text:
APU Configuration
@spblinux ... nice to see someone else pondering this topic
I see that you have roughly the same magnitude for your coefficients as I do. I also note that the coeffecients from the BF demo code indicate a passband attentuation of ~6dB. I haven't seen a filter design tool that would also allow you to specify attenuation but a filter can be attenuated by applying a common scale factor to all coefficients. The DC gain of a filter is the sum of the coefficients, which totals 0.51532 for the BF demo. Dividing each coefficient by this number shifts the magnitude response up so there is 0 attenuation in the passband. Now we can see that a filter generated using filterDesigner needs to have a stopband attenuation of ~30dB...
... so we can try different settings with our original attempt at replicating the BF coefficients and when we get this response we only need to scale the coefficients to determine values that best match the original BD demo filter.
I found that changing the Wstop parameter to 0.2928 produced a mag plot that was almost identical to the above...
By then scaling the coefficients so the gain of this filter matches the original BF demo coefficients we get virtually the same mag plot as the BF demo.
The RMS error between the original BF demo coefficients and these new ones after setting Wstop=0.2928 and scaling is 0.3% so that's close enough for me.
I think I can start experimenting with filter settings now.
spblinux last edited by
@MyAmigo Great! That is one more step to deal with the apu.
For all those without a copy of matlab. At http://t-filter.engineerjs.com/ very similar filter coefficients can be created:
TFilter uses int16_t numbers, sdk example apu/init.c uses uint16_t.
@manageryzy thank you. I thought the common coefficients were there to apply gain. I can confirm whether that is actually used by changing the values and seeing if it affects the performance of the hardware. Speaking of gain... there is a hardware function called audio_bf_set_audio_gain which I assume is adjusted to correct overall gain for the system so it is applied to all frequencies. Does that sound right?
I figured out how to generate a filter in Matlab using just the coefficients so I loaded the 17 coefficients from the BF demo into Matlab (after converting to fixed-point real numbers) and obtained the following impulse reponse (to confirm import)...
and the resulting magnitude response...
... assuming FS=48kHz. This is helpful as it suggests a Fpass of about 5kHz and an Fstop of about 10kHz if we use MatLab's filterDesigner tool. So I did that. The impulse and magnitude response for an equiripple, low pass, FIR filter with order N=16, Fpass=5kHz and Fstop=10kHz is as follows...
This is very close to the filter that was generated using just the demo coefficients so I'm definitely on the right track. I note that the coefficients are about 2x those of the demo and there is an additional ripple "hump" in there but this doesn't look too bad.
I feel like I'm close to a solution but I should be able to reproduce the coefficients from the demo exactly so I would like some feedback on this.
Knowing the specific parameters that were used to determine the demo FIR coefficients would solve my problem.
Thanks... Scott
@MyAmigo 0x03c3 is just a test value , i don't know why whese code got into drivers ... use your own coef
just generate a fir by matlab filter design tool, use fiter design tool quantilize these coeffs and copy them here
I figured out what the fixed precision values (from -1 .. +1) are as follows for both the PREV & POST FIR vectors...
I might be able to find a Matlab filter to match these coefficients but I'll be guessing so if you can provide a little more info I'll be able to move this further along.
What about the 3rd FIR filter vector?
uint16_t fir_common[] = { 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3, 0x03c3};
How is this used? You didn't show it in your earlier data flow diagram.
Thank you for your help. I really appreciate it.
Great thanks! Can you provide the Matlab code to do this? That way I don't have to guess which filter command to use.
signed fixed point number between -1 ~ 1
u can use matlab generate these coeffs
I tried to answer my own questions about the number format for the cofficients. A signed 16-bit representation of a real number is available with the half-precision floating-point format. Converting the coefficients with this format results in the ones starting with 0xF being very large numbers so this can't be right.
Are there other possible formats for floating point numbers that might be used here? It would be nice to hear from a developer of the APU hardware.
@manageryzy thank you.
This is helpful but I need to know more about the design of the FIR filters. There are 17 coefficients and I recognize that they are symmetric so that should narrow the options.
There are a variety of methods that may have been used to design a FIR filter:
- Window design method
- Frequency Sampling method
- Weighted least squares design
- Parks-McClellan method (also known as the Equiripple, Optimal, or Minimax method)
- Equiripple FIR filters designed using FFT algorithms
Someone must know the type of filters that are built into the hardware so please advise. If I have that information then I can use Matlab to calculate the coefficients for the filter used in the demo and then I will be able to create a filter with different properties.
Having an explaination of the values in the fir_prev_t definition ...
uint16_t fir_prev_t[] = { 0x020b, 0x0401, 0xff60, 0xfae2, 0xf860, 0x0022, 0x10e6, 0x22f1, 0x2a98, 0x22f1, 0x10e6, 0x0022, 0xf860, 0xfae2, 0xff60, 0x0401, 0x020b, };
... would be a big help as well. Are these real-number representations?
I can't move forward without assistance.
Help please!
This post is deleted!
This post is deleted!
This post is deleted!
although i can't tell you the details of apu , i can tell you some pipeline about it
+----------+ +----------+ +------------+ +-------+ +-----+ +--------------------- + +-----+ +-----+
| 8ch in | - > | buffer | - > | DAS BF | -> | gain | -> | FIR | -> | DownSample | -> | FIR | -> | FFT |
+----------+ +----------+ +------------+ +-------+ +------+ +---------------------+ +------+ +------+


text:
Blog written by Nick Mann, Habitat Aid
A very jolly green outing recently threw Black Friday into even sharper perspective. Habitat Aid made it into the top 50 green businesses in the West of England and I toddled up to Bristol for a prize giving event.
It's always nice to meet the kind of enthusiastic people who were there, even though it makes me feel like I'm a very weary 150. There was a tremendous range of businesses represented. You can be doing all sorts of things and be "green". There were sandwich makers, printers, water companies, PR companies, banks. These were companies in traditional areas doing things in a more sustainable way or promoting/servicing "green" companies. By the end of the evening I wasn't even sure what "green" meant.
At the other end of the spectrum were businesses firmly entrenched in recycling, alternative energy – you can imagine the kind of thing. I think my favourite firm was Geneco, quite rightly one of the winners. Oddly – which gave me pause for thought – we were the only people doing anything directly related to the natural environment. There's money in all this other stuff but not in plants. *Sigh*.
Anyway, it was a genuinely inspiring evening, and in sharp contrast to Black Friday which followed. Where did this wretched nonsense come from? It leaves me with the same kind of unpleasant taste as the Sunday Times Rich List. Have we come to this? It would be nice to think it will die a death.
I'm pretty confident that millenials will lead a move away from price driven consumerism and value ethical businesses more and more. As one such, it's our challenge to provide them with choice and reasonable prices. We simply can't provide the same slick level of service that Amazon does, but it's my hope that customers increasingly value the quality of our products and how we source them.

subset: commoncrawl


text:
* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project
Am J Physiol Regul Integr Comp Physiol 293: R47–R54, 2007. First published March 15, 2007; doi:10.1152/ajpregu.00745.2006. Low fat adiponectin expression is associated with oxidative stress in nondiabetic humans with chronic kidney disease—impact on plasma adiponectin concentration Rocco Barazzoni,1 Annamaria Bernardi,2 Franco Biasia,2 Annamaria Semolic,1 Alessandra Bosutti,1 MariaPia Mucci,3 Franca Dore,3 Michela Zanetti,1 and Gianfranco Guarnieri1 1 Clinica Medica, Dipartimento di Scienze Cliniche, Morfologiche e Tecnologiche, University of Trieste, Italy; Renal Unit, ULSS18, Rovigo, Italy; and 3Nuclear Medicine, Azienda Ospedaliera "Ospedali Riuniti," Trieste, Italy 2 Submitted 14 October 2006; accepted in final form 8 March 2007 adipose-derived circulating protein and it is reported to exert protective metabolic and vascular effects (1, 16, 18, 32). High circulating adiponectin is strongly associated with reduced cardiovascular risk under different clinical and experimental conditions (33, 40) and low adipose tissue adiponectin transcriptional expression is associated with hypoadiponectinemia and could contribute to insulin resistance and cardiovascular disease in obesity and type 2 diabetes (18). Chronic kidney disease (CKD) is a unique condition in that exceedingly high incidence of insulin resistance [in turn independently associated with enhanced cardiovascular events (34)] and cardiovascular morbidity and mortality [increasing from conservative to maintenance hemodialysis (MHD) treatment (24, 41)] is paradoxically associated with elevated plasma adiponectin. Although recent data (27) have questioned the previously reported protective cardiovascular impact of adiponectin in earlier stages of renal disease (3), available evidence indicates that highest total adiponectin increments are associated with lower cardiovascular risk in end-stage CKD (40), and all studies agree on protective effects of higher circulating adiponectin on metabolic risk factors (3, 27, 40). We also observed a positive association between plasma adiponectin and insulin-mediated glucose disposal using the gold-standard hyperinsulinemic-euglycemic clamp technique to measure insulin action in nondiabetic MHD patients (R. Barazzoni, G. Guarnieri et al., unpublished data). The above observations suggest that adiponectin-dependent metabolic and cardiovascular protection is preserved in advanced chronic uremia, although its effectiveness could be blunted by additional CKD-associated alterations and risk factors. Understanding the regulation of circulating adiponectin levels in advanced CKD is therefore of substantial clinical importance. CKD-associated hyperadiponectinemia could be due at least in part to reduced glomerular filtration rate and passive accumulation (13, 28). Whether changes in adiponectin adipose expression contribute to modulation of circulating adiponectin in different stages of advanced CKD remains, however, to be defined. Oxidative stress can contribute to insulin resistance and cardiovascular risk in chronic disease states, including obesity and diabetes (9, 11, 25), due to imbalance between oxidant generation and antioxidant defense systems. Systemic and tissue oxidative stress is also often reported in CKD (5, 7, 15, 23, 30, 31, 39). CKD-associated oxidative stress is likely to be, at least in part, independent of changes in body mass and fat (5, 7, 15, 23, 30, 31, 39), and it could, in turn, increase with progressive reduction of renal function with highest levels reported in MHD (5, 7, 15, 23, 30, 31, 39). Rapid reversibility of oxidative stress has also been reported after renal transplantation (38), further supporting its link with CKD and changes in renal function. A link between oxidative stress and altered adiponectin production has, in turn, recently emerged in experimental models (11, 14, 19, 35), as oxidative stress reduced Address for reprint requests and other correspondence: R. Barazzoni, Clinica Medica, Univ. of Trieste, Ospedale Cattinara, Strada di Fiume 443, 34100 Trieste, Italy (e-mail: [email protected]). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. adipose tissue; hemodialysis ADIPONECTIN IS THE MOST ABUNDANT http://www.ajpregu.org 0363-6119/07 $8.00 Copyright © 2007 the American Physiological Society R47 Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 18, 2017 Barazzoni R, Bernardi A, Biasia F, Semolic A, Bosutti A, Mucci MP, Dore F, Zanetti M, Guarnieri G. Low fat adiponectin expression is associated with oxidative stress in nondiabetic humans with chronic kidney disease—impact on plasma adiponectin concentration. Am J Physiol Regul Integr Comp Physiol 293: R47–R54, 2007. First published March 15, 2007; doi:10.1152/ajpregu.00745.2006.—In spite of association between high plasma adiponectin and high metabolic and cardiovascular (CV) risk, highest adiponectin increments retain CV and metabolic protective effects in advanced chronic kidney disease (CKD). Passive accumulation can favor CKD-associated hyperadiponectinemia but potential additional regulation by adipose tissue remains undefined. Oxidative stress (OS) is associated with metabolic and CV disease and with CKD [increasing from conservative treatment (CT) to maintenance hemodialysis (MHD)], and OS can reduce adiponectin expression in experimental models. OS (in the form of plasma thiobarbituric acid-reactive substances: TBARS), subcutaneous adipose adiponectin mRNA, and plasma adiponectin were studied in CKD patients (stages 4 and 5) on CT (n ⫽ 7) or MHD (n ⫽ 11). Compared with CT and controls (C: n ⫽ 6) MHD had highest TBARS and lowest adiponectin mRNA (P ⬍ 0.05) with lower adipose adiponectin protein (P ⬍ 0.05 vs. CT). MHD also had lower plasma adiponectin than CT, although both had higher adiponectin than C (P ⬍ 0.05). In renal transplant recipients (RT: CKD stage 3; n ⫽ 5) normal TBARS were, in turn, associated with normal adiponectin mRNA (P ⬍ 0.05 vs. MHD). In all CKD (n ⫽ 23), adiponectin mRNA was associated positively with adiponectin plasma concentration (P ⬍ 0.01). In all subjects (n ⫽ 29), adiponectin mRNA was related (P ⬍ 0.05) negatively with TBARS after adjusting for plasma C-reactive protein (CRP) or CRP and creatinine. Thus altered OS, adiponectin expression, and plasma concentration represent a novel cluster of metabolic and CV risk factors in MHD that are normalized in RT. The data suggest novel roles of 1) MHD-associated OS in modulating adiponectin expression and 2) adipose tissue in contributing to circulating adiponectin in advanced CKD. R48 OXIDATIVE STRESS AND FAT ADIPONECTIN IN CKD MATERIALS AND METHODS Study subjects and experimental protocol. We examined 18 Caucasian patients with advanced CKD [stages 4 and 5 based on estimated glomerular filtration rate (eGFR) according to the National Kidney Foundation classification (29)] divided in two groups undergoing CT (n ⫽ 7) or MHD (n ⫽ 11) treatment. An additional group of age-, BMI- and gender-matched patients treated with kidney transplantation [CKD stage 3; renal transplant (RT), n ⫽ 5] was also studied to assess potential reversibility of observed alterations. The study was approved by the local Ethics Committee, and all participants gave informed consent to it. In CT patients cause of renal failure was hypertension (n ⫽ 2), glomerulonephritis (n ⫽ 3), or not known (n ⫽ 2). In MHD, the cause of renal failure was hypertension (n ⫽ 4), glomerulonephritis (n ⫽ 4), polycystic kidney disease (n ⫽ 2), or bilateral nephrectomy (n ⫽ 1). In RT, cause of renal failure before transplantation was hypertension (n ⫽ 1), glomerulonephritis (n ⫽ 3), and polycystic kidney disease (n ⫽ 1). All patients were taking antihypertensive treatment that included ACE inhibitors in seven MHD, five CT, and two RT patients and Ca-antagonists in five MHD, four CT, and two RT patients. One MHD and one CT female patient had hypothyroidism treated with thyroxin with excellent clinical and biochemical control at the time of the study. None of the patients was treated with fish oil. All patients were selected to be ambulatory, nonobese, and nondiabetic with BMI above 20 and below 30 kg/m2 to avoid the potential confounding associations of obesity, diabetes, and cachexia with oxidative stress and altered adipocytokine levels (9, 11, 17, 36). Lack of diabetes was defined on the basis of fasting glucose besides medical history and lack of antidiabetic medications at the time of study or before it. No CKD patient in any group had had cardiovascular events or had a positive history for coronary artery disease on the basis of examination and detailed clinical history. Additional exclusion criteria were liver disease and nephrotic syndrome (defined as daily proteinuria ⬎3.5 g/1.73 m2). All control subjects were healthy, as assessed by medical history and clinical examination, as well as lack of medications taken at the time of the study. Control subjects were selected to be matched for age and gender to the patient groups, as well as within the same BMI limits. Patients underwent subcutaneous adipose tissue biopsy in the morning after the overnight fast. In MHD patients, samples were taken before the start of a dialysis session to minimize the potential effect of previous dialysis session per se on the studied parameters (7, 30, 31) [although no major acute effects of dialysis have been reported on plasma adiponectin (10)]. After obtaining a blood sample for hormone and TBARS measurement, local anesthesia was induced in the periumbilical skin region under sterile conditions. A superficial incision was then performed followed by removal of 50 –100 mg of subcutaneous fat that was immediately frozen in liquid nitrogen and subsequently kept at ⫺80°C until analyses. Body composition. Body composition was measured using multifrequency bioimpedence analysis (Sta-Bia Soft Tissue Analyzer, Akern, Pontassieve, Italy) in a quiet environment, with proximal electrodes placed on the dorsal side of wrist and ankle, and the distal electrodes on the second metacarpal (metatarsal)-phalangeal joint (limbs contralateral to the a-v fistula were used in hemodialysis patients) with limbs at 45° abduction (4, 20). Resistance and reactance data were normalized for height and analyzed to calculate body composition parameters (Bodygram Software). Adipose tissue adiponectin mRNA and protein content. To assess adiponectin transcriptional expression, total adipose tissue mRNA was extracted from ⬃40 mg of adipose tissue using the RNeasy Mini Kit (Qiagen, Cologne, Germany). One microgram of total RNA was reverse-transcribed (RNA Reverse Transcription KIT, Applied Biosystems, Foster City, CA), and adiponectin transcripts were amplified using the following primers and probes, selected using the Primer Express Software (Applied Biosystems): Forward primer: TCAATGGCCCCTGCACTACT; Reverse primer: GGGATGAGTTCAGCACTTAGAGATG; Probe: CCTCTTACCTATGTCCCTTCTCATGCCTTTCC. 28S rRNA was used as reference gene using the following primers and probe: Forward primer: TGGGAATGCAGCCCAAAG; Reverse primer: CCTTACGGTACTTGTTGACTATCG; probe: TGGTAAACTCCATCTAAGGCTAAATACCGGCA. Target and housekeeping genes were amplified separately using real-time polymerase chain reaction, and their final quantitation was achieved using a relative standard curve, as previously described (2). Adiponectin mRNA values were divided by the corresponding 28S rRNA value and expressed as arbitrary units. To further confirm changes in adiponectin gene expression at the posttranscriptional level, we measured adiponectin protein content in aliquots from the same adipose tissue sample. Because of low tissue availability, this measurement was performed in 6 CT and 7 MHD, while not in control or RT patients. Briefly, total protein was extracted from 40 –50 mg of adipose tissue homogenized in sucrose buffer (0.25 mM sucrose, 10 mM HEPES, 0.2 mM EDTA) containing protease inhibitors. The homogenate was centrifuged at 2,500 rpm for 10 min, and the supernatant was transferred to a fresh tube and again centrifuged at 13,000 rpm at 4°C for 10 min. The supernatant was then divided into two aliquots; equal volumes of 10% TCA were added and incubated at ⫺20°C for 45 min. Samples were then centrifuged at 9,000 rpm at 4°C for 30 min. The pellet was washed with 90% acetone, evaporated, and suspended in 30-l solubilization buffer containing 40 mM Tris base and 2% SDS. After measurement of total protein concentration from the purified sample, 10 g total adipose tissue protein were used to measure total adiponectin concentration using a commercially available kit (ALPCO Diagnostics, Salem, NH) following the manufacturer's recommendations except for a lower AJP-Regul Integr Comp Physiol • VOL 293 • JULY 2007 • www.ajpregu.org Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 18, 2017 adipose tissue adiponectin transcript levels in vitro and in animal studies (11, 14, 19, 35). No information is available on the potential interactions between adipose tissue adiponectin and oxidative stress in human disease and in CKD, in particular. In the current study, we cross-sectionally investigated changes in oxidative stress (plasma thiobarbituric acid reactive substances: TBARS), subcutaneous adipose tissue adiponectin expression, and plasma adiponectin, as well as their potential relationships in patients with advanced CKD (stages 4 and 5) undergoing MHD (n ⫽ 11) or conservative treatment (CT; n ⫽ 7). It was hypothesized that 1) fat tissue adiponectin expression declines with increasing oxidative stress in patients undergoing MHD treatment and that 2) adiponectin expression is associated with parallel changes of its plasma concentration. It was further hypothesized that oxidative stress and adiponectin expression would, in turn, be normal in an additional group of nondiabetic renal transplant recipients. TBARS were selected as an oxidative stress marker because they reflect lipid peroxidation (10, 13, 18, 34) and were reported to be directly linked to adipose tissue adiponectin expression in animal models (11), as well as to adiponectin plasma concentration in nonrenal obese patients (11). In addition, TBARS were reported to be increased in subcutaneous adipose tissue samples from CKD patients (12). All patients were selected to be free of obesity and diabetes to avoid the confounding effect of these potential independent causes of oxidative stress and altered adiponectin production (9, 11, 17). The potential involvement of inflammatory state as reflected by the validated index C-reactive protein was also assessed since inflammation can occur in advanced CKD, is commonly negatively associated with circulating adiponectin (1, 32), and could negatively affect its adipose tissue expression (6). R49 OXIDATIVE STRESS AND FAT ADIPONECTIN IN CKD RESULTS Anthropometric, clinical, and biochemical parameters in control and CKD subjects. MHD, CT, and control subjects were comparable for gender, age, body mass index and body fat (Table 1). The groups also had comparable plasma insulin and glucose concentrations, as well as similar blood pressure recordings. Plasma creatinine concentration was higher by design in CKD groups with intermediate values in CT and highest levels in MHD. As expected, eGFR was lowest in MHD and within stages 4 and 5 for CT patients. Plasma high-sensitivity CRP was higher in MHD than in all other groups. Plasma adiponectin, adipose tissue adiponectin mRNA, and plasma TBARS. Plasma concentrations of TBARS were higher in MHD than in both CT and control subjects (Fig. 1A). Subcutaneous adipose tissue adiponectin mRNA levels were comparable to normal values in CT but substantially lower in MHD (Fig. 1B). Plasma adiponectin concentration was higher in both MHD and CT than in control subjects, but this increment was, however, less pronounced in MHD (Fig. 1C). Adipose tissue adiponectin protein level was also lower in MHD than in CT patients (7.2 ⫾ 0.8 vs. 18.3 ⫾ 5 pg/100 ng total adipose tissue protein; P ⫽ 0.043). Plasma adiponectin, adipose tissue adiponectin mRNA, and plasma TBARS in renal transplant recipients. To assess the potential impact of renal transplant on the observed alterations, we studied an additional group of nonobese, nondiabetic (as defined above for patients from other groups) RT recipients (n ⫽ 5, 3M, treated with hemodialysis before transplantation, time from transplantation 116 ⫾ 88 mo, range 47–228). Differences between RT and other groups were assessed using ANOVA and Student's t-test or Wilcoxon test. RT patients had age (64 ⫾ 6 years, range 55– 67), body mass index (25.9 ⫾ 4, range 22–29.6) and body fat (26.4 ⫾ 11%, range 15– 40) comparable to the other experimental groups. Plasma glucose and insulin concentrations were also not different from all other groups (P ⬎ 0.05). RT patients had HS-CRP comparable to that of control and CT groups and lower than MHD (0.2 ⫾ 0.4 mg/dl, range 0.02– 0.9, P ⬍ 0.05 vs. MHD). Plasma creatinine was lower than both CT and MHD but higher than control subjects (1.5 ⫾ 0.2 mg/dl, range 1.3–1.7, P ⬍ 0.05 vs. all other groups) with eGFR of 44.9 ⫾ 4.9 ml䡠min⫺1 䡠1.73 m⫺2 (P ⬍ 0.05 vs. all other groups). Compared with MHD, RT had lower TBARS and higher adiponectin mRNA (Fig. 2) with both values comparable to CT and control subjects. Plasma adiponectin was conversely comparable in the MHD and RT groups (Fig. 3). Plasma adiponectin was also higher in the smaller RT than in the control group (P ⬍ 0.05, not shown). Plasma adiponectin to adipose tissue adiponectin mRNA ratio. The ratio between plasma adiponectin and adiponectin mRNA was calculated in all subjects as a potential index of hormone accumulation independent of its transcriptional ex- Table 1. Various parameters in chronic kidney disease subjects Sex (M/F) Age, yr BMI, kg/m2 Body fat, % SBP, mmHg DBP, mmHg Insulin, U/ml Glucose, mMol Total cholesterol, mg/dl Triglycerides, mg/dl hs-CRP, mg/dl Creatinine, mg/dl eGFR, ml 䡠 min⫺1 䡠 1.73m2 Dialysis, mo Control CT MHD 3/3 64⫾11 (52–78) 26.2⫾3.1 (22–29.3) 33.1⫾8 (19–41) 135⫾15 (122–155) 82⫾8 (72–90) 12.6⫾8 (3.5–22.1) 5⫾0.4 (4.1–5.1) 201⫾11 (172–250) 125⫾26 (38–215) 0.11⫾0.1 (0.03–0.4) 0.8⫾0.1 (0.7–0.9) 87⫾8.9 (80–101) / 4/3 68⫾7 (59–77) 26⫾3.7 (21–29.4) 30.6⫾9 (20–45) 140⫾22 (108–158) 87⫾12 (70–98) 14⫾10 (4.7–30) 4.8⫾0.5 (4–5.5) 207⫾13 (154–245) 195⫾22 (136–299) 0.44⫾0.6 (0.02–1.2) 4.2⫾1.3 (2.5–6.5)* 16.7⫾5.9 (9.5–27.9)* / 6/5 69⫾11 (46–80) 24.2⫾2.5 (21.8–28.6) 28.8⫾11 (9–45) 137⫾18 (105–155) 82⫾10 (73–95) 11.8⫾6 (3.5–17.4) 4.6⫾0.6 (3.9–5.4) 163⫾12 (117–213) 144⫾18 (88–221) 1.99⫾1.3 (0.3–4)† 8.9⫾1.5 (6.5–10.3)† 5.8⫾1.2 (4.3–8)† 31⫾21 (6–78) Values are presented as means (SD for range). Sex, age, body mass index (BMI), percent body fat, systolic (SBP) and diastolic (DBP) blood pressure, plasma insulin and glucose concentrations, plasma total cholesterol and triglyceride concentrations, plasma high-sensitivity C-reactive protein (hs-CRP), plasma creatinine, estimated glomerular filtration rate (eGFR) and dialysis duration in control subjects and in chronic kidney disease patients undergoing conservative treatment (CT) or maintenance hemodialysis (MHD). *P ⬍ 0.05 vs. control and MHD; †P ⬍ 0.05 vs. Control and CT, ANOVA and Student's unpaired t-test. AJP-Regul Integr Comp Physiol • VOL 293 • JULY 2007 • www.ajpregu.org Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 18, 2017 sample dilution (1:2,500: determined with preliminary tests) for final spectrophotometrical reading. Plasma biochemical profile. Plasma TBARS concentration was measured using a commercially available kit (Oxitek, Zeptometrix Co, Buffalo, NY) following the manufacturer's recommendations (intraassay coefficient of variation: 4%, interassay coefficient of variation: 5.1%). A commercially available ELISA kit was also used to measure plasma total adiponectin (B-Bridge International, Sunnyvale, CA) (intraassay coefficient of variation: 4.2%, interassay coefficient of variation: 5.6%). Total adiponectin was chosen since it has been directly demonstrated to modulate metabolic and cardiovascular risk in advanced CKD (3, 27, 40). Plasma insulin concentrations were measured by radioimmunoassay (Linco, St Louis, MO). Blood glucose concentration was measured by reflectometer (Roche Diagnostics, Indianapolis, IN). High-sensitivity C-reactive protein (HS-CRP) plasma concentration, a marker of systemic inflammation, was measured using a commercially available ELISA kit (Diagnostics Biochem, London, Ontario, Canada). Plasma creatinine concentration was measured using standard methods, and glomerular filtration rate (GFR) was calculated using validated formula based on plasma creatinine according to Modification of Diet in Renal Disease Study Group equations (22). Statistical analysis. ANOVA followed by Student's t-test or nonparametric Wilcoxon test (analyses of TBARS and adiponectin mRNA, as well as plasma adiponectin to mRNA ratio), were used to compare variables between the experimental groups. Log transformation was applied in linear regression analyses and for stepwise multiple regression analyses of plasma TBARS and adiponectin mRNA due to nonnormal data distribution. P values of 0.05 or less were considered statistically significant. R50 OXIDATIVE STRESS AND FAT ADIPONECTIN IN CKD DISCUSSION Fig. 1. A: plasma thiobarbituric acid-reactive substances (TBARS) concentration. B: adipose tissue adiponectin mRNA. C: plasma adiponectin concentration in nonuremic control subjects and in chronic kidney disease (CKD) patients undergoing conservative (CT) or maintenance hemodialysis (MHD) treatment. *P ⬍ 0.05 vs. Control and CT; $P ⬍ 0.05 vs. Control and MHD groups, ANOVA and Student's unpaired t-test or Wilcoxon test. pression (Fig. 3). This ratio increased from control to MHD group and was significantly higher in the latter than in all other groups. RT and CT also had higher adiponectin to adiponectin mRNA values than the control group. Association of oxidative stress with adipose tissue adiponectin expression. In linear regression analysis in all subjects (n ⫽ 29), adipose tissue adiponectin mRNA was related negatively (P ⬍ 0.05) with plasma CRP (r ⫽ ⫺0.57), plasma creatinine (r ⫽ ⫺0.64) and log plasma TBARS (r ⫽ ⫺0.68, Table 2 and Fig. 4). In multiple regression analysis (Table 3), log plasma TBARS remained associated with adipose tissue adiponectin The current data demonstrate a novel link between increased oxidative stress and declining fat tissue adiponectin expression in patients with advanced CKD undergoing MHD compared with conservative treatment. Lower adiponectin mRNA was, in turn, notably associated with lower plasma adiponectin concentration, as well as lower tissue adiponectin protein content. Increased oxidative stress and reduced adiponectin expression and plasma concentration represent a novel cluster of cardiovascular risk factors that could contribute to excess metabolic and cardiovascular risk in MHD patients compared with patients undergoing CT (3, 27, 40). To the best of our knowledge, this is the first evidence of the above associations in renal disease models or in human disease in vivo. The above findings also support a novel active role of adipose tissue in the regulation of circulating adiponectin in advanced chronic kidney disease. Oxidative stress and adipose tissue adiponectin expression. Causes of oxidative stress in advanced renal failure are multifactorial, including both enhanced production of oxidant compounds and impaired antioxidant defense systems (5, 7, 15, 23, 30, 31, 39). Uremia per se could promote oxidant production as indirectly confirmed by a positive relationship between creatinine levels and oxidative stress markers observed in previous studies (39) and confirmed by the current results (not shown). Hemodialysis has been proposed to enhance systemic oxidative stress both acutely (in a time-dependent fashion) and chronically, although these effects remain, in part, controversial (7, 30, 31) and were not directly addressed in the current study. In the absence of known anthropometric confounding factors, we demonstrated changes in subcutaneous adipose tissue adiponectin expression opposite to those in lipid oxidative stress in three major stages of kidney disease, such as advanced CKD on CT, advanced CKD on hemodialysis treatment, and kidney transplantation. Negative relationships were accordingly observed between subcutaneous adipose tissue adiponectin ex- AJP-Regul Integr Comp Physiol • VOL 293 • JULY 2007 • www.ajpregu.org Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 18, 2017 mRNA (F ⫽ 9.41; P ⬍ 0.01), after adjusting for plasma hs-CRP and also after adjusting for both plasma hs-CRP and creatinine (F ⫽ 5.1; P ⬍ 0.05). Similar results were observed when the three groups of CKD patients (n ⫽ 23) were included without control subjects. On the other hand, hs-CRP or creatinine were no longer significantly associated with adiponectin mRNA after adjusting for plasma TBARS (not shown). Considering CKD and control subjects together (n ⫽ 29), no correlations were observed between plasma adiponectin and adiponectin mRNA (r ⫽ 0.30; P ⫽ 0.14). Because different adiponectin excretion can alter the association between its mRNA and plasma concentration in renal failure compared with control subjects, we also separately analyzed the whole group of renal failure patients and the control groups (Fig. 5). A positive correlation was observed between the variables in all CKD patients (n ⫽ 23, P ⫽ 0.01, Fig. 5), while no significant associations were, in turn, observed in the six control subjects alone (P ⫽ not significant, Fig. 5). In multiple regression analysis, adipose tissue adiponectin mRNA remained significantly associated with circulating adiponectin in CKD patients (P ⬍ 0.05) also after adjusting for plasma hs-CRP that could potentially alter adiponectin secretion (6) (not shown). R51 OXIDATIVE STRESS AND FAT ADIPONECTIN IN CKD Fig. 2. Plasma TBARS (A), adipose tissue adiponectin mRNA (B), and plasma adiponectin concentration (C) in MHD and renal transplant (RT) patients. *P ⬍ 0.05 vs. Control, Student's t-test or Wilcoxon test. tissue in patients with advanced chronic kidney disease. Oxidative stress is notably a potential negative modulator of cardiovascular risk in kidney disease (15, 23), and the current data indicate that its clustering with low adiponectin expression and plasma concentration could contribute to this negative impact. Adipose tissue adiponectin expression and adiponectin plasma concentration. The active metabolic and cardiovascular impact of adipose tissue has been established in recent years in metabolic disease states (9, 11, 17). This potential role remains, however, to be defined in uremia due to the relevant role of passive accumulation in causing increased plasma concentrations of several hormones (13, 28). Increasing ratio of circulating adiponectin to its adipose tissue expression from healthy subjects to end-stage renal disease in four different control or patient groups, indeed, suggests increasing passive accumulation in renal failure. The latter could, in turn, contribute to increasing plasma adiponectin concentration in the presence of comparable adiponectin transcript levels in RT and CT groups, while the highest relative contribution of passive accumulation could further account for preserved adiponectin concentration in spite of very low adiponectin transcript levels in MHD. On the other hand, the marked decline in fat tissue adiponectin expression in MHD could have played a major role in blunting circulating adiponectin increments, resulting in circulating horTable 2. Linear correlation between adipose tissue adiponectin mRNA and plasma TBARS, creatinine, hsCRP, age, BMI, and body fat in all study subjects Fig. 3. Ratio between plasma adiponectin and adipose tissue adiponectin mRNA in nonuremic control subjects (Control) and in CKD patient groups (CT, MHD, and RT). $P ⬍ 0.05 vs. Control and RT-CT groups; *P ⬍ 0.05 vs. Control, ANOVA, and Wilcoxon test. Subject Characteristics (n ⫽ 29) r P TBARS, log nmol/ml Creatinine, mg/dl hsCRP, mg/dl Age, yr BMI, kg/m2 Fat, % ⫺0.68 ⫺0.64 ⫺0.57 0.09 0.16 0.15 ⬍0.0001 0.002 0.014 ⬎0.2 ⬎0.2 ⬎0.2 TBARs, thiobarbituric acid-reactive substances; hsCRP, high-sensitivity C-reactive protein. AJP-Regul Integr Comp Physiol • VOL 293 • JULY 2007 • www.ajpregu.org Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 18, 2017 pression and lipid peroxidation markers in all study subjects. Because proinflammatory mediators have been recently reported to negatively modulate adiponectin expression in subcutaneous adipose tissue in nonrenal patients (6) and inflammation can occur in advanced stages of CKD, the validated clinical marker of inflammation C-reactive protein was measured in all patients and included in statistical analysis. CRP was negatively related with adiponectin expression [in agreement with the above observations (6)]. Adjustment for plasma CRP concentration did not, however, modify the relationship between adiponectin expression and circulating TBARS, suggesting that the latter is at least in part independent of inflammation. It should be pointed out that associations may suggest but not prove cause-effect relationships. Lipid oxidative stress has been, however, recently reported to negatively modulate adiponectin expression in vitro and in animal models of metabolic disease (11, 14, 19, 35). On the basis of available knowledge, the current findings therefore support a role of oxidative stress to downregulate adiponectin expression in fat R52 OXIDATIVE STRESS AND FAT ADIPONECTIN IN CKD mone levels lower than those of patients undergoing conservative treatment and similar to those of patients with intermediate residual renal disease following transplantation. The current data therefore provide the first direct evidence supporting an active role of adipose tissue adiponectin expression in modulating its circulating levels in CKD. The functional impact of reduced adiponectin expression was notably further supported by the lower adiponectin protein content in adipose tissue of MHD compared with conservative treatment patients and by the positive association between adiponectin transcript levels and plasma concentration in all CKD patients. The data suggest that modulation of oxidative stress and adipose tissue adiponectin expression could represent a potential target for therapeutic strategies aimed at enhancing plasma adiponectin and reducing CKD-associated metabolic and cardiovascular risk (3, 27, 34, 40). Previous reports notably agree with the current data in indicating lack of increments of circulating adiponectin in renal patients undergoing hemodialysis compared with conservative treatment, in spite of presumable extreme reductions of renal function in the hemodialysis groups (8, 37). In the above studies, it is well possible that lack of plasma adiponectin increments in hemodialysis resulted from a decline in adipose Table 3. Multiple regression analyses (F value) of plasma TBARS and adiponectin mRNA in all subjects Adjusted Value Independent variable: Plasma TBARS Adiponectin mRNA, au a 9.41† b 5.10* a: adjusted for plasma hs-CRP; b: adjusted for plasma hs-CRP and plasma creatinine. *P ⬍ 0.05; †P ⬍ 0.01. Fig. 5. Positive correlation between log subcutaneous adipose tissue adiponectin mRNA and plasma adiponectin concentration in CKD patients (CT, MHD, RT; n ⫽ 23). No correlation was observed in the smaller control group considered alone. tissue contribution with a parallel relative increment of passive accumulation (8, 37). The only available report of adipose tissue adiponectin expression in chronic kidney disease (with no information on oxidative stress) showed reduced adipose tissue adiponectin mRNA in end-stage renal disease patients compared with healthy control subjects, and it was concluded that adipose tissue does not actively contribute to regulate circulating adiponectin in CKD (26). The above study most importantly did not extend to different degrees or treatments of renal failure (26). Plasma adiponectin was not available in the majority of patients or in any control subjects (26). In addition, collection of adipose tissue samples in control subjects occurred during surgery and anesthesia, which could also have potentially directly or indirectly (i.e., via the underlying disease) affected adiponectin expression (26). It is therefore likely that the above differences and the less comprehensive study design and population (26) contributed to different conclusions. Patients with obesity or diabetes were excluded from this study, since we aimed at excluding known sources of oxidative stress and adiponectin suppression (as well as inflammation) independent of kidney failure or its treatment per se (9, 11, 17). The current results provide a strong rationale for future studies to directly investigate the potential independent role of diabetes in the regulation of adiponectin adipose tissue expression and plasma concentration in advanced CKD. In this study, total adiponectin was measured since it has been so far reported to be associated with positive metabolic and cardiovascular end points in advanced CKD (3, 27, 34, 40). Altered adiponectin AJP-Regul Integr Comp Physiol • VOL 293 • JULY 2007 • www.ajpregu.org Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 18, 2017 Fig. 4. Negative log correlations between plasma TBARS and subcutaneous adipose tissue adiponectin mRNA in all subjects (control, CT, MHD, RT; n ⫽ 29). OXIDATIVE STRESS AND FAT ADIPONECTIN IN CKD ACKNOWLEDGMENTS We thank A. de Santis for skillful technical assistance. We are most grateful to Prof. Lucio Torelli, Statistics Department, University of Trieste, Italy, for advice and support in statistical analyses. REFERENCES 1. Axelsson J, Heimburger O, Lindholm B, Stenvinkel P. Adipose tissue and its relation to inflammation: the role of adipokines. J Ren Nutr 15: 131–136, 2005. 2. Barazzoni R, Zanetti M, Bosutti A, Biolo G, Vitali-Serdoz L, Stebel M, Guarnieri G. Moderate caloric restriction, but not physiological hyperleptinemia per se, enhances mitochondrial oxidative capacity in rat liver and skeletal muscle–tissue-specific impact on tissue triglyceride content and AKT activation. Endocrinology 146: 2098 –2106, 2005. 3. Becker B, Kronenberg F, Kielstein JT, Haller H, Morath C, Ritz E, Fliser D. Renal insulin resistance syndrome, adiponectin and cardiovascular events in patients with kidney disease: the mild and moderate kidney disease study. J Am Soc Nephrol 16: 1091–1098, 2005. 4. Chumlea WC, Guo SS, Kuczmarski RJ, Flegal KM, Johnson CL, Heymsfield SB, Lukaski HC, Friedl K, Hubbard VS. Body composition estimates from NHANES III bioelectrical impedence data. Int J Obes Relat Metab Disord 26: 1596 –1609, 2002. 5. Canaud B, Cristol JP, Morena M, Leray-Moragues H, Bosc JY, Vaussenat F. Imbalance of oxidants and antioxidants in haemodialysis patients. Blood Purif 17: 99 –106, 1999. 6. Degawa-Yamauchi M, Moss KA, Bovenkerk JE, Shankar SS, Morrison CL, Lelliott CJ, Vidal-Puig A, Jones R, Considine RV. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor. Ob Res 13: 662– 669, 2005. 7. Descamps-Latscha B, Drueke T, and Witko-Sarsat V. Dialysis-induced oxidative stress: biological aspects, clinical consequences, and therapy. Semin Dial 14: 193–199, 2001. 8. Diez JJ, Iglesias P, Fernandez-Reyes MJ, Aguilera A, Bajo MA, Alvarez-Fidalgo P, Codoceo R, Selgas R. Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease. Clin Endocrinol (Oxf) 62: 242–249, 2005. 9. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 52: 1– 8, 2003. 10. Filippidis G, Liakopoulos V, Mertens PR, Kiropoulos T, Stakias N, Verikouki C, Patsidis E, Koukoulis G, Stefanidis I. Resistin serum levels are increased but not correlated with insulin resistance in chronic hemodialysis patients. Blood Purif 23: 421– 428, 2005. 11. Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest 114: 1752–1761, 2004. 12. Gotoh M, Nagase S, Aoyagi K, Hirayama A, Takemura K, Ueda A, Tomida C, Kikuchi C, Koyama A. Thiobarbituric acid reactive substances are increased in the subcutaneous fat tissue of patients with end-stage renal disease. Nephrol Dial Transplant 12: 713–717, 1997. 13. Guebre-Egziabher F, Bernhard J, Funahashi T, Hadj-Aissa A, Fouque D. Adiponectin in chronic kidney disease is related more to metabolic disturbances than to decline in renal function. Nephrol Dial Transplant 20: 129 –134, 2005. 14. Hattori Y, Akimoto K, Gross SS, Hattori S, Kasai K. Angiotensin-IIinduced oxidative stress elicits hypoadiponectinaemia in rats. Diabetologia 48: 1066 –1074, 2005. 15. Himmelfarb J, Stenvinkel P, Ikizler TA, Hakim RM. The elephant in uremia: oxidant stress as an unifying concept of cardiovascular disease in uremia. Kidney Int 62: 1524 –1538, 2002. 16. Kawanami D, Maemura K, Takeda N, Harada T, Nojiri T, Imai Y, Manabe I, Utsunomiya K, Nagai R. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun 314: 415– 419, 2004. 17. Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G. Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 52: 1779 –1785, 2003. 18. Kobashi C, Urakaze M, Kishida M, Kibayashi E, Kobayashi H, Kihara S, Funahashi T, Takata M, Temaru R, Sato A, Yamazaki K, Nakamura N, Kobayashi M. Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res 97: 1245–1252, 2005. 19. Kurata A, Nishizawa H, Kihara S, Maeda N, Sonoda M, Okada T, Ohashi K, Hibuse T, Fujita K, Yasui A, Hiuge A, Kumada M, Kuriyama H, Shimomura I, Funahashi T. Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation. Kidney Int 70: 1717–1724, 2006. 20. Kyle UG, Bosaeus I, De Lorenzo AD, Deurenberg P, Elia M, Gomez JM, Heitmann BL, Kent-Smith L, Melchior JC, Pirlich M, Scharfetter H, Schols AMWJ, Pichard C. Composition of the ESPEN Working Group: Bioelectrical impedance analysis—part I: review of principles and methods. Clin Nutr 23: 1226 –1243, 2004. 21. Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT. Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 55: 249 –259, 2006. 22. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130: 461– 470, 1999. 23. Locatelli F, Canaud B, Eckardt KU, Stenvinkel P, Wanner C, Zoccali C. Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 18: 1272–1280, 2003. 24. Luke RG. Chronic renal failure—a vasculopathic state. N Engl J Med 339: 841– 843, 1998. 25. Madamanchi NR, Vendrov A, Runge MS. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25: 29 –38, 2005. 26. Marchlewska A, Stenvinkel P, Lindholm B, Danielsson A, PecoitsFilho R, Lönnqvist F, Schalling M, Heimbürger O, Nordfors L. Reduced gene expression of adiponectin in fat tissue from patients with end-stage renal disease. Kidney Int 66: 46 –50, 2004. 27. Menon V, Li L, Wang X, Greene T, Balakrishnan V, Madero M, Pereira AA, Beck GJ, Kusek JW, Collins AJ, Levey AS, Sarnak MJ. AJP-Regul Integr Comp Physiol • VOL 293 • JULY 2007 • www.ajpregu.org Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 18, 2017 polymerization with reduced high-molecular weight forms is emerging as a modulator of metabolic and vascular complications in metabolic diseases (21). It is possible that changes in the ratio of adiponectin circulating forms could be influenced by CKD stage and oxidative stress, and these issues could be addressed in future investigations. It should also be pointed out that renal transplant patients were treated with immunosuppressive therapy, including prednisone in two patients and methylprednisolone in one, while dexamethasone was reported to acutely and moderately reduce adiponectin secretion from human adipocytes by ⬃10% (6). Although it is not known whether this effect occurs in vivo following sustained administration, treatment could have caused a potential moderate reduction of adiponectin transcript levels and plasma concentration with no impact on the study's conclusions of positive effects of renal transplantation on oxidative stress and adiponectin expression (which would be if anything underestimated). In conclusion, the current data demonstrate that increased oxidative stress is associated with declining adiponectin transcriptional expression in fat tissue in patients undergoing MHD compared with conservative treatment. Oxidative stress and adiponectin expression are, in turn, normalized in renal transplant recipients. Reduced adiponectin expression appears to have a negative impact on plasma adiponectin concentration in MHD. Increased oxidative stress with reduced adiponectin expression and plasma concentration represent a novel cluster of risk factors potentially contributing to enhance metabolic and cardiovascular disease in MHD patients. On the basis of available knowledge, the data support a novel role of oxidative stress in the modulation of adiponectin expression and of adipose tissue as an active player in the regulation of circulating adiponectin in advanced CKD. R53 R54 28. 29. 30. 31. 32. 34. 35. Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol 17: 2599 –2606, 2006. Merabet E, Dagogo-Jack S, Coyne DW, Klein S, Santiago JV, Hmiel SP, Landt M. Increased plasma leptin concentration in end-stage renal disease. J Clin Endocrinol Metab 82: 847– 850, 1997. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39 Suppl 1: S1–S266, 2002. Oberg BP, McMenamin E, Lucas FL, McMonagle E, Morrow J, Ikizler TA, Himmelfarb J. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int 65: 1009 –1016, 2004. Pupim LB, Himmelfarb J, McMonagle E, Shyr Y, Ikizler TA. Influence of initiation of maintenance hemodialysis on biomarkers of inflammation and oxidative stress. Kidney Int 65: 2371–2379, 2004. Rajala MW, Scherer PE. Minireview: The adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 144: 3765–3773, 2003. Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A. Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Care 27: 2450 –2457, 2004. Shinohara K, Shoji T, Emoto M, Tahara H, Koyama H, Ishimura E, Miki T, Tabata T, Nishizawa Y. Insulin resistance as an independent predictor of cardiovascular mortality in patients with end-stage renal disease. J Am Soc Nephrol 13: 1894 –1900, 2002. Soares AF, Guichardant M, Cozzone D, Bernoud-Hubac N, BouzaidiTiali N, Lagarde M, Geloen A. Effects of oxidative stress on adiponectin 36. 37. 38. 39. 40. 41. AJP-Regul Integr Comp Physiol • VOL secretion and lactate production in 3T3–L1 adipocytes. Free Radic Biol Med 38: 882– 889, 2005. Stenvinkel P, Barany P, Heimburger O, Pecoits-Filho R, Lindholm B. Mortality, malnutrition, and atherosclerosis in ESRD: what is the role of interleukin-6? Kidney Int 61 Suppl 80: 103–108, 2002. Tentolouris N, Doulgerakis D, Moyssakis I, Kyriaki D, Makrilakis K, Kosmadakis G, Stamatiadis D, Katsilambros N, Stathakis C. Plasma adiponectin concentrations in patients with chronic renal failure: relationship with metabolic risk factors and ischemic heart disease. Horm Metab Res 36: 721–727, 2004. Vural A, Yilmaz MI, Caglar K, Aydin A, Sonmez A, Eyileten T, Acikel C, Gulec B, Kozak O, Oner K. Assessment of oxidative stress in the early posttransplant period: comparison of cyclosporine A and tacrolimusbased regimens. Am J Nephrol 25: 250 –255, 2005. Witko-Sarsat V, Friedlander M, Khoa TN, Capeille're-Blandin C, Nguyen AT, Canteloup S, Dayer J-M, Jungers P, Drueke T, and Descamps-Latscha B. Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol 161: 2524 –2532, 1998. Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 13: 134 –141, 2002. Zoccali C. Cardiovascular risk in uraemic patients—is it fully explained by classical risk factors? Nephrol Dial Transplant 15: 454 – 457, 2000. 293 • JULY 2007 • www.ajpregu.org Downloaded from http://ajpregu.physiology.org/ by 10.220.33.1 on June 18, 2017 33. OXIDATIVE STRESS AND FAT ADIPONECTIN IN CKD


text:
Client Testimonials
Dwyer & Coogan was very responsive to every question I raised as the process ensued. They were extremely timely in communication and took the time to explain details in full. I would specifically like to recommend Carolanne as she was extremely thoughtful and helpful throughout the process. Her availability to speak in a timely fashion was key to success. The entire process is stressful and can often be very lengthy and it's great to know you have someone who understands your plight and will fight for you in an extremely convoluted legal system.
I would highly recommend Dwyer & Coogan and specifically Carolanne to assist you.
We put our trust in Caroleann Gallagher and we were not disappointed , she fought for us all the way to the end of our case . We never were involved in a law suit before and Caroleann helped us through the process and kept us informed of every step. Over time she became more of a trusted friend than our lawyer and we will always be grateful for her hard work.


text:
The sun graced us with all it's glory today.
It was the perfect day to start our nature study with The Nature Connection.
As we listened, drew pictures and wrote the sun warmed our backs and the breeze ruffled our hair. Katie asked me if we could do this every day because "she loved it". Words every home schooling Mom wants to hear!
Mandy chose writing as her way of observing. There is no wrong way. Then she got out her camera and took pictures of the mushrooms that had set up shop in our backyard by way of the recent torrential rains.
We learned the calls of the Redwing Blackbird and the Cardinal. Broken eggs were sited (new baby birds! Killdeer?) but a robin's nest was also destroyed during the rain storms and 5 baby birds will not be learning to fly this year.
The Nature Connection is wonderful in that it guides your study of the outdoors but it lets you make it your own. Each day is a new adventure!
The girls challenged each other at the end of the day to see who could remember the most observations. Nothing like a good friendly challenge to motivate!
I even made my own observations. I truly did not want to go inside. I am hoping to incorporate this into our daily school work. The fresh air and peace of the outdoors is just what frazzled Moms and cranky kids need. Actually, we could all benefit from it.
I recommend buying a copy of this book for you and your child(ren). Summer would be the perfect time to start a nature study whether you home school or not. I purchased one copy on ebay and one on amazon. I believe it is around $10. It's a lovely way to spend time together.


text:
Manufacturing type — Manual laborDesigner — Felix Schwake
Height total ca. 60cmOutside ca. 100cm x 100cmSeat ca. 80cm x 70cmArmrest, ca. 10cmMultilayer piano lacquer, multilayer clear coat, mirror surface polished by hand
Please fill out the form to share this content.
This model has been added to your "whish-list" and now it can be requested.


text:
There are many steps to building a successful high school football program. There, of course, is a need for committed coaches and players. That goes without saying.
Building a program at the lower levels is vital, too.
In addition, a program needs a good training staff, as well as volunteers who enjoy teaching kids the game.
It's not an easy proposition. And then there's the extra perks that not all programs can provide.
At Wayne Hills, a championship style program has been in effect for nearly two decades. And the commitment not only comes from the administration, coaches and players. There's also a tremendous amount of work from a number of the players' parents, mainly the moms.
Starting in early August, and lasting until school starts in September, the football players enjoy breakfast, or lunch, before, or after practices, in the school cafeteria. During the season, there's a beautiful dinner served before games, or if it's a Saturday contest, breakfast is offered to the players.
THANK YOU SO MUCH, TO (left to right), Lynn Pellegrino, Stephanie Petracco, Albina Sportelli, Terriann LoVerde, Ann Fiumarelli, Jill Gawrych, Cindy Skiba and Sandy Kenny, for doing so much to keep the football program at Wayne Hills thriving once again.
And I'm not talking about a small portion of food. The Wayne Hills football moms go out of their way to make sure everyone has seconds. And the mothers are there to serve the food, and they ask for nothing in return.
The players have long appreciated what their parents do to make a game day extra special. And the players reciprocate, but honoring their mothers at the Mother-Son brunch in October, and the Father-Son Beefsteak on Thanksgiving Eve.
Wayne Hills football coach Wayne Demikoff couldn't say enough good things about the work the football moms (and dads) perform.
"They're incredible," said Demikoff. "There are no other words. Breakfast before practice, lunches in between double sessions. Pre-game meals, that are so delicious. There's nothing like it. On behalf of our coaches and players, a huge THANKS to everyone who helped make this such a great season, once again."


text:
"As good as the 2011 Mustang GT 5.0-liter car is, there will always be room for improvement. One of the companies with a long history of doing exactly that is ROUSH Performance. About the time you read this, ROUSH Stage 2 Mustangs will be shipping from their Livonia, MI, factory to customers all over the country."
Read the full story: 2011 ROUSH Stage 2 Mustang is a Track Warrior (StangTV)


text:
Narrandera hospital nurses are still subjected to regular threats and abuse; are working long hours in isolation; and left "very vulnerable" due to lack of security staff, according to the NSW Nurses Midwives' Association (NSWNMA).
The NSWNMA said they are yet to receive a response from NSW Government to concerns over nurse safety and workloads raised in a protest rally in Narrandera in August.
Linda Sommerfield, local secretary for the NSWNMA, said, "Nurses are verbally abused and threatened on a weekly if not daily basis. There have also been a number of [incidents of] physical violence.
"The security guard is rostered for five, eight-hour shifts [per week], leaving nurses very vulnerable when he's not there."
Murrumbidgee Local Health District (MLHD) – the NSW Government regional body who make staffing decisions for the hospital – denies suggestions they are ignoring concerns surrounding nurse safety and patient care.
"The safety and wellbeing of our nursing staff, patients and visitors is paramount and violence and abuse is not tolerated," a MLHD spokesperson said.
The spokesperson said Narrandera hospital received $55,300 for a duress alarm upgrades, which was completed in August 2016.
The MLHD spokesperson did not mention any more recent measures taken in response to incidents of verbal and physical abuse against nurses at Narrandera hospital after August 2016.
Nurses are unable to speak out about the details of abuse incidents because they arebound by confidentiality clauses in their contract and code of conduct.
Ms Sommerfield wants to see a security guard present at the hospital after office hours every day and night of the week.
"Do we really have to wait until a nurse gets seriously hurt before something is done?
"We don't want to be on the front page of the news or on the news headlines, like other hospitals have been in the past with nursing staff recently with being assaulted or harmed."
"Metro hospitals have fulltime security personal and more nursing staff working."
While Sydney hospitals have rules around the ratio of nurses to patients that must be in the hospital, country hospitals like Narrandera do not.
NSWNMA are campaigning for the government to mandate patient to nurse ratios across all regional hospitals.
Ms Sommerfield is concerned that no nurse is rostered on to look after the Emergency Department (ED) in Narrandera. Instead, general ward nurses cover ED when required.
"The nurse who leaves the ward to attend to ED presentation works in isolation and a lot of the time it will be for the whole shift. There is no one to relieve them. This nurse is often exhausted and hungry".
In response to this claim the MLHD spokesperson said, "the hospital has the ability to roster additional staff during busy periods to ensure patient and staff safety".
Ms Sommerfield said, "nurses are already working excessive hours. "There is no one to call on to cover extra shifts. We have had agency nursing staff working at the facility for a number of months now."
She said a doctor shortage in town was also putting increasing pressure on Narrandera hospital nurses "Sometimes, there are no doctors on call in town which is the case more often of late.
This then increases presentation to the emergency department and workload of nurses," she said.
"It's hard to get doctors here. We are very lucky to have the wonderful doctors we have who work extremely long hours to care and provide a service for our community."
"[But] people are coming to the hospital sicker because they can't get into a doctor or cannot afford one to due to financial hardship.
"We are asking for a nurse to be rostered to work in the emergency department independent from the ward and in addition to current staffing levels across all shifts.
"We are very lucky to have such a beautiful hospital and such a great community… but if we lose our hospital, what then?"
NSWNMA are asking the community to contact their local MP to let them know they support their campaign for better staffed country hospitals.
They also direct people to their Facebook page www.facebook.com/safe patientcare
The union campaign coincides with the release of government survey which reveals bullying and harassment by senior managers rife across NSW public hospitals.


text:
Construction Consumer Products Metals & Materials Safety Environment Transportation Chemicals Energy Medical Quality
Proposed Standard for Laboratories Working With Cannabis
ASTM International's cannabis committee (D37) is developing a proposed standard that will provide recommendations for laboratories involved in the industry.
According to members, the standard (WK63913) will outline best lab practices, recommended certifications, various types of analyses, and the quality assurance functions for labs working with cannabis. Cary Black, consultant for Orion GMP, added that the standard will address issues that may be unique to such labs, including personnel, security, sample handling and disposal, and data management and reporting.
"Whether it be the determination of purity, levels of pesticides or terpenes, or other analytes, consistent procedures across the industry are required," says Black.
Laboratories analyzing products from the cannabis industry will find the standard useful as it aims to represent best practices across the industry with strategies that are consistent with various regulatory agencies and governing bodies.
ASTM welcomes participation in the development of its standards. Become a member at www.astm.org/JOIN.


text:
AbleData does not produce, distribute or sell any of the products listed on this website, but we provide you with information on how to contact manufacturers or distributors of these products. If you are interested in purchasing a product, you can find companies who sell it below.
Removable Page Fluffers are do it yourself page turners designed for children with disabilities to turn the pages of a book.
Step One: Chose one of the following materials.
Step Two: Glue any of the above options to a square of tagboard, making it removable.
Step Three: Choose one of the following materials and attach to the above material chosen.
To improve your search results use quotation marks when searching for a specific phrase.
For example, if you search for substance use, a search WITHOUT quotation marks would find listings that include the words
"substance" OR "use." A search WITH quotation marks ("substance use") would find listings only with the whole phrase "substance use."
Are you sure you want to delete this item?


text:
Real Estate
If you want to fix or restore your home, home improvement grants present free money to Individuals who can use some financial help in the case of protecting the cost of house repair. They offer assets for home reworking, repairs, and enhancements. Technology shortly becomes outdated, so investing in new wiring, and other home office parts, will not generate further revenue at the time of the sale. The Capital Area is filled with dwelling enchancment professionals that may show you how to design, create, and keep your dream home and yard.
Dwelling enchancment is the fervour homeowners undertake to keep up the look and worth of their property. Based on Transforming's Price VS Worth chart , which measures the average price for residence enchancment tasks that retain their value at resale, householders that installed a picket deck recouped on average almost 75 percent of the venture's value once they sold the home.
Residence Enchancment Guide
A simple home design software program may also help you visualize your venture.


text:
Kubrat Pulev has been suspended by the Californian State Athletic Commission until July and ordered to attend a sexual harassment prevention class after grabbing a female reporter by the face and kissing her on the lips.
The Bulgarian boxer attended a CSAC hearing on Tuesday to listen to a tearful testimony by the interviewer, Jennifer Ravalo, following the incident after a boxing match in March.
Pulev, a heavyweight contender known as "The Cobra," was was given a four-month suspension backdated to the incident and ordered to attend sexual harassment prevention classes and pay a $2,500 fine before he can fight again in the state of California.
Pulev, who has only one loss in 27 fights, grabbed Ms Ravol's face and kissed her in the middle of a live interview moments after knocking out Romania's Bogdan Dinu in the seventh round of a March fight in Costa Mesa, California.
One of Bulgaria's most popular sportsmen, Pulev apologised for his actions during the hearing as his girlfriend, the Bulgarian pop star Andrea, sat behind him, wearing dark glasses.
Attorneys for Pulev said that the fighter had got caught up in the moment following his big win and "didn't have his wits about him" when he kissed the reporter.
Pulev and his lawyers argued in the hearing that Ravalo did not appear to be very upset about the incident because she joined the boxer and his team at a post-match celebration later that night.
But Ravalo said in tearful testimony that Pulev also grabbed her buttocks off-camera following the interview, leaving her feeling humiliated, and has not apologised in the two months since.
"I did not want him to kiss me," Ravalo said.


text:
As someone who knows quite a bit about HC, it's not surprising the for profits are fighting Colorado's bid for Single Payer big time as keeping the system as dysfunctional as it is is good for business because, as the esteemed Gordon Gekko so famiously said, "Greed is good.".
Coloradans for Coloradans, an ad-hoc group opposing single payer in Colorado, revealed that it raised $1 million over the first five months of this year. The group was formed to defeat Amendment 69, the ballot measure before voters this year that would change the Colorado constitution and permit a system that would automatically cover every state resident's health care.
The anti-single-payer effort is funded almost entirely by health care industry interests, including $500,000 from Anthem Inc., the state's largest health insurance provider; $40,000 from Cigna, another large health insurer that is current in talks to merge with Anthem; $75,000 from Davita, the dialysis company; $25,000 from Delta Dental, the largest dental insurer in the state; and $100,000 from SCL Health, the faith-based hospital chain.
Under the new system, there would be no health insurance premiums or deductibles, and all health and dental care would be paid for by the state through a new system called ColoradoCare. The plan calls for raising $25 billion through a mix of payroll taxes, along with bringing down costs through negotiations with providers.
The filing reveals that the anti-single-payer group has retained the services of Global Strategy Group, a Democratic consulting firm that has served a variety of congressional candidates and is currently advising Priorities USA Action, one of the Super PACs backing Clinton's bid for the presidency.
Just another reason why Bernie is the choice for yours truly. :)
When you listen to this, the corruption of WS is clearly revealed for all to see.


text:
CMMI Level 3 Company
We help large businesses to seamlessly migrate large volumes of content from their existing platforms to the Kentico CMS through our Kentico Migration and Upgrade services.
Raybiztech has the largest team of Kentico certified developers, with excellent expertise to provide best Kentico upgrade services to our clients to make performance improvements.
Drop us a line and we'll get in touch with you as quick as we can
It seems you have already submitted the contact request. We have received your request and get back to you soon!


text:
APCOA Parking (UK) operates across the on and off-street sectors, employing around 2,300 people. The company is part of a European group managing 1.4 million parking spaces in 17 countries. In the UK APCOA has over 80 off-street contracts, working in sectors such as airports, rail, hospitals and... continue
An unlikely name has cropped up in the world of civil enforcement. Balfour Beatty, best known for its construction projects, which has formed a partnership with North East Lincolnshire Council to manage both on and off-street parking. But civil parking enforcement (CPE) is just one of a broad range... continue
Britannia Parking operates a mix of permanent multi-storey car parks and temporary sites awaiting development. Founded in 1989, Britannia Parking has been operating in the parking industry for over 20 years and is owned and controlled by its directors. Britannia's portfolio is based around a... continue
CP Plus has built its business by specialising in the off-street sector,... continue
Creative Parking Solutions lays claim to being the first operator to offer enforcement of off-street car parks using automatic number plate recognition (ANPR). The company launched its proprietary TrafficGuard ANPR system in 2004 to monitor both limited free parking and paid-parking areas. Vehicles... continue
CSP has been specialising in venue and event parking management since winning contracts to run... continue
Empark, which operates some 375,000 spaces across Europe, has been operating in the UK for three years. Its biggest... continue
Euro Car Parks (ECP) has been active in the UK parking sector for more than 30 years, building up a portfolio of... continue
Excel Parking Group is a family of parking operators that work across the country, serving both public and private sector clients. Excel Parking Services focuses on the management of off-street car parks in town centres, at shopping centres and locations such as the rail and health sectors. Key... continue
Gallan Parking is a recent entrant to the town and city centre parking sector, specialising in turning underused derelict or vacant land into car parks. Launched in 2009 by... continue
The Green Parking brand made its UK debut at Parkex 2011, offering to undertake off-street parking... continue
Legion Parking Services' lineage dates back to the 1920s, when it started life as the Royal British Legion Parking... continue
MET Parking Services specialises in running both public and office car parks for private sector clients such as retailers, fast-food outlets and property companies. The company focusses on the use of automatic number plate recognition (ANPR) technology to monitor paid, limited waiting and... continue
Infrastructure and business services group Mouchel seeks to provide all aspects of the parking service from policy through to operation, allowing clients to select individual elements or procure a full service from initial policy development through to contract management. In developing... continue
National Car Parks, or NCP, has long been shorthand for car parking in Britain. Even after... continue
NSL Services has established itself as the market leader in the on-street parking enforcement sector, undertaking civil... continue
Observices Parking Consultancy (OPC) offers a range of parking management and enforcement solutions for landowners on a nationwide basis. The Hertfordshire-based company will patrol both public and staff parking areas, setting up payment and permit schemes where required. It also undertakes... continue
Ontime Parking Solutions is now providing a 'one-stop shop' parking enforcement service covering all parking and moving traffic... continue
Management company Parking Professionals is building up a portfolio of sites in London. For example, it has a five-year contract to run the car park at London's Wimbledon Bridge House — known locally as "The fridge on the bridge". Parking Professionals worked closely with... continue
Q-Park is a parking company that owns, leases and manages parking facilities across Europe.... continue
Hard work and determination have seen RCP Parking buck the economic trend this year – with new sites opening amid delight that the business... continue
Emma Sinclair, chief executive of Target Parking, was named Business Woman of the Year in the 'Start Up' Category... continue
Total Car Parks was launched in 2007 by Essy Eslamian, who has a senior management background in the hotel and restaurant businesses. Eslamian was keen to... continue
Town & City Parking (TCP) is an operator working for retailers and landlords in the private and public sector. The company, which is based in Perth, Scotland, has a nationwide reach. The company generates an annual turnover of £16m from the 1,100 car parks it runs for key clients such as... continue
Town Centre Car Parks (TCCP) is a division of Town Centre Securities, a Leeds-based property investment and... continue
Improving the perception of parking is a challenge that companies like VINCI Park UK are intent on tackling. Based in Watford,... continue
There are about 150,000 rail parking spaces across... continue
Local authorities often see outsourcing the enforcement, notice processing, car park management and... continue
Parking is a vital component of the Land Securities... continue
When a car is left without permission on private land, or overstays its allotted time in a... continue
A 'Charter for Hospital Parking' published by the British Parking Association (BPA) is backed by the NHS Confederation and the Healthcare Facilities... continue
Cranes on the skyline are a good indicator of a healthy economy. So, the... continue
Besides daily and season parking fees, there are several ways in which car parks... continue
More car park operators seem to feel that drivers place the cost of parking above location when... continue
Some 297 local authorities in England and Wales conduct civil parking enforcement (CPE) under the... continue
The on-street parking enforcement market is currently dominated by three major contractors — APCOA, NSL Services and VINCI Park... continue
There has been some consolidation in the UK parking market in... continue
The UK parking management sector is quite a diverse one, with a group of major international players at its... continue
Parking is an essential service in towns, cities, at airports, shopping centres, rail... continue
Car parking is everywhere, yet for drivers there often never seems to be enough space in the right place at just the right... continue
TransportXtra is part of Landor LINKS
© 2020 TransportXtra | Landor LINKS Ltd | All Rights Reserved
Subscriptions, Magazines & Online Access Enquires
[Frequently Asked Questions]
Email: firstname.lastname@example.com | Tel: +44 (0) 20 7091 7959
Shop & Accounts Enquires
Email: email@example.com | Tel: +44 (0) 20 7091 7855
Advertising Sales & Recruitment Enquires
Email: email@example.com | Tel: +44 (0) 20 7091 7861
Events & Conference Enquires
Email: firstname.lastname@example.com | Tel: +44 (0) 20 7091 7865
Press Releases & Editorial Enquires
Email: email@example.com | Tel: +44 (0) 20 7091 7875
Privacy Policy | Terms and Conditions | Advertise
Website design by Brainiac Media 2020


text:
Here are my current beauty favs! I hope you loves enjoy… I have also linked everything down below for you! 🙂
Fenty Lip gloss – https://rstyle.me/n/c3mxfrcb7hx
PCA Acne Gel – https://rstyle.me/~awkhj
Balm Dot Com – https://rstyle.me/n/cyqb26cb7hx
Glassier Concealer – https://rstyle.me/n/c6rgukcb7hx
Dermilogica exfoliant – https://rstyle.me/~awkhK
Rose Quartz face roller – https://amzn.to/2N5Sm45
Infinity Sun Self Tanner – https://amzn.to/2umATwF
Maybelline Master Chrome Highlighter – https://amzn.to/2zrGwiT
Beauty Blender Cleaner – https://rstyle.me/n/c5zgercb7hx
Urban Decay Petite Heat palette – https://rstyle.me/n/c5zgmccb7hx


text:
1) Victoria Street, Manchester; 2) London Road, Manchester
Arthur Fitzwilliam Tait
- Art Funded
- 2007
- Dimensions
- 61 x 86 cm
- Vendor
- Michael Fulda, Fulda Gallery
Victoria Street, Manchester is taken from the front of Manchester's Exchange building and the bridge in the distance carries the main line railway into the then newly-built Victoria Station. London Road, Manchester is taken near the junction with Auburn Street and the ramp leads to London Road (now Piccadilly) Station. Paintings of Manchester from this time are very rare and these works give a very vivid impression of the look and atmosphere of the city in the mid 19th century.
Clarendon Gallery, Manchester; Raymond Slater, NW Holz; Bonham's, 2002; Michael Fulda.
Manchester Art Gallery
Mosley Street, Manchester, Greater Manchester, M2 3JL
0161 235 8888
Opening times
Monday 11am–5pm. Tuesday-Sunday 10am–5pm, including bank holiday Mondays. First Wednesday of every month open until 9pm. Closed Good Friday, 1 January, 24–26 and 31 December.


text:
Current stop: Sri Lanka
The countryside wore a dress of green and white–tea bushes and waterfalls. A delicate sweep of rolling hills that gave way to the great rain forest Sinharaja beyond.
I will be honest: I picked this book because I was out of town and finished my previous book and forgot to pack another, and this was a cheap Kindle download. I have learned my lesson and will do a bit more research in the future.
This book just wasn't for me. The tale was too romanticized and the dialogue was especially unbelievable. As a character proposes, he says to his beloved "love of my life, beat of my heart, rose of my garden, foam on my beer, cherry on my ice-cream sundae, will you marry me?" I…I just can't get on board with that. Do people really talk like that? I find it hard to believe, and I personally would not take any seriously if they said something like that to me. I just don't buy into over-the-top romanticism.
The plot itself was disjointed and choppy. The main character, Khadeeja, is (understandably) upset when, after her father's death, she finds out that she was adopted. I had a lot of issue with the way her adoption was treated–basically, Khadeeja was a cute little girl the mother stumbled upon and decided she just had to have, and adopted without even consulting her husband. How could you do that to a child? Adoption, just like conceiving a child, is an important discussion that should be had between both parents. I took issue to the fact that this wasn't even looked at as a strange or unusual thing, it was basically just a side note in the story. When this type of controversial event occurs in a novel, I like there to be some criticism or unpacking by the characters, but it was woefully lacking.
Khadeeja, in her anger at discovering she was adopted, goes on a personal journey that leads her to meet a young man. Around this point I almost gave up on the novel. He was, from the very beginning, a complete and utter asshole. Yet for some reason we are supposed to forgive him and we are supposed to root for a relationship to form between him and Khadeeja, we're supposed to feel sorry for him (he had a terrible childhood!) but none of this excuses the selfish, abusive behavior he inflicts upon Khadeeja.
The writing is choppy, the dialogue forced, time lines shift in a confusing manner, and there are weird moments where the story is suddenly told through emails or letters which just does not flow well with the style of the rest of the novel. It was depressing to me to have serious issues brought up (adoption, abuse, etc) with absolutely no thoughtful analysis.
I kept hoping that the characters would engage in some critical thought or an important lesson would be learned, but I was disappointed. I did enjoy the descriptions of Sri Lanka (when description was present–the book really is almost entirely painfully written dialogue), and I will say I would love to actually visit someday.
I know it doesn't really matter, but I also despise the cover of this book. It has no connection to the content whatsoever.
Next stop: Bangladesh.


text:
0 Pre-Owned 2013-nissan-altima-4dr-sdn-i4-2-5-sv Terre Haute Indiana
Sorry, no exact matches were found
You can modify your search criteria and try again. Otherwise, you can use our Auto Finder to be notified of new matches by email. You can also call our sales team at (833) 202-0575 for help locating the perfect vehicle at Engine5 Responsive!
Here are some other vehicles you may be interested in:
#P611, 44,817 mi
#P611, 44,817 mi, TWILIGHT, Sport Utility, AUTOMATIC, FWD
#P613, 37,930 mi
#P613, 37,930 mi, BLK CHERRY, Sport Utility, AUTOMATIC, FWD
#P511A, 90,692 mi
#P511A, 90,692 mi, SIGNAL RED, Sport Utility, FWD
#P561A, 96,111 mi
#P561A, 96,111 mi, Sterling Gray Metallic, Sport Utility, AUTOMATIC, FWD
#P608, 75,175 mi
#P608, 75,175 mi, SILVER, 4dr Car, AUTOMATIC, FWD
#K810A, 159,279 mi
#K810A, 159,279 mi, Tuxedo Black Metallic, Sport Utility, AUTOMATIC, 4WD
#P596, 76,991 mi
#P596, 76,991 mi, SNOW WHITE, Sport Utility, AUTOMATIC, FWD
#P595, 92,799 mi
#P595, 92,799 mi, Ruby Red Metallic Tinted Clearcoat, 4dr Car, AUTOMATIC, FWD
#P593, 79,584 mi
#P593, 79,584 mi, Monsoon Gray metallic, 4dr Car, AUTOMATIC, AWD
#P589, 50,869 mi
#P589, 50,869 mi, DARK GRAY, Sport Utility, AUTOMATIC, FWD
All pricing and details are believed to be accurate, but we do not warrant or guarantee such accuracy. The prices shown above, may vary from region to region, as will incentives, and are subject to change. Vehicle information is based off standard equipment and may vary from vehicle to vehicle. Call or email for complete vehicle specific information.


text:
Writer-director-actress Katie Aselton has some good mumblecore pedigree. She's married to Mark Duplass. After screening her new film The Freebie at Sundance, she's taking it to SXSW. Aselton and Dax Shepard play a couple who decide to spice up their love life by agreeing to let each other have a one night stand, no strings. The combination of sexual license and challenge is reminiscent of last year's Humpday. Doesn't exactly set the pulses racing, so we'll have to wait to see how this one plays out.
Tags: Dax Shepard, Katie Aselton, Sundance Film Festival, SXSW Film Festival, The Freebie


text:
CLEAN CARFAX/ ONE OWNER/ BACKUP CAMERA/ SUNROOF/ BLINDSPOT MONITOR/ LEATHER/ HEATED SEATS/ DUAL ZONE AUTOMATIC CLIMATE CONTROL/ ALL WHEEL DRIVE!! The 2015 Honda CR-V enriches its class-leading formula with a host of improvements, including much better fuel economy. If you're shopping for a top-shelf compact SUV, the CR-V remains one of your best bets. The EX-L adds roof rails, heated side mirrors, an auto-dimming rearview mirror, dual-zone automatic climate control, leather upholstery, satellite radio and a seven-speaker sound system. Advertised offer to those who finance through the dealership with $1995 down. Free one year warranty is added to any warranty that you purchase. Call today and speak to any of our many sales associates who will gladly assist you in anything you may need to become its next proud owner.
Sport Utility
4 Cylinder Engine, 4-Wheel Disc Brakes, A/C, A/T, ABS, Adjustable Steering Wheel, All Wheel Drive, Aluminum Wheels, AM/FM Stereo, Auto-Dimming Rearview Mirror, Automatic Headlights, Auxiliary Audio Input, Back-Up Camera, Bluetooth Connection, Brake Assist, Bucket Seats, Cargo Shade, CD Player, Child Safety Locks, Climate Control, Cruise Control, CVT Transmission, Daytime Running Lights, Driver Adjustable Lumbar, Driver Air Bag, Driver Illuminated Vanity Mirror, Driver Vanity Mirror, Engine Immobilizer, Floor Mats, Fog Lamps, Front Head Air Bag, Front Side Air Bag, Gasoline Fuel, Heated Front Seat(s), Heated Mirrors, Intermittent Wipers, Keyless Entry, Leather Seats, Leather Steering Wheel, MP3 Player, Multi-Zone A/C, Passenger Air Bag, Passenger Air Bag Sensor, Passenger Illuminated Visor Mirror, Passenger Vanity Mirror, Pass-Through Rear Seat, Power Door Locks, Power Driver Seat, Power Mirror(s), Power Steering, Power Windows, Privacy Glass, Rear Bench Seat, Rear Defrost, Rear Head Air Bag, Satellite Radio, Security System, Stability Control, Steering Wheel Audio Controls, Sun/Moon Roof, Sun/Moonroof, Temporary Spare Tire, Tire Pressure Monitor, Tires - Front All-Season, Tires - Rear All-Season, Traction Control, Trip Computer, Variable Speed Intermittent Wipers, Woodgrain Interior Trim


text:
Our Process
Our Web Design Process has been designed to gather information about your business and create a product that is truly yours. Our process allows for input, review periods, research, planning and more.
Research & ConsultationOur initial meeting will be focused around gathering details, brainstorming ideas, setting a timeline and setting a budget. Once we've got those items completed, we will start researching and designing simple drafts for your review.
Our content writer will also start helping you organize any existing content or drafting new content.
Our SEO guru will start reviewing your old website & ranking (if applicable) to see what areas need to be improved.
Content, Early Design & ReviewsDuring this period, we will start drafting the rough concepts for your approval. These concepts are interactive and allow you to see an early version of your Website on any device you have available.
Our content writer (if required) will be drafting and working on your final version of your content for your review.
Our review periods will take place in person and we will walk you through each section of the website to answer any questions you may have.
Final Review & Beta TestingWith the preview drafts approved, we finalize and polish up your Website. During this period, we do extensive testing (which may include limited public beta testing) and do one final review session with you.
We also setup on-going maintenance requirements, provide training and setup analytics for various aspects of your website.
The Website is reviewed to ensure it meets the quality standards we expect for all of our work.
Website Launch, & Server SetupYour Website is ready to go live! We setup your server, optimize your Website, setup your SEO, analytics and so much more. You get to sit back and watch the results!
We setup regular meetings and checkups to make sure you have everything you need, and we are always available for support.


text:
Scenarios ERP Business Management Applications
My current accounts solution is going obsolete; what system will adapt to suit my business processes, without paying for additional functionality that I don't need?
This will depend on the size of your organisation and the growth rate expected in the coming years.
We are experiencing inefficiencies within the business, I need a system that gives full visibility on our processes & where we are losing money in order to maximise our performance and margins?
With a fully integrated ERP system G/L postings can be traced right back to original source transactions. With Microsoft Dynamics NAV flexible integration tools enable you to seamlessly integrate with third party systems and powerful reporting tools allow you to monitor your businesses performance.
Webinar: Sophos – The future of IT Security is Synchronized Security
(21/02/2018 at 11:00 - GMT)
Datapac is pleased to invite you to the upcoming webinar from our partners Sophos "The future of IT Security is Synchronized Security" on February 21st at 11am.
Webinar: Intercept X - The most comprehensive endpoint protection
(07/03/2018 at 14:00 - GMT)
Datapac is delighted to extend invitation to the upcoming Sophos webinar "Intercept X - The most comprehensive endpoint protection" on March 7th at 2pm.
"At Barretstown, we rebuild the lives of children, and their families, affected by childhood cancer and other serious illnesses. We serve 5,000 campers a year and have 1200 volunteers each year. Communication is crucially important and Datapac has helped us to streamline, improve and ensure efficiency."
"Datapac has provided us with a fantastic product and world-class levels of service and support. Whenever people ask me about our experience with Datapac I'm always ready to sing their praises and I would happily recommend their services to any organisation."
"For many years Datapac has been our sole supplier for the maintenance of Personal Computers and Peripherals in Ireland. Through their Service Centres in Wexford and Dublin, Datapac provides excellent support to our businesses throughout the country and consistently meets the SLA targets which we have set. The skill, expertise and experience of their engineers and other technical support personnel are of the highest standard."
"The value of dealing with an HP Gold partner in this process can't be underestimated. Datapac provide us with a local touch and can cover the full range of our IT requirements, but when there is a specific technical requirement like this, they can bring the specialist technical resources of HP to the table. HP and Datapac had a thorough discussion with us around our requirement - and had really done their homework - and then were able to provide us with a very highly specified test platform for us to prove the application on before we committed to purchase."
Datapac understands our needs and requirements and has the expertise and experience to follow through on all our requests. Our constant need to reduce costs has been assisted by Datapac's ability to suggest alternative solutions and methods whilst improving both efficiency and productivity. Our partnership with Datapac is akin to having an IT department on site that we simply could not provide ourselves.


text:
DC STEM Network Calendar
- This event has passed.
Broadcom MASTERS Science and Engineering Project Showcase
October 20, 2018 @ 1:00 pm - 4:00 pm
|Broadcom Foundation and the Society for Science & the Public invite groups to attend the Broadcom MASTERS Science and Engineering Project Showcase on Saturday, October 20, 2018 from 1:00pm- 4:00pm. The public is encouraged to come and meet the top 30 Broadcom MASTERS finalists, learn all about their projects, and interact with science organizations. These talented 6th, 7th, and 8th grade finalists are eager to share their enthusiasm for science and engineering with other students!


text: Today in a week I am sitting in an airplane to Oosaka. Today the JRP arrived. All the hotels are booked. And the fligt ticket is ready to be used. The minus 7 days countdown also means, that I have to start to assort my equipent and my cloths. Tomorrow I will check for missing stuff I have to buy. Rechargeable batteries are at the top, since the last times I always got stopped by a dead camera sooner or later. On temperatures below zero a full power cell is crucial, because they will loose half of their capacity. And I need to clean up the house. I will not return from holiday back into this actual existing chaos.


text:
You still need to know where you are and where you are headed. The same is true for annual planning.
You still need to know where you are and where you are headed. The same is true for annual planning.
One thing (unfortunately) that we do know is that most start-up businesses never reach the heights that match the dreams of the founders…yet others are a run-away successes. I'm not yet putting my enterprises in the category of 'runaway' successes – but we are managing to serve many customers, grow, and have a good time while we are doing it. So, we are getting something right.
"Dance with the one that brung ya". Did you know that the same, rather poor grammar rule, also applies to social leadership and even on social media?
Many of these jobs come with very attractive six figure salaries, and for anyone interested in data and analysis, could provide extremely rewarding careers. Demand is likely to rocket, so getting into the industry in its early days could set you up for a future-proofed career.
Most of us don't think successful leaders have an introverted leadership style, since, by all appearances, extroverted people make wonderful public speakers and engaging networkers.
Just like a child, companies take a village to run efficiently. This raises a need for boardrooms. For any board to be effective, it needs to have a strong capable leader.
Register for more Exclusive .CEO Registry Member Features, CEO News and Updates.


text:
Certificates attached to LocationsAnswered
Is there anyway to use your certifications in connection to a location on the schedule?
For Example:
- Cook A is certified on Fryside, Grill, and Sautee, and Fry Open
- Cook B is certified on Fryside, Fry Open
- Cook C is certified on Fryside, Fry Close and Sautee
With that in mind, if I could attach certification to the house shift locations, the scheduler could then WARN me if I schedule someone that is not certified for a position.
If I dropped Cook C on my Wed shift for Fry first on that requires a fry certification and a Fry Opener certification, I should get a warning. However if I drop Cook A or Cook B it should be fine.
In the same manner, if my Float shift on Sunday requires a Grill, Sautee, and Fryside certification, the only cook that I could use to fill that without a warning would be Cook A
If you got REALLY, REALLY crazy, those certifications for the staff should be attached to passing a curriculum in Schoox :)
1 comment
Hello Bo,
Thank you for contacting HotSchedules Customer Care! I apologize for the inconvenience, but this is not currently a function of the software. However, I would be glad to submit this suggestion on your behalf as an enhancement/modification request for our Product Team. These requests are reviewed and prioritized quarterly.
Also, we encourage you to visit our Community and share your ideas there! Other customers can see your ideas and vote on them which gives our Product team great insight into what our customers would like to see. Our community link is listed below:
We always welcome your suggestions to improve our services.
Thank you!
Please sign in to leave a comment.