years.3,4 Early identification of sepsis is important as mortality rates as high as 7% per hour delay in diagnosis for the first 6 hour.5
Traditionally, blood cultures have represented the only reliable means for establishing bloodstream infection. However, the yield is positive only in 30–40% of the cases and the blood cultures remain sterile in approximately one-third of sepsis cases.6,7 Long turnaround time is another hindrance in timely detection of sepsis. Due to these limitations, a large armamentarium of biomarkers has been investigated over the past decade, out of the plethora of biomarkers, procalcitonin (PCT) and C-reactive protein (CRP) have been the most commonly used ones, but even these have limited sensitivity and specificity to distinguish sepsis from other inflammatory conditions and in predicting prognosis. Biomarkers are the molecules that are objectively quantified and are used as the markers of various processes (biological and pathogenic), or to assess responses to a therapy.8 Currently, despite the presence of multiple novel and promising biomarkers, very few have been validated for the use in clinical practice with acceptable sensitivity and specificity.
Nucleosomes consists of deoxyribonucleic acid (DNA) and histone proteins. The core is an octamer comprising of histones H2A–H2B and H3–H4, surrounded by double-stranded DNA.9,10 The whole complex is integrated into vesicles bounded by membrane. This complex is ingested by the macrophages under physiological conditions. In sepsis, the high rate of apoptosis leads to saturation and impairment of phagocytosis mechanism producing higher concentrations of nucleosomes in the circulation.10,11 Multiple prospective, observational studies have shown that the patients with sepsis and septic shock had raised levels of plasma nucleosomes.12–14
Tissue inhibitors of metalloproteinases (TIMPs) are selective inhibitors of matrix metalloproteinases (MMPs).15 The various studies have shown positive correlation between mortality and elevated levels of TIMP1, TIMP2, and MMPs in sepsis patients.16–19 Nucleosomes and TIMP1 are the two such biomarkers, whose validity and utility in predicting severity, organ dysfunction, and mortality in sepsis has been proven in multiple previous studies. However, given the paucity of literature answering better biomarker, we planned this prospective, observational study to compare nucleosomes vs TIMP1 in predicting mortality in sepsis.
After obtaining institute ethics committee approval and written informed consent from participants or their legally acceptable representatives, 80 patients were recruited in this prospective observational study from May 2018 to July 2019. The study was registered in the National Clinical Trial Registry of India (www.ctri.nic.in CTRI/REF/CTRI/2018/05/013770). Patients in sepsis/septic shock, aged between 18 and 75 years of both genders were included in this study. Patients with advanced malignancy, immunocompromised or transplant recipient, radiation therapy, coronary artery disease, and heart failure were excluded.
The patient in sepsis or septic shock on admission to ICU or who went into sepsis or septic shock subsequently in ICU was included in this study and quantification of biomarker was done within 24 hours of diagnosis of sepsis/septic shock. In this study, sepsis was defined using systemic inflammatory response syndrome (SIRS) criteria. The patients were recruited in the study if they met at least two of the following four criteria: Temperature, >100.4°F or <96.8°F; heart rate, >90/min; white blood cell (WBC) count, >12,000/μL or <4,000/μL or with 10% immature/band forms and respiratory rate >20 breaths/min or arterial carbon dioxide tension (PaCO2) <32 mm Hg. In this study, SIRS was chosen over quick sequential organ failure assessment (qSOFA) as studies have shown that qSOFA is more specific but less sensitive than having two of four SIRS criteria for early identification of infection induced organ dysfunction.20
Once the patient was recruited in the study, the following baseline characteristics was recorded demographic characteristics (age, gender, and weight), type and source of admission, primary diagnosis, comorbidities, source of infection (clinically), blood culture report (if available), day of ICU admission, day of inclusion in the study, acute physiology and chronic health evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score within 24 hours of inclusion in the study. Subsequently, the worst reading of APACHE II and SOFA score, TLC and maximum temperature each day was recorded. Also, the duration of vasopressors, culture sensitivity, duration of antibiotics, length of stay (LOS), and total length in hospital were recorded.
A 10 mL of venous blood, either from percutaneous route or central line was obtained within 24 hours of the diagnosis of sepsis or septic shock. Whole blood was collected in a covered test tube. After collecting whole blood, it was allowed to clot by keeping it undisturbed at room temperature for 15–30 minutes. The sample was centrifuged at 1,000–2,000g for 10 minutes in a refrigerator refrigerated and the clot was separated. The resulting supernatant serum was immediately transferred into a clean polypropylene tube by using a Pasteur pipette. The sample was maintained at 2–8°C while handling. If the serum was not analyzed immediately, it was kept in 0.5 mL aliquots and stored at –20°C. The quantification of the nucleosomes and TIMP1 was done using ELISA (Orgentec ELISA Immunoblot).
Sample Size Calculation and Statistical Analysis
The sample size was calculated based on a study by Nino et al. in which they used a multivariate model to elucidate the role of TIMP1 in predicting mortality in septic patients.13 Calculating the mean ± Standard deviation (SD) of TIMP1 in the survivor group of 294.8 pg/μL and in the non-survivor group of 497.5 pg/μL and taking power of study to be 80% and alpha error of 5%, 37 cases were required. However, the higher incidence of sepsis associated mortality of 55–65% has been reported in two studies from the Indian subcontinent.21,22 We assumed a higher overall mortality of 50 ± 5% in our study (as opposed to 12% of the reference study), a sample size of 80 was calculated.
All collected data were tabulated in the Microsoft Excel™ (Microsoft Corp., Redmond, WA). The data was analyzed by using statistical software Stata 14.0. Normality of data was assessed by drawing normal distribution curve. The data were presented as median and inter-quartile range (IQR) for continuous variables and as absolute numbers or percentages for categorical variables (sex, comorbidities, etc.) Wilcoxon rank–sum test was used to compare the values of biomarker between survivor and non-survivor. Categorical data were expressed as frequency and percentage. The receiver operating characteristics (ROC) curves were constructed for serum nucleosomes and TIMP1 as a predictor of mortality and best cut-off values were obtained from Youden’s index (Sensitivity + Specificity − 1) for obtaining specificity and sensitivity and to discriminate between survivors and non-survivors. Using appropriate cut-off values, logistic regression analysis was carried out to estimate the odds of mortality. DeLong test was used for comparison between the ROC curve for two biomarkers; p ≤0.05 was considered statistically significant.
In this prospective observational trial, 80 patients were recruited during the study period. The baseline demographic parameters of the patients admitted with sepsis or septic shock are displayed in Table 1. The mean age of the patients included in the study was 46.1 ± 19.6 years. A total of 51.2% of the enrolled patients were male. Pneumonia, including ventilator associated pneumonia (VAP), community acquired pneumonia (CAP), and hospital acquired pneumonia (HAP), along with abdominal and urosepsis was the predominant diagnosis at the admission contributing 31.2 and 30%, respectively. Postoperative complications, trauma, tropical illness, encephalopathies, and liver disease contributed to the rest of the diagnosis at admission. Septic shock was present in 76.1% of the cases during the inclusion in the study. The mean values of APACHE II and SOFA scores were 17.8 ± 6.9 and 7.9 ± 2.7, respectively.
|*Age (Mean ± SD)||(46.1 ± 19.6)|
|Diagnosis at ICU admission|
|Pneumonia (HAP/CAP/VAP)||25 (31.2)|
|Postoperative complications||8 (10)|
|Tropical illness||8 (10)|
|Liver disease||5 (6.2)|
|Septic shock||61 (76.2)|
|Severity score at admission [Mean (± SD)]|
|APACHE II||17.8 (6.1)|
|Median (min-max)||Median (min-max)|
|TIMP1 (pg/µL)||136.9 (84.6–1585.5)||217.8 (92.6–1352.2)||0.002|
|Nucleosomes (pg/µL)||185.0 (68.0–1721.0)||345.0 (65.0–1584.2)||0.004|
Comparison of Serum Nucleosomes and Tissue Inhibitor of Metalloproteinase1 in Predicting Mortality
The optimal cut-off point for TIMP1, as determined by ROC curve analysis, was 149.4 pg/μL. Using the above cut-off, sensitivity was 71.4% and specificity was 53.3%. Similarly, the optimal cut-off point for nucleosomes was 215 pg/μL, providing sensitivity and specificity of 71.4 and 57.7% respectively. The AUROC for TIMP1 and nucleosomes to discriminate between survivors and non-survivors were 0.70 (95% CI, 0.58–0.81) and 0.68 (0.56–0.80), respectively Figure 1.
For comparison between the ROC curve for two biomarkers, DeLong test was used. Although independent, TIMP1 and nucleosomes have statistically significant capacity to discriminate between survivors and non-survivors (p-values 0.002 and 0.004, respectively), superiority of one biomarker over other in discriminating between survivors and non-survivors was not observed (Table 3). Tissue inhibitor of metalloproteinase1 and nucleosomes sensitivity and specificity calculation with odds predicting death are displayed in Tables 4 and 5. With the cut-off for the biomarkers (as determined by ROC curve analysis), the odds ratio (OR) for predicting death was 2.86 (95% CI, 1.13–7.21) and 3.42 (1.35–8.68) for TIMP1 and nucleosomes, respectively.
|TIMP1 (pg/µL)||149.4||71.4||53.3||0.70 (0.58– 0.81)||0.69|
|Nucleosomes (pg/µL)||215.0||71.4||57.7||0.68 (0.56–0.80)|
|TIMP1 (pg/μL)||Survivors||Non-survivors||OR (95% CI)||Sensitivity (95% CI)||Specificity (95% CI)||p|
|≤149.47||24||10||1||71.4 (53.7–85.4)||53.3 (37.9–68.3)||0.026|
|Nucleosomes (pg/μL)||Survivors||Non-survivors||OR (95% CI)||Sensitivity (95% CI)||Specificity (95% CI)||p|
|≤215.05||26||10||1||71.4 (53.7–85.4)||57.7 (42.2–72.3)||0.009|
Bivariate analysis was done between biomarkers and the clinical parameters such as temperature, TLC, SOFA, APACHE II, duration of vasopressors, duration of antibiotics, and LOS. The correlation coefficient and p values for each variable is shown in Table 6. For TIMP1, the correlation was found between TIMP1 value and the duration of vasopressor and LOS (r = 0.27, p = 0.03; and r = 0.22, p = 0.04, respectively). For nucleosomes, there was no significant correlation between nucleosomes value and the variables.
|Vasopressors (Noradrenaline) (days)||0.27||0.03||0.17||0.18|
Comparison of Biomarkers between Variates
A comparison of biomarkers between the variates (such as gender, presence or absence of septic shock, hospital outcome, type, and source of admission culture results) is shown in Tables 7 and 8. None of the mentioned variates showed a significant difference between the level of biomarkers.
|Variables||TIMP1(pg/μL) Median (min-max)||p|
|Septic shock absent||172.0 (84.6–1585.5)||0.50|
|Septic shock present||171.0 (84.7–1352.2)|
|Hospital discharge||217.8 (92.6–1352.2)||0.65|
|Hospital death||243.0 (125.0–320.5)|
|Type of admission|
|Surgical elective||160.0 (84.6–1585.5)|
|Surgical emergency||207.0 (96.0–789.7)|
|Source of admission|
|Culture positive||199.2 (98.2–1352.2)||0.28|
|Culture negative||153.8 (84.6–1585.5)|
|Variables||Nucleosomes (pg/μL) Median (min-max)||p|
|Septic shock present||248.0 (65.0–1584.2)||0.50|
|Septic shock absent||215.2 (74.0–1721.0)|
|Hospital discharge||345.0 (65.0–1584.2)||0.79|
|Hospital death||302.2 (185.0–396.2)|
|Type of admission|
|Surgical elective||234.2 (85.2–1721.0)|
|Surgical emergency||245.0 (65.0–900.1)|
|Source of admission|
|Culture positive||248.5 (65.0–1584.2)||0.83*|
|Culture negative||215.2 (68.0–1271.0)|
Logistic Regression Model for Association between Covariates and ICU Outcome
A logistic regression model was built with a purposeful selection of covariates which showed that the presence of septic shock and positive cultures were statistically associated with ICU mortality (OR = 10.0, 95% CI = 2.1–47.1, p = 0.001 and OR = 3.3, CI = 1.25–9.04, p = 0.014, respectively).
Independent Predictors for ICU Mortality: Multivariate Logistic Regression Model
Multivariate logistic regression model was constructed by the method of intentional selection of covariates obtaining the end model with four statistically significant variables (culture positive, nucleosomes levels, septic shock, and tropical fever) as the independent predictors for ICU mortality.
This study was designed to compare between the two biomarkers, TIMP1 and nucleosomes, in predicting mortality in sepsis. The validity of both biomarkers has been established separately in independent studies on disease severity, organ dysfunction, and mortality in sepsis. The area under the ROC curve for TIMP1 and nucleosomes to discriminate between survivors and non-survivors were 0.70 (95% CI, 0.58–0.81) and 0.68 (0.56–0.80), respectively. Although independent, TIMP1 and nucleosomes have statistically significant capacity to discriminate between survivors and non-survivors (p = 0.002 and p = 0.004, respectively), superiority of one biomarker over the other in discriminating between survivors and non-survivors was not observed.
In this study, mean and median values of TIMP1 was 309.9 pg/μL and 171.5 ng/mL respectively. Nino et al., in a multicentric prospective cohort analysis, observed the mean value of 320.1 ng/mL.16 A higher mean value of TIMP1 was observed in another study analyzing TIMPs in plasma obtained from patients with severe sepsis, where the mean value of 429 ng/mL.17 Similarly, Bojic, et al., in a prospective, observational study, observed a median TIMP1 value of 558.7 ng/mL in their sepsis cohort.18 Higher mean/median values in their study could be explained by relatively sick patient population in the latter studies, in which the mean values of APACHE II scores were 25.8 and 21.5 which was higher than this study, in which the mean value of APACHE II scores was 17.8. The mean value of nucleosomes in this study was 354.1 ± 367.9 pg/μL. Most of the studies mention the concentration of nucleosomes in terms of units/mL, as the ELISA kits used in them have quantified the values in units/mL.13,14 So, the direct comparison is not feasible in view of the differences in units between the studies.
The mean value of TIMP1 was lower in survivors than non-survivors (mean ± SD; 233.2 ± 298.6 pg/μL vs 408.5 ± 386.7, p = 0.002) in this study. Similar results have been observed in other studies. The mean values for TIMP1 were lower in survivors than non-survivors [294.8 (95% CI, 273.1 ± 316.6 ng/mL) vs 497.5 (95% CI, 411.8 ± 583.2) p = <0.0001] in a multicentric prospective study.16 In a study done recently, the authors noted a significant difference in nucleosome concentrations between survivors and non-survivors (p = 0.007).12
The optimal cut-off point for TIMP1, as determined by ROC curve analysis, was 149.4 pg/μL which gives the rea under curve–receiver operating characteristic curve (AUC–ROC) of 0.70 (95% CI. 0.58-0.81) to discriminate between survivors and non survivors. Similar to our study, other studies have found significantly elevated levels of TIMP1 in non-survivors.16,18,19 The ability of TIMP1 to discriminate patient’s death within the first 30 days was analyzed and result similar to this study was observed in the study conducted by Nino et al., where AUC–ROC for TIMP1 was 0.68 (95% CI, 61.9–75.6).16 These findings conclude that there is moderate-to-poor performance of TIMP1 to discriminate between survivors and non-survivors. A marginally better result was obtained in a study by Hoffman, in which ROC curves for TIMP1 measurements confirmed that TIMP1 was a good predictor for outcome (AUC = 0.78; p <0.01).19 However, the optimal cut-off for TIMP1, as determined by ROC curve analysis, was 3,200 ng/mL, which was significantly higher than the cut-off of 149.4 ng/mL used in this study. The higher cut-off in this study could be explained by the fact that the mean values of APACHE II score was 23 ± 4 which is significantly higher than the mean values of APACHE II score of 17.8 ± 6.9 in our study. Hence, the higher severity of illness could have contributed to the difference in values.
Similarly, the optimal cut-off point for nucleosomes by ROC curve analysis was 215 pg/μL. The AUC–ROC in this study was 0.68 (95% CI, 0.56–0.80) which showed the result that was similar to the TIMP1, in which nucleosomes had a moderate-to-poor ability to discriminate between survivors and non-survivors. Mortality prediction models was utilized by the study by Duplessis to predict 28-days mortality using nucleosomes obtained at baseline in sepsis patients, in which an AUC value of 0.75 (0.62–0.87) was obtained.12
In a multicentric prospective cohort study by Nino et al.,16 they performed a bivariate analysis using logistic regression with a TIMP1 value against survival at 30 days. The OR and p value for predicting survival at 30 days were 1.002 and less than 0.001, respectively. The OR for predicting death was 3.42 (95% CI, 1.35–8.68; p = 0.009) for nucleosomes. There has been no direct analysis computing OR for nucleosomes in predicting survival and death. However, Chen et al.,14 in a multiple logistic regression analysis observed circulating nucleosomes to be an independent predictor of sepsis (OR, 4.60; 95% CI, 1.62–12.78; p = 0.004).
Bivariate analysis showed significant correlation between TIMP1 and duration of vasopressor as well as that between TIMP1 and LOS (r = 0.27, p = 0.03 and r = 0.22, p = 0.04, respectively). A similar finding was observed in study by Bojic,18 where a significant correlation was found between TIMP1 and duration of vasopressors. Similar to this study, analyses performed by Hoffman19 and Ashoori17 also did not find a significant association between TIMP1 and other covariates.
There was no significant correlation between nucleosomes value and the clinical parameters. Chen et al.14 observed a significant correlation between the admission level of circulating nucleosomes and APACHE II score (r = 0.24, p = 0.01), but not with SOFA score. This could be explained by a relative higher APACHE II score (mean of 19) in their study compared to mean of 17.8 in this study.
Comparison between the levels of biomarkers with other categorical variables (such as gender, presence or absence of septic shock, hospital outcome, type, and source of admission culture results) was performed using Wilcoxon rank–sum test and Kruskal–Wallis test (depending on the variables in categorical parameter). None of the mentioned variates showed a significant difference between the level of biomarkers.
Multivariate logistic regression with adjusted OR was used to find the independent factors associated with ICU mortality. An end model with four statistically significant variables (culture positive, nucleosomes levels, septic shock, and tropical fever) emerged as the independent predictors for ICU mortality (Tables 9 and 10).
|Variables||Outcome (ICU)||Unadjusted OR (95% CI)||p|
|Male||22 (53.6)||19 (46.3)||0.80 (0.33–1.95)||0.63|
|Female||23 (58.9)||16 (41.0)|
|Septic shock absent||17 (89.4)||2 (10.5)||10.0 (2.1–47.1)||0.001|
|Septic shock present||28 (45.9)||33 (54.1)|
|Type of admission|
|Medical||25 (55.5)||20 (44.4)||0.94 (0.59–1.48)||0.18|
|Surgical elective||8 (66.6)||4 (33.3)|
|Surgical emergency||8 (42.1)||11 (57.9)|
|Source of admission|
|Emergency||35 (49.3)||24 (40.7)||1.80 (0.81–4.03)||0.29|
|Ward||10 (52.6)||9 (47.4)|
|OT||0 (0.0)||2 (100)|
|Culture negative||36 (66.5)||19 (34.5)||3.3 (1.25–9.04)||0.014|
|Culture positive||9 (36.0)||16 (64.0)|
|Variable||OR (95% CI)||p|
|Culture positive||3.68 (1.14–11.99)||0.030|
|Septic shock||14.78 (2.30–95.03)||0.005|
|Tropical fever||11.55 (1.56–85.30)||0.016|
Reviewing across the different studies of biomarkers (TIMP1 and nucleosomes) for discriminating between survivors and non-survivors using AUC–ROC, both TIMP1 and nucleosomes showed moderate-to-poor ability, with both having approximately similar values (0.70 and 0.68, respectively). An ideal biomarker should be characterized by high sensitivity and specificity. Unfortunately, neither of the two markers can predict the outcomes with perfect diagnostic accuracy. The sensitivity and specificity of each of these analyzed biomarkers are quite low. However, it is possible that the predictive value might increase significantly when both these biomarkers are analyzed in a combination. The primary objective of this study was to compare nucleosomes and TIMP1 in predicting mortality in sepsis. To the best of our knowledge, this is the first study comparing the outcomes between these two biomarkers. The optimal cut-off was obtained by ROC curve analysis and DeLong test was used for comparison between the ROC curve for two biomarkers. The analysis confirmed that although median values of TIMP1 and nucleosomes have statistically significant capacity between survivors and non-survivors (p = 0.002 and p = 0.004, respectively), superiority of one biomarker over the other in discriminating between survivors and non-survivors was not observed (p = 0.69).
This study has some limitations. First, this study involved single-point analysis of biomarkers in a single-center ICU. The changes in the dynamics of the biomarkers with changes in disease severity was not assessed. Also, observation for the values of biomarkers was done only in a single group of patients and there was no control group; hence, confounding variables or bias could not have been effectively eliminated. Second, a larger study population is required to validate the findings of this study and to allow the prognostic relevance of changes in biomarkers to be assessed. Third, we did not exclude various factors that may have influenced the estimation of biomarkers, including the ongoing medical therapies (e.g., heparin-based anticoagulants) and/or postsampling auto-degradation.
To conclude, the two biomarkers, nucleosomes and TIMP1 showed statistically significant ability to discriminate between survivors and non-survivors; however, superiority of one biomarker over other in predicting mortality was not observed.
Concept and design: KL and KP; Conduct of study: RN, KL, and KP; Statistical analysis: KP; Manuscript writing: RN, KL, and KP; Manuscript editing: KL, KP, SD, SK, ARK, and YSK; Sample processing and analysis: SMK. All authors read and approved the final manuscript.
AVAILABILITY OF DATA AND MATERIALS
Available on request.
ETHICS APPROVAL AND CONSENT TO PARTICIPATE
Institute Ethics approval was obtained from Institute Ethics Committee for Post-Graduate Research, All India Institute of Medical Sciences, New Delhi (Ref No. IECPG-170/23.08.2018, RT-26/07.09,2017, letter dated 18 September 2017; Chairman Prof. SC Tiwari). Informed consent was obtained from the participants or their legally acceptable representatives for participation in the study.
CONSENT FOR PUBLICATION
Written, informed consent was obtained from the participants or their legally acceptable representatives for publication of the manuscript. Individual consent form is kept by the author and clinical notes with the institute and these are available on request for review by Editor-in-Chief.
The authors declare that they have no competing interests.
TRIAL REGISTRATION: Clinical Trial Registry of India CTRI/REF/CTRI/2018/05/013770.
Nitin Rai https://orcid.org/0000-0003-3351-4553
Puneet Khanna https://orcid.org/0000-0002-9243-9963
Seema Kashyap https://orcid.org/0000-0002-8746-9017
Lokesh Kashyap https://orcid.org/0000-0002-5281-9857
Rahul Kumar Anand https://orcid.org/0000-0002-7852-1231
Shailendra Kumar https://orcid.org/0000-0003-1140-5444
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18. Bojic S, Stevuljevic JK, Aleksi A, Gacic J, Memon L, Ogrizovic SS. Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in sepsis after major abdominal surgery. Dis Markers 2018:5064684. DOI: 10.1155/2018/5064684.
19. Hoffmann U, Bertsch T, Dvortsak E, Liebetrau C, Lang S, Liebe V, et al. Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis: prognostic value of TIMP1 in severe sepsis. Scand J Infect Dis 2006;38(10):867–872. DOI: 10.1080/00365540600702058.
20. Marik PE, Taeb AM. SIRS, qSOFA and new sepsis definition. J Thorac Dis 2017;9(4):943–945.
22. Mohan A, Shrestha P, Guleria R, Pandey RM, Wig N. Development of a mortality prediction formula due to sepsis/severe sepsis in a medical intensive care unit. Lung India 2015;32(4):313–319. DOI: 10.4103/0970-2113.159533.
© The Author(s). 2022 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.


Matt 'Miller' Leaves KKEG
February 5, 2014 at 3:47 PM (PT)
CUMULUS MEDIA Rock KKEG (THE KEG)/FAYETTEVILLE-NW ARKANSAS Brand Manager/PD MATT "MILLER" EXITS . Miller started as a Remote Tech and SUNDAY morning jock in 2007 at KKEG and moved to BOB & TOM producer and nights, host, He was upped to Brand Mgr/PD of KKEG/KLSZ and to program to KKGB/LAKE CHARLES in 2011.
"Great people have sat behind that mic at KKEG and now I can say I was one of them," he said. "There were ups and downs. I don't regret a day of it."
MILLER is looking for his next adventure. He can be contacted at firstname.lastname@example.org.


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This is the third book in The Brides of Hope Mountain series, Ursula’s story. With her sisters married and down in civilization, Ursula is the lone hold out in isolation on the mountain. She has her skills and hones a new one- ax throwing. She has her Bibles and has set scripture to song. As spring comes, Ursula decides to do a brave thing and climb down the mountain as God leads. She comes upon an injured Wax Mosley and helps him back up the mountain and nurses him back to health.
*Beneath all the misery was a song. A private song for him alone, almost like the angel had followed him into hell. That single secret song kept him from dropping so far down into the hot black misery he would never be able to get back up.*
Her Secret Song wraps up the story of the Nordegren sisters and the Warden family to a satisfying conclusion. Ms. Connealy describes the terrain beautifully. There are funny moments and exciting chases, stalking and captures.
Wax Mosley saw Ursula as an angel come to his rescue. He re-evaluated his life and came to know God in a more personal way that changed his behavior.
We can learn from Ursula in her isolation. She relied on God and always had a song in her heart even amongst difficulties.
*I received a complimentary copy of this book from Bethany House on behalf of the author. I was not required to give a favorable review. All opinions are my own.*I give this 4 stars and a strong faith thread.
With an imaginative premise of three sisters raised in the tops of the mountains in rural Colorado in the 1870s, Mary Connealy has created a clever and humorous series that climaxed with Her Secret Song starring Ursula Nordegren. Raised by their grandparents and warned about the dangers existing down in the valleys, the girls learned to be self-reliant but lacked knowledge about society. Mary Connealy’s sense of humor shines through her stories, and this series has been a favorite of mine.
“Grandma had only taught them to count to one hundred. It seemed unlikely they’d ever have more than one hundred of anything, so Grandma thought going higher was a waste of time.”
Populated with amusing and endearing characters and full of madcap adventures, this tale captured my imagination and kept me turning pages. Although this was Ursula’s story, characters from the other books in the series popped up and added to the fun. Ursula is an interesting character, at times timid but also courageous when circumstances warranted bravery. Jake “Wax” Mosby is a hired gun who is trying to mend his ways and live uprightly. When he’s rescued by Ursula and introduced to her family, things get a little crazy.
“The hatchet hit hard and stuck. ‘Right where I aimed.’ She felt proud of her skill. That was a sin, but before she repented, she enjoyed the shocked expression on her sisters’ faces.”
“He glared down the mountainside. He had no wish to climb down. Being shot off a mountain cured a man of climbing.”
If you’re in the mood for some humorous historical fiction, this series The Brides of Hope Mountain is sure to please. This series is bound for my keeper shelf.
*I voluntarily reviewed a complimentary copy from the author and Bethany House Publishing. All opinions are my own.
After a rough winter spent alone, Ursula Nordegren realizes she must overcome her fears of the outside world and begins a trek down Hope Mountain. Along the way she finds a badly wounded stranger and realizes God may have used her decision to leave as a way of saving the man.
Wax Mosby was climbing Hope Mountain in part to atone for his terrible choices. He was hired to drive out the Warden family and now knows he was duped. But when he's wounded during the climb, the last person he expects to rescue him is a beautiful blond woman with the voice of an angel.
As both Ursula and Wax weigh the costs of living new lives, the two find an unlikely bond. And they're joined by Ursula's sisters and the Warden family as the final showdown over the family ranch looms with the coming of spring.
Buy Her Secret Song at Amazon
Buy Her Secret Song at Christianbook.com

domain: literature


text:
Hello dear community,
On March 15th I sent out an email that broke my heart. Today I am so happy to send this one out letting you know we will reopen June 1st! Although we are able to open May 19th, I feel like I would like to see how the first week or so goes before taking the leap as there are many recommendations that need to be followed to keep us all safe.
Here are some of the changes that are required:
I know it sounds like a lot of rules, but this is the way we need to do it to ensure everyone's safety. The teachers are so excited to see you all. We will sort out the passes as we go, as monthly passes were suspended so will need to reactivated on your first class back. We also have a new price list - we have had to make some increases but monthly passes remain the same. We are currently fine-tuning the June schedule and will have it posted within the week.
We look forward to welcoming you back June 1st, in the meantime our online classes will continue on our Facebook group. Please feel free to contact me with any questions.
To provide a safe, nurturing and cozy environment to connect with your true self and find peace. We want to be your home for Yoga in Port Coquitlam.
Our Port Coquitlam studio offers several styles of Yoga including:
A unique, comfortable experience, centered around the healing power of sound, featuring several gongs and alchemy crystal singing bowls.

domain: hobby


Glastonbury police released the following information on arrests and infractions. Inclusion on this list does not indicate a conviction.
Steven Osip, 45, and Jessica Johnson, 21, both of 194 House St., Glastonbury, were both arrested on charges of disorderly conduct after police responded to their home on a report of a domestic dispute. They were each released on a written promise to appear in court on Feb. 1.
Jason Allen Thomas, 31, of 109 Concord Circle, Wethersfield, was arrested on a single count of violation of probation after turning himself in to the Glastonbury Police Department at 7 a.m. He was held in lieu of $200,000, and was arraigned in Manchester Superior Court later that day. The warrant for his arrest stemmed from a prior arrest for first-degree robbery with a firearm.
Louis S. Moore, 20, was arrested on charges of second-degree breach of peace and possession of drug paraphernalia after police say he struck and spit on a parked car on Hebron Ave. He was released on a written promise to appear in court on Feb. 13.
Derek Pierini, 29, of no certain address, was arrested on charges of third-degree burglary, first-degree larceny and second-degree criminal mischief by members of the Glastonbury Police Deparmtent and the Connecticut Department of Corrections Parole Fugitive Investigations Unit at a residence in Hartford. The charges stemmed from an investigation into a residential burglary on Glastonbury Hunt Lane on Jan. 18, where jewelry, electronics and a vehicle were stolen. Evidence linked Pierni to the burglary, police said. He was held in lieu of $75,000 bond and turned over to parole officers for a violation of parole. He is due in court on Feb. 13.
Wayne D. Massa, 47, of 155 Burnside Ave., 2nd floor, turned himself to police on a warrant charging him with failure to respond to an infraction regarding an original charge of possession of less than 0.5 ounces of cannabis. He was released on $300 bond and is due on court to answer to those charges on Feb. 8. Massa also turned himself in on a separate warrant charging him with second-degree failure to appear, operating a cell phone without a hands free device and operating under suspension. He was released on $4,000 bond for that warrant, and is due in court for those charges on Feb. 13.


text: Entertainment TV Ellen Pompeo Breaks Her Silence After Justin Chambers' 'Grey's Anatomy' Exit Justin Chambers was an original cast member of the medical drama with Ellen Pompeo By Maria Pasquini Maria Pasquini Associate Editor, Human Interest - PEOPLE People Editorial Guidelines Published on January 11, 2020 02:45 PM Share Tweet Pin Email Grey’s Anatomy won’t be the same without Justin Chambers. On Saturday, one day after news broke that Chambers was leaving the show after 16 seasons, costar Ellen Pompeo briefly addressed his exit on Twitter. Responding to a Tweet from Vanity Fair about the news, which proclaimed that “#GreysAnatomy is about to feel one of its biggest losses yet,” the actress, 50, shared that she couldn’t agree more. “Truer words have never been spoken,” Pompeo wrote of her fellow original cast member, including a broken heart emoji. ABC confirmed to PEOPLE on Friday that Chambers, 49, had left the show after 16 seasons. His final episode aired on Nov. 14, 2019. Chambers was an original cast member of the medical drama with Pompeo. Justin Chambers’ Dr. Alex Karev Left Grey’s Anatomy on a Heroic Note: Revisit His Final Moments “There’s no good time to say goodbye to a show and character that’s defined so much of my life for the past 15 years,” Chambers said in a statement to PEOPLE. “For some time now, however, I have hoped to diversify my acting roles and career choices. And, as I turn 50 and am blessed with my remarkable, supportive wife and five wonderful children, now is that time.” Chambers added, “As I move on from Grey’s Anatomy, I want to thank the ABC family, Shonda Rimes, original cast members Ellen Pompeo, Chandra Wilson and James Pickens, and the rest of the amazing cast and crew, both past and present, and, of course, the fans for an extraordinary ride.” Deadline was the first to report the news of Chambers’ exit. Mitch Haaseth/ABC Because Chambers’ last episode aired on Nov. 14 — he was absent from the midseason finale and it was explained that he was taking care of his ailing mother — the character will not get a send-off episode. Chambers and Pompeo ended their time on the show with a bang as in his final episode, the show’s 350th, during which his character stands up for Meredith Grey (Pompeo) as she faced the medical board to determine if she could have her medical license reinstated following an insurance fraud scandal. In his final frames, Alex was among his friends and colleagues as Meredith’s lawyer revealed that his efforts worked — and Meredith’s license was reinstated. It remains to be seen how the show will explain Alex’s exit. Grey’s Anatomy‘s midseason premiere airs on Jan. 23 at 9 p.m. ET on ABC.

domain: entertainment


Ridgecrest Neighborhood Association Board of Directors Meeting
- Date: 12/10/2019 7:00 pm - 9:00 pm
- Location: Ridgecrest Elementary School Library
16516 10th Avenue NE
Shoreline, Washington 98155
Ridgecrest Neighborhood Association Board meets the second Tuesday of each month. Neighbors and business owners are invited to attend to learn about what is going on in our neighborhood. You are welcome to speak during the public comment period at the beginning of the meeting. We discuss matters that affect us in Ridgecrest, schedule community information meetings, plan events and work on grant worthy neighborhood improvement projects and much more.


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Around a third of food worldwide is grown using freshwater irrigation, however much of that water comes from unsustainable resources. By 2050, it is predicted that food production will need to increase by nearly 50% to sustain our rapidly growing global population. Food security is also one of the key issues affecting the Middle East and a core focus of King of Abdullah University of Science and Technology’s (KAUST) research agenda.
One solution has come in the form of Red Sea Farms, a KAUST startup spinout. Co-founders Mark Tester and Ryan Lefers are KAUST scientists who collaborated to create new greenhouse solutions as part of their research. Mark is a botanist with decades of experience researching salinity tolerance in plants and Lefers is an agricultural engineer who completed his PhD in saltwater cooling for greenhouse environments.
“The problem is that globally our food systems are profoundly unsustainable,” says Tester. “We have to change our overdependence on water, and one way to achieve this is to substitute some of the water we use with salty water. Therefore, Red Sea Farms aims to develop and deploy economically viable saltwater-based agricultural systems.”
Greenhouse Saltwater Technology To Feed The Future
After years of laboratory research and testing, the startup formed in early 2018 and was incorporated in Saudi Arabia soon after. The concept for Red Sea Farms was powered by a fusion between the fields of science and engineering. “I’m the plant guy,” says Tester, “And he’s [Ryan Lefers] the engineering guy, and together we are able to deliver saltwater agricultural systems.”
The startup received early-stage funding from KAUST’s Innovation Fund and Research Products Development Company, the venture investment arm of King Abdullah City of Science and Technology (KACST) based in Riyadh. Together the partners jointly invested $1.9 million USD of seed funding.
“We’re now building a pilot facility at KAUST to demonstrate to customers and investors that the system really works,” said Lefers.
“Not all of the funding was equity-linked which was very important for us,” says Tester, “The generosity of KAUST enabled us to get going and support us in building the pilot greenhouse.” The 2,000 square meter greenhouse pilot is the next stage to deliver sales of their salt-water grown tomatoes and greenhouse technology. “We have many enquiries already and we will hopefully be lining up our first sale soon.” Tester adds.
Red Sea Farms Wins Saudi Finals of Entrepreneurship World Cup
In June this year, Red Sea Farms pitched and won at the Saudi finals of the Entrepreneurship World Cup (EWC). The startup will go on to pitch at the national finals alongside winners from over 60 countries globally. “Winning the Saudi finals was a fantastic experience,” says Tester, “And it is very exciting to be in the global finals.” The startup will be competing for a million dollars in prize money.
In the future, Red Sea Farms will develop produce and salt-tolerant crops to significantly change and improve the way food is grown globally. The future for the startup is bright, with opportunities in food production, farming technology development and consultancy. As explained by Tester, “We are one part engineering company, selling coolant systems to install in greenhouses. And one part farmers, developing new saltwater tolerant plants which can be sold as produce directly to consumers.”
Learn more about the Entrepreneurship World Cup
KAUST to host over 100 startups from 64 countries for Misk’s Entrepreneurship World Cup
KAUST Startups Sweep Wins at Misk’s Entrepreneurship World Cup
KAUST Startup Spinout Red Sea Farms Closes $1.9 Million Investment

domain: agronomy


text:
19th century oak bonnetiere from the Brittany region of France with bears carved on the door, circa 1870.
Louis XV style bonnetiere
French Homme Debout
18th century French cherry bonnetiere in Louis XV style.
Nice Louis XIV oak bonnetiere from the Southwest of France.
Early French bonnetiere in fruitwood from Vendee Region

domain: history


text:
Not content merely to conquer our existing world, James Cameron figured he’d build one of his own. This summer, Disney’s Animal Kingdom in Orlando will cut the ribbon on “Pandora — the World of AVATAR,” a new attraction replicating the lush world from Cameron’s immensely profitable 2009 sci-fi film. The director, producer, and heads of construction for the developing theme park all appeared in a new behind-the-scenes video preview that gives prospective viewers an eyeful of what the creator claim to be the most technologically sophisticated amusement at Disney, if not in the world.
James Cameron - Page 2
Sigourney Weaver is something of a sci-fi movie icon. Since her performance in Alien, she’s made a ton of appearances in all kinds of movies about the weird and the wonderful, from The Cabin in the Woods to WALL-E to a brief but not unwelcome scene in this summer’s Ghostbusters. She was also one of the best parts of James Cameron’s Avatar, playing Dr. Grace Augustine, one of the scientists in the Avatar Program who started a research program to learn more about the planet Pandora and its inhabitants. She’s read the scripts for Cameron’s planned sequels, and, according to her, they’re “amazing.”
It was just this past April that blockbuster alchemist James Cameron made the promise/threat of four sequels to his massively lucrative sci-fi fantasy Avatar. Having apparently calculated “eight years or so” as the optimal amount of time to let Avatar fever percolate before reaching a boiling point, the filmmaker hinted at plans for his follow-up(s) while accepting his honorary membership into the Society of Motion Picture and Television Engineers on Friday night. Indiewire reports that while entering an elite group of industry professionals devoted to expanding the technological reach of film, Cameron stated his intentions to bring Avatar even further into the future with groundbreaking techniques and equipment.
Mahershala Ali might have caught the villain bug. Currently he plays Cottonmouth, the powerful and terrifying bad guy featured in the first season of Netflix and Marvel’s Luke Cage, and soon he might appear as another villain type in James Cameron’s live-action adaptation of Alita: Battle Angel.
At this point, it might be more interesting if James Cameron’s Avatar sequels never come to fruition — like maybe this is his most elaborate project of all, a practical joke that spans years or even decades. That doesn’t seem to be the case, as Cameron’s ambitious plans have only grown more so, swelling to four sequels that he plans to release, well, eventually. Movie magic takes time, people. But for now, Cameron has some new plot details to support the bold claim that he’s making three more installments in the franchise.
James Cameron has been toying around with a Terminator 2: Judgement Day 3D release for some time-- last year he announced that he was working on it, and that it would arrive in theaters around the time of the film’s 25th anniversary. Seeing as that deadline’s come and gone, it looked like a remaster was not to be. Fortunately, according to Collider, Cameron is still working on it, as announced on the Terminator 2 official Facebook page yesterday with a cool new poster:
Yep, that Alita: Battle Angel movie is still happening. With James Cameron set to produce, Robert Rodriguez at the helm, and Rosa Salazar on board to play the titular cyborg Alita from the manga series, all that’s left to do is to find the rest of the cast. And it looks like Christoph Waltz is in talks to play a pretty major role.
While many people stood in line for Marvel’s big announcements at Comic-Con International , other science-fiction fans were being treated to a panel discussion on the 30th anniversary of Aliens. Director James Cameron and his cast and crew talked about the experience of making the original film, but those also interested in the future of the franchise were treated to Cameron’s first impression of the oft-delayed Neill Blomkamp Alien 5.
Today brings news that San Diego Comic-Con will play host to a special panel to celebrate the 30th anniversary of Aliens, James Cameron’s sequel to Ridley Scott’s sci-fi horror classic. Cameron himself will be in attendance along with Sigourney Weaver, who is still talking up Neill Blomkamp’s new Alien sequel despite reports that the project had been delayed due to Scott’s own Alien prequel plans.
The release of Star Wars: The Force Awakens last Christmas was one of the most anticipated events of the season, and naturally everyone had an opinion. From Twitter misanthropes to awestruck fan site die-hards, all four corners of the internet were buzzing with approval or disappointment.


text:
The GEP Global Supply Chain Volatility Index showed declining demand for raw materials, commodities, and other components needed to provide finished goods and services in December. That indicates a growing risk of an upcoming recessionary period. More businesses are safety-stockpiling inventories as a reaction to COVID-19 infections in China and increased concerns about future supply and pricing. This is partly reversing destocking efforts seen in the previous six months.
Greater safety stockpiling and the worsening of labor shortages caused the GEP Global Supply Chain Volatility Index to rise from 1.15 in November to 1.61 in December, halting global supply chain improvements that began in the summer of 2022.
The key findings from December’s report include:
- Demand for components, raw materials, commodities, and any other items companies need to provide their goods and services declined further in December
- Global business reports of safety stockpiling are up since November, a key factor behind December’s Index increase
- Companies report an uptick in labor shortages, causing supplier capacity to be stretched
- Global supply shortages are at their lowest level since September 2020 as suppliers continue to adjust to market conditions
- Transportation costs are at their lowest in over two years, highlighting weaker pressures on shipping, train, air and road freight
- Supply chains feeding into Europe are the most stretched, compared to Asia and North America
The GEP Global Supply Chain Volatility Index is produced by S&P Global and GEP and is derived from S&P Global’s PMI surveys, sent to approximately 27000 companies in over 40 countries that account for 89% of global gross domestic product (source: World Bank World Development Indicators).

domain: news


text:
Physics-based computer simulation of the long-term effects of cardiac regenerative therapies
- Lik Chuan Lee, Joakim Sundnes, Martin Genet, Samuel T. Wall
- in 2016
- Cited Count
- World Scientific
In this paper, we describe the application of an integrated electromechanics-growth computational model to simulate the long term effects of cardiac regenerative therapies in a left ventricle (LV). The electromechanics-growth model couples biophysically detailed cellular-based laws that describe the short term events occurring in the excitation-contraction coupling process in the cardiomyocytes, to a phenomenological law that describes the long-term process of growth and remodeling in the cardiac tissue. Two clinically relevant phases depicting the progression and subsequent treatment of heart failure were simulated using this model. These phases are namely, (1) the long-term remodeling process induced by a myocardial infarction and (2) the long-term response following regeneration of the infarct. Our model predictions show that the abnormal myofiber strain values surrounding the infarct can drive the post-infarct LV hypertrophy, whereas a subsequent normalization of the myofiber strain after infarct regeneration can lead to a reduction in the LV size. These findings are consistent with some of the observations found in the experiments and clinical studies of cardiac regenerative therapies.
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domain: medical


Acquire a distinctive sound of power in your obstacle-dominating rig by purchasing a brand new Borla Long Tube Header (17081) for your 1997 Automatic or Manual Transmission 4WD V6 Jeep Wrangler with a 4.0L engine. Your Long Tube Header Complete system will include headers, collector/muffler, pan-e-vac tubes, stainless steel Stage 8 self-locking bolts, and gaskets. Racers agree that this system is so much quieter than anything else! BORLA is the choice of major vehicle manufacturers for their performance and racing programs.
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- 1997 4WD V6 Jeep Wranglers with a 4.0L engine
- Automatic and Manual Transmissions


text:
Cenan M. Antowan, M.D.
- Pediatrics - General
Primary LocationPediatrics 4801 Alberta Ave.
El Paso, TX 79905
Phone (915) 215-5700
- American Board of Pediatrics – Pediatrics
- Pediatrics | Texas Tech University Health Sciences Center El Paso | El Paso, TX
- Doctor of Medicine | University of Baghdad - College of Medicine | Baghdad, Iraq


text:
Our team has developed a specialized practice in the field of Data Protection. Our experience includes analysis of the applicable regulation for compliance by foreign and domestic clients regarding attainment, treatment, use and transfer of personal data and sensible personal data activities, in order to determine the obligations in connection therewith.
In addition, we advise our clients in the review and preparation of private information policies and management of information guidelines for compliance with Mexican law, as well as with privacy notices for the activities that require it, such as internet web sites or others services platforms which include the attainment of information.
We represent our clients in administrative processes before the Transparency, Access to Information and Personal Data Protection National Institute.
Write to us and we will get in touch with you.

domain: law


Jul 18, 2011, 12:48 PM EDT
Matthew Pouliot wrote last week that Detroit’s primary focus heading into the trade deadline should be rotation help, so not surprisingly Jon Paul Morosi of FOXSports.com reports that the Tigers are interested in Orioles starter Jeremy Guthrie.
Guthrie has a hideous 3-13 record, but his 4.45 ERA and 80/36 K/BB ratio in 123 innings are pretty close to his career norms and he’s typically been a solid mid-rotation starter.
He’s also 32 years old and earning $5.75 million, so while Guthrie has been the Orioles’ Opening Day starter in three of the past four seasons and is under team control via arbitration in 2012 it would certainly make sense to shop him for long-term help.
Morosi says the Orioles “will want pitching in return” if they deal Guthrie, but ultimately the market for him will be determined largely by whether superior starters like Ubaldo Jimenez and Hiroki Kuroda are also being shopped. Guthrie isn’t going to be any contender’s No. 1 target, but if the price is right he’s a reasonable fallback option.
- And That Happened: Wednesday’s scores and highlights 25
- David Price surrenders nine consecutive hits to the Yankees in the worst start of his career 20
- Video: Jorge Soler homers in his first major league at-bat 22
- Adam Wainwright has a “dead arm” 32
- HBT Daily: Alex Gordon and the Royals keep on rolling 12
- And That Happened: Tuesday’s scores and highlights 43
- Mariners extend general manager Jack Zduriencik’s contract 14
- Money, money, money (and Bud Selig’s nirvana) 16
- The Cubs grounds crew was short staffed because the Cubs were trying to avoid Obamacare (247)
- Forgiveness for Pete Rose? Not in this lifetime (144)
- Great Moments in Drug Testing and Punishment: The NFL Edition (99)
- Cuban outfielder Rusney Castillo to sign with the Red Sox for $72 million (96)
- A pitch clock in Major League Baseball? No thanks. (92)


text:
Fentanyl is far more powerful than the street drugs of yesteryear, with some experts estimating that it’s 50 times more potent than heroin or morphine. Unlike other street drugs, fentanyl addiction can begin from the first moment the drug is taken, and can cause a plethora of issues that the user or addict faces in the long term.
A lot of people misunderstand the potency and addictiveness of this drug. To shine more light on the topic, the team at SJRP Drug and Alcohol Rehab Florida have created a helpful infographic that can give you a better idea of just how scary (and fast) the path to addiction with this drug truly is.
If you or a loved one is suffering from fentanyl addiction, there are a variety of resources available to you that can help. Learn more by visiting SJRP.com online.


text:
3 edition of Works for clavier. found in the catalog.
Works for clavier.
George Frideric Handel
|Series||Kalmus study scores ; 765|
|The Physical Object|
|Pagination||124 p. : music ; 18 cm.|
|Number of Pages||124|
The first book of Bach's Das Wohltemperierte Klavier (The Well-Tempered Clavier) was complete by Bach gave the present title to the work, which was composed "for the use and practice of musical youth eager to learn and for the amusement of those already skilled in this study." Bach composed a paired Prelude and Fugue in each of the 24 keys to demonstrate the viability of the new "equal. The Well-Tempered Clavier, Books I and II (Complete) By Johann Sebastian Bach Piano Book Item: $ Add to Cart Add to List. Share. Product Details. Description. All 48 preludes and fugues, from Books I & II, in all major and minor keys. Bach-Gesellschaft edition. ry: Piano Collection.
The two works are now usually considered to comprise The Well-Tempered Clavier and are referred to respectively as Books I and II. 3 scores found for "Well-Tempered Clavier Book One - Prelude and Fugue No. 6" Similar items. Details. Details. Johann Sebastian Bach: The Well-Tempered Clavier, Complete Piano solo Schirmer (3) $ - See. The Paperback of the Well Tempered Clavier - Book 1: Piano Solo by Johann Sebastian Bach at Barnes & Noble. FREE Shipping on $35 or more! Due to COVID, orders may be : Schirmer, G., Incorporated.
Join Classical Music Only and discover unknown masterpieces, create endless lists, see discussions of your favorite composers on your personalized homepage timeline and much more! clbcarman. The Well-Tempered Clavier, Book II. recording The Well-Tempered Clavier, BWV – soloist. András Schiff. Watch. 2. continue. 0. Original MIDI Files, Images, RealAudio Files, Recommended Recordings, a Bach Works Catalog, Links, and More The Clavier-Büchlein for Wilhelm Friedemann Bach Little Clavier Book.
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Rows Keyboard and Lute Works is the topic of the fifth series of the New Bach Edition. Keyboard Works (Klavierwerke) by Johann Sebastian Bach traditionally refers to the Nos. toChapter 8 in the BWV catalogue, listing compositions for a solo keyboard instrument like the harpsichord or the e the fact that organ is also a keyboard instrument, and that in Bach's time the.
Beethoven studied all the accessible works of Bach profoundly (including The Well-Tempered Clavier) and frequently quoted them in his sketchbooks, often with direct bearing on his own works.
Chopin is nowhere more characteristic than when he shows his love Cited by: 3. 11 rows This page lists the fugal works of Johann Sebastian Bach, defined here as the fugues. Bach gave the title Das Wohltemperirte Clavier to a book of preludes and fugues in all 24 major and minor keys, datedcomposed "for the profit and use of musical youth desirous of learning, and especially for the pastime of those already skilled in this study".
Some 20 years later Bach compiled a second book of the same kind, which became known as The Well-Tempered Clavier, Part. Browse: Bach, J S - The Well-Tempered Clavier, Book 1 This page lists all recordings of The Well-Tempered Clavier, Book 1 (Das Wohltemperiertes Klavier, BWV) by 4/5.
J.S. Bach: The Well-Tempered Clavier, Book I, BWV - 2. Prelude And Fugue In C Works for clavier. book, BWV Kenneth Gilbert. This recording offers a perfect introduction to Georg Philipp Telemann's oeuvre of works for keyboard. Amongst the vast body of compositions produced by this immensely prolific composer, the keyboard music is often given short shrift/5(2).
Works: Preludes & Fugues (24), BWV Review: Bach’s Well Temepred Clavier Book 1 from a Legend Review: Well Tempered Clavier Book 1 from Robert Levin Review: Bach & Shostakovich Preludes & Fugues from Olli Mustonen Review: Edward Parmentier Plays Bach's Well-Tempered Clavier.
Andras Schiff – J.S. Bach: The Well-Tempered Clavier Book 1 () Blu-ray i AVC + BDRip p/p. Published Febru The Well-Tempered Clavier is acknowledged to be one of the most significant works ever written for the keyboard.
Each of these 24 preludes and fugues encapsulates its own mood, and Bach’s. Reviews of Instrumental Works: Bach's Well Tempered Clavier from Barenboim (D. Satz] | Review: Well-Tempered Clavier Book I - played by Daniel Barenboim [P.
Bright] | Review: Well-Tempered Clavier Book II - played by Daniel Barenboim [P. Bright] Discussions of NonVocal Works: Goldberg Variations BWV - played by Daniel Barenboim.
⇒ 23 more: Prelude and Fugue No.2 in C minor, BWV • Prelude and Fugue No.3 in C♯ major, BWV • Prelude and Fugue No.4 in C♯ minor, BWV • Prelude and Fugue No.5 in D major, BWV • Prelude and Fugue No.6 in D minor, BWV • Prelude and Fugue No.7 in E♭ major, BWV • Prelude and Fugue No.8 in E♭ minor, BWV Authorities: WorldCat; VIAF: ; LCCN:.
Johann Sebastian Bach The Well-Tempered Clavier (24), collection of preludes & fugues, Book I, BWV (BC L). BACH Well-Tempered Clavier (complete) • András Schiff (pn) • ECM (4 CDs: ) András Schiff is an old hand at Bach, having recorded most of the composer’s major solo and concerted keyboard works, including a previous WTC for Decca back in the s.
Over the course of reviewing numerous artists performing Bach’s keyboard works on piano, I’ve consistently cited András. Bach later compiled a second book of the same kind, datedbut titled it only "Twenty-four Preludes and Fugues." The two works are now usually considered to make up a single work, The Well-Tempered Clavier, and are referred to respectively as Books I and II.
Here is an affordable edition of the complete 48 preludes and fugues in all major and minor keys. Reprinted from the authoritative Bach-Gesellschaft edition, the book also features handy explanation of ornaments in English plus tempo indications and music corrections.
"His art was of an encyclopedic nature." — Grove's Dictionary of Music and Musicians. Buy Siegbert Rampe's album titled W. Bach: Clavier Works to enjoy in your home or car, Due to COVID, orders may be delayed.
Thank you for your patience. Book Annex Membership Educators Gift Cards Stores & Events Help Auto Suggestions are available once you type at least 3 letters. Publish your book with B&N. Learn : $ Distinguished Bach specialist Sir András Schiff returned to the BBC Proms in to present Book II of The Well-Tempered Clavier.
Extending the variety already evident in Book I (available on ), Bach’s effortless brilliance and new-found sonorities push harmony and counterpoint further than ever with a combination of ancient and.
My top 5 from both books of the Well-Tempered: Honorable mention: e minor, book II (love the fugue); b minor, book I (ditto, so long and mournful); C major, book I (there’s beauty in simplicity).
a minor, Book II. The chromatic, winding prelude. Pieces by Johann Sebastian Bach listed by difficulty. Difficulty 1 (2). The Well-Tempered Clavier, Book 1, BWV – 1.
C major, BWVPrelude (1' 30") Prelude in C major, BWV a/1 (1'). Difficulty (5). Fifteen Inventions, BWV – 1. C major, BWV (1') Fifteen Inventions, BWV – 4.
D minor, BWV (1') Fifteen Inventions, BWV – 6. E major, BWV (3' 30"). Provided to YouTube by Believe SAS The Well-Tempered Clavier, Book 1, BWV Prelude in C Major Luke Faulkner Top 10 Most Famous Classical Piano Works ℗. When the pianist András Schiff took a break halfway through his magnificent performance of Bach’s “Well-Tempered Clavier,” Book I, on Saturday night at the 92nd Street Y, the intermission Author: Anthony Tommasini.The two works are now usually considered to make up a single work, The Well-Tempered Clavier, and are referred to respectively as Books I and II.
About this Piece. Suggest a correction for this page. Page # of # The Well Tempered Clavier, Book I, BWV - Prelude and Fugue No. 22 in B-flat minor, BWV Raymond Smullyan.Well-Tempered Clavier - Book 2 - Prelude & Fugue No.
03 in C-Sharp Major, BWV II. Fugue.

domain: library


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Ever had a night like this? You swing by the store to pick up just one thing, but as you wait in line at the checkout a chocolate bar or bag of chips catches your eye. You know these aren’t good for you but you feel compelled to buy them anyway and scarf them down in the car on the way home. Here are some tips to break this unconscious cycle and get your brain out of binge mode.
Most people have experienced some version of the scenario above at some point in their lives. The inevitable outcome is that by the time you pull into your driveway, regret is kicking in hard and you are feeling awful about yourself. Most people think that this is due to a lack of will-power; while that may be the case, it isn’t the main reason for most people.
One of the major problems is that many foods – especially the ones with lots of added sugar, salt and fat – are so tasty that they actually overwhelm the brain’s circuitry. When you eat them, your brain cranks out large amounts of dopamine, which is a neurotransmitter associated with reward that drives you to eat that food again…and again…and again, and want it even more. Eventually, just looking at the food or even thinking about it can trigger a dopamine release – along with a strong craving to satisfy the desire to eat it. Once this occurs, your brain has been hijacked and is in full-fledged binge mode.
Here are some steps you can take to break out:
Visualize the Good
The brain can get hijacked via a number of mechanisms and temptation can seemingly strike out of nowhere. For instance, you walk through a food court and catch a whiff of freshly baked bread or cinnamon rolls. When this happens, many people try and reason with themselves thinking, “I shouldn’t eat that” or “that food is bad for me”. This is effective about two percent of the time, as our brain doesn’t care about logic at this point; it has been hit with a biochemical desire for something, and it wants it NOW.
To get your brain back to a place where you are in control, try to visualize a better outcome that is also rewarding, just in a different way. In the example above, try thinking “I have a delicious healthy lunch waiting for me back home that I can enjoy soon enough. It’s going to taste great AND I’ll feel good afterwards.” Changing the focus of your thoughts will put you back in the drivers seat and keep you focused on the outcome you want, rather than one you don’t.
Here’s another scenario: you’re driving along and see a sign for your favorite fast-food restaurant. You realize you’re hungry and the thought of eating your favorite cheesy fries pops into your head. Suddenly, you feel compelled to make an unexpected stop at the drive-thru and are about to cut across three lanes of traffic to do so.
Don’t stop. Instead consider this: studies show that addictive cravings tend to fizzle as soon as the object in question becomes unattainable. In other words, once you get a few miles down the road, you’ll likely discover that you didn’t really need those extra-large cheesy fries after all.
Consider the Aftermath
When you’re brain is being hijacked by the thought of eating super-stimulating foods, it’s reward system is keyed into one thing and one thing only: the immediate sensory pleasure of eating that food. You can regain control by thinking past eating the food to the consequences of eating that food. For example, if the thought of having a big ice-cream sundae pops into your head and you are feeling helpless to fight it, go with that thought, but extend your visualization to what happens next. Once you think about the guilt that comes the next day or the indigestion that always occurs after you eat ice-cream, you undercut the reward value of the food and the food in question will lose much of it’s appeal.
Your brain works for you; when it starts to think otherwise, use the suggestions above to assert who’s boss. After trying these suggestions in earnest, if you still feel helpless when confronted with cravings, amino acid therapy may help.

domain: food


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Straddling Lombardy and Piedmont, the great lakes of northern Italy have been a popular holiday destination since Roman times, evidenced by the array of lavish villas and sumptuous gardens which line the shores. Away from the affluent holiday centres is a feast of walking trails exploring the forested valleys, mountain tops and traditional villages which have retained their unique character. The old tracks which cross the mountains on the west side of Lake Como, used even today by the local people to reach the alpine pastures called 'Monti' ('Munt' in the local dialect) have been transformed into a series of way marked trails offering exceptional views. This program takes in the highlights of Lake Como within a flexible framework with a selection of walks of varying lengths and difficulty to choose from along the Monti Lariani (Lario being the ancient name of Lake Como). With accommodation in a small family run hotel there is ample opportunity to experience the excellent regional cuisine allowing a complete appreciation of the area.
DAY 1 Arrive Menaggio (Lake Como) DAYS 2-4 Day walks to explore the small towns, viewpoints, forests and Monti above Lake Como and visit the gardens of Villa Carlotta in Tremezzo and Villa Melzi in Bellagio (3-7hrs daily) DAY 5 Trip concludes
Daily from 1 Apr to 22 Oct
High season is from 28 Jun to 30 Sep (3 star hotel option) Trips run from 1 Apr to 22 Oct for 4 star option and 15 Apr to 5 Oct for 3 star hotel option. A discount is available for low season departures in the 4 star category from 1 Apr to 9 Apr and 16 to 22 Oct - upgrade supplement is applicable in conjunction with the discount.
*4 breakfasts *4 nights in a 3 star hotel on a twin share basis with ensuite facilities (upgrade to 4 star hotel and/or lakeview room (supplement applies), hotel taxes extra - payable locally) *transfer on day 3 to start of walk in Cavargna *information pack including route notes & maps per room booked *emergency hotline


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mohankasi wrote:Thank you for the response and allow me to try explaining again. I will start at Restoran Kari Kepala Ikan Deen ( 065NU70), which is along Jalan Dato K Padmanaban. If I need to go to Immaculate Conception Church ( 065RMHM) which is along Jalan Seremban, I need to go around the PD Roundabout (065M10Y). I can't just cut across at the junction which comes just after Jabatan Pendaftaran Negara Malaysia PD (065L3FW). The road too need to be changed from Jalan Port Dickson to Jalan Seremban. This is the road leading out of the roundabout, across the defunct railway line, and infront of the Police IPD Port Dickson (065K5RS) to the Church. Am attaching another picture of the journey. My journey is coloured green. The blue colored journey is wrong and needs to be corrected. But if I am from Jala Seremban and need to go Restoran Kepala Ikan Deen I just go straight, infront of the IPD, Jabatan Pendafaran and to the Restoran. Another issue here is if one comes along Route No.5, and needs to go to the church, you need to go around the roundabout too. The defunct railway line runs in between the two roads, Jalan Dato K Padmanaban and Jalan Seremban (named Jalan Port Dickson (066J84R) in Papago S1) Hope I have made it clearer now.
ok. I will rectify it.

domain: geography


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|Home page Politics|
Malala Yousafzai, the Nobel Prize winning activist who narrowly avoided being death after being shot by the Taliban, has revealed that she intends to study at a British university.
She told head teachers at the Association of School and College Lecturers annual conference on Saturday: "I'm in Year 13 and I have my A Level exams coming and I have received a conditional offer which is three As, that is my focus right now."
"I have applied to study PPE so for the next three years I will be studying that."
Ms Yousafzai had said she had also applied to study at Durham, LSE, and Warwick, which all make A*AA offers for PPE.
At Oxford, the standard offer is AAA. Ms Yousafzai did not reveal which college she had applied to, but previously said she had attended an interview at Lady Margaret Hall.
She also told the conference she would be juggling her studies with running the Malala Fund, an international charity which advocates for all girls to have access to 12 years of education.
Speaking about her Oxford interview, Ms Yousafzai said: “It was the hardest interview of my life. I just get scared when I think of the interview.”
If she does take up an offer from Lady Margaret Hall, she will be following in the footsteps of her hero Benazir Bhutto, the former Prime Minister of Pakistan, who graduated from the college in 1977.
Ms Yousafzai has lived in Birmingham since 2012, where she was treated after surviving an assassination attempt by the Taliban. She will be taking her A-Levels in history, maths, religious studies and geography the private girl’s school Edgbaston High.
While living under Taliban rule, Yousafzai had written a blog under a pseudonym which featured her thoughts on girls’ education.
She received the Nobel Peace Prize for her work on girls’ education in 2014.
2017.03.13 / 15:24


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Titan Presents: Eric Prydz and Camelphat plus special guests on Saturday 18th September 2021
For the most up-to-date information about this event, please go here: Titan Presents: Eric Prydz and Camelphat plus special guests Festival Guide
Soundcrash, Treatment and Louder presents:
TITAN is back... This time we’re going outdoors and taking the party to the heart of Cardiff Bay and our epic new outdoor festival location Alexandra Head.
We've put together two monstrous line ups and will be bringing more lights, video and sound than ever before... This is going to be one special event, the likes of which Cardiff has never seen before.
On Saturday 18th September 2021, we host true electronic music royalty Eric Prydz, returning to Wales for the first time in over 10 years. Sharing the bill we welcome back to Titan the absolute juggernauts that are Camelphat. To top it off we’ve added Franky Wah, Cristoph, Yousef and Syreeta to the the monumental proceedings...
You maybe wondering where Alexandra Head is?! Located in the heart of the Cardiff Bay Barrage, Alexandra Head offers a unique chance to experience what will be a truly epic outdoor event with incredible views of Cardiff Bay.
VIP Ticket includes:
- VIP Platform
- VIP Entrance
- VIP Area
- VIP Bar + Cocktail Bar
- VIP Luxury Toilets
Please note: The event information above has been added by the organiser. Whilst we try to ensure all details are up-to-date we do not make any warranty or representation as to the accuracy or completeness of the information shown.


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Hi there Fellow Psychonauts, Planetary Wanderers and Friends,
This is my first blog post to welcome you to my site. The picture is of the Himalayas that I took from a small plane whilst on my travels in India and Nepal. The saying was given to me as I watched the dawn break over the mountains. I thought I was on the moon – the landscape was so lunar, pure and compassionate. Truly the ‘Roof of the World’.
I hope Life is filling you full of wonder and that your adventures and travels are bringing you joy. This is just a brief hello in case you have stumbled upon the site or whether you are one of the first readers to have discovered my book dedicated to Gaia The Wilderness Diary – published 21st December 2012 via the Amazon CreateSpace Team – and are looking for more info.
It’s all been quite a journey and learning curve to get to this point… so bear with me as I get up to speed with the Virtual World! I’ll be posting regular updates and answering any questions via my blog so stay tuned.
Meanwhile, check out the gallery for some sample drawings from The Wilderness Diary.
Here’s to the magic…


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Study of ANAVEX2-73 in Patients With Rett Syndrome
Phase 2 safety, tolerability and efficacy study is designed as a double-blind, randomized, placebo-controlled study. 7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of patients with RTT 18 years or older. A voluntary option will be offered for all patients who meet the exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.
- Rett Syndrome
- Eligible Ages
- Between 18 Years and 45 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Aged ≥ 18 years, inclusive.
- Diagnosis of classic RTT, according to 2010 criteria (Neul et al., 2010), and a MECP2 mutation.
- Current pharmacological treatment regimen, including supplements, has been stable for at least 4 weeks.
- If on antiepileptic drugs (AEDs), 1-4 AEDs allowed. Treatment must be stable (drug, dose, interval of administration) for 30 days prior to enrollment.
- Ability to keep accurate seizure diaries or have caregiver who can keep accurate seizure diaries.
- Confirmation from the participant that, if of childbearing potential is not pregnant through urine pregnancy testing. Female patients of childbearing potential and at risk for pregnancy must agree to abstinence.
- Prior to the conduct of study-specific procedures, the subject's parent/caregiver/LAR must provide written informed consent. If applicable, the research team must attempt to obtain consent from both parents.
- Patients who have a progressive medical or neurological condition that in the opinion of the Investigator would interfere with the conduct of the study.
- Current clinically significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study.
- History of clinically evident stroke or clinically significant carotid or vertebrobasilar stenosis or plaque or other history of neurologic (e.g., head trauma with loss of consciousness) or psychiatric condition that the Investigator deems may interfere with interpretability of data.
- Indication of liver disease, defined by serum levels of ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3x upper limit of normal (ULN) as determined during screening.
- Treatment with immunosuppressive medications (e.g., systemic corticosteroids) within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last 3 years.
- Other clinically significant abnormality on physical, neurological, laboratory, or electrocardiogram (ECG) examination (e.g., atrial fibrillation) that could compromise the study or be detrimental to the participant.
- Any known hypersensitivity to any of the excipients contained in the study drug or placebo formulation.
- Other co-morbid or chronic illness beyond that known to be associated with RTT.
- Subjects who plan to initiate or change pharmacologic or nonpharmacologic intervention during the course of the study.
- Subjects on potent CYP 3A4 and CYP2C19 inhibitors and inducers.
- Subjects taking another investigational drug currently or within the last 30 days.
- Any other criteria (such as a clinically significant screening blood test result), which in the opinion of the Investigator could interfere with the study conduct or outcome.
- Patients with hepatic and renal impairment.
- Phase 2
- Study Type
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- 21 participants: 6 PK open-label followed by 15 double-blind, randomized, placebo-controlled
- Primary Purpose
- Triple (Participant, Care Provider, Investigator)
- Masking Description
- Double-Blind, Randomized, Placebo-Controlled
|Week 0-7: Take 1 ml orally of the product daily (solution of ANAVEX2-73)||
|Week 0-7: Take 1 ml orally of the product daily (placebo)||
- Anavex Life Sciences Corp.
Study ContactWalter Kaufmann, MD
This Phase 2 safety, tolerability and efficacy study is designed as a double-blind, randomized, placebo-controlled study.
This is a 7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of patients with RTT 18 years or older. A voluntary option will be offered for all patients who meet the exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.


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Judge Carolyn H. Nichols, elected to the Court of Common Pleas in 2011, conducts felony jury trials in criminal court, with equal justice, protecting the rights of crime victims, and the accused; she works to create opportunities for positive reentry to prevent recidivism. She attended public schools and graduated from Temple University JD, LLM, and Eastern University MBA programs.
Her professional career spans over 20 years of public service, including Legislative Assistant to former Councilwoman, Augusta Clarke; Assistant City Solicitor, Deputy Secretary of External Affairs for the Mayor’s Office, and Deputy Finance Director, managing the Minority Business Enterprise Council. In 2014, Philadelphia City Council honored Judge Nichols for receiving the City Office of Economic Opportunity’s Guardian of Economic Inclusion Award for her service as MBEC Director. Judge Nichols has received recognition for her community service, including the Overbrook High School Hall of Fame. In 2007 and 2008, Judge Nichols was honored by the Philadelphia Tribune as one of the City’s Most Influential African Americans. She was co-counsel for the Huntingdon Valley swimming pool racial discrimination case in 2009, in which minority children were denied access to the Club’s pool. The case received international attention.
Judge Nichols is active in mentoring, and peace building programs in public schools to stop violence, and to disrupt the school to prison pipeline with groups such as School Dist. FACE (Family and Community Engagement). She promotes inclusion and dialogue with groups such as, Mothers in Charge to stop the senseless youth homicides; PhilaPosh for worker safety; Truman Project for international understanding; Masjidullah; Al Aqsa Islamic Society; Jewish Federation of Greater Phila; Greater Phila Hispanic Chamber Commerce; BMEC (Black male educators); and NewCore – generating conversations on race and ethnicity. Judge Nichols initiated a dialogue group with African American and Jewish professional women with the American Jewish Committee. She is a member of the Philadelphia Education Fund, Education First Compact, to improve public education in local schools. During the 2008 Presidential Campaign, she helped deploy 8,000 attorneys at polling places across PA, for PA Voter Protection, and served on the Board of Governors, Recording Academy, Philadelphia Chapter (Grammys).

domain: politics


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THE EXPERIENCED FAUX FINISHING PAINT PROFESSIONALS
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Working in both residential and commercial environments, More Than Murals is there to meet all of your decorative faux finishing needs. We are a full service decorative paint finishing company serving the greater Houston area. With well over 20 years of combined hands-on, related industry experience backing the name, you can feel confident knowing we go above and beyond when it comes to taking care of your home.
Since 2002, More than Murals has been transforming ordinary houses into the home of your dreams. Making an artistic vision a reality takes skill and dedication, which you will be sure to get by working with our expert staff. Your home can be stunning and display depth that basic painting cannot demonstrate. The trick is getting trained and skilled professionals who have the ability to listen to your wants and needs and then bring them to fruition with a makeover for your interior walls. Unlock the potential your interior walls could have with artistic vision.
Artistic inspiration to complete your decor just happens to be our specialty. We are committed to investing the time needed to getting to know more about the wants, needs and individual style of each of our clients; this is the best way to be able to provide customized results for your residential painting project.
LET US TAKE YOUR HOME FROM ORDINARY TO EXTRAORDINARY
Nationally recognized for our award winning decorative faux finishes, our professional grade services include decorative wall painting, murals, trompe l’oeil, faux painting, furniture and cabinet refinishing, gilding color design services and more. Traditional to contemporary, old world to metallic plasters are just a few of our areas of expertise. Interior or exterior, residential and commercial projects, we do it all. Please feel free to browse the finishes gallery for examples of our work.
WE WILL CREATE AN UNIQUE AND STUNNING FINISH FOR YOUR SPACE
No job is too big or too small, call (832) 257-9285 to schedule a no cost consultation today!
Our service includes but not limited to: Baytown, Bellaire, Bunker Hill Village, Conroe, Cypress, Galveston, Houston, Hunters Creek Village, Katy, Kingwood, Lake Jackson, Magnolia, Missouri City, Montgomery, Houston, Pearland, Piney Point Village, Rosenberg, Spring, Sugar Land, Texas City, The Woodlands, Tomball, Westchase

domain: artistic


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JULy 2019 | Volume 181
A funny, clever and poignant take on show business.
What do you do when your past catches up to you and demands retribution? Island Productions presents The Understudy, directed by Mel Tuck and starring Sarah Boes, Michael Germant and Drew Henderson. Playwright Theresa Rebeck’s complex love triangle opens August 1st at PAL Studio Theatre in Coal Harbour.
The Understudy: Charged with running the understudy rehearsal for Franz Kafka's undiscovered masterpiece in its Broadway premiere, Roxanne finds her professional and personal life colliding when Harry, a journeyman actor and her ex-fiancé, is cast as the understudy to Jake, a mid-tier action star yearning for legitimacy. As Harry and Jake find their common ground, Roxanne tries to navigate the rehearsal with a stoned lightboard operator, an omnipresent intercom system, the producers threatening to shutter the show and her own careening feelings about both actors and her past. Will the show go on?
"…deliver[s] a clever indictment of contemporary theatre while making the characters' personal circumstances ever more Kafkaesque: They are no more in control of the forces of celebrity, art, money, and Broadway than they are of their own fates." — The New Yorker
The Understudy received its World Premiere on the Nikos Stage during the Williamstown Theatre Festival in Williamstown, Massachusetts, on July 23, 2008. It premiered off-Broadway at Roundabout’s Laura Pels Theatre in New York a year later.
“The Understudy is an unstable mixture of satire, sentimental comedy and a smidgen of farce.” — The New York Times
The Understudy runs for six shows, August 1-10. Opening night August 1, 8:00 pm.
Tickets are $20. Seniors & Students $10. August 8 tickets are half-price at $10.
PAL Studio Theatre is located at 581 Cardero St, Vancouver, BC V6G 3L3.
get in touch with vancouverplays:
Vancouver's arts and culture website providing theatre news, previews and reviews


Last night I attended the first Ealing Council LDF Advisory Committee Meeting. The Local Development Framework is our National Government’s ‘vehicle’ for Local Authorities to define their preferred use of land within their borders for the next 15 years.
Attendees attending the meeting who were allowed to speak were seven Councillors and a handful of Council Officers. I was one of a precious, small group of residents who were invited to attend as observers. It reminded me of attending a lap dancing club where you could watch the girls ‘dance’, but you were not allowed to touch them.
Chairing the meeting was Leader of the Council Councillor Julian Bell. He was on his first day of holiday from his day job at The Houses of Parliament.


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My shop is open and I am accepting orders However due to the Covid-19 outbreak and in compliance with social-distancing advice, I will be posting orders only once a week. Orders will be sent out by First class Royal mail service. Please be aware that there may be slight postage delays during this time. Thank you for your continued support and understanding at this challenging time.
Handmade Ceramic Plaque to brighten any room.
Hand carved beach design. Glazed using lovely summery colours and in my own kiln at the end of my garden.
Glaze colours: Blues, green and white
Lead free glazes.
Please note each Plaque is unique to the other and this listing is for the plaque pictured.
Indoor decoration only.
The beach, the sea, summer, sand :)
Shipping & delivery
This item will be posted to you by H00t Ceramics within 3 days of receiving payment.
|Shipping destination||Cost||Additional items|
You have 14 days, from receipt, to notify the seller if you wish to cancel your order or exchange an item.
Unless faulty, the following types of items are non-refundable: items that are personalised, bespoke or made-to-order to your specific requirements; items which deteriorate quickly (e.g. food), personal items sold with a hygiene seal (cosmetics, underwear) in instances where the seal is broken.


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Educating Instead of Medicating
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