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Pathophysiology/Complications
Leucine 7 to Proline 7 Polymorphism in the Preproneuropeptide Y Is Associated With Proteinuria, Coronary Heart Disease, and Glycemic Control in Type 1 Diabetic Patients
Kim Pettersson-Fernholm, MD12,
Matti K. Karvonen, DMSC3,
Jaana Kallio, MD3,
Carol M. Forsblom, DMSC12,
Markku Koulu, DMSC3,
Ullamari Pesonen, DMSC3,
Johan A. Fagerudd, DMSC12,
Per-Henrik Groop, DMSC12 and
FinnDiane Study Group
1Department of Medicine, Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland
2Folkhälsan Research Center, Biomedicum, University of Helsinki, Helsinki, Finland
3Department of Pharmacology and Clinical Pharmacology, University of Turku, Turku, Finland
Address correspondence and reprint requests to Per-Henrik Groop, Folkhälsan Research Center, Biomedicum Helsinki (C318b), University of Helsinki, P.O. Box 63, FIN-00014, Finland. E-mail: per-henrik.groop{at}folkhalsan.fi
Diabetes Care 2004 Feb; 27(2): 503-509. https://doi.org/10.2337/diacare.27.2.503
Figures & Tables
OBJECTIVE—Neuropeptide Y is a potent vasoconstrictor thought to enhance the development of atherosclerosis. The leucine 7 to proline 7 (Leu7Pro) polymorphism, located in the signal peptide part of the human preproneuropeptide Y, has been associated with serum lipid levels, intima-media thickness of the common carotid arteries, and diabetic retinopathy in type 2 diabetic patients. Therefore, we investigated the impact of the Leu7Pro polymorphism on diabetic nephropathy, cardiovascular risk factors, and cardiovascular disease in type 1 diabetic patients.
RESEARCH DESIGN AND METHODS—A total of 996 patients from the Finnish Diabetic Nephropathy study were studied in a case-control, cross-sectional study. The carrier frequency of the Pro7 substitution was 13% in the entire study population.
RESULTS—The Pro7 substitution was more common in patients with proteinuria than in those with a normal albumin excretion rate (16 vs. 11%, P < 0.05). Patients with the Pro7 allele had worse glycemic control (HbA1c 8.8 vs. 8.5%, P < 0.005), more coronary heart disease (CHD) (14 vs. 8%, P < 0.05), and higher serum triglycerides (1.65 vs. 1.35 mmol/l, P < 0.005) than patients with the wild-type genotype. There were no differences in the plasma neuropeptide Y levels between the patients with Pro7 compared with those with the wild-type genotype. The Leu7Pro polymorphism was independently associated with HbA1c (P < 0.001), proteinuria (P < 0.01), and CHD (P < 0.01) in multiple regression analyses.
CONCLUSIONS—We conclude that the Leu7Pro polymorphism may contribute to the genetic susceptibility to diabetic nephropathy and CHD in type 1 diabetic patients, possibly by influencing glycemic control and triglycerides.
AER, albumin excretion rate
CHD, coronary heart disease
ESRD, end-stage renal disease
Leu7Pro, leucine 7 to proline 7
NPY, neuropeptide Y
prepro-NPY, preproneuropeptide Y
RIA, radioimmunoassay
Diabetic nephropathy is associated with a high risk for coronary heart disease (CHD) and early mortality. Although risk factors such as poor glycemic control, hypertension, and dyslipidemia contribute to nephropathy, they cannot entirely explain why it develops in only a subset of patients. Evidence suggests that a genetic predisposition is involved in the pathogenesis of diabetic nephropathy, but the genetic factors are still unknown (1).
Neuropeptide Y (NPY) is a 36-amino acid polypeptide mainly present as an intact peptide in the central and peripheral nervous system, several peripheral organs, and plasma. NPY has been shown to regulate renal blood flow and to alter renal hormone levels such as renin (2). At least two of five known NPY receptors are expressed in the kidney. Stimulation of these receptors has resulted in a decrease in glomerular filtration rate, aldosterone concentration, plasma renin activity, and increase in sodium excretion (3). Furthermore, since interventions that block the renin-angiotensin-aldosterone system alter the renal function in diabetic nephropathy (4), it could be hypothesized that NPY is involved in the pathogenesis of the disease.
The gene that codes NPY is located on chromosome 7 p15.1. A functional leucine 7 to proline 7 (Leu7Pro) polymorphism located in the signal peptide region of the human preproneuropeptide Y (prepro-NPY) was recently observed. This signal peptide region, which is cleaved off during the peptide maturation process, is important for the proper folding and packaging of the NPY peptide, and a substitution can result in a loss of directing activity of the signal sequence (5). This Leu7Pro polymorphism has been associated with variation in blood pressure (6), serum total and LDL cholesterol (7), serum triglycerides (8), and accelerated progression of carotid atherosclerosis in both obese healthy subjects (6) and patients with type 2 diabetes (9). Type 2 diabetic patients with the Pro7 substitution had a higher prevalence of diabetic retinopathy (10). Whether the Leu7Pro polymorphism is associated with diabetic nephropathy is not known. Therefore, the present study was undertaken in order to evaluate whether the Leu7Pro polymorphism of the prepro-NPY is associated with diabetic nephropathy, cardiovascular risk factors, or cardiovascular disease in a cohort of Finnish type 1 diabetic patients.
RESEARCH DESIGN AND METHODS
This study is part of the ongoing Finnish Diabetic Nephropathy (FinnDiane) study, a comprehensive, multicenter, nationwide project with the aim to characterize 25% (n = 8,000) of all adult patients with type 1 diabetes in Finland. In 1999, there were 1,700 patients in the FinnDiane database representing ∼5% of all type 1 diabetic patients in Finland. All patients with an ascertained renal status (n = 1,006) were included in the present study. These patients had been recruited from 20 referral centers. The patients were required to be C-peptide negative (<0.3 nmol/l) and to have permanent insulin treatment initiated before the age of 35 years and within 1 year of the diabetes diagnosis. Six patients with residual C-peptide secretion and four with evidence of nondiabetic kidney disease were excluded. Renal status was based on the albumin excretion rate (AER) in at least two of three consecutive overnight or 24-h urine collections or the presence of end-stage renal disease (ESRD). A total of 321 patients had normal AER (<20 μg/min or <30 mg/24 h), 166 patients had microalbuminuria (AER 20–200 μg/min or 30–300 mg/24 h), and 325 patients overt proteinuria (AER >200 μg/min or >300 mg/24 h). A total of 184 patients were classified as having ESRD and were either on dialysis (n = 44) or had had a kidney transplant (n = 140). Patients with normal AER were required to have had diabetes for >15 years to qualify for the study. Plasma NPY was measured in all normoalbuminuric and proteinuric patients (n = 76) with the Pro7/− genotype and in 164 age- and BMI-matched normoalbuminuric and proteinuric patients with the wild-type genotype. Information about antihypertensive treatment, lipid medication, and cardiovascular disease, including CHD, acute myocardial infarction, and stroke, was also obtained from medical records. The patient had CHD when there was a verified acute myocardial infarction, previous coronary artery bypass surgery or angioplasty, or permanent nitroglycerine treatment. Informed consent was obtained from all subjects participating in the study. The protocol followed the principles expressed in the Declaration of Helsinki and was approved by the local ethics committees of each center.
Serum and urine creatinine levels for calculation of creatinine clearance were measured at a central laboratory by a modified Jaffé reaction (Boehringer Mannheim, Mannheim, Germany). Urinary albumin concentration was measured with radioimmunoassay (RIA) (Pharmacia, Uppsala, Sweden) and serum C-peptide concentrations with a Human C-peptide RIA kit (Linco Research, St. Charles, MO). HbA1c, serum cholesterol, and serum triglycerides were locally measured using standardized assays in each referral center. The normal range for HbA1c was 4.0–6.0% in 75% of the local laboratories and the upper normal value was <7.0% in all centers, whereas the normal range for triglycerides was 0.4–1.7 mmol/l in 55% of the centers, the upper normal range was <2.0 mmol/l in 90% of local laboratories and <3.0 mmol/l in all centers. Serum cholesterol and lipoproteins were analyzed using routine standardized laboratory methods at each center. All local laboratories participated in a national quality assessment program. The estimated glucose disposal rate, which measures insulin sensitivity, was calculated according to a formula as suggested by Williams et al. (11). Plasma NPY was measured using a commercial RIA kit (EURIA-NPY; Euro-Diagnostica, Malmö, Sweden).
Prepro-NPY genotypes were determined by an investigator unaware of the phenotypes using the previously described method (7). Due to failure of the PCR, one patient remained ungenotyped.
Data are means ±SE or median (range) value unless otherwise indicated. Categorical variables were compared using the χ2 test or Fisher's exact test. Normally distributed continuous variables were tested with Student's t test, and non-normally distributed variables were logarithmically transformed or assessed with the Kruskal-Wallis or Mann-Whitney tests. Data were adjusted for HbA1c and BMI when appropriate. Pearson correlation coefficient was used to evaluate the correlation between the plasma NPY level and a continuous variable. To evaluate the independent association between categorical or continuous variables, a multiple logistic or linear regression model was used with a means substitution of absent data. Analyses were carried out using a Statistica 4.1 statistical package (Tulsa, OK). A P value <0.05 was considered statistically significant.
The clinical characteristics of the study population are shown in Table 1. A more detailed description has been previously reported (12).
Patients homo- and heterozygous for the Leu7Pro genotype were pooled in all further analyses because there were only four patients homozygous for the Pro7 allele. The frequency of the Pro7 substitution was 10.9% in the patients with normal AER, 10.2% with microalbuminuria, 16.2% with proteinuria, and 13.0% with ESRD (χ2 = 5.48 and df = 3, P = 0.14). The Pro7 substitution was thus more common in patients with overt nephropathy compared with the patients with normal AER (χ2 = 4.00 and df = 1, P < 0.05). The genotype frequencies in all four groups were in Hardy-Weinberg equilibrium.
Patients with the Pro7 substitution had higher values of HbA1c, triglycerides, and BMI and a higher prevalence of CHD (Table 2). Since a majority of patients with ESRD had a renal transplant and were normoalbuminuric at the time of investigation, and since there may be a survival bias in this group, analyses were also performed without ESRD patients. HbA1c, triglycerides, BMI, and the prevalence of CHD were also significantly higher when ESRD patients were excluded (Table 3). In addition, total cholesterol was also higher in these patients, whereas the estimated glucose disposal rate was lower and insulin dose higher in females with the Pro7 substitution.
The plasma NPY was 111.5 ± 3.0 in those with the wild-type genotype and 110.3 ± 4.4 in those with the Pro7 substitution (P = NS). No differences were detected when males and females were analyzed separately. There were no differences when those with proteinuria and normal AER were analyzed separately or when the patients were divided into quintiles according to their plasma NPY (data not shown). The plasma NPY was 96.7 ± 2.7 in those with normal AER compared with 121.3 ± 3.5 in those with proteinuria (P < 0.001). There were correlations between plasma NPY and HbA1c (r = 0.24, P < 0.001), total cholesterol (r = 0.40, P < 0.001), LDL cholesterol (r = 0.23, P < 0.001), and serum creatinine (r = 0.51, P < 0.001). However, the correlation between plasma NPY and these variables were significant only when proteinuric patients were included in the analysis, but nonsignificant when only patients with normal AER were analyzed (data not shown).
In a multiple backward stepwise linear regression analysis, the Leu7Pro polymorphism of the prepro-NPY was independently associated with HbA1c (Table 4). Similarly, the polymorphism was independently associated with proteinuria and CHD in a multiple backward stepwise logistic regression analysis (Table 5).
In this study, the Pro7 substitution of Leu7Pro polymorphism of the prepro-NPY was associated with HbA1c, triglycerides, BMI, and total cholesterol. Furthermore, the Pro7 substitution was also independently associated with proteinuria and CHD in multiple regression analyses. We cannot exclude the possibility that an unknown polymorphism in close linkage disequilibrium with the Leu7Pro could be responsible for the results. However, experimental studies indicate that the Leu7Pro polymorphism influences the heart rate level, growth hormone, free fatty acid, insulin concentration, and plasma NPY (13,14), indicating that the polymorphism is potentially functional. There is a considerable variance in NPY levels during normal activities, and therefore differences in plasma NPY between genotypes have been observed only during standardized conditions, i.e., during cycle-ergometer exercise test, in healthy young subjects (13,15). This may explain why we could not detect any differences in the plasma NPY levels. The correlation between plasma NPY, serum lipids, and proteinuria is most likely explained by higher plasma NPY levels in patients with impaired renal function (16), since triglyceride-rich lipoproteins are a key feature of diabetic nephropathy (17). It is of note that the half-life of plasma NPY is rather short, only 4 min (18), which can also explain the lack of association between the polymorphism and the plasma levels. Furthermore, since NPY is present in the central and peripheral nervous system, kidney, and endothelium, it is possible that the effect is not mediated via plasma NPY.
Our patients with the Pro7 substitution had higher serum triglycerides, a phenomenon that was previously seen in preschool-aged boys (8). However, in our study the association was observed within the entire cohort, predominantly in females. A suggested effect of the Pro7 substitution on lipolysis has also been studied in healthy nondiabetic control subjects, where subjects with the Pro7 substitution had a lower free fatty acid level (19). This finding does not, however, contradict our results because free fatty acid levels do not appear to be an important determinant of triglyceride levels (20). The differences in triglycerides between the genotypes were observed when analyzed both with and without the patients with ESRD and after adjusting for HbA1c. At this point, how the polymorphism causes a potentially altered NPY effect on serum lipids is not known, although an altered triglyceride metabolism via specific stimulation of lipoprotein lipase has been suggested (21). The Leu7Pro polymorphism has also been suggested to alter the composition of the lipoprotein particles affecting the postprandial lipid metabolism (22).
The observed association between the prepro-NPY Leu7Pro polymorphism and HbA1c is a novel finding and was detected in both sexes, although the association was stronger in women. HbA1c was higher in those with the Pro7 substitution both when patients with and without ESRD were analyzed and after adjusting for BMI. It was also independently associated with HbA1c in a multiple linear regression analysis. The mechanism is unknown but could be due to differences in insulin sensitivity, although a recent study (19) did not show an association with Leu7Pro and insulin sensitivity, insulin secretion, or glucose metabolism. That study was, however, performed in healthy control subjects, whereas our study comprised type 1 diabetic patients with various stages of late complications. The association between HbA1c and the Leu7Pro genotype and its possible connection with insulin sensitivity is also supported by the fact that the estimated glucose disposal rate was lower and insulin dose higher in female patients with the Pro7 substitution. Interestingly, the association between the Leu7Pro genotype and insulin dose disappeared when it was adjusted for HbA1c, suggesting a possible link between Leu7Pro, insulin sensitivity, and HbA1c. Our results may indicate a role for NPY in the glucose metabolism, although the mechanisms need to be further investigated.
The lipid profile, BMI, and HbA1c may partly explain why there was more CHD and proteinuria in patients with the Pro7 substitution than in those with the wild-type genotype. This is supported by the outcome in a forward logistic regression model with proteinuria as dependent variable. When the variables most strongly associated with the Leu7Pro in a univariate analysis (HbA1c and serum triglycerides) were added to this model, the association between proteinuria and Leu7Pro was no longer significant (data not shown). However, the Leu7Pro polymorphism was independently associated with proteinuria and CHD in a backward stepwise logistic regression analysis with known cardiovascular risk factors as covariates. In this backwards model, Leu7Pro was independently associated with proteinuria although serum triglycerides and HbA1c were included in the model, thus suggesting that there could also be a direct effect of the Leu7Pro on the renal function. This is further supported by experimental studies showing that higher growth hormone levels increase the AER (23), which is interesting because the Leu7Pro polymorphism has been shown to increase growth hormone levels (14). Furthermore, in vitro studies have shown a possible link between NPY and atherosclerosis because NPY has been shown to stimulate vascular growth (24). NPY is also a potent vasoconstrictor of renal arteries (25) and decreases renal blood flow and glomerular filtration (26), which could indicate a direct influence on the kidneys contributing to the pathogenesis of diabetic nephropathy.
The association between the Leu7Pro and diabetic nephropathy was only seen between those with normoalbuminuria and proteinuria. The fact that there was no association between the Leu7Pro and microalbuminuric patients may be explained by the fact that these patients had a rather long duration of diabetes and, according to recent epidemiological data, there is frequently a regression toward normoalbuminuria in this phenotype (27). Consequently, these patients cannot necessarily be considered to have true diabetic nephropathy. The lack of association between the Leu7Pro polymorphism and those with ESRD could be due to a survival bias, since those with ESRD have a high mortality rate. This is further supported by the fact that the Leu7Pro was also associated with CHD and several cardiovascular risk factors in this study. Furthermore, any population substratification with respect to Finnish ancestral history is unlikely in this study because the prevalence of the Pro7 substitution and the main results did not differ when the southwest and "isolate" eastern regions were analyzed separately (data not shown), as suggested by Perola et al. (28). In conclusion, the Leu7Pro polymorphism of the prepro-NPY may contribute to the genetic susceptibility of diabetic nephropathy and CHD, possibly by influencing the glycemic control and lipid metabolism, in type 1 diabetic patients.
Clinical characteristics of 996 type 1 diabetic patients included in the study
Clinical characteristics according to the Leu7Pro polymorphism of the NPY gene in all patients
Clinical characteristics according to the Leu7Pro polymorphism of the NPY gene excluding ESRD patients
Multiple backward stepwise linear regression analysis with HbA1c as dependent variable when excluding the patients with ESRD
Multiple backward stepwise logistic regression analyses
This study was supported by the Finnish Medical Society, Samfundet Folkhälsan, Folkhälsan Research Foundation, The Wilhelm and Else Stockmann Foundation, the Perklén Foundation, and the Liv och Hälsa Foundation.
We acknowledge our laboratory technician Tarja Vesisenaho and research fellow Carola Saloranta for their skillful contributions. Finally, we acknowledge the physicians and nurses in each center participating in the collection of patients: Central Finland Central Hospital: A. Halonen, A. Koistinen, P. Koskiaho, M. Laukkanen, J. Saltevo, and M. Tiihonen; Central Hospital of Aland Islands: A-C. Blomqvist, M. Forsen, H. Granlund, and B. Nyroos; Central Hospital of Kanta-Hame: P. Kinnunen, A. Orvola, T. Salonen, and A. Vähänen; Central Hospital of Kymenlaakso: R. Paldanius, M. Riihelä, and L. Ryysy; Central Hospital of Lansi-Pohja: P. Nyländen and A. Sademies; Central Ostrobothnian Hospital District: S. Anderson, B. Asplund, U. Byskata, and T. Virkkala; Kainuu Central Hospital: S. Jokelainen, P. Kemppainen, A-M. Mankinen, and M. Sankari; Lapland Central Hospital: L. Hyvärinen, S. Severinkangas, and T. Tulokas; Mikkeli Central Hospital: A. Gynther, R. Manninen, P. Nironen, M. Salminen, and T. Vänttinen; North Karelian Hospital: U-M. Henttula, A. Rissanen, H. Turtola, and M. Voutilainen; Paijat-Hame Central Hospital: H. Haapamäki, A. Helanterä, and H. Miettinen; Satakunta Central Hospital: M. Juhola, P. Kunelius, M-L. Lahdenmäki, P. Pääkkönen, and M. Rautavirta; Savonlinna Central Hospital: T. Pulli, P. Sallinen, H. Valtonen, and A. Vartia; Seinajoki Central Hospital: E. Korpi-Hyövälti, T. Latvala, and E. Leijala; South Karelia Hospital District: T. Hotti, R. Härkönen, U. Nyholm, and R. Vanamo; Tampere University Hospital: I. Ala-Houhala, T. Kuningas, P. Lampinen, M. Määttä, H. Oksala, T. Oksanen, K. Salonen, H. Tauriainen, and S. Tulokas; Turku Health Center: I. Hämäläinen, H. Virtamo, and M. Vähätalo; Turku University Central Hospital: M. Asola, K. Breitholz, R. Eskola, K. Metsärinne, U. Pietilä, P. Saarinen, R. Tuominen, and S. Äyräpää; Vasa Central Hospital: S. Bergkulla, U. Hautamäki, V-A. Myllyniemi, and I. Rusk.
M.K.K., M.K., and U.P. hold stock in Hormos Medical (Finland).
Accepted November 4, 2003.
Received June 27, 2003.
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Diabetes Care Feb 2004, 27 (2) 503-509; DOI: 10.2337/diacare.27.2.503
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Industrial Building originally used by roofing products company. There are 2 buildings. Main, front building has new floors, paint in office area and 2 bathrooms. There are three grade level roll up doors. Rear warehouse has 2 dock high doors and a roll up door facing main building for easy transitioning between buildings. Racks and shelving to remain with building as well as storage trailer.


text:
Democratic group targets Republican…
Democratic group targets Republican congressional districts
By Sandra Emerson | semerson@scng.com |
The Democratic Congressional Campaign Committee is going after Rep. David Dreier's seat for the 2010 midterm election.
Because voters in the 26th Congressional District district have been trending Democratic, party officials are targeting Dreier, they said.
"Overall the DCCC is paying really close attention to … eight districts represented by Republicans currently that President Obama won last November and that have changing demographics," said Andrew Stone, Western Regional press secretary of the Democratic Congressional Campaign Committee – a Washington, D.C.-based organization that supports Democratic House candidates.
As of May, 40 percent of voters in Dreier's district are registered as Republicans while 35 percent are registered as Democrats.
One year earlier, the ratio was 42 percent Republican, 34 percent Democrats.
"The margin in the 26th in just over two years is under 11 percent and continues to decline. It's now less than that 4.83 percent," Stone said. "There's a trend that's continued."
Dreier, R-San Dimas, was first elected to Congress in 1980. San Dimas, Claremont, Upland, Glendora, Montclair, Rancho Cucamonga, La Verne, Covina, San Gabriel and Walnut are among the cities in the 26th District.
Officials from Dreier's office declined to comment for this story.
If Dreier managed to get re-elected in 2008 during one of the toughest races for the Republican Party, it is not likely a Democratic candidate can unseat him in 2010, according to Neil Newhouse, a partner with Public Opinion Strategies.
Dreier handily beat Democratic challenger Russ Warner 53 percent to 40 percent in the 2008 election.
The lowering number of registered Republicans does not necessarily mean the voters joined the Democratic Party, said Matt Schumsky, executive director of the San Bernardino County Republican Party.
Many voters who left the party became independent voters, he said.
But Democrats are encouraged by a demographic shift in Dreier' district.
Since 2000, the Hispanic population in the district has increased by more than 30 percent, and the Asian population has increased by 27 percent.
Both groups tend to favor Democrats.
Under any circumstances, unseating Dreier won't be easy, Pitney said.
"You have a longtime incumbent who is very good at raising money and who is not going to get caught napping," he said.
"If they couldn't take him out during a presidential election, which was the absolutely best possible circumstance for the Democrats, it isn't likely they can take him out during a midterm when things might not look as favorable," Pitney said.
sandra.emerson@inlandnewspapers.com
Sandra Emerson | Reporter
Sandra Emerson covers San Bernardino County government and politics for the Southern California News Group.
semerson@scng.com
Follow Sandra Emerson @ReporterSandraE

redpajama_set_name: RedPajamaCommonCrawl


We're cold. You're cold. Why not stop in for some Valentine's Day flowers, and check out our all-winter specials? And don't forget our free delivery and ordering services.
Posted on February 14, 2015 by S M and filed under Baby, Baby Food, Dairy, Flowers, Gluten Free, Grocery, Snacks, Specials and tagged Baby Food Dairy Baby Snacks Specials Grocery Gluten Free Flowers.


text:
Granuflo
Home » News » Granuflo » Californian Joins MDL Linking NaturaLyte, GranuFlo and Sudden Cardiac Arrest
Californian Joins MDL Linking NaturaLyte, GranuFlo and Sudden Cardiac Arrest
February 3, 2015 By: Steve Cid Granuflo
A California resident is the most recent complainant in the ongoing federal court battle against Fresenius Medical Care (FMC), the world's largest dialysis services and products company. Mr. Ronnie Miller, the Plaintiff, is the anticipated Administrator of the estate of Lula Brown, who died of sudden cardiac arrest in December, 2011, after a dialysis treatment at Davita-Tree Dialysis, in Fresno, California.
The complaint has been centralized along with over 2,200 other Fresenius dialysis lawsuits in MDL No. 2428 (Fresenius Granuflo/Naturalyte Dialysate Products Liability Litigation) in U.S. District Court, District of Massachusetts. A central complaint in the litigation is that the use of NaturaLyte and/or GranuFlo Dry Acid concentrates in dialysis treatments caused serious health problems, including cardiopulmonary arrest, and or sudden cardiac arrest resulting in death.
The complaint states that not only were the two products defective but that Fresenius, the Defendant, failed to warn the patients and the medical community of their defective nature until March 2012, after the results of an internal study had been anonymously leaked to the FDA, forcing an FDA recall.
NaturaLyte and Granuflo and sudden cardiac arrest
NaturaLyte and GranuFlo are acid concentrates, which when combined with a bicarbonate concentrate, make a dialysate, which is used in hemodialysis, a procedure used to cleanse the blood of waste products in patients with end-stage renal disease or kidney failure. According to the Master Complaint, the keys of dialysis are 1) removal of waste products from the body; 2) the promotion of electrolyte balance in the blood; and 3) the addition of bicarbonate to the patients' blood to correct acidosis.
Acetates are introduced into the blood during dialyses which are then converted by the liver into bicarbonate, a necessary component of the dialysis process. However, NaturaLyte and GranuFlo contain sodium diacetate (two acetates), whereas other dialysis products contain only one acetate. The two acetate molecules in NaturaLyte and GranuFlo are then converted into two molecules of bicarbonate which, for dialysis patients, is a dangerously high level of bicarbonates in the blood, a condition called alkalosis. Alkalosis has been determined to be a significant risk factor for cardiopulmonary arrest.
Internal study of NaturaLyte & GranuFlo and sudden cardiac arrest leaked
The problems with the products came to light as the result of an internal study done by Fresenius in 2010 as a response to 941 incidents of cardiac arrest in 667 FMC-owned clinics (FMC owns its own clinics and sells dialysis products and equipment to other independent operators). The study found a risk factor of sudden cardiac arrest six times higher than expected if the patients received treatment with either NaturaLyte or GranuFlo if they already had higher than normal bicarbonate levels in the blood.
In November 2011, a year later, Fresenius distributed a warning to health care professionals in Fresenius-owned clinics to exercise extreme caution when using GranuFlo in hemodialysis treatments because of the findings of the 2010 study. It did not, however, issue any warning to non-Fresenius clinics and the 100,000 dialysis patients receiving treatment with NaturaLyte and GranuFlo in those clinics.There are currently more than 5,700 dialysis centers providing service to approximately 400,000 dialysis patients in the United States.
FDA issues recall linking NaturaLyte, GranuFlo and sudden cardiac arrest
On March 2, 2012, an anonymous complaint to the FDA raised concerns about elevated bicarbonate levels and NaturaLyte and GranuFlo dosage errors causing cardiopulmonary arrests after dialysis treatments. The internal November 2011 memo to Fresenius-owned clinics was also leaked to the FDA.
As a result of the FDA's new knowledge of the serious problems associated with NaturaLyte and GranuFlo, Fresenius Medical was forced to issue an "urgent product notification" on March 29 to all non-Fresenius owned clinics informing them of the significant risk factor of alkalosis and urging a high level of judgment when treating dialysis patients with the two products.
At the same time, the FDA issued a recall of Granuflo and NaturaLyte products, which the FDA upgraded in June 2012 to a Class I Recall. This type of recall is reserved for products in which there is a "reasonable probability that the use of or exposure to a violating product will cause serious adverse health consequences or death".
The first bellwether trials in the Fresenius MDL are expected to begin in January 2016.
New York Times, Dialysis Company's Failure to Warn of Product Risk Draws Inquiry, http://www.nytimes.com/2012/06/15/health/fda-investigates-fresenius-for-failure-to-warn-of-risk.html?_r=0
Glasgow Daily Times, Suits Filed Over Dialysis Product, http://www.glasgowdailytimes.com/news/suits-filed-over-dialysis-product/article_22247c42-5bfa-11e4-95f8-571b55b328d6.html


Some really interesting flora in this area.
These little guys are totally all about frogs.
The pointy one is floating above the base below it.
Those suckers were so weird!
The sun. I love the magic lines.
One of the small outposts in this zone.
Loved this cool gadget they had in the center of the outpost.
Cool observatory at the outpost.
This building had such a neat interior too. Loved this little place.


The CNT-Scan MiniModule is a high-precision measurement module for frequencies up to 300 kHz, for measurement of duty cycles/PWM signals, cycle/pulse duration measurement as well as event counting.
Speed measurement (RPM) is calculated directly in the module and displayed as value on the CAN bus. Additionally, the time/event offset between adjacent channels can be measured. The inputs are completely electrically isolated and connected sensors can be powered directly from the module. Each measurement mode requires only one signal input, however, one signal input can simultaneously collect two measurement parameters from the same physical signal - thereby allowing for up to 8 logical channels.
User selectable per-channel triggering for On and Off signal levels is supported. The On-/Off-Trigger thresholds are individually adjustable for each channel. Switchable AC coupling allows for suppression of undesired DC offset of the input signal.
High frequencies as well as low frequencies are automatically captured with constant high accuracy. This applies also to short and long periods and pulses.


MANILA -- Secretary of State Rex Tillerson laid out the most specific preconditions yet for U.S.-North Korea talks, soon after the United Nations Security Council adopted the largest economic sanctions package ever against the regime.
The regime must stop missile launches, Tillerson told reporters in Manila. Though the administration has still not ruled out a preemptive military strike against the North, talks are the preferred option to convince North Korea to completely halt its nuclear program. Tillerson did not specify how long the missile launches would have to be suspended as a precondition to launch talks.
"We will know it when we see it," he said. "If they can demonstrate they are ready to sit with the spirit of finding a way forward in these talks by no longer conducting these missile tests -- so this is not a 'give me 30 days and we are ready to talk' -- it's not quite that simple."
These preconditions provided some context for Tillerson's comments on U.S.-North Korea talks earlier this year.
"North Korea must take concrete steps to reduce the threat that its illegal weapons programs pose to the United States and our allies before we can consider talks," Tillerson said at the U.N. in late April.
The secretary of State has repeatedly said that sitting down with North Korea would benefit the regime. He said dialogue will lead the regime to "feel secure and prosper economically." Two days earlier, the U.N. had voted on its strongest sanctions ever against the North after it launched two intercontinental ballistic missiles in July. The sanctions prevent North Korean exports of iron, lead and seafood. The U.N. says the measures will cost the North over $1 billion a year in hard currency. And they will also ban countries from green-lighting the admission of more North Korean laborers, who are said to economically fuel the country's illicit programs.
North Korean workers, who allegedly send their earnings to the regime, have been mentioned by Tillerson in the past. And he talked about them again during a lunch meeting with Japan and South Korea. He reiterated the intention of the U.S. to urge countries in Africa, Asia and the Middle East to stop utilizing North Korean contract labor.
"What we tell people is to stop supporting the regime and let people return home," Tillerson said. "This is a human rights concern because of the unfair treatment, trafficking conditions and misuse of wages."
Tillerson has also been mulling what actions the U.S. should take in response to Russia's expulsion of a large number of American diplomats in Russia. The U.S. will have a response by Sept. 1, he told Russian Foreign Minister Sergey Lavrov in their meeting on the sidelines of the ASEAN ministerial meeting. Tillerson asked Lavrov "several clarifying questions" about the decision, which was announced soon after the passage of sanctions legislation targeting Russia, which neither Tillerson nor President Trump support.


This project was sponsored by ETI Technologies and it first appeared last year on Resin Crafts Blog. All the opinions and wording is mine alone. To see more information on sponsored posts please see my Disclosures page. There are also many affiliate links in this post which means if you click through and purchase something through those links I get a small commission at no extra cost to you. Thanks for reading!
For this project you'll follow the mixing steps for EasyCast which are included in the package. First, be sure that you applied two coats of mold release and conditioner spray to your mold. Then mix the EasyCast parts A and B as instructed. For some of the pieces, I used my previously made Skull Mold as well, but that is not required.
Pop the bubbles with a micro-butane torch .
After it is poured and the bubbles are popped, let the pieces cure for at least 24 hours, perhaps longer. Remove the castings from the mold once it has cured.
Spray five of the pieces with the Envirotex Resin spray to make them nice and shiny. Paint the other five pieces with black paint.
Spray paint the 12″x12″ tile with metallic silver spray paint . Use washi tape to create your grid. There you have it! A fun DIY Halloween Tic-Tac-Toe Game for your coffee table that is both decorative and fun to play! Instead of X's and O's you have black and clear game pieces. So much fun!
**Another EasyCast project with full tutorial can be found here: Resin Flower Paperweight.
I hope you like this DIY Halloween Tic-Tac-Toe game! I had so much fun making it! What do you think? Let me know in the comments.
If you like these projects, please pin this image to Pinterest!
Sheri has been creating all of her life in various ways and finds great purpose and empowerment in creating something new. When she's not in the workshop or craft room she is making memories with her husband, four kids, perfect dog and ornery cat.
What a cute idea! I haven't tried working with epoxy yet, but love to dabble in crafts every now and then. I would love to try this out in a non seasonal theme to let it last all year long, too. Thank you for sharing!


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Who are you trying to please? The answer to this question defines our priorities and purpose, as well as our sense of peace. Looking back, the answer transformed beautifully as I drew nearer to God.
God made His home with me in high school.
Throughout my childhood I had developed into an extreme perfectionist, striving to succeed in every area of life with the utmost pride.
A quiet arrogance rested on my spirit.
However, by God's grace, I was introduced to Jesus Christ by a friend.
The Holy Spirit quickly stirred up awe in my heart over His flawless life, sacrificial love on the cross, and stunning resurrection.
I realized that I was far from perfect—a soul separated from God by my wilful disobedience.
Although I may have appeared to my community as a "good girl" on the outside, achieving high marks in academics and athletics, on the inside I recognized my jealous, critical, and selfish thoughts and my moral failures.
I knew I needed forgiveness from the Maker of the Universe. Placing my trust in Jesus was the Way.
What was I free from?
The slavery of sin, of worshipping my merits instead of my Creator.
I was free from living in darkness, away from the love, truth, and kindness of God.
Lastly, I was free from meeting the world's expectations, because Christ's love had made me a worthy child of God.
I soon learned I was to do all things for God's fame, not my own.
My actions should lead to people seeing Him instead of myself.
All I had—intellect, athleticism, esteem—was truly His, undeserved blessings He had graciously given.
More than that, those blessings, which everyone so treasured and praised, were no longer to be my identity.
My worth was no longer defined by my performance, but in my faith in Jesus as my Savior.
Despite being washed in the good news of Christ, I still had a lot of room to grow.
God had led me to Cornell, but my faith would be put to the test.
I quickly succumbed to the pressure to pursue a well-respected career, and to promote liberal ideas from pop culture and evolution that didn't match up with the Bible, God's trustworthy Word.
I justified many of my ambitions for the future by saying it was for God, and yet secretly I retreated back into the prison cell of perfectionism.
Perfectionism is a prison cell. Only Jesus offers freedom.
Crushed by low grades and desperate to impress my peers, I did not center Jesus in the picture at all.
A nice afterthought in times of trouble, He was part of my motivation but definitely not the whole.
I eventually played with the idea of doing health work abroad, or jumping into journalism, simply so I could wander around the world.
In the midst of this, I had joined the Christian group on campus called Cru.
That God-honoring community encouraged me to share the gospel without shame, and I was eager to serve.
At that point, however, I wasn't fully examining my self-centered heart and the dangerous division within it.
Amazingly, in the midst of all that, a Christian young man expressed interest in me.
A man who was slowly but surely being called by God to leave the Ivy-League norm.
Initially I was doubtful about his pursuit.
I rejected the poor man multiple times, and yet they were conflicted and half-hearted no's.
While holding onto dreams of travel and independence, I admired his strong godly convictions and how he treated me with great care, humility, and respect.
As his love deepened for me and showed itself with incredible patience, faithfulness, and hope, my walls faded fast.
I agreed to start a relationship, knowing the goal was marriage but immaturely pushing it to the back of my mind.
I had begun this commitment, but my career aspirations remained the same.
One month into our courtship I went to Peru for a public health internship.
The only Christian in a group of 6 interns in a foreign country, for the first time I was isolated spiritually—no church or fellowship.
This is when I began studying the Scriptures on my own in depth for the first time.
After discouraging days working at a medical clinic, I would spend hours on our apartment's roof, reading through the New Testament, praying, and singing to my Savior.
The gospel's imprint on my heart intensified, and I discussed it with Isaias over Skype, falling further in love with the Lord and the man who listened.
After this and a semester at Cornell, I also decided to study abroad in Thailand, thinking I could fulfil my travel itch while Isaias did a semester internship away from campus.
And in the end, these two international experiences had unexpected results.
First of all, living abroad was not all roses and butterflies.
I enjoyed the vibrancy and novelty of the Hispanic and Asian settings, but also faced trying times.
The Lord used homesickness, culture shock, lack of Christian community, and encounters with a very broken, evil world to open my eyes.
The organizations I worked with had good intentions and helped people's physical needs, but I yearned to do more.
I longed to not only provide temporary solutions for the patients, villagers, and students we served, but to share with them about their loving Creator.
Instead of being inspired to be a travel journalist, I struggled in these foreign lands and especially missed Isaias.
If I were to be abroad, I thought, it would have to be as a missionary with him.
I wrestled with these revelations once Isaias confided with me his desire to be a pastor, potentially making me a pastor's wife.
Here we were, two Cornellians considering what it would mean to let go of the typical Ivy League track.
What would our families and friends think if we went into ministry?
I encouraged him to listen to the Lord, while at the same time clinging to others' expectations and the remnant of my desire for self-glory.
If I chose to marry Isaias and follow his lead, my primary priorities would be to support his ministry and to raise our children—God's design for the marriage relationship between man and wife.
Graduate school, big city living, more travel and a high reputation would all take the back seat, be up in the air, or simply not be options.
The question I asked in the beginning popped with more weight than ever before… Who was I trying to please?
My pride hungry heart? My peers and parents?
Or God, the One who had died to make me His?
To answer, I looked to God's words.
While I didn't necessarily want to be wealthy, I was tempted by the desire to be known and respected by the world's standards.
1) Marriage to Isaias, a man God had so preciously placed in my life and whom I would love to serve alongside for God's Kingdom.
2) A life of glamour, self-pride, and comfort, but a weak walk with God and a solo, tiring pursuit of worth apart from Christ.
I, again by grace, decided to let God establish my steps.
Today, I'm wed to Isaias – a wonderful man of God, and we have a beautiful baby girl.
Nowadays most ladies are pushed to pursue a career.
Even those with Christian parents are told to use the gifts God has given them in the workplace.
2) that homemaking is boring and wastes her talents.
What many miss, and what the Scriptures have pointed out to me, is that the responsibility of raising children in the Lord is selfless, wondrous and rewarding work, and taking on the Biblical role of helping your husband is very much linked to the home.
When you see in God's Word about how He defines femininity and womanhood, it's so precious.
The Proverbs 31 woman actively has her hands at work, being an entrepreneur and teacher in her own way for the household.
Her gifts, drive, and dedication display themselves in sacrificial work on behalf of her family and community.
She is raising the next generation in godliness.
Her husband and children trust her deeply.
In the end it is not beauty or accomplishments that define her, but her devoted fulfilment of God-given responsibilities.
I understand why many women shy away from this design because it is super, super humbling to work at home, especially because our culture belittles the "housewife".
I had developed so much pride in my achievements, and the thought of settling down once seemed like giving up.
Many people wonder why I'm back in my small hometown, when I went to an Ivy League school.
It's easy to get disheartened, but I'm reminded that the Lord's work is the most noble of all.
Who are you serving: yourself, earthly ideals, or our heavenly God?
Who are you serving: yourself, earthly ideals, or our heavenly God? Choose God.
Dani is a current seminary wife, young stay-at-home mommy and recent Cornell alumna eager to share how freedom and truth beautifully come together in Christ! Join her at her blog, Free Indeed, to discover the love Jesus so graciously gives us, both in the everyday and extraordinary and to explore His Word through deep devotionals, faith-filled fiction, personal tales, and colorful photography. Read her newest FREE eBook, Abiding in the Vine: How to Dwell Deep In Christ, by signing up for her weekly newsletter.
The distinction, I've learned, is between listening to what others have to say and letting them have full control to run your life!
Edmund, it is definitely true that we must take counsel and consider others in our actions! Thanks for sharing your experience. The premise of this story was not to discount that truth, but to show the surpassing worth of knowing Christ (Philippians 3:8). The life we now live is for Christ, in obedience to His Word! We must not be controlled by anything except our love for Jesus. God Bless!
What an honest post! This has been a blessing to read and will bless many Christ loving women. In a world where your worth is based on your career, where you've been, and how much you have, it is encouraging to read how Christ can transform us into living a Christ-centered life where HE brings us into HIS vision of worth as we are obedient to HIS calling. Thank you Dani for sharing a honest piece.
Thank you so much for your feedback, Veronica. You're right – Dani's post is such a blessing – so honest and so challenging.
Thank you for reading Veronica! You worded it perfectly; God is indeed so gracious and powerful in drawing us to Himself and His purpose, away from the world. God Bless!
Wow! Thank you for sharing. I too have been transformed. HE lives within me! All Glory be to our God most high!
Praise the Lord you've experienced His grace! What freedom we have in Him! Blessings, Jerri!


Today was the big day for the new RV-10 project. Where the -9A empennage was delivered by UPS in two cardboard boxes, this one was delivered by ABF and the boxes looked almost like the wing kit.
Here are some of my contract laborers. They are ready to get started. They sort of know what to expect, too, since we just did all of this. One of the first things they said after opening the boxes was "yes, the famous blue plastic is back" referring to the plastic film that all of the alclad surfaces are shipped with.
It didn't take long for me to get the boxes opened up. I got a volunteer to help with the inventory list and before long we were checking off each of the items in the kit.
Dude, these are big skins. The tail of this plane is going to be huge. I've seen several of these planes up close, and the sense I've gotten is that they're big RV-9s. There are plenty of differences though, and I'm going to have to pay attention so I don't mess something up.
Here's an interesting, and welcome, development. In past kits all of the rivets and hardware were shipped in brown paper bags with nothing more than a bag number on the outside to identify it's contents. I remember a while back reading about Van's getting a new bagging machine, and boy is it cool. Each bag has it's contents clearly labeled on the plastic. Not only that, the bags are transparent, making it much easier to do the inventory.
I already have lots of rivets left over from the -9A, so I refilled my rivet bottles and put the rest of the rivets away for safe keeping.
An hour or so of sorting and organizing and I had another nicely labeled organizer. My wife likes to make fun of the way I label everything. I even put a label on the labelmaker, which is really funny to her for some reason. Maybe I should put a label on myself as "Goofy RV Builder."
Here's another new development: no more instruction book. Everything is spelled out on the newer, smaller, plan set. These are on 11x17 paper and the steps they want you to complete are listed right next to the images of the parts. While this is unsettling at first, I think I'm going to really like this configuration. It should make searching for the right plans page a thing of the past.


text:
Centrochria deprensa is een vlinder uit de familie spanners (Geomteridae). De wetenschappelijke naam van deze soort is voor het eerst geldig gepubliceerd in 1913 door Prout.

De soort komt voor in tropisch Afrika.

deprensa
Dier uit het Afrotropisch gebied

redpajama_set_name: RedPajamaWikipedia


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text:
'Homelessness and the three faces of poverty': HPH lecture on 9th June, central London
June 3, 2015 June 6, 2015 Jon Kuhrt
Hugh Price Hughes was an energetic and enterprising Methodist Minister who founded the West London Mission in 1887. He was a proponent of what he called 'Social Christianity' which was in contrast to the Christianity he saw around him, which in his words has 'been too speculative, too sentimental, too individualistic.'
His founding of the West London Mission embodied his desire to see the Christian faith have a social and political impact and to be 'applied to all aspects of life'. Right from its start, as well as having thousands come to its weekly services, WLM established a soup kitchen, a food depot, a clothing store as well as a labour exchange for the unemployed and a 'Poor Man's Lawyer'. Later they would establish the first ever Creche for working mothers and open hostels for unmarried mothers who had to leave home.
Today, WLM employs over 70 people in a wide ranging work with people affected by homelessness, addictions and offending. It is my privilege to lead this work.
Three faces of poverty
Every year, a series of lectures is held in memory of Hugh Price Hughes at Hinde Street Methodist Church, where WLM is now based.
I will be giving the closing lecture in this year's series on Tuesday 9th June. I will be speaking on 'Homelessness and the three faces of poverty'. I will be talking about how homelessness in the UK embodies the fusion of these three faces of poverty and how this needs to inform our practical, political and theological response.
The lecture starts at 7.30pm on Tuesday 9th June and is at Hinde Street Methodist Church, London W1U 2QJ which is 5 minutes walk from Bond Street tube.
Entrance is free and everyone (but especially R&R readers) are very welcome!
See here for all details.
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This 1925 Wisden was recently rebound in brown boards with the title and year in gilt to the front board and spine..
The binding is in fine condition.
Both wrappers are retained and are in very good,bright , condition with no marks or blemishes.


text:
Home NEWS Ballinasloe Christian Fellowship granted permission for new place of worship
NEWSPROPERTY
Ballinasloe Christian Fellowship granted permission for new place of worship
Ballinasloe Christian Fellowship have been granted permission to use an existing building as a place of worship and local youth centre.
Galway county council gave permission for the converted use of the building in Dunlo township, Ballinasloe.
Council planners carried out an inspection of the site earlier this month and raised no objection to the application.
Operating hours on Sunday morning and Wednesday evening should be agreed with the planning authority before the centre opens.
No music or other amplified noise can be broadcast into the street, or in such a manner as to be a nuisance to neighbours.
It was also stipulated that no signage or advertisement structures outside of what was contained in this application can be put up without a further grant of planning permission.
Plans for the place of worship were first submitted to Galway County Council by the Ballinasloe Christian Fellowship in late July.
Galway county council gave permission for the planning application with a total of four conditions attached.
Ballinasloe Christian Fellowship


Section 113 of the South African Companies Act No. 71 of 2008 ("Companies Act") regulates the proposals of amalgamations or mergers of companies in South Africa. The Companies Act provides that amalgamation or merger can be proposed between two or more profit companies including a holding company and its subsidiary companies.
A proposed amalgamation or merger can only be given effect to if the board of each amalgamating or merging company considers whether, upon implementation of the amalgamation or merger, each amalgamated or merged company will satisfy the solvency and liquidity test.
If the board has a reasonable belief that the proposed transaction will satisfy the solvency and liquidity test, it may submit the agreement for consideration to the shareholders at a shareholders' meeting for final consideration.


I am serious CityTV. I am absolutely horrified by your choices of judges for Canada's Got Talent. Who the hell are these people? Nothing against them personally, as I am sure they are very nice individuals, but COME ON.
Dan Levy would have been perfect. ABSOLUTELY PERFECT for the role of one of the judges. And I am pretty sure he would have taken the job, as he isn't doing anything major right now (I swear...the Hills ending was the best and worst thing ever).
But instead of Dan you pick Martin Short and 2 other people I have never seen before. I mean, we have all heard Stephan Moccio's Olympic anthem I Believe (...and I believe most people will off themselves if they ever hear it again), but I have never actually seen him.
The last judge is Measha Brueggergosman. Once you get over the fact that NO ONE is going to be able to pronounce her name...you then land on the fact that she is an Opera singer. Clearly she should be on the panel because everyone listens to Puccini on the daily and Opera is the new Rap. Eye roll.
And then of course the host is some person from Breakfast Television in Toronto...don't even get me started.
Agh. I need to go sleep off this devastation.


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Dedicated to unappreciated care partners worldwide. Thank you for all you do.
Yes; I know. I know what you think.
But you know little of me and/or the situation in which my care partner and I find ourselves. You think you do, but you don't. Pretty much the only people who get it are those who have been through it, and you clearly haven't otherwise you wouldn't say the things you do and I wouldn't need to write this letter to you.
I either live with my care partner or I visit her/him almost daily. I spend endless hours and fleeting moments with him/her talking nonsense and singing and just being together, because one day soon s/he will be gone. Every minute with him is torture; every second with her is precious. I know by the way s/he rocks back and forth when s/he wants to get up and get moving, and by the look on his/her face and the feel of her/his hand in mine if s/he is able to stand unassisted. Mostly s/he's not, so I am by her/his side whenever I can be. When s/he is able, we shuffle around wherever we happen to be to get some exercise.
I know by the way she pats her hair that she loves the fact that it's "done." I know the colour and brand of her nail polish because I supply it. I know when she had her last manicure because I was the one who gave it to her.
I know by the way he touches his face that the cut just above his left brow worries him. I know the kind of aftershave he prefers, so I buy it to help him know he's the same man he used to be: the man who was and still is the love of my life. I know by the way he reaches out to me when I'm near that my presence is important whether he recognizes me or not.
I know when his/her sleep is unnatural by the slackness of his/her mouth and the rhythm of his/her breathing. It breaks my heart that s/he is being medicated for normal behaviour which could be addressed and resolved without drugs. I can't change that; I would if I could.
What I can change is a soiled adult brief, and I do so often. No one showed me how. I figured it out myself, just as I've learned everything else I wish I'd never had to learn about being a caring partner to someone who lives with dementia. I didn't asked for this. I never wanted it. But here I am. What can I do?
I recognize her wheelchair by the stain on the seat. When she can't feed herself, I help her to eat like she helped me when I was a baby. When she's able to eat by herself, I celebrate a small victory. I help her engage with her shrinking world, not simply exist in it.
I see her/him in ways you can't even begin to imagine. We are reflected in the mirror of each other. I have cried with her/him, comforted her/him and felt the sting of her/his acid Alzheimer's tongue. I pray for her/him to stay and go. I watch her/him look death in the eye and grab life by the horns every day despite her/his illnesses. I am her/his cheerleader, her/his advocate, her/his voice. I am her/his child/parent/spouse/sibling. Our souls are linked; our destinies are intertwined. We are more deeply connected than we have ever been.
Who are you? You are a casual observer making ill-informed assumptions and coming to erroneous conclusions based on incomplete information. You mean less than nothing to me. My care partner means everything to me. I have experienced first hand the effects of decisions I'm told are in his or her best interests, but which in reality have little or nothing to do with her/his health and well-being and everything to do with convenience, reducing costs and conserving her/his wealth for someone else's use once s/he's gone.
The effects of the decisions in which I have no say include the cuts, bruises and other conditions about which you feel compelled to apprise me. Your thoughtless and insensitive comments add salt to other wounds you cannot see. You don't know me. You don't know my circumstances. You don't know my parent/spouse/sibling/child although you may think you do, and because you think you do you also think you have a right to judge me or her/him or the situation in which we find ourselves.
The next time you feel tempted to comment, judge, berate or advise me on aspects of my care partner's condition or my role in her/his life, please consider all of the above and mind your own business instead of mine.
I don't need or want your judgment or your unsolicited advice.
I cannot thank you enough for this forum, you get it! A life no one understands until they have walked it. I smile and nod when people that have no idea give advice. Little do they know I'm hanging on by a thread.
So touching and sadly, so true.
This is the attitude i have worked relentlessly for 35 years to change – that malignant philosophy of care that is nothing more than neglect pure and simple – the ageist, stereotypical, cruel, inhumane attitudes that others feel they know better must cease, so our population living with dementia are treated with the respect and value they deserve.
Every single person is an individual in their own right. We are all a product of our own personal life transitions. Thus, if we do not know the person beyond the condition, there is no way in the world we can truly care for them in a way so they may continue to live life in an uplifting, joyous way, thrive, blossom, and not be plagued by the loneliness and despair poor care creates.
Maintaining personhood, and the place each person holds in the world, maintains life!!!!
"Every single person is an individual in their own right. We are all a product of our own personal life transitions. Thus, if we do not know the person beyond the condition, there is no way in the world we can truly care for them in a way so they may continue to live life in an uplifting, joyous way, thrive, blossom, and not be plagued by the loneliness and despair poor care creates.
Loved this Susan! I couldn't have said it better myself.
If a non-caregiver walked just a 1/2 block in a caregiver's shoes, they would be astounded.
Made me cry. So very true, so very poignant. Yes, all my siblings mean well, especially when they give me brilliant ideas about how to make my parents' life more "fun" – take them to movies! Go for ice cream! Yes, nice ideas, just not that easy in reality. I appreciate their love and support, and sometimes don't know how to stress how complicated caregiving is, without sounding like a wanky whiner. Which I'm not. Thanks for pointing this out, and for putting it in the right perspective. I've never come across people openly critical of my caregiving, but I can sense that it would be horribly cruel – what right have we to judge others? We've become such a bullying, critical society that it behooves everyone to look very closely in the mirror.
Thanks Lorrie, I'm glad the post touched your heart. It's exceedingly difficult for non-caregivers to understand what it's like to be the primary care partner to someone who lives with dementia. It may even be impossible. It's gratifying to know that some people try.
However, online forums and support groups are rife with care partners whose family members either do not participate in giving care, who do not support the primary caregiver, and even, sadly, who actively try to make the primary caregiver's job harder than it already is. I know it sounds inconceivable that people should do that, particularly family members, but it happens. This places additional stress on care partners, who, as you know from your own experience are already stretched beyond most people's capacity to cope.


Pravin Gandhi has authored a 14-part column on Software Products Marketing, in the Express Computers magazine.
Right-Brain person, often at the same time.
Pravin Gandhi worked at Tata Consultancy Services for 15 years, a journey that took him from programmer to Head of Software Products Group. He was responsible for the creation and marketing of several software products from the TCS house.
participating in international exhibitions; creating marketing communication.
Since then he has been an entrepreneur; and Software Products & Marketing Consultant. In 1998, he created the personal investment software nVEST. He has been consulted for executive information systems; E-Learning; intranet applications; Company and Product Positioning; Branding; and creating Multimedia CD-ROM communication.
Pravin Gandhi has considerable experience in creating branded software products. He has created 2 of the 3 Best Buys (CHIP Magazine Apr' 2000).
Communication Skills and Personality Development Workshops.
Pravin Gandhi is a Mechanical Engineer from V.J.T.I., Mumbai, and Master of Science in Industrial Engineering from Georgia Tech, Atlanta, USA.


Here are pictures of two palettes I use. The smaller one with the paint built up that looks like a bunch of Giacometti figures is used in a little room in the house with a small north light for still life painting when I think I need intense light. The bigger one is the one I use in my studio where the light in more diffused and is about two years old so the paint hasn't built up yet.. I clean the palette after I paint but I don't remove the colors from the edges and it builds up over time. The palettes look cool grey in terms of color but are actually warm grey of a middle value-the cool north light is on them in the pictures.
Laying out a palette in words is more complex than laying one out in paint because I have to think about things as compared to when I am painting; there I am just sort of reacting to what is in front of me or in my mind. But here is a try anyway.
Most of my paint is Winsor and Newton because I have become used to the particular hues over many years, especially yellow ochre and raw umber, which seem to have more variation between producers. I always seem to have yellow ochre, naples yellow, cadmium orange, ivory black, raw umber, raw sienna, burnt umber, ultramarine blue, cadmium red, alizarin crimson and English red light, which is made by various manufacturers and which I prefer as my general flesh red. Burnt umber, cerulean blue, cobalt blue, manganese blue, and cadmium yellow light are nearby but not always laid out on the palette. I also will use some of the Williamsburg colors of various shades at times but evidently not too often as a tube lasts for years.
I can't settle on green. For years I always had sap green on the palette but now it has been replaced with Viridian. But I also use sap green, permanent green, cadmium green light and Terra Verte. I also mix many of the greens.
I have used Cremnitz white exclusively. I like Old Holland and Winsor Newton equally in that white.
Also nearby are some tubes of old paint that the painter Charles X. Carlson gave me. He died in 1990 and most are very old. Many don't have labels and there are some odd reds and yellows that I don't recognize but use at times. I also have some of the pigments that Charlie got from the printmaker Luigi Rist and I will use them at times. None are marked as to their official color and they seem to be different than the hues I usually use.
Finally, I have a number of pigments I bought at the Sennelier shop in Paris with the green storefront that is across the Seine from the Louvre. Most are earth pigments with funny names. What a place! Ghosts of everyone from Manet to Picasso and Matisse are there.


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Sword Art Online the Movie Ordinal Scale Blu-ray
There's limited quantity of Sword Art Online the Movie Ordinal Scale Blu-ray available at this price. Order now before they're gone!
4.5 star rating out of 5
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Not Eligible For Promotional Discounts
Description After its overwhelmingly successful worldwide theatrical release, Sword Art Online the Movie -Ordinal Scale- makes its debut on Blu-ray and DVD! The ...
About Sword Art Online the Movie Ordinal Scale Blu-ray
After its overwhelmingly successful worldwide theatrical release, Sword Art Online the Movie -Ordinal Scale- makes its debut on Blu-ray and DVD!
The NerveGear, the world's first dedicated full-dive device developed by the genius programmer, Akihiko Kayaba in 2022…a revolutionary machine that opened up infinite possibilities for the world of VR (Virtual Reality). 4 years later…. A next-generation, wearable multi-device called the Augma has been released to compete with the NerveGear's successor, the Amusphere. A cutting-edge machine boasting the ability to enhance AR (Augmented Reality) to the maximum, the Augma offers a safe, user-friendly experience, as it can be used while the player is awake, making it an instant hit. Its most popular title is an ARMMORPG developed exclusively for the Augma, "Ordinal Scale (a.k.a. OS)."
Kirito is about to join Asuna and the others as an Ordinal Scale player, but they're about to find out that it isn't all fun and games…
Special Features: Audio Commentary by creators and Japanese cast: Tomohiko Ito, Shingo Adachi, Reki Kawahara, Yoshitsugu Matsuoka, Haruka Tomatsu, and Sayaka Kanda, Special Short Animation: Sword Art OFFline -Ordinal Scale-.*
*Special Features subject to change. Includes English subtitles.
Due to licensing and contract restrictions, this product can be sold and shipped to the US, Canada, South America and Central America only. This product cannot be shipped to Japan. All sales are final. It may be returned for an exchange if defective, but unfortunately we are unable to offer refunds.
Ordering Note: All sales for this item are final. It may be returned for an exchange if defective, if a replacement is not available a Gift Card will be issued.
DetailsPublisher: ANIPLEX OF AMERICAMedia: Blu-raySpoken Language: English, Japanese
Publisher: ANIPLEX OF AMERICA
Media: Blu-ray
Spoken Language: English, Japanese
Subtitle Language: English, Spanish
Themes: Adventure, Battles, Video Games
Age Rating: 16+
Run Time: 120
Dimensional Weight: 1
Region Code: A
Shipping Info All Canadian and International orders are held until all items are in stock. For domestic orders, If an order is placed with in-stock items as well a...
All Canadian and International orders are held until all items are in stock.
For domestic orders, If an order is placed with in-stock items as well as pre-order or back ordered items, the order will remain unshipped until all products are in-stock with the following exceptions:
If you have another order that is fully in-stock, when we process that order, we will occasionally ship all products that are available on ALL of your orders with this shipment.
Our system will occasionally release domestic orders for partial shipping based on our order volume, usually 50% of your products have to be in-stock, however when this occurs it will pull in-stock products from your other orders if applicable.
Generally, the rules stated above are followed, however we reserve the right to partial ship at any time. Therefore, if you are wanting something shipped immediately it is recommended to place separate orders for your in-stock vs. pre-order products.
By DateBy Rating
5 star rating out of 5
Best Anime Movie I've seen so far!
by Deus Ex Machina -
I say this because I'm a die hard SAO fan! But fan or not this movie is a legitimate must see!
IF YOU DON'T LIKE IT DON'T BUY IT LOL
by dominic
Saw this at the movies when it came out. It was amazing and I can't wait for Season 3. I'm a fan of the series and yes I know it is overrated but if you dont like it, dont complain lol. im buying because i enjoy it that much
More of the same SAO. - No Spoilers -
by Ori
This will be a spoiler free review of the film itself. I watched this on release date in Japan so I can't speak for how good the dub or subs are.
If you have seen the series then you basically know what to expect going into this movie. In all ways the film is essentially just another SAO story arc.
The plot is the SAO standard: There's a hot new game (this time using augmented reality instead of virtual reality), something bad is happening to certain players, and a mysterious villain. There are quite a few flashy fights and they give literally every character from the series some screen time.
Visuals: There are more details in the environments than usual, especially during the action sequences, and some of the effects look a little better but otherwise it is essentially the same.
Audio: There is new soundtrack with new versions of the existing music just like they did with the second season of the TV series. The music and sound effects are used just as they are in the series.
I love this movie!!
by Rebeccah -
I'm a big fan of this anime, and I love this movie!! I preordered it, and it came a lot earlier than I thought it would. I am going to really enjoy it. 😊
Delightedly Surprised
by Ren Silverstar -
I'm not usually a big fan of movies for anime TV series, so I was delightedly surprised to discover that I ADORED this one. It seriously has most of what I loved about the series: great characters, a story line that drew me in, wonderful, fluffy Kirito x Asuna moments and more. People who like seeing Asuna in action won't be disappointed, as she was quite the bad---. (Also people who like seeing her naked, but I'm not really one of those, heh...) Yes, there were a couple far-fetched moments where even I was, like, "Oh come on that could never happen!" (What would SAO be without those?! LOL) but I totally don't care I still loved it! XD As others have said, if you love SAO, especially the Aincrad arc, you'll most likely enjoy this movie :)
This was an Awesome movie!!
I love this movie!! I preordered this, and I love it. The dubbed was really well done! I'm a big SAO fan, so I thought this movie was really well made.
Can't wait to watch!
by Aaron -
I'm a big fan of this series and loved both seasons and EX. I wish I could have seen it in theaters but I can't wait to watch this movie on Blu-Ray!
a bit expensive for a movie, but still a great release
by DAVID -
This was a great release from Aniplex. It may be a bit expensive, but most of their releases are. The dub was great in this movie, as well as the sub, though I preferred dub, personally. It does a nice job tying into what is going to become Season 3, also.
by Ciarito
I've been a massive SAO fan since I first seen it last year; almost obsessively to be honest. I've found it to be the most heart-warming anime there is.
This movie has definitely lived up to its reputation and has the full package. If you haven't found a favourite anime yet then 100% Sword Art Online is the series for you. In fact even if you have not watched anime before then I highly recommend it.
Such a big part of my life, I love you SAO!
More than I imagined!!
by Ryan -
As a fan of the show, this movie was a perfect addition to the story. A must see to all fans. The fights were fun and detailed and they really did a great job expanding on Kirito and Asuna's relationship.
Absolutely adored this movie
by Lucy
I absolutely adored everything about this movie (apart from the couple of fan service moments, but you'll find those in pretty much any anime). This was my first time purchasing anything that was put out by Aniplex, so I was expecting that, for 40 dollars, I'd get at least a booklet with the DVD. Nope, nothing, but apparently it's normal for Aniplex to overcharge. The movie was totally worth it, though!
Amazing movie anyone who enjoyed SAO should see even if they disliked it after arc 1.
by Tempus
This movie was great. I love SAO but like many was disappointed with the 2nd arc, though I enjoyed GGO. This movie incorporates what we know of SAO but takes it in a slightly new direction & has a intriguing plot. The movie didn't air in theaters near me and I've only managed to see it after buying it on this site. I'd recommend this movie to anyone who's seen SAO and while I think others would enjoy it as well the references to the show wouldn't be as well understood by those who haven't watched SAO though it does give a brief description of what the first arc consisted of so you wouldn't be lost really if you hadn't seen SAO.
S.O.A. The Original Scale rocks!
by Christopher -
S.O.A. The Original Scale is awesome! It stands on its own or as an addition to g he on going saga! I have heard a lot of so, so reviews. S.O.A. is like Robotech was to Mech/sci-fi. I would highly recommend it!
Ordinal Scale
by Makayla
After seeing the movie in theaters, I was very much looking forward to having the blue-ray. I pre-ordered it, and received it soon after it became available. I enjoy the animation and production of the film. It is more of a stand alone story, but well worth watching.
by Dauntless48 -
Loved the movie! Definitely go with the Blu-Ray version for the extra $10 rather than the DVD. Quality is excellent!
An excellent movie
by PABLO -
Sword Art Online is one of those series that doesn't need presentation. Still, this movie works independently (if you want). The quality of the anime is even higher than the series. The story is self-contained with a satisfying ending.
I will recommend this to anyone who likes Sword Art Online and/or to those who want more after watching the anime or reading the light novels.
I like to pretend this movie doesn't exist.
by R3
I'm a huge SAO fan. I have all the blurays as well as the light novels. You can be sure I was super hyped for this movie. But after watching it, I really wish it didn't exist.
It starts off good and progresses very well up until the 3rd act where the entire thing just becomes an ex machina out of left field with a dash of "cameo from everyone ever."
The resolution makes no sense and only works "because they said so." Then they tried to shoehorn in a segway into Alicization which just feels completely out of place.
This movie is just over-the-top fan service that simply doesn't deliver on what makes SAO enjoyable.
If you enjoy stories with pandering action sequences where the good guy wins "because reasons," then by all means check this out. Otherwise, I recommend avoiding it and going straight to Alicization (which would incidentally save you from the ludicrous price point this is being sold at).
by Braeden -
It came fairly quickly, there was no damage, and the box was super strong, thanks right stuf team!
Great Movie
by Ezra -
Have been a dan since the first episode premiered. This movie makes you want to experience vr and ar in real life and has a good story.
No Latin American Dub
by Axel Katsuragi
I would more than gladly buy the movie since the story is great, but the fact that it has no Latin American Spanish dub kinda kills it for me, please add the spanish dub and I'll buy it in a heart beat.
Logging back to SAO
by Saul -
The shipping was fast, I really enjoyed the anime so I was thrilled when I finally bought it. The packaging was nice and original and the movie was worth it, I highly recommended getting this if you're an SAO fan. 👌
by T -
This was definitely a movie worthy of the SAO series. What I liked most about it was how the character's lines and actions throughout were what you've come to expect from everything seen in the SAO series from seasons 1 and 2. The voice acting was on point and the visual effects were very impressive. One of the best animation movies I've seen in a while.
If you're a fan you need this movie in your collection.
by AirAssault -
Wow! This movie is just awesome! So many nods to the fans. Many returning characters, music and animation is great. Also, its canon, it was meant to start from where S2 left off and leads right into S3. Buy it if you are a fan, seriously worth it.
SAO but in IRL
by Salty -
Ordinal Scale is a must see and must own for an SAO fan!
I never saw it in theaters and I got bummed when I missed my chance. When I saw this listed with RightStuf I jumped on it instantly!
If you've never seen the movie, it takes a pretty big leap with the SAO Crew into the real world with Augmented Reality! As per movies and OVAs go, this one is one of my favorites, the story is captivating and it's a great time for an SAO fan!
I had to Buy this when it got its USBD
by joseph -
I love SAO , so when the Movie was a Option to Buy in USBD with the Lossless Dub Audio i snag that up on day 1 of Pre-order , ALL ABORD THE PROGRESSIVE MOVIE TRAIN CHOO CHOO
Sword Art Online Box Set Blu-ray
Sword Art Online Aincrad Part 1 Novel Volume 1
Sword Art Online Alicization Turning Novel Volume 11
.hack//Legend of the Twilight Manga Omnibus (Vols 1-3)
PSYCHO-PASS The Movie Blu-ray/DVD
Accel World Novel Volume 1
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Sword Art Online II Box Set Blu-ray
Sword Art Online Alicization Blu-ray
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