text:
High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes.
We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels.
In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10–1.64) and 1.99 (1.55–2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10–1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06–1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343).
Citation: Menzaghi C, Bacci S, Salvemini L, Mendonca C, Palladino G, Fontana A, et al. (2013) Serum Resistin, Cardiovascular Disease and All-Cause Mortality in Patients with Type 2 Diabetes. PLoS ONE 8(6): e64729. https://doi.org/10.1371/journal.pone.0064729
Editor: Francesco Dotta, University of Siena, Italy
Received: January 16, 2013; Accepted: April 18, 2013; Published: June 3, 2013
Copyright: © 2013 Menzaghi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This research was supported by Accordo Programma Quadro in Materia di Ricerca Scientifica nella Regione Puglia-PST 2006 and PO Puglia FESR 2007–2013, Italian Ministry of Health grants RC2011, RC2012, European Foundation for the Study of Diabetes/Pfizer grant (CM) and National Institutes of Health grant HL073168 (AD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: CM received funding from the EFSD/Pfizer. MF is a PLOS ONE Editorial Board member. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.
Cardiovascular disease (CVD) is a major cause of morbidity and mortality among patients with type 2 diabetes [1]. Although several components of the diabetic milieu contribute to the increased risk of CVD associated with diabetes, insulin resistance and inflammation have been recognized as particularly important pathogenic factors [2]. Both conditions have been linked to cytokines released by the adipose tissue and collectively known as adipokines [3]. Among these is resistin, a 12.5 kDa cysteine-rich protein, which, in humans, is primarily secreted by macrophages [4], [5]. Several cross-sectional studies based on resistin serum levels and/or tissue expression have pointed to this molecule as a pro-inflammatory adipokine contributing to atherosclerosis and the clinical phenotypes resulting from it [5], [6], [7], [8], [9], [10], [11]. High serum resistin levels have also been found, although with some inconsistencies, to predict incident cardiovascular events in prospective studies [12], [13], [14], [15], [16], [17]. This evidence, however, mostly concerns the general population since the few published studies of resistin as a CVD marker in diabetic subjects are small, limited to Asian individuals, and contradictory in their findings [9], [11], [18]. Given that cardiovascular risk may be differently shaped in non diabetic as compared to diabetic individuals answering the question of whether or not resistin plays a role in the development of CVD also among the latter group is definitely needed. To address this question, we analyzed data from over 2,300 European subjects with type 2 from four different studies: two case-control collections of such patients with and without evidence of coronary artery disease (CAD), a prospective cohort of patients with type 2 diabetes followed over time for incident major cardiovascular events and another prospective cohort of patients with type 2 diabetes followed over time with regard to all-cause mortality.
Case-Control Studies
Gargano heart study (GHS)-cross sectional design.
This study includes 798 European subjects from Italy with type 2 diabetes (ADA 2003 criteria) who were consecutively recruited at the Endocrine Unit of IRCCS "Casa Sollievo della Sofferenza" in San Giovanni Rotondo (Gargano, Center East Coast of Italy) from 2001 to 2008, as part of an ongoing investigation on the genetics of CAD in type 2 diabetes [19], [20] (Figure S1).
Cases are patients who underwent coronary angiography and had a stenosis >50% in at least one coronary major vessel or with previous myocardial infarction (MI). Controls include asymptomatic patients without signs of myocardial ischemia at resting and maximal symptom limited stress ECG. The latter was conducted on a treadmill according to a Bruce protocol after cardiovascular drugs as β-blockers and Ca-channel blockers were stopped for 48 hours. The test was defined as maximal if 85% of the predicted heart rate for the participant's age was reached. Ischemia was defined as a horizontal or downsloping ST segment depression of 1 mm or more calculated at 0.08 s after the J point (i.e. the junction between QRS complex and ST segment) or the development of typical angina pectoris.
Serum resistin was measured in 776 (97%) participants.
Joslin Heart Study (JHS).
This study consists of a series of 868 CAD cases and controls, all with type 2 diabetes (ADA 2003 criteria), who lived in the greater Boston area and received treatment at the Joslin Clinic and/or the Beth Israel Deaconess Medical Center (BIDMC) at the time of their recruitment [21].
All participants were self-reported non-Hispanic Whites. Case participants with CAD were a random sample of patients with type 2 diabetes who had a stenosis greater than 50% in a major coronary artery or a main branch thereof that was documented by cardiac catheterization at the BIDMC between 2001 and 2008. Sixty percent of the case patients received diabetes management care at the Joslin Clinic. Control participants without CAD were randomly selected from among Joslin patients who were identified between 2001 and 2008 as fulfilling the following criteria: (1) current age between 55 and 74 years; (2) type 2 diabetes for 5 years or more; (3) negative cardiovascular history (i.e., normal resting electrocardiogram, absence of cardiac symptoms, and no hospitalization for cardiovascular events); and (4) non inducible ischemia to an exercise treadmill test performed for screening purposes.
Serum resistin was measured in 861 (99%) participants.
Prospective Studies
GHS-prospective design.
This study comprises 368 patients with type 2 diabetes and CAD (as previously defined), who were all case participants of the GHS-cross sectional design (Figure S1). Follow-up information on outcomes was collected yearly from 2002 to 2011. The only exclusion criterion was the presence of poor life expectancy for non diabetes-related diseases. The end-point was a combination of major cardiovascular events including cardiovascular death (i.e. according to the international classification of diseases' codes: 428.1- ninth edition - and I21.0–I21.9, I25.9, I46.9–I50.9, I63.0, I63.9, I70,2– tenth edition), non-fatal MI and non-fatal stroke [22]. For all non-fatal MI and strokes, confirmation of the events was obtained from the hospital medical records. In the case of patients who did not show up at the scheduled clinical control, information on the incident cardiovascular events was obtained through telephone interviews with the patients or their primary care physicians or from death certificates.
Serum resistin was measured in 359 (98%) participants.
Gargano Mortality Study (GMS).
One thousand and twenty-eight patients with type 2 diabetes (ADA 2003 criteria) were consecutively recruited from November 1th 2000 to September 30th 2005 at the Endocrine Unit of IRCCS "Casa Sollievo della Sofferenza" in San Giovanni Rotondo, for a study having all-cause mortality as the end-point (Figure S1). The only exclusion criterion was the presence of poor life expectancy due to non diabetes-related disorders. This cohort was followed until 2010 by obtaining information on the participants' vital status by direct contact with patients and/or their relatives or by queries to the registry offices of the cities of residence. Such information was available in 838 individuals whose data were therefore analyzed in the present study. One hundred and three of the GMS participants are also participants of the GHS-prospective design (Figure S1).
Serum resistin was measured in 779 (93%) participants.
Data Collection and Definitions
Clinical data were obtained from a standardized interview and examination. Body mass index (BMI) was calculated by dividing the weight (in kilograms) by the square of height (in meters). Smoking habits and history of hypertension (as indicated by the presence of anti-hypertensive therapy), dyslipidemia (as indicated by the presence of anti-dyslipidemic therapy), and MI as well as glucose-lowering treatment were also recorded at time of examination. Data regarding medications were confirmed by review of medical records. Those who reported smoking cigarettes regularly during the year before the examination were considered current smokers.
In the GHS-cross sectional and-prospective designs and GMS, blood samples were collected between 8∶00 and 9∶00 AM after an overnight fast. In the JHS, blood samples were obtained between 7∶00 AM and 6∶00 PM without the requirement of fasting. Serum aliquots were stored at −80°C. Peripheral whole blood cells (PWBC) RNA was obtained from 68 fasting patients with type 2 diabetes, with no clinical evidence of CVD (38 males/30 females, age 65.1±7.0 years, BMI 30.9±5.0 kg/m2, HbA1c 7.9±1.7%) by PAXgene Blood RNA collection tubes (PreAnalytiX, GmbH, Germany). These patients, not belonging to any of the previous samples, were consecutively recruited at the Endocrine Unit of IRCCS "Casa Sollievo della Sofferenza" in San Giovanni Rotondo, with the specific purpose of correlating gene expression levels on PWBC with clinical features and/or biomarkers levels.
Each study protocol and the informed consent procedures were approved by the local Institutional Ethic Committee IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) "Casa Sollievo della Sofferenza" for GHS and GMS and by the Joslin Committee on Human Studies and the Beth Israel Deaconess Medical Center Committee on Clinical Investigations for JHS. All participants gave written consent.
Measurement of Circulating Resistin Levels
Serum resistin concentrations were measured by a commercial ELISA (Bio Vendor, Brno Czech Republic) at the Research Unit of Diabetes and Endocrine Diseases in San Giovanni Rotondo, as previously described [23]. Inter- and intra-assay coefficients of variation were 3.2–4% and 6.3–7.2% respectively.
Measurement of RETN mRNA Levels
Total RNA from PWBC was extracted using PAXgene Blood RNA kit (PreAnalytiX, GmbH, Germany). RNA was eluted in RNAse free-water and stored at −80°C until used. Total RNA yield and purity were determined spectrophotometrically using the NanoDrop ND-1000 (Wilmington, DE, USA). Integrity of resuspended total RNA was determined by electrophoretic separation and subsequent laser induced florescence detection using the RNA 6000 Nano Assay Chip Kit on the Bioanalyzer 2100 (Agilent Technologies, Waldbronn, Germany).
Five hundred nanograms of RNA were reverse transcripted by AMV Reverse Transcription System (Promega Corp., Wis, USA) and used as template in subsequent analyses. RETN (Hs00220767_m1) and GAPDH (Hs99999905_m1) gene expression assays on demand kit reagents Applied Biosystems (Foster City, CA) were used to quantify in triplicates relative gene expression on ABI-PRISM 7500 Applied Biosystems (Foster City, CA). RETN transcription levels were normalized using the GAPDH housekeeping gene. RETN/GAPDH mRNA ratios were obtained from the equation 2−ΔCt, where ΔCt is the difference in threshold cycles between RETN and GAPDH.
Statistical Methods
Patients' baseline characteristics were reported as mean±standard deviation (SD) and percentages for continuous and categorical variables, respectively. Correlations between continuous variables were assessed by Pearson coefficient.
In case-control studies, the association between resistin circulating levels and CAD was assessed with univariate and multivariate logistic regression models with CAD status as the dependent and resistin as the independent variable. Separate analyses were performed for continuous resistin values and tertiles of its distribution. The strength of the associations was estimated by means of odds ratios (ORs), along with their 95% Confidence Intervals (95% CI), per SD increase in baseline resistin level and for tertiles of its distribution. In addition, a test for linear trend in OR estimates over resistin tertiles was performed by including resistin tertiles (coded as 1, 2, and 3) as a continuous variable into the logistic model.
In both prospective studies, the time variable was defined as the time between the baseline examination and date of the event (namely, major cardiovascular events for GHS-prospective, and all-cause mortality for GMS), or, for subjects who did not experience any event, the date of the last available clinical follow-up. Incidence rates for the endpoint of interest were expressed as the number of new events per total number of person-years (py) and were compared between baseline serum resistin levels tertiles using a Poisson regression model. In addition, a test for linear trend in incidence rates over resistin tertiles was performed by including resistin tertiles as a continuous variable into the Poisson model.
Univariate and multivariate Cox proportional hazards regressions analyses were performed to assess the association between resistin values or tertiles of its distribution and the event occurrence. Risks were reported as Hazard Ratios (HR) along with their 95% CI per SD increase in resistin levels and for tertiles of its distribution. Test for linear trend in HR estimates over resistin tertiles was performed by including resistin tertiles as a continuous variable into the Cox proportional hazard models. Adjusted survival curves were derived from the Cox proportional hazard models, using the direct approach [24].
Predicted risk probabilities were derived from the Framingham Risk Score (FRS), which is an established risk model for cardiovascular event in the general population [25] and from the UKPDS risk engine, which is a model for the risk of coronary heart disease in type 2 diabetes [26]. Models' calibration, i.e. the agreement between observed outcomes and predictions, was assessed using the survival-based Hosmer-Lemeshow (HL) goodness-of-fit test [27], a chi-square test based on grouping observations into deciles of predicted risk and testing associations with observed outcomes. Models' discrimination, i.e. the ability to distinguish subjects who will develop an event from those who will not, was assessed by computing the modified C statistic for censored survival data [28], [29]. Comparison between C-indices was carried out following Pencina and D'Agostino's approach [29].
Reclassification improvement offered by resistin was quantified using the survival-based net reclassification index (NRI) following the Kaplan-Meier approach with one-sided bootstrapped p-values based on 1000 re-samplings with replacement [30], [31] and by Integrated Discrimination Improvement (IDI) (28). Since no established risk cut-offs were available for our high risk patients as those affected by diabetes, we computed the categories-free version of NRI (i.e. cNRI) [31]. The main difference consists in the definition of a reclassified subject: for the NRI a subject has to move from one risk-category to another one; the cNRI requires that the subject's risk probability changes, without any limit, to define an upward or downward reclassification. cNRI is a more objective measure of improvement in risk prediction while NRI has a more attractive interpretation for clinicians. The time horizon of risk prediction was set to 7 years. (i.e. upper cut-off of the 3th quartile).
A p-value <0.05 was considered as significant. All analyses were performed using SAS Release 9.1.3 (SAS Institute, Cary, NC, USA).
Case-Control Studies
Clinical features of participants in the GHS-cross sectional design and the JHS are summarized in Table 1. In both studies, serum resistin concentrations were significantly higher in CAD-positive cases than in CAD-negative controls (Table 1). For each SD increment in resistin levels, the odds of CAD increased by ∼30% in the GHS cross-sectional design (OR = 1.29, 95% CI: 1.10–1.51, p = 0.002) and by ∼80% in the JHS (OR = 1.83, 95% CI: 1.49–2.24; p = 3.53×10−12) (Table 2). This association was unaffected by adjustments for age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies (Table 2). The linear relationship between resistin levels and CAD risk was confirmed in an analysis by resistin tertiles (Figure 1). In both studies, individuals in the second tertile had an OR of CAD that was intermediate between the first and third tertiles, with p-values for linear trend of 0.012 for the GHS-cross sectional design and 3.76×10−11 for the JHS (Figure 1).
ORs were estimated by logistic regression after adjusting for age, sex, smoking habits, BMI, HbA1c and insulin, antihypertensive and antidyslipidemic therapies.
Given the role of resistin in low-grade inflammation, we also tested plasma fibrinogen as a covariate. After adjustment for this variable, the association between resistin and CAD in the GHS-cross sectional design was no longer significant (Table 2). Data on fibrinogen levels were not available for the JHS.
It is of note that serum resistin levels in CAD negative controls from both GHS-prospective design and JHS were significantly higher than those previously measured in our laboratory [23] in non diabetic controls (p<0,001 and <0,01, respectively; data not shown).
Prospective Studies
The GHS-prospective design.
The clinical features of study participants are summarized in Table 3. During follow-up (5.4±2.5 years), 58 cardiovascular deaths, 6 non-fatal MIs and 9 non-fatal strokes occurred, corresponding to an overall annual incidence rate of 3.8% (73 events/1,934 py). Given that this cohort comprises only very high risk individuals (i.e. diabetic patients who already suffered by coronary stenosis and/or previous MI), it is not surprising that most of major cardiovascular events are represented by death. Each SD increment of serum resistin levels was associated with a 31% increase in the risk of major cardiovascular events (HR = 1.31, 95% CI: 1.13–1.53; p = 3.38×10 –4). As in the case-control studies, the association was not affected by adjustment for age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies (HR = 1.31, 95% CI: 1.10–1.56; p = 0.003), but was attenuated and lost significance after adjusting for fibrinogen levels (HR = 1.18, 95% CI: 0.97–1.45; p = 0.099).
After stratification by tertiles of baseline resistin levels, the incidence rate of major cardiovascular events was 2.4% (17 events/711 py) in the first, 3.5% (23 events/665py) in the second, and 5.9% (33 events/558 py) in the third tertile (p for trend = 0.001). Accordingly, the HR of major cardiovascular events progressively increased across resistin tertiles, and persisted after adjustment for age, sex, smoking habits, BMI, HbA1c and insulin, antihypertensive and antidyslipidemic therapies (HR = 1.68, 95% CI: 0.80 to 3.53 and HR = 2.79, 95% CI: 1.37 to 5.69 in the second and third tertile, respectively; p for trend = 0.004) (Figure 2).
Curves are estimated by Cox regression after adjusting for age, sex, smoking habits, BMI, HbA1c and insulin, antihypertensive and antidyslipidemic therapies.
Survival C statistic, IDI and cNRI indices were used to evaluate the incremental prognostic information of serum resistin for major cardiovascular events as obtained by the FRS [25] and the UKPDS risk engine [26]. Time horizon prediction was set to 7 years, replacing the baseline survival probability accordingly. Patients whose information of some clinical variable used in FRS and/or UKPDS risk engine was not available (n = 61) were excluded.
FRS did not perform well in our sample with survival C statistic being equal to 0.584 (95% CI: 0.510–0.657). The addition of serum resistin produced a significant (p = 0.028) improvement, with survival C statistic becoming 0.640 (95% CI: 0.568–0.713). Both models resulted well calibrated (HL p-values being 0.532 and 0.256, respectively). Moreover, a significant improvement in discrimination was also detected by IDI: 0.022, 95% CI: 0.004–0.048, p = 0.003. Finally, the addition of serum resistin to the FRS allowed to reclassify correctly 95/298 patients (cNRI = 0.433, p = 0.006): 92/244 (37.7%) and 3/54 (5.6%) in those without and with incident events, respectively.
The UKPDS risk engine too performed poorly (survival C statistic = 0.674; 95% CI: 0.607–0.741). The addition of serum resistin produced a significant (p = 0.025) improvement (survival C statistic = 0.704; 95% CI: 0.641–0.766). Both models resulted well calibrated (HL p-values being 0.169 and 0.176, respectively). In contrast, resistin addition did not result in a significant IDI (0.005; 95% CI: −0.01–0.024, p = 0.286). Finally, the addition of serum resistin to the UKPDS risk engine allowed to reclassify correctly 98/298 patients (cNRI = 0.459, p = 0.004): 94/244 (38.5%) and 4/54 (7.4%) in those without and with incident events, respectively.
The GMS.
Given that CVD is the main cause of death among patients with type 2 diabetes, we assessed the role of serum resistin in predicting all-cause mortality in a cohort of such patients. The clinical features of the GMS participants are summarized in Table 3. During follow-up (7.6±2.1 years), 150 deaths occurred, corresponding to an annual incidence rate of 2.7% (150 events/5,659 py).
Serum resistin predicted the risk for all-cause death with an HR of 1.18 (95% CI: 1.12–1.27; p = 1.5×10−6) per SD increment. One hundred and three GMS participants overlapped with those of GHS-prospective design. Exclusion of these subjects did not substantially alter the results (HR = 1.17, 95% CI: 1.07–1.27; p = 0.00047). Similar results were obtained in the whole cohort after adjusting for age, sex, smoking habits, BMI, HbA1c and insulin, antihypertensive and antidyslipidemic therapies (HR = 1.16, 95% CI: 1.06–1.26; p = 0.001).
The all-cause mortality rates in the first, second, and third tertile of resistin levels were 1.8% (36 events/2,022 py), 2.8% (52 events/1,862 py), and 3.5% (62 events/1,775 py), respectively (p for trend = 0.001). At variance with the linear trend observed in both cross-sectional studies and the GHS-prospective design, the adjusted HRs for all-cause mortality were similar in the second and third tertile (HRs = 1.72, 95% CI: 1.11 to 2.68, and 1.81, 95% CI: 1.16 to 2.82, respectively, p for trend = 0.019) (Figure 3). Also at odds with the other studies, the association between resistin and mortality remained significant, though less robustly, after adjusting for fibrinogen levels (HR per resistin SD = 1.15, 95% CI: 1.05–1.27; p = 0.03).
Curves are estimated by Cox regression after adjusting for age, sex, smoking habits, BMI, HbA1c and insulin, antihypertensive and antidyslipidemic therapies.
Correlation between Serum and mRNA Resistin Levels
Since the data above indicate that serum resistin is a marker of cardiovascular risk in patients with type 2 diabetes, we measured RETN mRNA levels in circulating PWBC and serum resistin levels in 68 diabetic patients in order to obtain mechanistic insights on the biology of serum resistin variability. The two variables were positively correlated (rho = 0.343, p = 0.006) (Figure S2).
Despite improvements in the treatment of CVD and in the control of risk factors, individuals with type 2 diabetes remain at increased cardiovascular risk as compared to the general population [32] with cardiovascular events being the most important cause of death in these patients [1]. Discovering novel biomarkers able to predict CVD in diabetic patients is therefore urgently needed to decrease the burden of this devastating complication.
To the best of our knowledge, this is the first study to show that elevated serum resistin concentration is a risk factor for CVD in patients with type 2 diabetes of European ancestry. While a rich literature exists on serum resistin as a cardiovascular risk factor in the general population [13], [14], [15], [16], [17], data concerning the type 2 diabetes population have been thus far sparse, contradictory, and limited to Asian individuals [9], [11], [18]. Two small cross-sectional studies of patients with type 2 diabetes from Japan and Korea described an association of serum resistin with CAD and stroke, respectively, but a third study on 343 diabetic Korean patients failed to confirm such findings in a prospective setting. By contrast, we have obtained strong and consistent evidence of association between serum resistin and CVD from both cross-sectional and prospective studies on patients with type 2 diabetes of European ancestry. This effect of resistin is independent of the most established cardiovascular risk factor including sex, smoking habits, BMI, HbA1c and insulin, antihypertensive and antidyslipidemic therapies. However, if the analysis is adjusted for fibrinogen, the association is no longer significant, suggesting it is mediated at least in part by low-grade inflammation – an established cardiovascular risk factor. Whether resistin is a true risk factor which may causally contribute to CVD or, in contrast, a simple biomarker of pro-inflammatory status, cannot be addressed by our study.
We wanted to investigate whether serum resistin provides incremental information in predicting major cardiovascular events as obtained by well established models such as the FRS and the UKPDS risk engine [25], [26] which, similarly to other models, are known not to perform well in the subset of patients with type 2 diabetes [33], [34]. Thus, it was not unexpected that both models performed poorly also in our sample in predicting major cardiovascular events. Of note, the addition of serum resistin improved the two models in terms of both discriminatory and reclassification performance. Such improvement was not only statistically significant, but also of clinical relevance. Further larger studies, are needed to deeper address the relative importance of resistin as an additional marker of clinical utility. for predicting CVD in patients with type 2 diabetes.
Our study also shows for the first time that serum resistin is an independent predictor of all-cause mortality in a study comprising 779 patients with type 2 diabetes. In contrast to what was observed with CVD risk, the association with mortality is only modestly affected by adjustment for fibrinogen levels. Therefore, though fibrinogen is not the best marker of low-grade inflammation, it may be hypothesized that the effects of resistin on all-cause mortality are mediated by mechanisms that are independent of this pathway. The possibility that different mechanisms underlie the effects of resistin on CVD and all-cause mortality is also suggested by the fact that the relationship between resistin levels and all-cause mortality does not appear to be linear as that between resistin and CAD or major CVD events. Consistent with such hypothesis, the association between resistin and all-cause mortality observed in the general population [35], [36], [37] seems to be independent from cardiovascular mortality [35], [36]. Unfortunately, data on cause of death that could confirm this finding among type 2 diabetes patients were not available in the GMS.
An additional finding of our study is that RETN mRNA in PWBC is correlated to serum resistin. This result, which is consistent with the observation that human resistin is mainly produced by macrophages [5], strongly suggest that resistin circulating levels are modulated by gene expression levels. The mechanism(s) underlying such modulation are not yet known and need further studies to be unraveled.
One strength of our study is the overall sample size, consisting of a total of 2,313 diabetic patients from two cross-sectional and two prospective investigations, and the completeness of clinical information, including standardized clinical evaluations and hard end-points validated by medical records or death certificates. Another strength is the fact that the resistin measurements were centralized and all the samples were handled identically. In this context, the observed difference in serum resistin concentration between the two cross-sectional studies, with JHS participants having 20–30% lower mean levels as compared to GHS individuals, is somewhat surprising. One possibility is that such difference was due to the different proportion of patients treated with lipid lowering agents in the two studies (77% in the JHS as compared to 48% in the GHS). Such agents are mainly statins, which are known to decrease serum resistin levels [38]. This hypothesis is supported by the observation that participants in the GHS-cross sectional design who were on statins had serum resistin levels 10–15% lower than patients who were not on statins (data not shown). At variance, given that no substantial effects of fasting on resistin levels have been described [39], we can exclude that the observed difference in serum resistin levels between GHS and JHS is due to the different fasting status of the two studies.
Despite these differences, the fact that the association between serum resistin and CAD, that was found in the GHS-cross sectional was fully replicated in the JHS makes our finding especially convincing.
Of note, resistin levels in CAD-negative controls from both GHS-cross sectional and JHS were clearly higher than those from non diabetic controls [23].
The major limitation of our study is represented by the lack of C-reactive protein measurements which surely would have help clarify the link between resistin and chronic inflammation state. In fact, the role of fibrinogen on inflammation remains largely speculative, thus making not possible to draw firm conclusions about the biology underlying the association we observed in our present study.
Finally, whether our finding can be generalized to other populations of different ethnicity having different environmental and/or genetic background remains to be established. This issue deserves particular attention given that a different genetic regulation in different ethnic groups has been hypothesized for serum resistin [40]. Therefore, additional studies are certainly needed to confirm our present finding in a broader context.
In conclusion, our study is the first to show that high serum resistin (a likely consequence, at least in part, of increased resistin mRNA expression) is a risk factor for CVD and all-cause mortality in patients with type 2 diabetes of European ancestry. Further studies are warranted to determine whether this biomarker can be used in a clinical setting to improve the stratification of diabetic patients with regard to their risk for CVD and death.
Supporting Information
Figure S1.
Diagrams and participants of Gargano Heart Study and Gargano Mortality Study in whom serum resistin levels were available. Gargano Heart Study (GHS)-cross sectional design includes 776 European subjects with type 2 diabetes mellitus (T2DM), 360 CAD positive and 416 CAD negative as defined in methods. GHS-prospective design comprises 359 patients with T2D and CAD who were all case participants of the GHS-cross sectional design as described in methods. Gargano Mortality Study (GMS) comprises 779 patients with T2D as describes in methods. One hundred and three of the GMS participants are also participants of the GHS-prospective design (gray box). Raw data on resistin levels and association with related variables can be provided upon request for collaborative purposes.
Figure S2.
Correlation between serum and mRNA resistin levels. Correlation between serum and mRNA resistin levels in 68 patients with type 2 diabetes. RETN mRNA levels in PWBC are expressed as arbitrary units (AU) of RETN/GAPDH ratios.
We are indebted to the staffs and participants of the GHS, JHS and GMS for their dedication and contributions.
Author Contributions
Conceived and designed the experiments: C. Menzaghi SB MF SDC AD VT. Performed the experiments: LS C. Mendonca GP CDB AM SP EM SR GF DM. Analyzed the data: C. Menzaghi SB GP AF FP AD. Contributed reagents/materials/analysis tools: SB EG AK MF SDC FP AD. Wrote the paper: C. Menzaghi AD VT.
- 1. Seshasai SR, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, et al. (2011) Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med 364: 829–841.
- 2. Haffner SM (2006) The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. Am J Cardiol 97: 3A–11A.
- 3. Scherer PE (2006) Adipose tissue: from lipid storage compartment to endocrine organ. Diabetes 55: 1537–1545.
- 4. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, et al. (2001) The hormone resistin links obesity to diabetes. Nature 409: 307–312.
- 5. Reilly MP, Lehrke M, Wolfe ML, Rohatgi A, Lazar MA, et al. (2005) Resistin is an inflammatory marker of atherosclerosis in humans. Circulation 111: 932–939.
- 6. Burnett MS, Lee CW, Kinnaird TD, Stabile E, Durrani S, et al. (2005) The potential role of resistin in atherogenesis. Atherosclerosis 182: 241–248.
- 7. Langheim S, Dreas L, Veschini L, Maisano F, Foglieni C, et al. (2010) Increased expression and secretion of resistin in epicardial adipose tissue of patients with acute coronary syndrome. Am J Physiol Heart Circ Physiol 298: H746–753.
- 8. Pischon T, Bamberger CM, Kratzsch J, Zyriax BC, Algenstaedt P, et al. (2005) Association of plasma resistin levels with coronary heart disease in women. Obes Res 13: 1764–1771.
- 9. On YK, Park HK, Hyon MS, Jeon ES (2007) Serum resistin as a biological marker for coronary artery disease and restenosis in type 2 diabetic patients. Circ J 71: 868–873.
- 10. Ohmori R, Momiyama Y, Kato R, Taniguchi H, Ogura M, et al. (2005) Associations between serum resistin levels and insulin resistance, inflammation, and coronary artery disease. J Am Coll Cardiol 46: 379–380.
- 11. Tsukahara T, Nakashima E, Watarai A, Hamada Y, Naruse K, et al. (2009) Polymorphism in resistin promoter region at −420 determines the serum resistin levels and may be a risk marker of stroke in Japanese type 2 diabetic patients. Diabetes Res Clin Pract 84: 179–186.
- 12. Lubos E, Messow CM, Schnabel R, Rupprecht HJ, Espinola-Klein C, et al. (2007) Resistin, acute coronary syndrome and prognosis results from the AtheroGene study. Atherosclerosis 193: 121–128.
- 13. Hoefle G, Saely CH, Risch L, Koch L, Schmid F, et al. (2007) Relationship between the adipose-tissue hormone resistin and coronary artery disease. Clin Chim Acta 386: 1–6.
- 14. Weikert C, Westphal S, Berger K, Dierkes J, Mohlig M, et al. (2008) Plasma resistin levels and risk of myocardial infarction and ischemic stroke. J Clin Endocrinol Metab 93: 2647–2653.
- 15. Frankel DS, Vasan RS, D'Agostino RB Sr, Benjamin EJ, Levy D, et al. (2009) Resistin, adiponectin, and risk of heart failure the Framingham offspring study. J Am Coll Cardiol 53: 754–762.
- 16. Butler J, Kalogeropoulos A, Georgiopoulou V, de Rekeneire N, Rodondi N, et al. (2009) Serum resistin concentrations and risk of new onset heart failure in older persons: the health, aging, and body composition (Health ABC) study. Arterioscler Thromb Vasc Biol 29: 1144–1149.
- 17. Luc G, Empana JP, Morange P, Juhan-Vague I, Arveiler D, et al. (2010) Adipocytokines and the risk of coronary heart disease in healthy middle aged men: the PRIME Study. Int J Obes (Lond) 34: 118–126.
- 18. Lim S, Koo BK, Cho SW, Kihara S, Funahashi T, et al. (2008) Association of adiponectin and resistin with cardiovascular events in Korean patients with type 2 diabetes: the Korean atherosclerosis study (KAS): a 42-month prospective study. Atherosclerosis 196: 398–404.
- 19. Bacci S, Menzaghi C, Ercolino T, Ma X, Rauseo A, et al. (2004) The +276 G/T single nucleotide polymorphism of the adiponectin gene is associated with coronary artery disease in type 2 diabetic patients. Diabetes Care 27: 2015–2020.
- 20. Prudente S, Morini E, Larmon J, Andreozzi F, Di Pietro N, et al. (2011) The SH2B1 obesity locus is associated with myocardial infarction in diabetic patients and with NO synthase activity in endothelial cells. Atherosclerosis 219: 667–672.
- 21. Qi L, Parast L, Cai T, Powers C, Gervino EV, et al. (2011) Genetic susceptibility to coronary heart disease in type 2 diabetes: 3 independent studies. J Am Coll Cardiol 58: 2675–2682.
- 22. Bacci S, Rizza S, Prudente S, Spoto B, Powers C, et al. (2011) The ENPP1 Q121 variant predicts major cardiovascular events in high-risk individuals: evidence for interaction with obesity in diabetic patients. Diabetes 60: 1000–1007.
- 23. Menzaghi C, Coco A, Salvemini L, Thompson R, De Cosmo S, et al. (2006) Heritability of serum resistin and its genetic correlation with insulin resistance-related features in nondiabetic Caucasians. J Clin Endocrinol Metab 91: 2792–2795.
- 24. Ghali WA, Quan H, Brant R, van Melle G, Norris CM, et al. (2001) Comparison of 2 methods for calculating adjusted survival curves from proportional hazards models. JAMA 286: 1494–1497.
- 25. D'Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, et al. (2008) General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 117: 743–753.
- 26. Stevens RJ, Kothari V, Adler AI, Stratton IM (2001) Group UKPDS (2001) The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56). Clin Sci (Lond) 101: 671–679.
- 27.
D'Agostino R, Nam BH (2004) Evaluation of the performance of survival analysis models: discrimination and calibration measures. Handbook of Statistics, vol 23 Elsevier Science BV.
- 28. Uno H, Cai T, Pencina MJ, D'Agostino RB, Wei LJ (2011) On the C-statistics for evaluating overall adequacy of risk prediction procedures with censored survival data. Stat Med 30: 1105–1117.
- 29. Pencina MJ, D'Agostino RB (2004) Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med 23: 2109–2123.
- 30.
Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27: 157–172; discussion 207–112.
- 31. Pencina MJ, D'Agostino RB, Steyerberg EW (2011) Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med 30: 11–21.
- 32. Preis SR, Pencina MJ, Hwang SJ, D'Agostino RB Sr, Savage PJ, et al. (2009) Trends in cardiovascular disease risk factors in individuals with and without diabetes mellitus in the Framingham Heart Study. Circulation 120: 212–220.
- 33. Coleman RL, Stevens RJ, Retnakaran R, Holman RR (2007) Framingham, SCORE, and DECODE risk equations do not provide reliable cardiovascular risk estimates in type 2 diabetes. Diabetes Care 30: 1292–1293.
- 34. Chamnan P, Simmons RK, Sharp SJ, Griffin SJ, Wareham NJ (2009) Cardiovascular risk assessment scores for people with diabetes: a systematic review. Diabetologia 52: 2001–2014.
- 35. Lee SH, Ha JW, Kim JS, Choi EY, Park S, et al. (2009) Plasma adiponectin and resistin levels as predictors of mortality in patients with acute myocardial infarction: data from infarction prognosis study registry. Coron Artery Dis 20: 33–39.
- 36. Pilz S, Weihrauch G, Seelhorst U, Wellnitz B, Winkelmann BR, et al. (2007) Implications of resistin plasma levels in subjects undergoing coronary angiography. Clin Endocrinol (Oxf) 66: 380–386.
- 37. Zhang MH, Na B, Schiller NB, Whooley MA (2011) Association of resistin with heart failure and mortality in patients with stable coronary heart disease: data from the heart and soul study. J Card Fail 17: 24–30.
- 38. von Eynatten M, Schneider JG, Hadziselimovic S, Hamann A, Bierhaus A, et al. (2005) Adipocytokines as a novel target for the anti-inflammatory effect of atorvastatin in patients with type 2 diabetes. Diabetes Care 28: 754–755.
- 39. Weikert C, Westphal S, Luley C, Willich SN, Boeing H, et al. (2007) Within-subject variation of plasma resistin levels over a 1-year period. Clin Chem Lab Med 45: 899–902.
- 40. Menzaghi C, Trischitta V (2010) Genetics of serum resistin: a paradigm of population-specific regulation? Diabetologia 53: 226–228.


text:
Rainer Diaz-Bone & Robert Salais (Eds): The Économie des Conventions – Transdisciplinary Discussions and Perspectives.
The économie des conventions (economics of convention, EC) can be regarded as an influential transdisciplinary, pragmatic approach for the historical analysis of economic coordination and economic institutions. EC was developed first in France. For some years now international recognition and reception is rising. Historical Social Research/Historische Sozialforschung has published contributions about EC and applications of EC since 2009. In the present issue ongoing and critical discussion is presented, which addresses problems of institutional theory, methodology and conceptual aspects of EC. Furthermore, contributions are entailed in this issue, which apply EC as a transdisciplinary historical approach to new research objects. Also new perspectives for conceptual and methodological developments of EC are offered.
Christoph Classen, Susanne Kinnebrock & Maria Löblich (Eds.): Towards Web History: Sources, Methods, and Challenges in the Digital Age.
The process of digitization represents a twofold challenge both for historiography in general and, in particular, for historical communication research. Digitization has deeply changed research practice as well as the inter-disciplinary communication and is likely to do so in future. The contributions of this HSR Focus address a twofold conceptual challenge. In a first part, problems and chances of a contemporary history of digital media are discussed. In the second part the authors leave the level of conceptual considerations and turn towards the already established practice of digitization and the supply of sources in the net.
Furthermore this HSR contains a Mixed Issue with nine articles.

subset: commoncrawl


text:
Getting into late november i decided to head to the river and see if the spawn was coming to the end. i only saw 2 fish on redds which tells me that the spawn is coming to an end. threw some streamers, got into a good handful of fish so things should start picking up.
Sunday, November 27, 2016
Wednesday, November 23, 2016
The Uintas are shutdown
As i was dreading, we drove up into the uintas to try and hit a couple more lakes one last time but in a matter of 3 to 4 days the lakes froze over. we were driving up the highway and based on the fact that the lower lakes we passed were froze over there was no point in hiking up to the higher elevation ones. we did an immediate uturn and headed back down the mountain. we stopped at a couple of other spots but the fishing was garbage. this time of year is always tough
Wednesday, November 16, 2016
Last Hike?
This November the weather has been absolutely phenomenal. but weather is supposed to be coming this week, so me and scott figured this weekend could be the last chance we'd have for a hike in the uintas. i chose the spot and i feel fortunate to be able to take scott to someplace that he hasn't been. there was a particular lake that we had in mind with a few stops along the way. so instead of hiking straight to the main lake we took the scenic route so we could hit a couple of other lakes along the way. i had only taken this route once before and it was about 6 years ago. the last time i did not catch a single fish in the first 2 lakes but this time was different. the first lake scott did not rig up and just ended up being my spotter. the sun was just coming up so i was blinded for awhile. i did spot a fish cruising the shore but then soon lost it in the sun. luckily scott was able to see it and talk me thru it to the point of hookup. it was a decent little male brookie. we didn't spend much time at the first lake so we continued to hike up the trail above the tree line until we got to lake number 2 which set at just about 11,000 feet. the second lake is not much more then a puddle compared to a lot of uinta lakes and it doesn't look like it would be much more then maybe 12ft deep. my first cast and 3 strips later i was into a heavy fish. based on the size of the lake i was expecting to catch, if anything, maybe 10 inch fish or so. huh, definitely not the case, we caught 6 big and healthy bonneville cutts. the condition of these fish was incredible and based on the size the lake clearly does not get winter killed. these fish have been in there for awhile. after we spent a few hours there, it was hard to leave it, we took a slight detour to another lake that scott was showing on GPS. we hikes down to the detour lake and it was full of brookies but other then a few we they didnt seem real committed to the fly. we fished our way around and decided it was time to hit the main attraction. i had caught fish in there before and it was all 13ish inch cutties. i was up there this summer and saw a few really nice cutties dead along the shore. the fish were certainly bigger then i had seen before but couldnt figure out what was up with the about a half dozen dead fish. based on the size of the dead fish and on how the higher lake fished i had high hopes. we got to the lake and soon after i got blown up but something that i could tell was really big. my first thought was man these cutties really got big. as it splashed around i could tell it was a tank of a fish but then it ripped line off of my reel and the strength and size was confirmed. not only was the 22 inches a big surprise but the fact that it was a tiger trout blew us away. i had only seen cutties in there and according to the stocking report for the last 3-4 years only shows cutts being stocked. as kick ass as that fish was it ended up being the only fish out of that lake. it was an amazing day up to that point but then things started to go south from there. as we were on the back side of the lake, walking over a boulder field, i had a boulder roll on me and took a nasty fall. i fell on my shoulder and arm and with the burning sensation and the intense throbbing that i had in my arm i truly thought i broke it or at least fucked it up really good. my stomach was nautious for a few minutes. as it turns out it is just scraped up, bruised and sore as hell. on the hike out we had stopped to take some sunset photos and after a few shots we continued to hike back to the jeep. i had just told scott that we are only a couple minutes away from the jeep and then i realized that my hands were empty. when we stopped for photos i had set my rod down and forgot to pick it up. we had to walk back about 3/4 of a mile to get my shit. things were not going well after a good day of fishing. on the drive home we drove up on a truck and once we hit a long straight away i thought about passing the truck but then right away decided we were going fast enough and would stay behind the truck. instantly after i decided not to pass the truck he hits his brakes because 2 moose bolted a crossed the road in front of him. had i tried to pass the truck i would have drilled the moose and my jeep would have been done. what was such a great day of fishing turned out to be a nightmare after we were done, but certainly could've been worse had i chose to pass the truck.
Friday, November 11, 2016
Vets day
I had today off due to veterans day so like almost every year i went fishing on this day. on the way up i saw some turkey had a nice little 4 point muley cross the road in front of me and got held up by a sheep traffic jam. the weather was great but the fishing was slow. it was still an enjoyable 3 hours.
Tuesday, November 8, 2016
Me and Alanna
I took ali into the mountains this weekend hoping the lakes didnt have ice yet. we couldnt have asked for better november weather and there was no ice at all, but a slight trace of snow. we fished parts of 4 lakes that are in the immediate area and i caught fish out of 3 of them. all brookies today including some decent ones. ali even landed a couple.
Subscribe to: Posts (Atom)


text:
Burnaby – Metrotown
Neighbourhood amenities
Metrotown is dominated by the busy commercial stretch along Kingsway, the neighbourhood's northern perimeter, that includes three shopping malls. Metropolis at Metrotown is British Columbia's largest shopping mall with hundreds of stores, two department stores, movie theatres, dozens of restaurants and services like dentists and daycare. Nearby, The Crystal offers an authentic Asian shopping experience with scores of unique retailers and restaurants.
The malls are supported by a diverse range of independent shops, restaurants and services, including two major hotels, along Kingsway.
But there's more to Metrotown than shopping and eating. The Bonsor Senior Centre is a new facility alive with active seniors gathering for social activities, fitness classes and meetings. Next door, the Bonsor Recreation Complex offers a diverse range of fitness and arts programs for all ages, including swimming in its indoor pool, racquetball, basketball, dance and crafts, as well as soccer and baseball on its outdoor playing fields.
The area is dotted with numerous small neighbourhood parks. But they are dwarfed by nearby Central Park, a 90-hectare urban oasis of nature trails, playgrounds, fitness circuits, a 9-hole par 3 golf course, tennis courts and two ponds that sometimes freeze solid enough in winter to allow outdoor skating.
And if you can't find everything you need or want in Metrotown, Vancouver is only a short SkyTrain ride away from one of two stations that service the neighbourhood.
- Maywood Community School (K-7)
- Burnaby South Secondary (8-12)
- Moscrop Secondary (8-12)
This area is a major hub for shopping and has easy access to three major Skytrain stations; Metrotown, Patterson and Royal Oak. There's also a major transit loop at Metropolis at Metrotown with bus connections across the Lower Mainland
Metrotown real estate
Most of the real estate in the Metrotown are for sale are condos. The neighbourhood does supply a healthy amount of detached houses and townhouses for sale as well.
[insert_php]include ('content/tab-top.php');[/insert_php]
Error: Plugin access denied.
Please confirm that you have entered your plugin number and key correctly.
[insert_php]include ('content/tab-bottom.php');[/insert_php]


text:
Camisaac80 needed a new logo design and created a contest on 99designs.
A winner was selected from 83 designs submitted by 14 freelance designers.
Man Cave Ministry
This is a Christ centered men's retreat ministry. The focus is to provide a small cabin or similiar accommodation out in the forest where guys can go spend time alone reading, praying, and meditating surrounded by nature.
I'm not very creative by nature. This little chicken scratch logo just kinda popped into my head one day, but really I'm pretty open minded. Not really set on any colors other than green. This little project is completely a faith venture. There's no money in it for me. I'm just along for the ride:-)
Find out how a design contest works or learn more about our logo design services.


text:
"Woman says [Alabama Republican Senate candidate] Roy Moore initiated sexual encounter when she was 14, he was 32," by the Washington Post's Stephanie McCrummen, Beth Reinhard and Alice Crites.
The accusations, denied by Moore:
- "Leigh Corfman says she was 14 years old when an older man approached her outside a courtroom in Etowah County, Ala. She was sitting on a wooden bench with her mother, they both recall, when the man introduced himself as Roy Moore."
- "Alone with Corfman, Moore chatted with her and asked for her phone number, she says. Days later, she says, he picked her up around the corner from her house in Gadsden, drove her about 30 minutes to his home in the woods, told her how pretty she was and kissed her."
- "I wanted it over with — I wanted out," she remembers thinking. "Please just get this over with. Whatever this is, just get it over." Corfman says she asked Moore to take her home, and he did.
- "On a second visit, she says, he took off her shirt and pants and removed his clothes. He touched her over her bra and underpants, she says, and guided her hand to touch him over his underwear."
The fallout from Senate Republicans:
- Senate Majority Leader Mitch McConnell said Moore should drop out if the allegations prove true.
- Sens. John McCain and Rob Portman didn't use such qualifications, saying Moore should exit the race.
- Sen. Susan Collins: "If there is any truth at all to these horrific allegations, Roy Moore should immediately step aside as a Senate candidate."
- Go deeper: It's too late to withdraw Roy Moore's name from the ballot.
Another shoe drops: 5 women accuse comedian Louis C.K. of sexual misconduct in a new story this afternoon from the New York Times' Melena Ryzik, Cara Buckley and Jodi Kantornov.
Go deeper: We've updated our card deck with men accused of sexual misconduct.
2. What you missed
- The Senate tax plan is almost here. Summary.
- And the House has tweaked its final tax bill. More.
- Trump's ex-bodyguard said Russian offer to "send women" was rejected. Keith Schiller's news.
- Apple says it's eliminated the gender pay gap: Half of all new hires are from underrepresented groups, it claims.
- Silicon Valley's guilty conscience: After Sean Parker's comments on Facebook, we looked at techworld's internal crisis over the world they've created online. Details.
3. One partisan swing
The partisan gap in Americans' concerns about U.S.-Russian relations has widened — and flipped — since President Trump was elected last year, per a Pew report.


text:
Dear Bloggy Nation,
I am sorry I have been an awful blogger. No updates in almost a calendar week? blasphemy! let it not be heard of.
Ah, summer- when the days stretched out before me like the blue in the ocean. I blogged, I kept my house sparkling. I went to the Y twice a day. Ah, summer.
Actually, I really am so grateful to be working. Yes, it does change my days, clearly. But my last pay check came in from teaching last week, so good thing I have a job, right? I really like the ladies back in student affairs that I work with- they are a funny conglomeration (spelling?) but we all have each other's backs. and we laugh a lot. That is great news! Right now, in pharmacy admissions, we are finishing matriculating the incoming students- they will start sept. 18th with orientation. But they have to get a lot done by then- paperwork, immunizations, etc. etc. Its a lot of handholding, but its fun. Meanwhile, applications for the next admissions cycle are coming in and we're beginning to process those and get them ready for admissions committee meetings. Interviews will start in November and then begins the busier seasons of hosting kiddos on campus, etc.
Adam, meanwhile, is studying his little head off because he has his first BIG exam on Monday. Now so far, he has done very well on the quizzes. (Why does quizzes have 2 z's? that seems odd.) Anyways, sometimes he'll ask me to come in and help him study. So, I try. Yes, I try to pronounce the words. They are difficult. So, I kinda make up nicknames for the anatomy words. I don't know if thats too beneficial for his studying. But its fun! Its kinda like a game show, you know? And I'm bob barker with my long, skinny microphone. Right now, Adam is at the anatomy lab looking at cadaviers in preparation for the practical part of his test. He always smells so good after anatomy lab.
Well, the other day I told you all our exciting plans for the fall- but now we have a very very exciting addition!! On December 30th, Brooke and Free are coming to visit us!!!!!!
We are so happy that they can come and play in the snow with us and we can play boardgames and cards and sled and laugh just like old times in Waco! B & F are such loyal, thoughtful, hilarious, honest, fun, and wonderful friends. They would do anything for us and we love them! So, we are excited that they are coming to Erie as a finally married couple in December and we get to spend New Years Eve with them!
A few pictures to demonstrate whats going on around the house today:
exciting, no?
i need a timeout
Posted by the Jennings secede from the South at 6:04 AM
3 comments:
- Lora said...
It's tough to get the schedule all worked out when you first start work, but it will come. What a cute man and oh yeah, Adam is pretty handsome, himself.
- August 25, 2007 at 8:45 AM
- Brooke & Freeland said...
we feel so honored to be on your blog! Thanks for your sweet words! Good Luck on the exam A-dog. PS: 28 days until we get to see yall!!!
- August 25, 2007 at 9:56 AM
- kjds said...
You made your bed! Was that just for the pic? Just kidding!
I am praying for you as you work, balance home life, wifey-ness, and spending time with friends. It can be done! But you have to do some thinking & praying about priorities for the day, week, etc. Love to you guys!
- August 26, 2007 at 9:34 AM
Subscribe to: Post Comments (Atom)


text:
Recognize an overdose, save a lifeAmerican Society of Anesthesiologists (ASA)
Every day nearly 200 people die from an overdose of drugs or from alcohol poisoning, with opioids responsible for the majority. Recognizing the signs and knowing how to respond to medical emergencies, including carrying and administering naloxone in cases of opioid overdose, can save lives says the ASA.
Channels: Addiction, Alcohol and Alcoholism, Emergency Medicine, Pain, Patient Safety, Substance Abuse, Surgery, Embargoed Feed - hidden,
Keywords: Physician Anesthesiologists Week, opioid overdose, Opioid Overdose Deaths, Naloxone, physician anesthesiologists, Chronic Pain, Alcohol Poisoning, Patient Safety, Resuscitation, Opioid Epidemic, U.S. Surgeon General, Centers for Disease Control and Prevention (CDC), Pain Management, Pain Medicine, alternative pain management
National CRNA Week: The House of Representatives Recognizes the Contributions of Nurse AnesthetistsAmerican Association of Nurse Anesthetists (AANA)
In honor of National CRNA Week (Jan. 19-25, 2020), Reps. Jan Schakowsky (D-IL), Lucille Roybal-Allard (D-CA), and Sam Graves (R-MO) today introduced a bipartisan resolution on the House floor, "Recognizing the roles and the contributions of America's Certified Registered Nurse Anesthetists (CRNAs) and their role in providing quality health care for the public."
Channels: Healthcare, Nursing, Pharmaceuticals,
Keywords: House Of Representatives, Resolution, Contribution, Certified Registered Nurse Anesthetists, Patient Safety, Anesthesia, Healthcare, Pain Management
Russian expert is ready to comment on the coronavirusMoscow Institute of Physics and Technology (MIPT)
Channels: Genetics, Immunology, Infectious Diseases, Public Health, Respiratory Diseases and Disorders, China News,
Keywords: Genome, Coronavirus, Virus, virusology, Genetic Engineering, Coronaviruses, China, Sars Virus, Middle East Respiratory Syndrome, respiratory syndrome outbreak, RNA, genes, Disease, Immune System, immunogenic, Pneumonia, nCorona-2019
Embargo will expire:29-Jan-2020 4:00 PM EST
Released to reporters:24-Jan-2020 6:25 PM EST
A reporter's PressPass is required to access this story until the embargo expires on 29-Jan-2020 4:00 PM EST
The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application.
NSF Career Grant recipient advances physics research, outreach efforts at Mississippi StateMississippi State University
With help from a prestigious National Science Foundation Career Grant, a Mississippi State faculty member is working to advance his nuclear physics research and provide a new summer school experience for Mississippi students with Autism Spectrum Disorder.
Channels: Autism, Children's Health, Education, Nuclear Physics, Physics,
Supercomputer Simulations Reveal Details of Galaxy ClustersUniversity of California San Diego
A new study published late last year in the Monthly Notices of the Royal Astronomical Society explored the molecular gas within and surrounding the intracluster medium, which fills the space between galaxies in a galaxy cluster.
Channels: All Journal News, Space and Astronomy, Supercomputing, Technology,
Keywords: University of Washington, Galaxy Clusters, Supercomputer Simulations, San Diego Supercomputer Center, National Science Foundation (NSF) , NASA, Comet supercomputer, Star Trek, Hubble Space Telescope
FSU professor discusses Brexit and its consequencesFlorida State University
By: Bill Wellock | Published: January 24, 2020 | 3:35 pm | SHARE: On Jan. 31, after a national referendum, elections, negotiations and delays, the United Kingdom is scheduled to leave the European Union.The date marks the end of one political process and the beginning of another. When Brexit is official, the United Kingdom and European Union will begin negotiating a new trading agreement.
Channels: Brexit, U.S. Foreign Relations, U.S. Politics, Europe News, Local - United Kingdom, Politics Channel Featured Experts,
Why eating yogurt may help lessen the risk of breast cancerLancaster University
One of the causes of breast cancer may be inflammation triggered by harmful bacteria say researchers.
Channels: All Journal News, Cancer, Health Food, Nutrition, Stem Cells, Women's Health,
Keywords: Bacteriology, Breast Cancer, Carcinogens, Microbiology, Nutrition & Nutrients
Horror movies manipulate brain activity expertly to enhance excitementUniversity of Turku (Turun yliopisto)
Finnish research team maps neural activity in response to watching horror movies. A study conducted by the University of Turku shows the top horror movies of the past 100 years, and how they manipulate brain activity.
Channels: All Journal News, Behavioral Science, Neuro, Psychology and Psychiatry, Staff Picks,
Keywords: Behavioral Science
As Chinese celebrate Lunar New Years Eve and coronavirus continues to spread @umich experts available to discuss health, economy, engineering implicationsUniversity of Michigan
Researchers from public health, medicine, engineering,
Channels: Economics, Infectious Diseases, Public Health, Respiratory Diseases and Disorders, China News, Southeast Asia News, Engineering, Environmental Health,
Keywords: Coronavirus, China, Europe, Economy, Trade, Pandemic, Epidemiology


text:
I'd set it up for my Chruch so it can send out newsletters fast 'n cheap
All I Want for Christmas: Sendy
We asked SitePoint authors what developer toys they would want for Christmas, then managed to source them — without relying on Santa.
Despite the buzz in social media marketing, email marketing isn't dead and won't be any time soon.
If you own a blog or company website, and you don't have an email list of your blog readers or users of your product, you really should start now. Having a list of past and potential customers you can turn to when you have a new product is invaluable.
Why I wanted Sendy
While it's hugely valuable, email marketing can be expensive, especially when your website or company is just starting out. The cost of sending newsletters to, say, 10,000 subscribers via larger email providers can cost over $75. The larger the subscriber base, the more the bill adds up.
For a writer like myself whose blog posts seldom generate revenue (yet!), I consider it an extravagance to pay a large fee to send a weekly or monthly round-up of my published articles. When the SitePoint team asked me for my Christmas wishlist, my first pick was Sendy, a self-hosted email newsletter application that lets you send trackable email via Amazon Simple Email Service (SES).
The experience so far
So far the Sendy experience has been fantastic. I have only had to pay $0.10 per thousand emails sent, which is very cheap. I've also had great delivery results and the support from forum and email is pretty fast.
Unlike other email marketing provider, Sendy doesn't ship with pre-built email templates and an intuitive template builder. Since it's self-hosted, you will have to install and get it up and running yourself, or pay the Sendy team or a developer to get it done for you. But this also means it's more flexible, and can be perfectly tailored to your needs.
What would you do with a free Sendy license? Answer in the comments, we'll pick the best answers and give away 5 Sendy licenses to the winners.
I'd move some of my clients over to it. As much as I love MailChimp it's always good to own your data.
Aside the fact Sendy is cheap, it's a great alternative to the big guns like MailChimp and Aweber.
It seems like a good tool… Ideal for my startup project… I'll keep it in mind…
I am educational author & product creator and more recently have taken to programming.
Sendy looks extremely promising to create help people set their learning goals and automatically send them reminder emails.
With a Christmas gift such as this, I pledge to create an Auto-responder based course available for free by the end of Jan 2015.
6 more replies


text:
Know Before You Go
From the mainland, the island is clearly visible from the sea defenses of the settlement of Gedney Drove End. The Wash is quiet and desolate, with fast tides and dangerous mud and silt, so when in the area, stick to the marked footpaths. There are no organized tours or trips to the island, but online videos reveal that it can be reached by experienced kayakers with knowledge of the tidal conditions in The Wash.


text:
Note: I received this to review from netGalley.
Title: Rampant
Publisher: Harlequin
Imprint: Spice
Pub Date: 04/01/2010
Category: Erotica
The moment she arrives at her rented vacation cottage nestled in northern Scotland, Zoë Daniels feels it—an arousal so powerful she's compelled to surrender to the unusually forceful carnal desires…with nearly anyone who crosses her path.
Zoë knows she's not quite in control of herself and begins to wonder if there's any truth to the legend of Annabel McGraw, a powerful, promiscuous 18th century witch who once owned the cottage, and whose spirit is rumored to affect anyone who stays there. Zoë doesn't believe in anything that even hints at the occult, but now strange visions are turning frightening… and only one man's touch can bring her back to earth.
First off let me say that I love this cover. You know how I'm a cover whore, yes, yes, I know. I just loved the earthiness and the beauty of it. It strikes me as both sexual and pure and yes folks, I believe you can be both ;)
The setting for this story is a small coastal village in Scotland and I do love those kinds of settings. The fact that the plot involved a rather heavy portion of magic did help to add to the ambience of the story.
I liked Zoe, our heroine, she's a city girl hailing from London who's come for a vacation and to unwind from her hectic job in the city. The minute she enters the village, odd sensations and things begin to happen. What I liked about Zoe is that she's practical. She's a skeptic and doesn't give into flights of fantasy, but as the evidence stacks up that something magical and supernatural is going on she doesn't freak out and go running into the hills. What irritated me a little about her was that it did take quite a lot of freaky stuff to happen for her to fully admit that ghosts are real and even after she became convinced she was somehow communing with a dead woman she had the devil of a time accepting that magic is real. However, she didn't dither too badly and she had a good sense of humor which were definite points in her favor.
Grayson, our hero, was handsome, powerful and intelligent. I had a little bit of a hard time with him in the respect the he seemed clinical and detached, even during intense sexual or emotional encounters. Now, don't get me wrong, I lurve me some cold and emotionally unavailable types (don't get me started on my massive crush on Mr. Spock) but I just didn't always feel that he was having sex with or interacting with her as much because he wanted her or that he wanted answers. Plus the fact that the spirit of a long dead promiscuous woman was influencing everyone made it hard sometimes to suss out his real feelings and motives, at least for me.
The story itself is a little heavy on magic and mostly on negative magic, though there are a few nicer practitioners, it felt like it was hard to tell if a lot of the people were supposed to be good or bad. I wasn't always sure if I was supposed to root for them or against them, like them or hate them or pity them at times. It made it hard for me to get a firm bead on an emotional response to the story.
Also, I have an issue with the fact that every woman who owned her sexuality either was a witch and/or prostitute or was under the influence of a witch and/or prostitute. I would like to see us move beyond the need for justification in erotica and romance for a strong heroine to just own her sexuality without being a bitch, ho, or possessed by one. Just saying. Zoe did come to grips with the fact that she's always had a sexually vibrant nature that was hidden under the surface and brought out by Annabelle but it then came with the proviso that it ultimately would only have come out because of her one twu wuv, Grayson. Ladies, hear me on this: YOU DO NOT NEED A MAN'S PERMISSION TO OWN YOUR SEXUALITY. I'm waiting for Romancelandia to catch on to this. I do give Zoe credit, she noticed that she was aroused a lot more than usual and doing things she wouldn't normally do, but at no point did she freak out to the point where she started losing her self-worth and thinking that she'd been somehow soiled by her experiences. I respected that, a lot.
Ultimately, the romance between Grayson and Zoe was nice, but there was always magic somehow involved and it felt at times like it was either pushing them together or pulling them apart. For a lot of the book, even Zoe wondered if she and Grayson had anything real.
The side story of Annabel and what had happened to her was fascinating. I didn't always know if Annabel was someone I should really root for, she wasn't always a nice person and she kind of invited the problems that came her way, but I found her so vibrant and mischievous that I couldn't help but fall under her spell and like her a lot by the end.
At times the book felt longer than it needed to be, but overall it was enjoyable and an interesting story of the beauty and ugliness of passion and love.
My final grade is a C+
You can purchase this book here
Or here
Wolf Rain
21 hours ago


text:
My Latest Obsession: Sephora Favourites
Today's Prompt: Just for fun, your latest obsession. What can you not get enough of these days? In November I wrote a blog post going through my wishlist for the Sephora VIB sale. In that post (which you can read HERE) I mentioned that I love the "Sephora Favorites" line of value…View Post


text:
The sun will be the setting for your fabulous weekend at Lake Garda, secluded from the city and from the commitments .
We waited a long time and finally arrived ... we're talking about spring, of course! Days are getting longer, the sun has begun to warm up, the birds have begun to delight us with their chirps ... in a word, everything invites you to treat yourself to a weekend on Lake Garda! Camping Eden will reopen its doors on Saturday 20 April, on the occasion of Easter. How about coming to celebrate it with us?
"Magical" weekend on Lake Garda!
Lake Garda is truly spectacular and magical with its most varied landscapes and with the places that overlook it, one more beautiful than the other. But if we have called the paragraph "magical weekend on Lake Garda" with the magic adjective in inverted commas is also for a much more precise reason. On March 30, in fact, Year of Magic will be inaugurated at Gardaland Resort! It is a year entirely dedicated to the world of magic! Always, in the collective imagination, Gardaland is an oasis of fun and dreams for young and old, but the third element that makes the Park unique and determines its great success is magic! Starting from March 30th, some amazing innovations will be introduced in the Park: from the "Enchanted Forest" attraction to the magical theming of "Sequoia Magic Loop" up to the new Magic Elements show; from the unique events like Magic Spring to the spectacular set-ups of the Park up to the opening - on May 31st - of the highly anticipated Gardaland Magic Hotel! So take advantage of a weekend on Lake Garda, come and live a truly thrilling experience!
Weekend on Lake Garda in the name of sport!
For lovers of sport and sailing in particular, we would like to point out the inevitable appointment with the Garda Optimist Meeting, the event that represents the largest sailing event in the world of a single class, and for this reason already certified by Guinness World Records. The appointment, now in its 37th edition, is scheduled for April 18 in Riva del Garda: mark it immediately on the agenda! After you went to Riva, take the opportunity to come to Camping Eden to spend the Easter weekend on Lake Garda!
After watching the athletes practicing their sporting discipline, there will be plenty of opportunities to be "active" yourself. In our campsite, in fact, there are:
● fresh water pools of various depths
● waterslides
● sports fields
● children's playground
As for the housing units, you will be spoiled for choice. You can opt for one of the following solutions:
● pitches on terraces or bounded by hedges for your privacy
● fully equipped mobile homes
● perfectly furnished and maintained chalet in masonry What unites and embellishes the various proposals is certainly the breathtaking and incomparable view of the lake! We have thought of everyone: from singles to large families, from couples to groups of friends. Try to take a look at the gallery on our website and book immediately your weekend on Lake Garda!


text:
PG&E's real estate rumors
I sure hate to kick a bankrupt utility when it's down, but what are all these rumors floating around the commercial real estate world that Pacific Gas and Electric Co. is quietly -- very quietly -- placing its downtown San Francisco headquarters up for sale?
Sources tell me that PG&E is looking to unload more than 100 pieces of property throughout Northern California, and the crown jewel of the offering is the utility's headquarters building, which it would then lease back under a long-term contract.
However, PG&E is trying to keep the sales below the radar by going through investment banking channels rather than listing most of the properties outright, sources say. "I'd bet they're trying to not spook the market and get people even more worried about their situation," one broker said.
A spokesman for the utility insisted that there are "no current plans" to sell the headquarters but refused to say categorically that PG&E isn't pondering the idea.
MBA BY THE BAY: See how an MBA could change your life with SFGATE's interactive directory of Bay Area programs.
As for other properties that may be on the block, the utility hasn't updated its online portfolio of surplus assets in months, so it's impossible to say what may or may not be up for grabs.
Still, the rumored plan for the headquarters is for PG&E to sell off either one or both of its main headquarters buildings at Market and Beale streets in the Financial District, and then lease the property back from the new owner.
PG&E already leases part of its headquarters from Shorenstein Co. for about $233,000 a month. Likely buyers for the other utility buildings would include Shorenstein and Sam Zell's Equity Office Properties, which became a serious player in the Bay Area after merging with Spieker Properties.
Although PG&E does not publicly discuss its real estate assets, internal utility documents recently placed the value of the downtown headquarters at about $450 million -- before commercial office prices went into a tailspin.
This wouldn't make a huge dent in the roughly $13 billion PG&E owes its creditors. But, hey, every little bit helps.
COLLATERAL DAMAGE: Business hasn't improved at the former Afghan Treasures shop on Market Street, even after "Afghan" was dropped from the store's name right after the Sept. 11 terrorist attacks and it became just "Treasures."
"Business is down maybe 75 percent since then," said Hadi Faiez, a salesman at the store who is originally from Kabul. "No business now."
Treasures sells ethnic-type stuff from South Asia, Southeast Asia and Africa -- incense, carvings, that kind of thing. The only merchandise from Afghanistan is some carpets, which range in price from about $200 to $1,600.
Now that Afghanistan is being painted by the West as the source of all evil -- just as Iraq similarly represented the maw of hell for the previous Bush administration -- Faiez said he worries that Americans will never appreciate the many good things about his homeland.
"My people make a lot of nice stuff," he said. "Carpets, jewelry. Many nice things. Maybe no one will see that for a while."
I'd call that a safe bet.
GRIM PREDICTION: Famed architecture critic Ada Louise Huxtable, writing in the New York Times in 1966 about the city's decision to go ahead with construction of the huge World Trade Center:
"Who's afraid of the big, bad buildings? Everyone, because there are so many things about gigantism that we just don't know. The gamble of triumph or tragedy at this scale -- and ultimately it is a gamble -- demands an extraordinary payoff. The Trade Center towers could be the start of a new skyscraper age or the biggest tombstones in the world."
SOUTH OF THE BORDER: After checking out PG&E's headquarters the other day --
a bit out of my price range -- I strolled a few blocks over to the new Chipotle burrito restaurant near Mission and New Montgomery streets. They're the one with ads plastered all over Muni metro stations.
A nice enough place. Industrial-chic decor, with arty black-and-white photos on the wall. But nowhere will patrons see even a hint of Chipotle's dirty little secret: Its majority shareholder is none other than fast-food king McDonald's, home of the Happy Meal.
Manager Nels Nielsen smiled guiltily when I asked if his restaurant was ashamed of its corporate parentage.
"If people ask, I tell them," he said.
And if they don't ask?
"We're an independent corporation."
MUM'S THE WORD: Speaking of keeping one's corporate DNA under wraps, bet you didn't know that Bay Area lite-rock radio station KOIT and lite-classical KDFC are both owned by none other than the Mormon Church.
Explains a lot, if you ask me.


text:
Things you need to know
– Must bring current photo ID
– Must be 15+
– Unauthorised entry to the event (fence jumping, duplication of ticket etc etc) may result in a state-wide ban of up to 3 years and also handed over
to police where charges may be laid for trespassing.
– There is parking, drop off and pick up zones at event
– For accommodation please contact Rydges Mackay or Clarion Hotel. Buses will be running from Rydges Mackay Suites.
– No Refunds
– No Pass outs
– Drug Free event
– There will be food and drinks available for purchase at the event (Inc free water)
The following conditions apply; when purchasing a ticket for the event and when entering the event.
1. All of the conditions of entry listed below must be read in conjunction with the conditions shown on the Ticket and the conditions of entry, signage and statements displayed at the venue. Failure to adhere to any conditions of entry may result in refusal of entry to the event and/or removal from the event.
2. Children under the age of 15 are not permitted at the event. All patrons entering the event must have a valid ticket and all attendees must produce proof of age to gain entry to the event.
3. All persons attending the event must produce suitable identification and proof of age. No person will be admitted to the event without the appropriate identification and proof of age. No ID, no entry, no exceptions.
4. Persons attending the event under age 18 years old (Minors) It is recommended that all minors are accompanied by a responsible adult.
5. We play rain or shine.
6. Minors are not permitted to access licensed areas/bars on the event. Any minor caught attempting to gain illegal entry into these areas will be handed over to Police, or removed to a minor's handling area for removal from the event.
7. Minors/adults who breach any condition of entry and/or break any laws at the event, hereby indemnify the venue and Promoter for any loss, fine or penalty,
whether or not the venue or Promoter was negligent or otherwise.
8. The Venue and Promoter shall not be held liable for any loss, injury or damages sustained entering the venues or within the event whether caused by negligence of the Promoter or venue or otherwise.
9. No bottles, cans, liquids, foods, weapons, lasers, fireworks, umbrellas, other prohibited items, illicit drugs and alcohol are permitted at the event. Prohibited items confiscated will not be returned and persons caught with illicit drugs and alcohol will be handed over to Police.
10. Small still cameras, including digital cameras are permitted at the event but no sound or video recorders will be allowed inside the event. This event may be filmed, it is a condition of entry that you agree that your image may be broadcast.
11. Ticket holders to the event may be refused entry or removed from the event for
the following reasons:
- The ticket holder fails to comply with the conditions of entry for the event and/or
conducts an illegal activity at the event.
- The ticket holder fails to produce appropriate identification and/or proof of age
- The ticket holder refuses to have their clothes, bags, possessions and containers
searched at entry
- The ticket holder attempts to gain entry to the event with illicit substances
- The ticket holder is affected by the consumption of alcohol and/or drugs
- The ticket holder participates in any illegal activity and/or aggressive dancing,
moshing, stage diving and acts of intimidation
12. The Venue has a zero tolerance to drugs. Any person caught with illicit drugs
and substances will be handed to Police and you may face criminal charges.
13. Adult patrons attending the event who wish to consume alcohol will be wrist banded for access to licensed areas/bars. Anyone found to be supplying or
purchasing alcohol for a minor will be evicted from the event and possibly face criminal charges.
14. You may be subject to a pat down and bag search on entry to the event.
15. We may without prior written notice, invalidate any tickets that are reasonably believed to be in breach of these terms and conditions, no refund, replacement or compensation will be offered.
16. There are strictly NO PASS OUTS at all River Sessions events.
17. Line-up is subject to change without notice and varies in each city. Refunds will not be given for tickets in any case.
18. No animals are permitted on site (apart from authorised guide/companion dogs).
19. We will not take responsibility for cloaked items.
20. Any and all footage taken by patrons on camera, mobile phone or any recording device is subject to Copyright Laws. River Sessions and its artists give no
permission for filming, photographing or any recordings. Where used in any public medium without written authorisation from River Sessions, River Sessions may prosecute.
Unable to display Facebook posts.
Show error
Type: OAuthException
Code: 190
Subcode: 460
Please refer to our Error Message Reference.
Unable to display Facebook posts.
Show error
Type: OAuthException
Code: 190
Subcode: 460
Please refer to our Error Message Reference.


text:
Palma to Mahon Freight Ferry
New Email
New Mobile Number
Trailer / Caravan
Book a freight ferry from Palma to Mahon with AFerryFreight.co.uk!
See below for the Palma to Mahon ferry times; also find information on both Palma and Mahon ferry ports by clicking on the links below. Looking for the best deal? - Why not check out the alternative routes available and compare prices using Compare & Book opposite.


text:
Wat zal je doen?
- As a motivated developer, you have an eye for combining the art of design with the science of programming.
- A major portion of the position includes the conversion of both e-marketing content (i.e. emails, landing pages, interactive smart web forms and preference centers) and web application UI/UX design wireframes into actual code. Code that will produce the visual elements of our web content and applications.
- You will make the front-end of a design through back-end systems. For this, you will work closely with designers and bridge the gap between graphical and technical, taking an active role on both sides.
- As a developer, you are aware of the latest tech innovations. Your input and proactivity are highly appreciated by LeadFabric.
- You are responsible for the day to day maintenance of the company website (Drupal necessary, Wordpress optional).


text:
Pacific Northwest Consulting LLC's role at the City Park Apartment Homes (Formerly Governors Village) was to provide the Due Diligence and Property Condition reports for the investors. Once the properties were acquired, our role evolved to the position of Owners Rep./Construction Management for the renovation of the leasing office, exterior structure repairs, repainting and the site wok remediation, including landscaping and signage. PNWC managed the design consultants, general contractor as well as the construction budgets, change orders, construction schedules, and pay applications. Our firm performed weekly site meetings to review construction progress and to review issues as they arose.
Cumberland Holdings LLC has hired Pacific Northwest Consulting LLC to provide on going quarterly site inspections for fire life safety and maintenance review. Another service that PNWC is providing is the oversight of the annual testing and inspections for fire alarm, fire sprinkler, elevators, swimming pools, for their facilities.


text:
Join our team
This role is both technical facing and business facing and so you will need to have brilliant people skills and the ability to translate technical information to a non-technical audience and vice-versa. As a consultant, you will be providing guidance to customers and must be able to liaise with senior stakeholders and end users understand and document their needs.
The functional consultant is expected to lead client workshops and meetings, gather and document customer requirements and implement changes as part of an implementation team. From a quality assurance perspective, the functional consultant will be responsible for unit testing within the implementation team and supporting customers through more formal testing phases including the analysis/triage and resolution/bug fixing.
25 days holiday (pro-rata), Flexible working hours, Private medical insurance, Pension contribution, Life assurance,
Training and Development, Health & Wellness benefits, Food vouchers, Company Days
Customer engagement
Plan and lead customer workshops and meetings
Coordinate, as necessary, relationships with and between key stakeholder during the design, management and implementation of business change
Lead both formal demo and informal show & tell sessions
Requirements management
Analysis, design and documentation
Implementation and testing
Travel (50%+) will be required as part of this role.


text:
Montreal Travel Tips
Find a place to stay
Best Time to Travel
Montreal's a city of many colors, and whether it's the orange and auburn booms of fall's foliage, or the pristine white that comes after a hefty snowfall, the city's always glowing one way or the other. Winter here can be a bit of a drag, but if a little snow doesn't put you off, you'll love experiencing the local friendliness and hospitality, which can warm up even the harshest winter night. You'll also get a great chance to try winter pursuits like ice skating, skiing and sledging. Even so, it's hard to argue against summer being the best time to visit, as the weather heats up and the festival season kicks off with a bang.
Not to Miss
The smooth saxophones and rippling pianos echo across the city as the Montreal Jazz Festival gets into full swing every June and July. You can't help but get festival fever here, and whether it's summer's music and comedy events, or the Formula 1 bandwagon that's speeding into town, there's always something to celebrate. The Parisian influence comes to the fore, meanwhile, as you visit the historical center to walk along the cobbled streets of Old Montreal amid horse-drawn carriages clip-clopping by. Then there's the Underground City - where sheltered shopping, restaurants, and subway stations form the world's largest underground complex. As the name suggests, it's like a city within itself.
Getting around
Montreal is a haven for cyclists, and the cheap rates, countless places to drop off and pick up new bikes, and wide, boulevard-like bike lanes mean that hopping on a bike is one of the simplest and most peaceful ways to get around Montreal. There's a good bus and metro service if you need to get somewhere quickly, while getting to the city is also a doddle thanks to the airport which is located just a short drive from the urban center and handles a vast range of flights to major destinations across the world.
This part of Canada is famous for what is perhaps the ultimate comfort food - poutine. This slathering of crispy fries, thick gravy and fresh cheese curds is a Quebec classic, and insanely satisfying when done well - as it inevitably is in Montreal. The seeded bagel is another favorite, and the smell of flames baking dough is never far away. With influences from all over the world, Montreal's many restaurants serve everything from spicy Lebanese lamb, to Greek fish drizzled in lemony, olive oil dressing.
Customs and etiquette
Canadians are known for being refreshingly polite and friendly - so visitors should try to show similar respect and manners while in the country. Montreal is a largely French speaking city, although a healthy proportion of the population are English speakers as well. It's worth checking your bill when eating out - some of the city's restaurants include the gratuity but, generally, you'll need to tip around 15% for meals. Most people will tip taxi drivers, hotel workers, and hairdressers around 10% extra.
• Population: 1.68 million
• Spoken languages: French, English
• Electrical: Canada runs on 120V, 60 Hz current
• Phone Calling Code: +1 514911
Where to stay
Downtown MontrealAverage hotel pricesSearch for Downtown Montreal hotels
Old MontrealAverage hotel pricesSearch for Old Montreal hotels
Gay VillageAverage hotel pricesSearch for Gay Village hotels
Find your perfect holiday in Montreal
From 540 hotels.


text:
Roman Saini is teaching live on Unacademy Plus
UPSC CSE 2018 mains Ethics Integrity Aptitude Roman Saini
Home Explore Plus Q Search Courses, Topics&Educators Roman G 0 minutes today 130 credits GS Paper 4 2017 (Ethics, Integrity and Aptitude) Detailed Discussion Enroll 2.2 / Answers for UPSC CSE Mains 7 lessons, th 1m unacademy Previo Next > (a) official duties, -3:GS Paper 4 12017) 2 4-5 GS Paper 4 12017) 3 6-7:GS Paper 4 (2017 4, 8-9: GS Paper 4 [2017 9-27 8-34 example 9:21 Answer A conflict of interest involves choosing between competing loyalties which may corrupt our decision-making. Working in publie sector means doing what's best for the people. This may sometimes come in the way of our own selfish interests. :02 5. 10-11: GS Paper 4 12017) 8-13 6 12-13: GS Paper 4 12017) 8-27 Official duty- following orders of superior Publie interest- many slum dwellers will become homeless Personal interest- fear of transfer a.ter oressurelocal politicians 7. 14: GS Paper 4 (2017) 8:03 Stay tuned! Mora iessons w dded soon bn UNACADEMY PLUS Write Mains like a Topper 140+ in Essay & Pen Awesome Answers View Details La date to apply is 11th June 1-3: GS Paper 4 (2017)/ Notes
Analysis of 2017 paper https://unacademy.com/course/gs-paper-4-2017-ethics-integrity-and-aptitude-detai led-discussion-answers-for-upsc-cse-mains/FSF9WJGK
No time issues 130 marks 13 questions 150 13 words - 1950 words 250 words is not 15 marks it is rather 20 marks 20*6 120 marks 6*250 1500 words Total 3450 words
Some time issues GS Paper 1 2017 10 questions-10 marks-150 words = 1500 words 10 questions - 15 marks 250 words 2500 words Total 4000 words
Time issues 2013! GS Paper 1-25 questions-200 words each = 5000 words!
First half is relatively straight forward Focus on theory Lexicon is great It is really in your control It is 90% just like any other paper and there is less subjectivity Emotional Intelligence, CSR etc. are pretty scientific https://unacademy.com/lesson/citizens-charter/MMVJJ55T
First half is relatively straight forward Remember the definition of at least 100 terms Transparency Accountability Integrity etc. Basic Psychology Thinkers, Philosophers etc.
Warning Do not write unethical answers at any cost, no matter what! Even if you will cheat in the exam without any guilt, do not write it Here there will be a carry over effect and the examiner may give you less marks in other answers as well
Other Warning Do not become holier than thou You are not Jesus Christ Do not be Raja Harishchandra Show your weakness I will demolish all the slums no matter what"


text:
- Home
- Health & Beauty
- Vitamins & Supplements
- Vedic Care 100% Avipattikar Powder (Dietary supplement) 100 Grams
Product Description
Avipattikar is an Ayurvedic herbal formulation of fourteen wonderful herbs, that helps restore digestive health bybalancing digestive meaning of the name is A (free) form Vipatti (problems).By balanncing Pitta Dosha in body Avipattikar churna helps nourish,strengthen and protect the stomach and intestines. It is specifically recommended for people with Pitta body type who are prone to increased acidic content and associated probemls. By regulating Apan Vata in body it also helps in regulating bowel movement.
- Store in cool dark place and in as air-tight container
- Avoid exposure to moisture
- Keep out of reach of children
- Promotes apporpriate levels of acidity in the stormach and intestines
- Helps remove excess heat from the Gastro Intestinal tract
- Supports healthy elimination for individuals with pitta imbalances
Directions fpr use:
1/4 to 1/2 teaspoon wiht Warm water up to twice daily
This product contains suger and not recommended for diabetics.
Not recommended for pregnant women.
Health tip
Est way to deal with hyperacidity (a symptom of aggravated pitta) is to reduce the intake of acidty causing foods. Foods containing spices, oils and meat should be avoided. Alight walk aftre each meal is beneficla to digee the food easily. Amla juice or Gulkand (rose petal paste) is also beneficial in balancing a system nigh in acidity.
Manufactured By: Vedic Care, USA
Country of Origin: Product of USA
Product Weight: 100 Grams
Storage Instruction: Keep in cool and dry place.
Package: Packed


text: The worst which could happen against musicians happened in the morning May 16 at UppÍt FramÍts Barn, G—teborg, Sweden. Three instruments were stolen.1. Gibson Les Paul Custom Black, Humbucken Pick-ups, serial No. 823126672.Fender Stratocaster USA Black/White, serial No. 9271963. Fenix Jazz Bass, cream coloured with brown pick guard.If you know something in this matter, please call Fox Machine, Olle Hagberg +46 -31 - 42 14 06, Cell phone: +46 (0)708 18 55 23.