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Diabetic Cardiovascular Autonomic Nerve Dysfunction
Published Online: November 8th 2011 US Endocrinology, 2007;(2):66-74 DOI: http://doi.org/10.17925/USE.2007.00.2.66
Authors: Aaron I Vinik, Raelene E Maser, Abhijeet A Nakave
Introduction to Cardiovascular Autonomic Nerve Dysfunction
Cardiovascular autonomic neuropathy (CAN), a serious complication of diabetes,1–3 is often overlooked. CAN encompasses damage to the autonomic nerve fibers that innervate the heart and blood vessels, which may result in abnormalities in heart-rate control and vascular dynamics.4 There is now an appreciation that, prior to the advent of structural changes in the autonomic nervous system (ANS), there may be dysfunction (CAND), which can produce quite debilitating symptoms.
Cardiovascular autonomic neuropathy (CAN), a serious complication of diabetes,1–3 is often overlooked. CAN encompasses damage to the autonomic nerve fibers that innervate the heart and blood vessels, which may result in abnormalities in heart-rate control and vascular dynamics.4 There is now an appreciation that, prior to the advent of structural changes in the autonomic nervous system (ANS), there may be dysfunction (CAND), which can produce quite debilitating symptoms. If recognized for what it is, dysfunction of the ANS can be treated by therapeutic manipulations of the ANS using agents that restore balance to the sympathetic and parasympathetic nervous system. If left unbridled, persistent overactivity of the ANS will result in irreparable damage, culminating in hypertension, cardiac muscle dysfunction, and even ultimate failure.
This review discusses the clinical manifestations (e.g. resting tachycardia, orthostasis, orthostatic tachycardia and bradycardia syndromes, hyperhidrosis, sleep apnea, exercise intolerance, intra-operative cardiovascular liability, silent myocardial infarction, and increased risk of mortality) of CAN and CAND. Clinical manifestations of CAN and CAND may affect daily activities and promote life-threatening outcomes. With advances in technology for measuring the ANS, however, early stages of autonomic dysfunction can be identified with the use of independent, simultaneous measurements of sympathetic and parasympathetic function. This review, therefore, also addresses potential therapeutic choices that are available for the correction of functional defects of the ANS.
Epidemiology of Cardiovascular Autonomic Nerve Dysfunction
Determination of the prevalence of any form of neuropathy including CAND is difficult due to methodology differences that occur across studies. Factors that account for the variability of prevalence rates include but are not limited to:
differences with regard to the criteria used to define CAND;
various assessment modalities (type and number of tests performed) used to determine its presence; and
different patient cohorts studied (e.g. clinic versus tertiary referral centers), some of which have known biases.
A review of the literature1,5 confirms the effect of these factors, as prevalence rates ranging from approximately 1% for people with type 1 diabetes with short duration of diabetes6 to 90% for individuals undergoing a pancreatic transplant have been reported.7 Adding to the disparity in reported prevalence rates is the potential for the presence of confounding variables that are risk factors (e.g. age, gender, duration of diabetes, glycemic control, type of diabetes, obesity, hypertension, and history of smoking) and a variety of physiological and pathophysiological factors modulating heart rate variability (HRV) or the development of CAND and the presence of other diabetic complications (e.g. distal symmetric polyneuropathy, retinopathy).8–10 While the variation of prevalence rates across studies illustrates the difficulty of determining the true prevalence of CAND, it has been shown that:
autonomic dysfunction can occur early after diagnosis or even before diagnosis of diabetes;11
the prevalence of CAND increases with age, duration of diabetes, and poor glycemic control; and
other comorbid conditions influence prevalence.
Risk Factors for Altered Heart Rate Variability
Table 1 illustrates some of the risk factors for altered HRV. There is now further evidence that genetic factors may influence the balance between the two major subdivisions of the ANS. Acetylcholine is produced by the enzyme choline acetyltransferase, which uses coenzyme A (AcCoA) and choline as substrates for the formation of Ach. Upon release, Ach is metabolized into choline and acetate by acetylcholine esterase and other non-specific esterases. Choline is then transported back into the neuron, creating a reservoir for further synthesis of Ach. A G/T translocation of the genotype for the choline transporter (CHT1) has now been shown to be associated with a marked reduction in the low/high-frequency measures of HRV, which indicates disturbed sympathetic/parasympathetic balance.12 It has also become apparent that there is a long prodromal phase prior to the advent of structural damage to the ANS in which there is evidence of an inflammatory state preceding the advent of hyperglycemia. Furthermore, it is evident that a variety of polymorphisms are conducive to increasing or decreasing susceptibility to ANS dysfunction, culminating in CAN, as illustrated in Figure 1.
Table 2 summaries the cardiovascular effects of ANS dysfunction. These conditions may manifest as functional syndromes initially, but evolve into structural changes within the ANS.
Resting Tachycardia
Vagal impairment results in resting tachycardia and a fixed heart rate.13 Resting heart rates of 90–100 beats/min and occasional heart rate increments up to 130 beats/min occur. In those with evidence for combined vagal and sympathetic involvement, heart rate returns toward normal, but remains elevated. A fixed heart rate unresponsive to moderate exercise, stress, or sleep indicates almost complete cardiac denervation.14 Thus, heart rate may not provide a reliable diagnostic criterion of CAN unless it is increased (i.e. >100 beats/min in the absence of other causes).
An impaired ANS affects an individual's ability to tolerate exercise.15 Specifically, heart rate and blood pressure responses are reduced,16 along with a blunted increase in cardiac output.17 For diabetic people likely to have CAN, it has been recommended that cardiac stress testing be performed before beginning an exercise program.18 Furthermore, when healthcare providers discuss an exercise program with patients who have autonomic dysfunction, it should be emphasized that the use of heart rate as a gauge of exercise intensity is not appropriate. For these patients the intensity of physical activity can be monitored by using the Rating of Perceived Exertion scale.19,20 This scale utilizes an individual's subjective feeling of intensity. Alternately, the percent heart rate reserve, an accurate predictor of percent VO2 reserve, can be used to prescribe and monitor exercise intensity.19 Although currently there are insufficient data to recommend routine screening using an exercise electrocardiogram (ECG) test for asymptomatic patients, there are some data to support the use of stress imaging to identify diabetic individuals with pre-clinical coronary artery disease, particularly those with other comorbid conditions.21
Primary Hyperhidrosis
Activity of the sympathetic nervous system is essential in maintaining cardiovascular homeostasis.22 An imbalance in ANS activity can, however, result in a number of disturbing clinical manifestations. For example, hyperhidrosis and postural tachycardia syndrome (POTS) may result from overactivity of the sympathetic nervous system.22,23 Primary hyperhidrosis is characterized by profuse sweating and can affect the axillae, face, palmar surface of the hands, soles of the feet, and other areas of the body. It is a problem of sympathetic dysregulation of unknown cause characterized by excessive discharge of sympathetic cholinergic sudomotor nerves.24 The prevalence of hyperhidrosis in a survey sample of 150,000 households, with a response rate of 64%, was 2.9%.23 The prevalence of hyperhidrosis in the US was therefore projected to be ~2.8%.23
Orthostatic Tachycardia Syndromes
POTS is a mild form of autonomic dysfunction characterized by fatigue, exercise intolerance, light-headedness, and near syncope.25 A hallmark of POTS is that, during syncope, an individual's blood pressure is maintained, while heart rate increases dramatically. During tilt table testing, individuals with POTS had an increase of heart rate of ≥30 beats/min or a maximum heart rate of 120 beats/min within the first 10 minutes of being upright that was unassociated with profound hypotension.25 Although the pathogenesis of POTS is complex and heterogenous, POTS appears to be a manifestation of increased cardiac sympathetic nerve traffic and has been hypothesized to reflect compensatory sympathetic activation in response to decreased venous return to the heart.26 Suggested causes for reduced venous return include volume depletion, venous pooling, extravasation, or local sympathetic denervation.27 Although the prevalence of POTS is not clear, studies of POTS patients have reported an increased prevalence in females. For example, in a retrospective study of patients who presented to the Mayo Clinic with POTS during an 11-year period, 132 of the 152 patients (86.8%) were female.28 Bonyhay and Freeman have reported recently that there are physiological differences between males and females in muscle sympathetic nerve discharge characteristics.22 These differences may be responsible for the greater vulnerability of females to the effects of sympathetic fiber loss, contribute to the pathophysiology of POTS, and help to explain the greater prevalence of POTS in female individuals.
Prevalence surveys in the general population estimate that 2% of middleaged females and 4% of middle-aged males have obstructive sleep apnea (OSA),29 while in another study of males with type 2 diabetes a prevalence rate of 17% for OSA was reported.30 Furthermore, one in four diabetic patients with CAN have been shown to have OSA.31
Individuals with OSA have altered cardiovascular variability,32 with increased levels of sympathetic nerve traffic.33 Specific abnormalities of HRV evaluated via power spectral analysis for individuals with moderate to severe OSA compared with controls have been shown to include:
a decrease in the high-frequency component (measure of efferent vagal activity);
an increase in low-frequency normalized units (considered a marker of sympathetic modulation); and
an increase in the ratio of low to high frequency (an indirect index of sympathovagal balance).
Autonomic nervous system imbalance can predispose individuals with OSA to the development of cardiac arrhythmias.34
During sleep, increased sympathetic drive is a result of repetitive episodes of hypoxia, hypercapnia, and obstructive apnea acting through chemoreceptor reflexes.33 Increased sympathetic drive has been implicated in increased blood pressure variability with repetitive sympathetic activation and blood pressure surges impairing baroreflex and cardiovascular reflex functions.32
Several cross-sectional studies have shown a strong association between OSA and hypertension,35–38 with indications that OSA contributes to the genesis of hypertension,39,40 perhaps through an increase in sympathetic tone in the peripheral vasculature caused by chronically occurring repetitive hypoxia and arousal, initiating a rise in blood pressure.41 The etiological link between OSA and the development of hypertension has not, however, gone without debate. The debate has focused mainly around the association between OSA and obesity.42 It may be that the association between OSA and blood pressure involves both an obesity–hypertension link (sympathetic activation induced by obesity exerts tonic vasoconstriction that contributes to the increased blood pressure)43 and an independent role of OSA in the chronic rise in blood pressure.42 A direct relationship between the severity of OSA and the increase in blood pressure has been noted. Furthermore, the use of continuous positive airway pressure (CPAP) for the treatment of OSA has been shown to lower blood pressure44,45 and improve cardiovascular autonomic nerve fiber function for individuals with OSA.46,47 Withdrawal of CPAP for even a short period (i.e. one week) has been shown to result in a marked increase in sympathetic activity.48
A recent systematic review and meta-analysis of studies following effective weight loss in morbidly obese patients after undergoing bariatric surgery has shown that surgical treatment of obesity has striking effects on OSA (i.e. 85.7% of patients experienced resolution of OSA) and hypertension (i.e. 78.5% of patients experienced resolution or improvement of hypertension).49 Surgically induced weight loss has also been recently shown to improve measures of parasympathetic nervous system function six months and one year post-surgery.50 With weight loss, patients with OSA experience increased oxygen saturation and arterial oxygen content while decreasing arterial carbon dioxide levels. These physiological changes affect the neurological pathways (improving autonomic balance) and cerebral centers responsible for respiration. Appropriate therapeutic strategies for the treatment of OSA are patientdependent. However, measuring HRV during sleep has the potential to determine a patient's sympathovagal balance, identify at-risk patients, and assess the effect of various intervention strategies.51 The role of overactivation of the autonomic nervous system is illustrated in Figure 2.
Intra-operative and Peri-operative Cardiovascular Liability
Individuals with diabetes have a two- to three-fold increase in peri-operative cardiovascular morbidity and mortality. In diabetic patients undergoing general anesthesia, heart rate and blood pressure may decline to a greater degree during induction of anesthesia and increase to a lesser degree following tracheal intubation and extubation compared with non-diabetic subjects. It was recently reported, from a study of 50 diabetic patients who underwent an ophthalmosurgical procedure, that the incidence of hypotension during anaesthetic induction for patients with autonomic dysfunction (i.e. an abnormal expiration/inspiration (E/I) ratio) was 51.9% compared with 8.7% for those with normal E/I ratio (p=0.0019).52 Vasopressor support is needed more often in diabetic individuals with CAN than in those without.53 Normally, the autonomic response of vasoconstriction and tachycardia will compensate for the vasodilating effects of anesthesia. This response is, however, reduced in those with CAN. Reduced hypoxic-induced ventilatory drive54 and severe intra-operative hypothermia, causing reduced metabolism of medications and slow wound healing,55 have also been shown to be associated with CAN. Pre-operative screening for reduced HRV will alert the anesthesiologist and surgeon to patients who are at risk for potential intraoperative complications.
Orthostatic Hypotension
Orthostatic hypotension is defined as a fall in blood pressure (i.e. >30mmHg systolic or >10mmHg diastolic blood pressure) in response to postural change (i.e. from supine to standing).56 In some patients the fall in blood pressure may be asymptomatic, while in others it is disabling.57 Normally, a postural change results in activation of a baroreceptor-initiated centrally mediated sympathetic reflex resulting in an increase in peripheral vascular resistance and cardiac acceleration. Damage to the efferent sympathetic vasomotor fibers, particularly those in splanchnic vasculature,58 may result in orthostatic hypotension. In a recent study of 45 males with type 2 diabetes, the presence of sympathetic dysfunction and higher supine blood pressure was shown to be independently associated with the fall in systolic blood pressure during the transition from supine to standing.59
A decrease in total vascular resistance, reduced norepinephrine response relative to the fall in blood pressure, decreased cardiac acceleration and cardiac output, low blood volume, or reduced red cell mass may all contribute to the pathogenesis of orthostatic hypotension. In addition, other factors such as post-prandial blood pooling, the hypotensive role of insulin, and treatment of kidney or heart failure with diuretics leading to volume depletion may aggravate orthostatic symptoms.60 Symptoms of orthostatic hypotension may include weakness, faintness, dizziness, visual impairment, and even syncope following the change from lying to standing. Orthostatic symptoms can be misjudged as hypoglycemia and be aggravated by a number of medications (e.g. vasodilators, diuretics, phenothiazines, tricyclic antidepressants, insulin).
Silent Myocardial Ischemia/Cardiac Denervation Syndrome
Recognition of myocardial ischemia or infarction can be impaired as a result of reduced appreciation for ischemic pain. Figure 3 shows the results of 12 cross-sectional studies in which the frequency of silent myocardial ischemia was compared for those with and without autonomic dysfunction.1 An increased frequency of silent myocardial ischemia was shown in five of the studies. The point estimates for the prevalence rate ratios in the 12 studies ranged from 0.85 to 15.53. In a meta analysis, the Mantel-Haenszel estimates for the pooled prevalence rate risk for silent myocardial ischemia was 1.96, with 95% confidence interval of 1.53–2.51 (p<0.001; n=1,468 total subjects). Thus, a consistent association between CAN and the presence of silent myocardial ischemia was shown. Silent ischemia in diabetic individuals may result either from CAN or from autonomic dysfunction due to coronary artery disease itself, or both. Thirty-nine percent of diabetic patients and 22% of non-diabetic individuals in the Framingham Study had unrecognized myocardial infarctions. The difference was not, however, statistically significant.61 Results from the National Registry of Myocardial Infarction 2 did, however, show a difference. In this study, there were a total of 434,877 patients with a confirmed myocardial infarction. The results indicated that 33% did not have chest pain on presentation to the hospital. Of those presenting without chest pain, 32.6% had diabetes versus 25.4% (p<0.001) in the group with chest pain.62
In diabetic patients with exertional chest pain, a prolonged anginal perceptual threshold (i.e. the time from onset of 0.1mV ST depression to the onset of angina pectoris during exercise), was associated with autonomic dysfunction.63 The prolonged perception of anginal pain permits patients with CAN and coronary artery disease to continue exercising despite increasing ischemia.
Mechanisms that cause silent myocardial ischemia are complex and not completely understood. Possible mechanisms that have been suggested include: altered pain thresholds, subthreshold ischemia insufficient to induce pain, and dysfunction of the afferent cardiac autonomic nerve fibers.64 Results from the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study, an investigation that included 1,123 patients with type 2 diabetes, showed that cardiac autonomic dysfunction was a strong predictor of ischemia.65 Thus, cardiovascular autonomic function testing may be an important component in the coronary artery disease risk assessment of patients with diabetes.
Increased Risk of Mortality
Figure 4 summarizes the results from 15 studies that evaluated the association between CAN and mortality. The follow-up intervals in these studies ranged from one to 16 years. In all 15 studies, the baseline assessment for cardiovascular autonomic function was made on the basis of one or more of the tests described by Ewing.66 Total mortality rates were higher in subjects with CAN at baseline than in those whose baseline assessment was normal, with statistically significant differences in 11 of the studies. The pooled estimate of the relative risk, based on 2,900 total subjects, was 2.14, with 95% confidence intervals 1.83–2.51 (p<0.0001).1 However, if CAN was defined by the presence of >2 abnormal cardiovascular autonomic function tests, the risk increased to 3.45 (confidence interval 2.66–4.47).2
The mechanisms by which CAN leads to increased mortality remain obscure. Three large longitudinal cohort studies addressed the risk of mortality as a result of autonomic dysfunction. The Hoorn Study (a population-based study with 159 persons with type 2 diabetes) demonstrated that impaired autonomic function was associated with an approximately doubled risk of mortality.67 The Pittsburgh Epidemiology of Diabetes Complications Study, a large population-based cohort of 487 type 1 diabetic subjects followed for two years, revealed a relative risk for mortality of 4.03 for subjects with CAN compared with those without CAN.68 Adjustments in differences for markers of renal function, coronary heart disease, and hypertension determined at baseline reduced the relative risk of mortality to 1.37 for this cohort. In another investigation, a study cohort of 197 type 1 diabetic individuals with diabetic nephropathy were matched with 191 type 1 diabetic individuals with normoalbuminuria.69 During the 10 years of followup, 35 and 14% of the patients with and without nephropathy and abnormal HRV, respectively, died. In patients with nephropathy and reduced HRV, the investigators showed an adjusted hazard ratio of 6.4 (95% confidence interval 1.5–26.3; p=0.010) for a composite end-point of cardiovascular morbidity and mortality.
CAN has also been shown to be a significant predictor of death after Cox regression adjustment for perfusion defects.70 Finally, 123I-metaiodobenzylguanidine myocardial scintigraphy and CAN were independent predictors of a cardiac event. These data suggest that alteration of sympathetic innervation may be a contributing factor to mortality.71 Collectively, the results of these studies provide evidence that CAN increases the risk of mortality for people with diabetes
Diagnostic Assessment of Autonomic Function
The assessment of ANS should be based on the results of a battery of autonomic tests rather than on one single test. Both branches of the ANS can be evaluated, as shown in Table 3. HRV can be assessed either by calculation of indices based on statistical analysis of RR intervals (time domain analysis) or by spectral analysis (frequency domain analysis) of an array of RR intervals (see Figure 5). However, HRV alone is only one measure of a system (the ANS) with two independent components (sympathetic and parasympathetic). A second measure is required to fully characterize the two ANS branches, independently and simultaneously. Spectral analysis of both HRV and respiratory activity provides quantitative, independent, simultaneous, non-invasive measures of both autonomic branches (see Figure 5).
Spectral analysis involves decomposing the series of sequential RR intervals into its various frequency components. Traditionally, the sum of sinusoidal functions of different amplitudes and frequencies by several possible mathematical approaches such as the fast Fourier transformation (FFT) has been employed. However, the FFT requires assumptions and approximations to be made about the HRV and respiratory activity signals that are clinically limiting and affect the fidelity of the results. These assumptions and approximations include the need for a compromise between time and frequency fidelity and for the signal to be 'stationary' over the analysis interval. Continuous wavelet transforms (CWT) remove these assumptions and approximations and fundamentally enhance the fidelity of the results. The results (power spectrum) can be displayed with the magnitude of variability as a function of frequency. In other words, the power spectrum reflects the amplitude of the heart rate fluctuations present at different oscillation frequencies.72
The HRV spectrum without respiratory frequency analysis mixes sympathetic and parasympathetic components.73,74 Clinically, this is represented in the cardiogram as a mix of the sympathetically mediated mean heart rate changes coupled with the parasympathetically mediated respiratory sinus arrhythmia (RSA) changes. By adding spectral analysis of respiratory activity, the frequency of RSA is identified, eliminating the mixed measures.72–74 This second independent measure identifies the frequency range of parasympathetic influence on HRV. This frequency range is called the respiratory frequency range. The area under the HRV spectral curve over the respiratory frequency range is a measure of parasympathetic activity. The respiratory frequency range often overlaps the low-frequency range (see Figure 5). The area under the HRV spectral curve over the remaining low frequency range is the sympathetic activity.72
The combination of spectral analysis of HRV with spectral analysis of respiratory activity enables realtime, quantitative, non-invasive, independent, simultaneous measures of parasympathetic and sympathetic activity, both at rest and in response to various challenges. This technique enables early detection and quantification of CAND and CAN in terms that are clinically trendable and reflective of disease progression, therapeutic intervention, and outcomes.75
Commercially available computer programs (e.g. NeuroDiag II, ANSAR) are usually employed to assess autonomic nerve function. Conventional ECG equipment has also be used to compute:
1) coefficient of variation (CV) of RR intervals or spectral power in the high-frequency band at rest;
2) spectral power in the very low-frequency band;
3) spectral power in the low-frequency band;
4) HRV during deep breathing, including mean circular resultant of vector analysis or expiration/inspiration (E/I) ratio;
5) maximum–minimum 30:15 ratio;
6) Valsalva ratio; and
7) postural change in systolic blood pressure.
However, metrics (1) to (3) are measures that mix sympathetic and parasympathetic activity. Metrics (4) to (6) are approximations of changes in parasympathetic activity. The age-related normal ranges of the seven indices included in this battery have been determined. CAN has been defined as the presence of ≥3 abnormalities among these seven parameters (specificity: 100%). Borderline or incipient CAN is assumed when ≥2 abnormal findings are present (specificity: 98%).72,73 However, the progression or severity of CAN cannot be quantified using these measures. If a computer system is not available, the last four parameters should be determined. In this case definite CAN is diagnosed in the presence of ≥2 abnormal findings.
Potential Therapeutic Modalities for Cardiovascular Autonomic Neuropathy (CAN) and CAN Dysfunction
Table 4 summarizes the approach to diagnosis and symptomatic management of autonomic nerve dysfunction.1,74 Several studies have reported that it is possible to improve HRV. Results of the Diabetes Control and Complications Trial showed that improvement in glycemic control reduced the incidence of CAN and slowed the deterioration of autonomic dysfunction over time.6 A reduction of HbA1c from 9.5±0.4% to 8.4±0.5% has also been shown to improve HRV for individuals with early CAN, but autonomic function continued to deteriorate in patients with advanced CAN.75 In the Diabetes Prevention Program, lifestyle intervention (e.g. increased physical activity) improved autonomic function compared with the metformin or placebo arms of the study.76 Support for the notion that lifestyle intervention (e.g. diet, stress management, physical activity) has salutary effects on autonomic function was shown in patients with established coronary artery disease where baroreflex sensitivity increased by 2ms/mmHg.77 Although not all studies have found improved autonomic function as a result of exercise, several studies have shown beneficial effects. For example, Figure 6 demonstrates that walking a dog can shift an individual's ANS activity in favour of parasympathetic activity.78 Improvement in vagal activity with endurance training has also been shown in insulin-requiring diabetic individuals with early CAN.79 Perhaps a potential mechanism for improved nerve function is associated with enhanced cutaneous blood flow, as was found for type 2 diabetic individuals who were chronic exercisers.80
The development of CAN and CAND is a multifactorial process. Thus, it is likely that combination therapies directed at the various components of the pathogenic pathway will be needed to reduce the development of autonomic nerve fiber dysfunction. The Steno-2 study clearly showed that targeting hyperglycemia, hypertension, dyslipidemia, and microalbuminuria reduced the development of CAN.81
Angiotensin-converting enzyme (ACE) inhibition with quinapril for 12 months improved the parasympathetic/sympathetic balance in patients with CAN.82 Angiotensin receptor blockage (ARB) with 100mg/day of losartan for one year has also been shown to improve autonomic dysfunction.83 Furthermore, the investigators in this study showed that the combination of an ACE inhibitor and ARB may be slightly better than monotherapies. Although not studied yet, it would be interesting to examine the effect of even greater blockade of the renin–angiotensin–aldosterone system via the use of the new renin inhibitor. A more comprehensive review of other agents including aldosterone, calciumchannel, and beta blockers and their effect on HRV can be found elsewhere.84 Given that there are therapies that can reorient the functional abnormalities of the ANS toward improved function, the importance of determining the presence of CAN and CAND early cannot be overemphasized.
Autonomic dysfunction can now be divided into a prodromal functional phase manifesting as an imbalance in the autonomic nervous division of the sympathetic and parasympathetic nervous systems. Clinical presentations include hyperhidrosis, orthostatic tachycardia and bradycardia, sleep apnea, and anxiety/depression/panic disorders that, left untreated, culminate in structural changes in a variety of organ systems. Structural damage to the ANS, found in approximately one-quarter of type 1 and one-third of type 2 diabetic patients, is associated with a number of serious complications, including an increased risk of mortality. Various assessment modalities are available to determine the presence of CAND and CAN. Once determination of the presence of autonomic dysfunction has occurred, a number of therapeutic agents are available for the correction of functional defects in the ANS.■
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Chrysostomakis SI, Simantirakis EN, Schiza SE, Continuous positive airway pressure therapy lowers vagal tone in patients with obstructive sleep apnoea-hypopnoea syndrome, Hellenic J Cardiol, 2006;47:13–20.
Phillips CL, Yang Q, Williams A, et al., The effect of short-term withdrawal from continuous positive airway pressure therapy on sympathetic activity and markers of vascular inflammation in subjects with obstructive sleep apnoea, J Sleep Res, 2007;16: 217–25.
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Maser RE, Lenhard MJ, Irgau I, Wynn GM, Impact of surgically induced weight loss on cardiovascular autonomic function: oneyear follow-up, Obesity (Silver Spring) 2007;15:364–9.
Reynolds EB, Seda G,Ware JC, et al., Autonomic function in sleep apnea patients: increased heart rate variability except during REM sleep in obese patients, Sleep Breath, 2007;11:53–60.
Knuttgen D,Wolf M, Trojan S,Wappler F, Respiratory sinus arrhythmia as predictor of blood pressure stability during anaesthetic induction in diabetics, Anasthesiol Intensivmed Notfallmed Schmerzther, 2006;41:233–40.
Burgos LG, Ebert TJ, Assiddao C, et.al., Increased intraoperative cardiovascular morbidity in diabetics with autonomic neuropathy, Anesthesiology, 1989;70:591–7.
Sobotka PA, Liss HP, Vinik AI, Impaired hypoxic ventilatory drive in diabetic patients with autonomic neuropathy, J Clin Endocrinol Metab, 1986;62:658–63.
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India Wins the Asian Space Race to Mars
Indian Space Research Organization scientists and other officials celebrate the success of Mars Orbiter Mission at their Telemetry, Tracking and Command Network complex in Bangalore, India, Sept. 24, 2014.
Indian Spacecraft Successfully Reaches Mars
India has won the Asian race to Mars. India successfully placed a spacecraft into orbit of the "Red Planet" early Wednesday. The spaceship traveled hundreds of millions of kilometers from Earth over a 10-month period.
The Mars Orbiter spacecraft will take pictures of the Martian surface. It will also attempt to identify the amount of methane in the planet's atmosphere.
Scientists have been following the flight from the command center of the Indian Space Research Organization in Bangalore. Officials have named the spaceship "Mangalyaan," which means Mars craft in the Hindi language.
The scientists cheered and shook hands as the spacecraft entered into the orbit of Mars. Before that, they watched for a tense hour as Mangalyaan changed direction and fired its engines for about 24 minutes. The action helped the spacecraft slow down to enter into orbit.
Indian Prime Minister Narendra Modi congratulated his country on the successful flight.
"History has been created today. We have dared to reach out into the unknown and have achieved the near impossible."
Pavalla Bagla spoke with VOA's Victor Beattie from the command center in Bangalore. Mr. Bagla wrote the book Reaching for the Stars: India's Journey to Mars and Beyond. He noted India's success in placing a spacecraft into the orbit of Mars on its first attempt.
"Russia and America both failed in their maiden attempts. So this a glorious moment for India, and India has done it in the very first attempt. It really shows India's great technological progress."
"Could you tell me what you thought the chances were of a successful orbiting of Mars?"
"If you look at the success rate of missions to Mars, there have been, 51 missions to Mars, and more than half of failed. So the possibility of India's Mars orbiter mission, or Mangalyaan, succeeding was less than the flip of a coin, and that India managed to do it in its first attempt really shows the hard work and confidence which the Indian space agency had in its own program."
ISRO scientists and engineers watch Prime Minister Narendra Modi.
Mr. Bagla says the main geopolitical goal of this mission was to be the first in India's Asian space race with China. He adds that the Indian space program has yet to set a date for sending men into space.
Mr. Bagla noted that the success comes just days before Prime Minister Modi's first state visit to Washington, DC. He said Mr. Modi can bring with him a message that India is a nation that now possesses high technology.
I'm Anna Matteo.
*This report is based on stories from VOA reporters Victor Beattie and Anjana Pasricha. George Grow wrote it for Learning English. Caty Weaver was the editor.
orbit – n. the path or way an object travels in space around another object or planet; v. to travel in space around a planet or other object
planet – n. a large object in space that orbits the sun
surface – n. the outer side or top of something
command – adj. done on command or request; v. to order; to have power over something
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redpajama_set_name: RedPajamaCommonCrawl


After a period of relative inactivity, in 1978 Captain Beefheart re-emerged with a new Magic Band and a superb album, Shiny Beast (Bat Chain Puller). To promote it, they undertook a club tour of the US, to the delight of his devoted fans.
The wonderfully energetic show featured here was performed in a 200-seat supper club in Long Island on November 18th 1978 and broadcast on WLIR-FM and finds the band tackling material from the breadth of his career to date.


Fruit Sticks Minis - Blue, now available to Buy online at The Professors Online Lolly Shop as Sku: 3951 - While you are there, check out our other Confectionery too!
Available in a stunning Blue, these sweets will be sure to WOW your guests at your next event.
Other,Sweets of Gold supply this line of confectionery.


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Soylent halts sales of its powder as customers keep getting sick
Rob Rhinehart, Soylent's inventor, pours a glass of the drink in the company's offices in downtown L.A. last year.
(Anne Cusack / Los Angeles Times)
By Paresh Dave
Liquid meal maker Soylent is stopping sales of its flagship powder, warning that a handful of customers reported stomach sickness after consuming it.
Soylent had already halted shipments of its months-old nutrition bar because of customer complaints of diarrhea, vomiting and upset stomachs. In an announcement late Thursday, the Los Angeles company said there appears to be a common ingredient that's causing trouble in the latest version of its nutritional powder and its snack bar. The products share several common ingredients, Soylent said, but the investigation isn't complete.
Backed by more than $20 million in venture capital, Soylent has emerged as one of several popular start-ups hoping to change what and how people eat. Meant to be mixed with water or other liquids, the powder has enough fats, carbohydrates and other nutrients to replace a traditional meal, according to the company. People looking for a quick fix, such as software programmers in Silicon Valley, have become devotees.
On online forums, many Soylent users have continued to support the company -- some expressing disappointment that they won't be able to restock their pantry with bars immediately.
Soylent said there shouldn't be any issues with its premade drinks, which cost slightly more than just the powder. Twenty-eight meals worth of powder sells for $54.
The bar's manufacturer, Betty Lou's, has reportedly told other clients that it passed an FDA inspection this year and that the suspected issues don't originate from its work. Soylent's latest blog post backed the assertion. "Our tests all came back negative for food pathogens, toxins or outside contamination," the company wrote.
Soylent urged customers discomforted by version 1.6 of its powder to toss it. A newly formulated powder and bar that removes likely culprits will be available early next year at the latest, the company said. It vowed to share findings of its ongoing investigation with the FDA.
paresh.dave@latimes.com / PGP
Twitter: @peard33
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Paresh Dave was a Los Angeles-based tech reporter for the Los Angeles Times from May 2013 to September 2017.
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15 Biggest Celebrity Scandals Of 2017
Editorial credit: / Shutterstock.com
Operation Varsity Blues College Admissions Scam 2019: Everything To Know
Who knew that 2017 would end up being so dramatic! From countless sexual assault allegations to extortion and blackmail scandals to child abuse accusations, it is safe to say that this year we have seen it all! Since 2017 is about to finally come to a close, we are counting down the year's biggest celebrity scandals – here are the top 15!
15. Tiger Woods' DUI
Tiger Woods was arrested this past May for DUI after he was found asleep behind the wheel of his car in Jupiter, Florida. The toxicology report revealed that the pro golfer had traces of the painkillers Vicodin, Dilaudid, Xanax, Ambien and THC in his system. In August, he reached a plea deal with prosecutors where he agreed to plead guilty to reckless driving and enter a diversion program, perform 20 hours of community service, attend a workshop where victims of impaired drivers discuss how drunk driving damaged their lives and pay a $250 fine and make an additional donation of $250 to Palm Beach County Victim Services. If he completes all of this, his reckless driving charge will be expunged from his record.
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14. Louis C.K. Sexual Harassment Allegations
In a New York Times report, five women accused comedic actor Louis C.K. of sexual misconduct. Two women, Dana Min Goodman and Julia Wolov, allege that he exposed himself to them in his hotel room when they were hanging out while the three other women accused him of separate acts of sexual misconduct. Surprisingly, the comedian admitted in a statement that the allegations of sexual misconduct were true. "These stories are true. At the time, I said to myself that what I did was okay because I never showed a woman my dick without asking first, which is also true," he said. "But what I learned later in life, too late, is that when you have power over another person, asking them to look at your dick isn't a question. It's a predicament for them. The power I had over these women is that they admired me. And I wielded that power irresponsibly." As a result, FX Networks, which aired his show Louie, has announced that he will no longer serve as executive producer or receive compensation for four other shows he was involved with on FX, and his publicist has quit.
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13. Supergirl Showrunner Fired Following Sexual Harassment Claims
Andrew Kreisberg – executive producer of Supergirl, The Flash, Arrow, and Legends of Tomorrow – was fired this past November by Warner Bros. Television after 15 women and four men accused him of sexual harassment and other physical misconduct. Kreisberg has denied the allegations, claiming that he never inappropriately touched or massaged anyone and that he only made comments about women's appearances as it related to his job as an executive.
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12. Robin Thicke Child Abuse Allegations
Robin Thicke and Paula Patton spent a good portion of 2017 embroiled in a nasty custody battle over their son, Julian. Child services got involved after Julian told school officials that his dad had been spanking him really hard and punching him. A nanny also accused the singer of smoking marijuana in front of Julian and Patton alleged that Thicke showed up to their son's kindergarten graduation drunk. Patton then began restricting Thicke's access to their son and had his custody was temporarily suspended. In court documents, Patton claimed that Thicke had been physically abusive with her during their marriage and had also threatened her multiple times and cheated on her repeatedly. After all of the messiness, the former couple managed to come to come to a custody deal, which was mutually beneficial this past summer.
s_bukley / Shutterstock.com
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11. Harvey Weinstein Sexual Abuse Allegations
In October 2017, The New York Times and The New Yorker broke the news that dozens of women in the entertainment industry had accused Harvey Weinstein of sexual harassment, sexual assault, and rape. Since then, more than 80 women have come forward accusing the producer of such acts. Weinstein has since been fired from his own company (The Weinstein Company) and expelled from the Academy of Motion Picture Arts and Sciences and authorities in Los Angeles, New York City, and London have opened investigations into the disgraced producer.
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10. Mischa Barton Was the Victim of Revenge Porn
In March of 2017, Mischa Barton revealed that she had been the victim of revenge porn after an ex attempted to sell and release a sex tape of her that was taken without her knowledge or consent. Barton took him to court and she was able to get a five-year restraining order against the ex, Jon Zacharias and, as part of the agreement, he agreed to not "sell, distribute, show, give away or assign in any way any intimate photos or videos" of the actress.
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9. Matt Lauer Sexual Assault Allegations
Matt Lauer is one of the latest in the string of men who have been accused of sexual misconduct. He was fired from NBC after a female colleague accused him of inappropriate sexual behavior during the 2014 Sochi Olympics. Lauer apologized in a statement but claimed that some of what was being said was not true or mischaracterized. After his firing, more sexual misconduct allegations were reported, with one of the accusers alleging that the host locked her in his office in 2001 and then sexually assaulted her.
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8. Mel B and Stephen Belfonte Abuse and Blackmail Scandal
Mel B.'s divorce from her husband of 10 years, Stephen Belfonte, has been the most dramatic split this year. She's accused him of forcing her to have threesomes and taping the encounters to use against her if she left him, of getting their nanny pregnant and then forcing Mel to pay the nanny off, and of numerous incidents of physical abuse. She was granted a temporary restraining order against Belfonte after she claimed in court documents that she feared for her safety. The couple finally settled their bitter divorce in November of this year. According to the legal documents, Belftonte has to destroy any compromising videos of Mel and she will have to pay him spousal support for three years. They will also share physical custody of their daughter, Madison, and they have to sell the family home and divide the profits.
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7. Bill O'Reilly Fired from Fox News
Bill O'Reilly got his comeuppance this past April when The New York Times published an article that revealed how Fox News and its parent company 21st Century Fox along with O'Reilly had spent millions reaching settlements with five different women who had complained that he had sexually harassed or behaved inappropriately with them. Once advertisers began abandoning his show, an internal review revealed that more women had accused him of inappropriate behavior and O'Reilly was then fired.
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6. Danny Masterson Fired from The Ranch
Danny Masterson was fired from the Netflix show The Ranch after four women accused the actor of rape. The allegations date all the way back to 2004 when one of the accusers filed a complaint with the LAPD. The day before he was fired, it was reported that one of the accusers had confronted a Netflix exec for the show, Andy Yeatman, about Masterson not being fired from the show despite the rape allegations, and he reportedly said that the company didn't believe the accusations. Since his dismissal, Masterson has released a statement. "I am obviously very disappointed in Netflix's decision to write my character off of The Ranch. From day one, I have denied the outrageous allegations against me. Law enforcement investigated these claims more than 15 years ago and determined them to be without merit," he said. "I have never been charged with a crime, let alone convicted of one. In this country, you are presumed innocent until proven guilty. However, in the current climate, it seems as if you are presumed guilty the moment you are accused. I understand and look forward to clearing my name once and for all."
Featureflash / Shutterstock.com
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5. Kevin Hart Extortion Scandal
This past September, Kevin Hart found himself at the center of an extortion scandal when a model named Monia Sabbag secretly filmed him during an alleged sexual encounter. She reportedly demanded money from the actor in exchange for her not leaking the video; however, she denies having anything to do with the extortion attempt, but did claim to be intimate with Hart three times throughout the month of August. The FBI is currently investigating the extortion attempt, and Hart's wife, Eniko Parrish, who recently gave birth to the couple's first child, is standing by him in spite of his infidelity.
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4. Kevin Spacey Sexual Misconduct Allegations
Oscar-winning actor Kevin Spacey was dropped from his Netflix show House of Cards this past November after Anthony Rapp accused him of sexually assaulting him when he was 14 years old. While Spacey apologized to Rapp, claiming that he didn't remember the incident, more victims have since come forward, accusing the actor of sexual misconduct. Eight House of Cards employees have alleged that he created a "toxic" work environment and displayed "predatory behavior" while London's Old Vic theatre received 20 allegations against the actor for a "range of inappropriate behavior" during his time as the theatre's artistic director. Following the allegations, Netflix cancelled his upcoming Gore Vidal biopic and he was replaced with Christopher Plummer in the movie All the Money in the World.
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3. Ryan Phillippe's Ex Accuses Him of Assault
Ryan Phillippe was accused of assaulting his ex-girlfriend Elsie Hewitt this past summer. The 21-year-old model filed a civil suit against the actor for allegedly kicking, punching and throw her down a flight of stairs after an argument. She initially tried to have him criminally charged, but authorities closed the criminal investigation without filing any charges. She's seeking $1 million in compensation. Phillippe – who has denied the allegations – has filed his own countersuit and has requested that her suit be dropped and has accused her of having broken into his home that night and of trying to extort money from him.
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2. Ed Westwick Rape Allegations
Three women have come forward this past fall accusing former Gossip Girl actor Ed Westwick of sexual assault back in 2014. The first two claim that they were invited to the actor's home by a mutual friend and then were drinking before they passed out in a spare bedroom. On these two separate occasions, both women allege that Westwick then forced himself on them. The third woman claims that he groped her when she went to his house for a party with her ex-boyfriend only to find that the ex and Westwick were the only two there. The actor was set to star in an upcoming Agatha Christie special Ordeal by Innocence, but BBC will not be airing it because one of his victims has filed a police report with the LAPD and an investigation has been opened.
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1. One Tree Hill Showrunner Accused of Assault
Former One Tree Hill creator and showrunner Mark Schwahn has been accused of groping, as well as emotionally and psychologically traumatizing the cast, crew members and the writers on the show, including Sophia Bush, Hilarie Burton and Danneel Harris. Burton claims that his harassment of her began during season three when he decided that she would be his muse and he became the reason that she derailed her acting career after she left the show. Schwahn is currently the showrunner for The Royals; however, 25 women who worked on this set have also gone on record accusing him of harassment and psychological abuse. He has since been suspended and Lionsgate has launched an internal investigation.
Photo by David Fisher/REX
Cate has a B.A. and an M.A. in English Literature and has been the Managing Editor of Fame10 for more than 6 years. Despite having a love for the works of Thomas Hardy, Leo Tolstoy and Lord Byron, she also has an intense fascination with pop culture. When she isn't writing for Fame10, she's planning her next big adventure in Southeast Asia.
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Ideal ground floor apartment for summer holidays. This charming apartment in Ribera del Pez Luna, has a great location, being close to the leisure areas of Sotogrande. It has beautiful views on the marina. The accommodation consists of a living / dining room with access to a covered terrace and garden with views to the Marina.2 bedrooms with bathroom, fully equipped kitchen, marble floors throughout the property and fitted wardrobes in the bedrooms. Features; centralized air conditioning hot / cold. a private parking space.There is a communal area with swimming pool in the complex. Available only in short term rental. Do not hesitate to ask for prices. It has Wifi included.
Please, contact me about ref 155-02479P, ground floor apartment for rent in Sotogrande, or similar properties.


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Ulefone T2 Pro Design Revealed, Launching At MWC 2018
By Kristijan Lucic January 30, 2018, 5:01am
Earlier today, Ulefone has announced that it will announce a new smartphone at the Mobile World Congress (MWC) in Barcelona next month, and the company has just released a new image showing off that device. If you take a look at the provided image above, you will be able to check out the Ulefone T2 Pro from pretty much every angle, so there's not much to hide at this point, well, at least in terms of its design.
The company still did not reveal all that much spec info when it comes to this smartphone, but earlier today, the company did mention that the Ulefone T2 Pro will be the very first smartphone to ship with MediaTek's Helio P70 SoC. Ulefone also confirmed that the Helio P70 will be manufactured using a 12nm FinFET manufacturing process, and that Google's second-gen TensorFlow tech will be a part of the whole package. All in all, that chip is expected to offer really good performance, without being too hard on the battery. Ulefone also reports that the Helio P70 managed to outrun the Snapdragon 660 SoC on AnTuTu, as it managed to score more points overall, as a recent leak suggested. The Ulefone T2 Pro will sport a display with a 19:9 aspect ratio, which is also something that Ulefone confirmed earlier today.
If you take a look at the provided image above, you will notice that the fingerprint scanner is missing altogether, does that mean that the phone will ship with an in-display fingerprint scanner by Synaptics (Clear ID)? Well, it is quite possible, as this will be Ulefone's new flagship. The phone will be made out of metal and glass or it will sport a metal unibody build, one of the two, even though the former seems more probable based on the provided render. The device will also sport really thin bezels, and a notch at the top of its display. A 'chin' will be present below its display, as you can see, and a dual camera setup will be included on the back of this smartphone. As mentioned earlier today, the company will be located at booth 7I61 in Hall 7, from February 26 until March 1, just in case you're nearby.
January 30, 2018, 5:01am
Source: Ulefone Mobile (Twitter)
Android NewsChinese Smartphones


text:
Ada West District is one of the twenty-nine districts in Greater Accra Region, Ghana. Originally it was formerly part of the then-larger Dangme East District in 1988, which was created from the former Dangme District Council, until the western part of the district was split off to create Ada West District on 28 June 2012; thus the remaining part has been renamed as Ada East District. The district assembly is located in the eastern part of Greater Accra Region and has Sege as its capital town.

Background
The district is bordered to the north by North Tongu District and South Tongu District (both in the Volta Region), to the east by Ada East District, to the south by the Gulf of Guinea, and to the west by Ningo Prampram District and Shai Osudoku District. The total area of the district is 323.721 square kilometers. According to the 2010 census, the population of the district is 59,124 with 28,579 males and 30,545 females. The current population based Ghana Statistical Service record is 72,880.

References

Districts of Greater Accra Region

redpajama_set_name: RedPajamaWikipedia


text:
3.75 out of 5 stars from 5774 reviews 5,774
Like PAC-MAN MUSEUM on Facebook
Game Rating: E (Everyone)
E (Everyone)
Buy Game $19.99
Pac-Man Museum is now on Xbox Live! Pac-Man Museum includes 9 classic Pac-Man arcade games, including the original Pac-Man that spread Pac-Man Fever around the world in the 1980s. PAC-MAN stars in a nostalgia-packed collection of the greatest PAC-MAN games of all time. PAC-MAN MUSEUM will include classic PAC-MAN titles as well as newer releases, allowing gamers to play through the evolution of PAC-MAN from his humble beginnings from 1980 through current hits like PAC-MAN Championship Edition and PAC-MAN Battle Royale. To celebrate debut of "PAC-MAN and the Ghostly Adventures", the characters from the cartoon have burst into PAC-MAN MUSEUM! Head to the Pac-Room to check out more than 70 characters and items! Challenge your friends and the best players in the world on your favorite PAC-MAN game with worldwide leaderboards. PAC-Mania lives! Whether it's your first time playing or you are a Pac-Man expert, catch up on your Pac-Man history! It's fever time!
Original release date: 2/26/2014
Developer: BANDAI NAMCO Entertainment Inc.
Publisher: BANDAI NAMCO Entertainment Inc.
Offline players 1 - 4
Game Add-ons (1)
Get it here. Play it there.
Buy Xbox content on Xbox.com. Your Xbox 360 console will automatically download the content next time you turn it on and connect to Xbox Live.
All Game Add-ons
Ms.PAC-MAN
4 out of 5 stars from 134 reviews 134
Description | Share this
http://marketplace.xbox.com/en-US/Product/MsPAC-MAN/dee0e7b3-6ae6-4d99-8bb7-d0523140aca2?cid=SLink
Download "Ms. PAC-MAN"! Namco's Ms. PAC-MAN is one of the most popular video games in American arcade history! Who can forget the countless hours and quarters spent outrunning ghosts and chomping dots? Re-live the retro action with the queen of the arcades!
$4.99 Download to Xbox 360


text:
Russian Cops Searching for Owner of Assault Weapon Left at IKEA
RIA Novosti (Russia)
MOSCOW – A visit to Moscow's popular and crowded IKEA furniture stores can often be a trying experience, but somebody appears to have courted temptation by taking along their Kalashnikov. Russian online media reported Tuesday that police are looking for somebody who left an assault rifle in a coatroom at an outlet of the Swedish retailer in the Moscow suburb of Khimki. The 1974 Kalashnikov and more than 100 rounds of ammunition were discovered Tuesday morning at the... (GunPolicy.org)
Lire l'article complet : RIA Novosti (Russia)
Israël,Canada
Canadian Police Ruling on Handgun May Widen Rifle Magazine Loophole
Global News (Canada)
An RCMP decision on whether to approve an Alberta man's exotic pistol could widen a loophole doubling the legal magazine capacity for semi-automatic rifles. Last year Edward Osborne, a Calgary gun collector and competitive target shooter, imported a Czech-made VZ58 pistol, a shortened version of the popular CZ858 rifle, from the United States. "I like it because it's very unique," he said in an interview. "I like the VZ58 platform in general, and this is one that I'd... (GunPolicy.org)
Lire l'article complet : Global News (Canada)
Call for 'Peace Zones', More Gun Control in Venezuela
InSight Crime (Bogota)
Venezuela's President Nicolas Maduro has announced the creation of "peace zones" and his justice minister said the government should consider stricter gun control, a piecemeal approach in the face of rampant violence. According to El Universal, Maduro said the zones will be enforced through participation from state institutions and citizens, and will be implemented in "public spaces," highways, hospitals, schools and universities. "We have to create a system of... (GunPolicy.org)
Lire l'article complet : InSight Crime (Bogota)


09:00 Invited Lecture: Prof. Peter G. Frick, "Cascades and Dynamo in Fully Developed MHD Turbulence"
15 mins The time-varying nature of the asymmetrical flow of a shear-thinning polymer solution in transitional pipe flow.
15 mins Incorporation of acceleration effects into the one-dimensional-turbulence model, with application to turbulent combustion and shock-turbulence interactions.
13:30 Invited Lecture:Prof. Bettina Frohnapfel, "Skin Friction Drag Reduction in Turbulent Flows"
15 mins Perturbations evolution and streaks formation in turbulent channel flow.
15 mins CAN REYNOLDS STRESS TRANSPORT MODELS BE USED FOR LARGE EDDY SIMULATION?
15 mins "A Dynamic Subfilter-scale Stress Model for Large Eddy Simulations Based on Physical Flow Scales"


Unless you've been living under a rock, you've probably heard a thing or two about the increasingly popularity of installing solar panels on residential roofs as an alternative method to generating power for homes.
There are several reasons people consider this option, whether it be for financial reasons or whether they are committed to go-green, save-the-world initiatives. Certainly there are advantages to going solar in both of these cases.
But whether you are serious about converting to the solar side or whether you simply want to know what the buzz is about, knowing what financing options are at your disposal is helpful and instructive.
Essentially, when it comes to paying for solar power to come into your home, you have two choices: a Power Purchase Agreement (PPA) or a solar lease.
Let's discuss what a solar lease is and what the pros and cons are of this method.
Installing a solar power system for your home involves a lot of moving parts, people and organizations. For you, the customer, you're likely concerned with two things: cost and performance. In short, you want to know how it will benefit you (and be more beneficial than traditional electric power) and what it'll do to your pocketbook.
As you start the process of installing a system for your home, most companies will offer you either a lease or a PPA. Some give you the option, but most do not. With a solar lease, you are actually paying a fixed monthly fee for use of the system. Whereas with a PPA, you are paying according to how many kilowatts of power is generated. The good news about this difference is that no matter how hard your solar system is working, you'll pay the same every month.
Usually, the homeowner, or customer, is not required to pay anything up front for installation of the system.
The lease is usually 15 years. The customer is locked into that timeframe, but the system is transferrable to a new home or in the event a new owner moves into the current home.
In addition to paying a monthly fee, you must pay your traditional utility company for any additional regular electricity you may use.
Your monthly fees typically rise 3 percent to 4 percent per year; however, this is lower than the average 5 percent increases electric companies hand out.
Normally, the solar power provider will handle any needed repairs or maintenance of the system and equipment.
Your ability to secure a lease is dependent upon your credit.
With a solar lease, you may elect to buy the system later or at the end of your lease term at a residual price.
Affordability: You don't have to worry about down payments or up-front costs. Usually, putting any large-scale system in a home is going to cost a significant amount, but your solar power system won't require any out-of-pocket costs at the time of installation.
Flexibility: On the other hand, if you prefer, you may opt to make a down payment, thus lowering your fixed monthly costs.
No hassles: Because it is a lease, you don't own the equipment (think renting an apartment or home versus buying a place of your own), so any needed repairs or replacements won't cost you a dime, and you don't have to do the work.
Fixed monthly costs: Though the rates will go up on an annual basis, throughout the year, your monthly payments will stay the same. There will be no surprise rises in your payment.
If you have poor credit, you might not qualify.
You are not eligible for tax credits.
You are locked into a term, so if you are dissatisfied with the product, you still have responsibility to pay for it each month.


text:
Jameson was diagnosed with Stage 4 Neuroblastoma when he was only 4 months old in October of 2018. Jameson has been brave and handled treatment very well. He has been off treatment since May of 2019 and celebrated his first birthday this summer. He is quickly becoming a toddler and enjoying everything there is to learn through playing and exploring.
"We continue to monitor his progress with monthly tests and scans every three months. So far they've been wonderful," says Jameson's mom, Rachel.
Rachel went on to say, "Angels Among Us was the first charity I was made aware of after Jameson's diagnosis. Their assistance was immediate and abundant. The financial stresses a cancer diagnosis can have on a family are immense. When our world stopped turning, the rest of the world continued to revolve and the bills and responsibilities did not stop when our life as we knew it stopped. Angels Among Us made no hesitation in stepping up and offering the help we so desperately needed. Through Angels Among Us we were also connected with other families walking the same path. The companionship and connections made continue to help us feel like we're not alone in this."
Angels Nation continues to send the Camp family love and support!


You can easily request an appointment for your consultation or fitting by filling out the form below. Have a general question about our services, location, direction and hours? Feel free to call us at 781-335-4700, or email us below.


text:
Q: Cannot for the life of me install Ruby on Mac OSX 10.7.5 I swear, I have seen all the discussions of installing Ruby on stackoverflow...NOTHING helped. I have Xcode 4.1 installed as well as rvm 1.16.19.
libksba is installed.
There's SOME version of Ruby installed somehow but I don't know which version -- because if I execute ANY kind of Ruby command -- "ruby" by itself, "ruby --version," whatever, I get no response, and to get a prompt I have to ctrl/c.
Using RVM or not, whenever I try to install ANY version of Ruby, I get this output:
Error running 'env LDFLAGS=-L/opt/sm/pkg/active/lib CFLAGS=-I/opt/sm/pkg/active/include CPATH=/opt/sm/pkg/active/include -L/Users/Dauber/.rvm/usr/lib ./configure --enable-shared --disable-install-doc --prefix=/Users/Dauber/.rvm/rubies/ruby-1.9.3-p286', please read /Users/Dauber/.rvm/log/ruby-1.9.3-p286/configure.log
There has been an error while running configure. Halting the installation.
ruby-1.9.3-p286 is not installed.

Here's the output from the aforementioned configure.log:
[2012-11-08 20:46:41] env LDFLAGS=-L/opt/sm/pkg/active/lib CFLAGS=-I/opt/sm/pkg/active/include CPATH=/opt/sm/pkg/active/include -L/Users/Dauber/.rvm/usr/lib ./configure --enable-shared --disable-install-doc --prefix=/Users/Dauber/.rvm/rubies/ruby-1.9.3-p286 --with-gcc=clang
checking build system type... x86_64-apple-darwin11.4.2
checking host system type... x86_64-apple-darwin11.4.2
checking target system type... x86_64-apple-darwin11.4.2
checking for C compiler default output file name... configure: error: C compiler cannot create executables
See `config.log' for more details.

Now, a weird thing is that there's no file ANYWHERE in the system called "config.log," so I can't "see" it "for more details."
Another weird thing...I've compiled dozens of C programs on this machine using gcc and gcc-4.2 -- and I just tried AGAIN and they work fine, so I don't know exactly what the deal is there...
I've tried installing from https://github.com/kennethreitz/osx-gcc-installer to no avail; it made absolutely no difference.
This is all on my MacBook, running OSX 10.7.5. What's weird is...I've had ZERO problems on my iMac running the exact same version of Lion...in fact, I didn't even NEED to install Ruby - it happened to have 1.9.2 already on it; I just needed to add Rails and all worked perfectly...what the heck is so different that I can't get this stuff working on my MacBook???
AFTER PRUSSWAN'S LINK:
Long story short, the other post prusswan linked to mentioned that there's a bug in the Rails installer and that /etc/rvmrc needed to be changed. I made the changes but got the exact same error message as before when I tried to install ruby. This is what configure.log says now, though:
[2012-11-08 22:42:08] env LDFLAGS=-L/opt/sm/pkg/active/lib -L/Users/Dauber/.rvm/usr/lib CFLAGS=-I/opt/sm/pkg/active/include -I/Users/Dauber/.rvm/usr/include CPATH=/opt/sm/pkg/active/include ./configure --enable-shared --disable-install-doc --prefix=/Users/Dauber/.rvm/rubies/ruby-1.9.3-p286
current path: /Users/Dauber/.rvm/src/ruby-1.9.3-p286
command(8): env LDFLAGS=-L/opt/sm/pkg/active/lib -L/Users/Dauber/.rvm/usr/lib CFLAGS=-I/opt/sm/pkg/active/include -I/Users/Dauber/.rvm/usr/include CPATH=/opt/sm/pkg/active/include ./configure --enable-shared --disable-install-doc --prefix=/Users/Dauber/.rvm/rubies/ruby-1.9.3-p286
checking build system type... x86_64-apple-darwin11.4.2
checking host system type... x86_64-apple-darwin11.4.2
checking target system type... x86_64-apple-darwin11.4.2
checking for C compiler default output file name... a.out
checking whether the C compiler works... yes
checking whether we are cross compiling... no
checking for suffix of executables...
checking for suffix of object files... o
checking whether we are using the GNU C compiler... yes
checking whether gcc-4.2 accepts -g... yes
checking for gcc-4.2 option to accept ISO C89... none needed
checking whether we are using the GNU C++ compiler... yes
checking whether g++-4.2 accepts -g... yes
checking how to run the C preprocessor... gcc-4.2 -E
checking for grep that handles long lines and -e... /usr/bin/grep
checking for egrep... /usr/bin/grep -E
checking whether gcc-4.2 needs -traditional... no
checking whether the linker is GNU ld... no
checking whether gcc-4.2 -E accepts -o... yes
checking for real target cpu... x86_64
checking for ranlib... ranlib
checking for ar... ar
checking for as... as
checking for objdump... no
checking for gobjdump... no
checking for objcopy... no
checking for gobjcopy... no
checking for nm... nm
checking whether ln -s works... yes
checking whether make sets $(MAKE)... yes
checking for a BSD-compatible install... /usr/bin/install -c
checking for a thread-safe mkdir -p...  -d
use 'mkdir -p' as MKDIR_P
checking for dot... no
checking for doxygen... no
checking for pkg-config... pkg-config
checking for AIX... no
checking for ANSI C header files... yes
checking for sys/types.h... yes
checking for sys/stat.h... yes
checking for stdlib.h... yes
checking for string.h... yes
checking for memory.h... yes
checking for strings.h... yes
checking for inttypes.h... yes
checking for stdint.h... yes
checking for unistd.h... yes
checking minix/config.h usability... no
checking minix/config.h presence... no
checking for minix/config.h... no
checking whether it is safe to define __EXTENSIONS__... yes
checking for cd using physical directory... cd -P
checking whether -Wno-unused-parameter is accepted... yes
checking whether -Wno-parentheses is accepted... yes
checking whether -Wno-long-long is accepted... yes
checking whether -Wno-missing-field-initializers is accepted... yes
checking whether -Werror=pointer-arith is accepted... yes
checking whether -Werror=write-strings is accepted... yes
checking whether -Werror=declaration-after-statement is accepted... yes
checking whether -Werror=shorten-64-to-32 is accepted... yes
checking whether -Werror=implicit-function-declaration is accepted... yes
checking whether -Wall -Wextra is accepted... yes
checking whether -ggdb is accepted... yes
checking whether -fvisibility=hidden is accepted... yes
checking whether -Wl,-unexported_symbol,_Init_* is accepted... yes
checking for special C compiler options needed for large files... no
checking for _FILE_OFFSET_BITS value needed for large files... no
checking for _LARGE_FILES value needed for large files... no
checking whether byte ordering is bigendian... no
checking for an ANSI C-conforming const... yes
checking whether char is unsigned... no
checking for inline... inline
checking for working volatile... yes
checking for long long... yes
checking for off_t... yes
checking char bit... ./configure: line 8508: syntax error near unexpected token `rb_cv_char_bit,'
./configure: line 8508: `    AC_COMPUTE_INT(rb_cv_char_bit, CHAR_BIT,'

So it looks like the ./configure file that's generated generates with a typo or something...

A: Follow this guide which covers how to set up Ruby using RVM.

A: Wow...I can't believe it, but I found the answer to my own question, and it was very DUH.
I should have used the "rvm remove" command -- tried that, and suddenly like magic I can now install any and all versions of Ruby to my heart's content.
Now to see if Aptana will let me create a new Rails project. :)
Thanks for the feedback, all...

redpajama_set_name: RedPajamaStackExchange


text:
New Jamaican Prime Minister Opposes Anti-Gay Discrimination
Evan Hurst January 05, 2012
This is welcome news, indeed, from Jamaica, which has a reputation for being one of the most anti-gay nations on the planet:
Jamaica's newly elected first female prime minister, Portia Simpson Miller, says discrimination against gay people is wrong. "No one should be discriminated against because of their sexual orientation," Simpson Miller said during a recent election debate, adding that unlike her predecessor she would be open to appointing a qualified gay person to her cabinet.
It doesn't mean the nation will change overnight — has the United States? No — but to have such a prominent voice arguing against discrimination is huge.
discriminationhomophobiaJamaica


text:
Q: Hiding specific icons/markers on text generated vector layer I'm displaying a vector layer with pois, generated from a text file:
lat lon icon    iconSize    iconOffset  title   description
56.030325   14.4774116666667    http://www.medinsbiologi.se/hano/Foto.png       -10.5,-25   102_1   UV-foto

Code to draw layer:
        var pois = new OpenLayers.Layer.Vector("Provpunkter",
        {
        projection: map.displayProjection,
        strategies: [new OpenLayers.Strategy.Fixed()],
        protocol:   new OpenLayers.Protocol.HTTP(
            {
            url:        "../poi/DynPOIHano.txt",
            format:     new OpenLayers.Format.Text(
                {
                extractStyles: true,
                extractAttributes: true
                })
            })
        });

The layer shows up fine, and I have added descriptions to each poi. Now I'd like to be able to hide some of these markers depending on icon type, with a button somewhere else on the page. I've tried using features.style:
function hideFeatures() {
    var features = pois.features;
    for( var i = 0; i < features.length; i++ ) {
    features.style.display = 'none';
    }
    pois.redraw();
    }

but I don't seem to be able to identify the layers icons. Are they considered features, icons or markers? I know this can be done with the built-in OpenLayers.Control.LayerSwitcher() and by adding multiple layers, but would like to avoid that approach.

A: You can use an attribute form the feature to determine if the feature should be visible. I haven't tested it, but i think this should work:
$.each(pois.features, function (index, feature) {
  if ( feature.attributes.description == 'UV-foto' )
    feature.style.display = 'none';
});

A: Ok, it seems the "icon" in my text file was not interpreted as an attribute at all, but as an externalGraphics link. Logical off course, I just didn't get it. So now I'm able to access my icons with:
function hideFeatures() {
var feature = pois.features;
        for( var i = 0; i < feature.length; i++ ) {
            if (feature[i].style.externalGraphic == "http://www.medinsbiologi.se/hano/ikon/Foto.png") {
            feature[i].style= { display: 'none' };
            }
        }
        pois.redraw();
        }

Piece of cake... ;)


text:
Library is a social network oriented around knowledge
What is the library of the future? Let me try to reformulate the concept of the library in a vision.
Just as Last.fm is a social network oriented around music or WeRead.com is about reading, library is a social network oriented around knowledge. It is a social organism, so it grows and evolves, just as other organisms do. It is not a machine. It is also an open system in which both its input and output are free. And finally, library is a knowledge technology, it's a way we "know" stuff.
The important collections libraries have are not made of books, but made of people. There are lots of different carriers of knowledge in libraries: books holding knowledge on paper, databases containg knowledge in bits, people having knowledge in heads. People are the most important carriers of knowledge. In them, there's the social and knowledge capital libraries have.
To start social interactions library enables communication in an open, transparent way. Building on top of that, library enables conversation, that is a communication within a set of people known to each other. Library is designed to connect users. It helps to connect expert users within a specific domain. Library provides access to knowledge but also provides access to the holders of knowledge. It offers information services but also enables its users to offer information services to each other.
This is similar to the difference between centralized and peer-to-peer services. Centralized services (such as Napster) have one central source (server, repository) and are therefore highly dependent on it. Peer-to-peer (P2P, such as Skype) model uses multiple distributed sources so the overall function of a system is independent on any of its constituent parts. Library is a peer-to-peer system because it not only offers its own sources and services but also provides a social protocol for users to offer to each other resources they control and services they are able to supply.
Library doesn't organize knowledge but empowers its users to organize it. It enables users to create knowledge in a way so that it can be shared. Public knowledge interactions are recorded and stored for re-use. In this body of recorded knowledge there are explicit links that can be followed. These links make sense because they have meaning. The meaning of link is defined by how it's being used and this meaning is encoded in the link in a structured way. Library enables to link everything and in this way attach a description.
The borders of a library are not clearly defined, so no one can say where it begins and where it ends. But library has a well designed space that it can offer to its users. It provides a habitat for knowledge interaction. It's an environment designed for social interactions and knowledge exchange. In this respect, library provides lots of affordances, it's an opportunity-rich environment.
Library provides an intriguing interface for its users. One part of this interface is the interface for the library, the other part is the interface for interacting with other users. Yet, the interface to a library is transparent for its users. Users don't come to realize that they're interacting with a library. Because it's barrier-free it makes the institution in library's core invisible.
Labels: library
Library is a habitat for knowledge interaction