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L-Carnitine, Acetyl-L-Carnitine, and Propionyl-L-Carnitine
L-Carnitine [known chemically as R(−)--hydroxy--
(N,N,N-trimethylammonio)butyrate; molecular weight:
161.2 g/mol] is a water-soluble quaternary amine that facilitates
lipid metabolism.
Only the L isomer is biologically
active. Humans acquire varying amounts of L-carnitine
from dietary sources, but a dietary requirement has not
been established. The goal of this chapter is to survey the
literature on the clinical findings on L-carnitine and its esters
acetyl-L-carnitine and propionyl-L-carnitine. Due to
space constraints, this is not an exhaustive review. Readers
are directed to the references for more information.
The human body synthesizes L-carnitine from the essential
amino acids lysine and methionine in amounts that are
limited but adequate for the maintenance of normal health
(1). L-Carnitine participates in reversible transesterification
reactions, in which an acyl group is transferred from
coenzyme A to the hydroxyl group of L-carnitine (Fig. 1).
Acetyl-L-carnitine, propionyl-L-carnitine, and other esters
are biosynthesized in this manner. Carnitine and acetyl-Lcarnitine
(and lesser amounts of other esters of carnitine)
are also obtained from the diet (1).
Transfer of Long-Chain Fatty Acids from Cytoplasm
into Mitochondria
Long-chain fatty acids, as free acids or coenzyme A esters,
cannot cross the mitochondrial inner membrane.
In contrast, long-chain acylcarnitine esters rapidly cross
this membrane, facilitated by a carrier protein, carnitine acylcarnitine
translocase (CACT) (2). In the cytoplasm,
transesterification of long-chain fatty acids from coenzyme
A to L-carnitine is catalyzed by carnitine palmitoyltransferase
I (CPT I), an integral protein of the mitochondrial
outer membrane. This enzyme serves as the primary
regulator in partitioning fatty acids toward oxidation in
mitochondria or triglyceride synthesis, and its activity is
regulated principally through inhibition by malonyl-CoA
(3). On the matrix side of the mitochondrial inner membrane,
the acyl group of the carnitine ester is transferred to
intramitochondrial coenzyme A and carnitine is released
(2). This reaction is catalyzed by carnitine palmitoyltransferase
II (CPT II), an enzyme bound to the surface of the
membrane (2). L-Carnitine, either nonesterified or as a
short-chain acyl ester, may then exit the mitochondrion
via CACT
Acyl-coenzyme A ester
Reduced coenzyme A
Acyl-L-carnitine ester
Transesterification reaction between L-carnitine and coenzyme A.
Transfer of Chain-Shortened Fatty Acids from
Peroxisomes to Mitochondria
Very long-chain fatty acids are not metabolized in the mitochondria.
Instead, they enter peroxisomes and undergo
one or more -oxidation cycles, leading to the generation
of medium-chain acyl-CoA. These acyl groups are
then transesterified by carnitine octanoyltransferase for
export from the mitochondria (2). Medium-chain acylcarnitine
esters exported from peroxisomes are transported
into mitochondria by CACT, and the acyl moieties are
transesterified to coenzyme A and oxidized (Fig. 2) (2).
Modulation of the Acyl-CoA/CoA Ratio
in Cellular Compartments
Coenzyme A participates in many metabolic processes in
the cellular cytoplasm and organelles. However, neither
coenzyme A nor its thioesters can cross the membranes
separating these compartments. Thus, in each compartment,
sufficient nonesterified coenzyme A must be made
available to maintain metabolic activities in that part of
the cell. Because of its ability to be transported across
organelle membranes and undergo rapid transesterification
with coenzyme A, L-carnitine facilitates availability
of adequate amounts of the deacylated coenzyme. In mitochondria,
the amount of acetyl-CoA generated from
rapid -oxidation of fatty acids or carbohydrate utilization
L-Carnitine and acetyl-L-carnitine transport and function. Abbreviations: Carn, L-carnitine; AcCarn, acetyl-L-carnitine; OCTN2, organic cation transporter
2; UnTr, unidentified transporter(s); LCA-CoA, long-chain acyl-coenzyme A; MCA-CoA, medium-chain acyl-coenzyme A; VLCA-CoA, very long-chain acyl-coenzyme
A; LCA-Carn, long-chain acylcarnitine esters; MCA-Carn, medium-chain acylcarnitine esters; Ac-CoA, acetyl-coenzyme A; CPT I, carnitine palmitoyltransferase
I; CPT II, carnitine palmitoyltransferase II; CAT, carnitine acetyltransferase; COT, carnitine octanoyltransferase; CACT, carnitine-acylcarnitine translocase; PDH,
pyruvate dehydrogenase complex.
may exceed the capacity of the citric acid cycle to release
the coenzyme. Transesterification of acetyl units to
L-carnitine, catalyzed by carnitine acetyltransferase
(CAT), frees intramitochondrial coenzyme A for participation
in subsequent cycles of substrate utilization (3,4).
Lowering of the acetyl-CoA/CoA ratio stimulates pyruvate
oxidation, secondary to an increase in pyruvate dehydrogenase
complex activity (4). Acetyl-L-carnitine can
be removed from the mitochondrion via CACT for use in
the cytoplasm, for export and use in other cells or tissues,
or for excretion (3,4). This function has long been viewed
primarily as a means to dispose of acetyl units from mitochondria.
However, export of acetyl-L-carnitine fromsome
cells and tissues (e.g., liver and kidney) may be important
for supply of this metabolite to other tissues (e.g., brain),
where it may have specific functions in addition to its
use as a substrate for energy production. Moreover, by
modulating the intramitochondrial acetyl-CoA/CoA ratio,
L-carnitine plays a significant role in regulating glucose
metabolism in skeletal muscle and heart (4).
Membrane Phospholipid Remodeling
L-Carnitine and extramitochondrial CPT are important
modulators of long-chain fatty acid utilization for
membrane phospholipid biosynthesis and remodeling.
L-Carnitine acts as a reservoir of long-chain fatty acids
for incorporation into erythrocyte membrane phospholipids
during repair after oxidative insult (2) and for
use in the synthesis of dipalmitoylphosphatidylcholine,
the major component of surfactant, in lung alveolar
cells (2).
Other Reported Actions of L-Carnitine and/or Its Acetyl
and Proponyl Esters
L-Carnitine may mimic some of the actions of glucocorticoids
in vivo. In HeLa cells, L-carnitine reduces
glucocorticoid receptor- affinity for its steroid ligand and
triggers nuclear translocation of the receptor (5). It suppresses
glucocorticoid receptor–mediated tumor necrosis
factor- and interleukin-12 release by human primary
L-Carnitine, Acetyl-L-Carnitine, and Propionyl-L-Carnitine 109
monocytes stimulated with lipopolysaccharide ex vivo
(5). All of these effects of L-carnitine are concentration
dependent. In rats and mice, L-carnitine is found to
markedly suppress liposaccharide-induced cytokine production,
improving their survival during cachexia and
septic shock (5). In humans, L-carnitine supplementation
of surgical and AIDS patients decreased serum tumor
necrosis factor- concentration (5). Glucocorticoids also
increase the expression and activity of urea cycle enzymes.
Hyperammonemia associated with chronic valproic acid
therapy and with several inborn errors of metabolism,
including CACT deficiency and medium-chain acyl-CoA
dehydrogenase deficiency, is attenuated by L-carnitine
administration. It has been experimentally found that
L-carnitine supplementation protects against lethal ammonia
intoxication in mice (6). One suggested mechanism
for these effects of L-carnitine is increased synthesis and
activity of urea cycle enzymes, a process also responsive to
L-Carnitine is a peripheral antagonist of thyroid hormone
action in some tissues (7). It inhibits thyroid hormone
entry into cell nuclei. In a controlled clinical trial,
L-carnitine was shown to reverse or prevent some symptoms
of hyperthyroidism (7).
Acetyl-L-carnitine may directly or indirectly reverse
age-associated mitochondrial decay (8). It acts as a chaperone
to protect macromolecules, including CAT, from
structural alteration and/or loss of function. Acetyl-Lcarnitine
partially reverses age-associated loss of mitochondrial
membrane potential and decline in membrane
cardiolipin concentration, and protects against oxidative
damage to mitochondrial DNA (8).
L-Carnitine inhibits arachidonic acid incorporation
into platelet phospholipids, agonist-induced arachidonic
acid release, and arachidonic acid–inducedNADPH
(nicotinamide adenine dinucleotide phosphate)-oxidase
activation (9). It has been proposed and some evidence
has been obtained to support this notion that acetyl-
L-carnitine stimulates or upregulates expression of heat
shock proteins, redox-sensitive transcription factors, and
sirtuins that protect against oxidative cellular damage (10).
These actions may be particularly important in modulating
the aging process and in slowing the progression of
neurodegenerative diseases.
Dietary Intake and Biosynthesis
Meat, fish, chicken, and dairy products are rich sources of
dietary L-carnitine (1). Plant-derived foods contain very
small amounts of the substance. Most commercially available
infant formulas contain L-carnitine, either provided
from the milk component or supplemented, as in the
case of soy-protein-based formulas. There is no recommended
dietary allowance or dietary reference intake for
In mammals, L-carnitine is synthesized from
ε-N-trimethyllysine, which is derived from posttranslationally
methylated lysine residues in proteins, and
protein turnover (1). In normal humans, the rate of synthesis
is estimated to be approximately 1.2 mol/kg body
weight/day (1). The rate of L-carnitine biosynthesis is regulated
by the availability of ε-N-trimethyllysine. Thus,
conditions that increase protein methylation and/or protein
turnover may increase the rate of L-carnitine biosynthesis
Dietary L-carnitine may be absorbed through active or
passive mechanisms. Evidence from several in vivo and
in vitro studies indicates that L-carnitine is actively transported
from the small intestinal lumen into enterocytes
(11). However, the preponderance of data suggests that
intracellular L-carnitine in the intestinal mucosa does not
cross serosal membranes by an active transport mechanism.
Absorption of dietary L-carnitine and L-carnitine
supplements appears to occur primarily by passive diffusion
(11). In humans, approximately 54% to 87% of dietary
L-carnitine is absorbed, depending on the amount
in the diet. The bioavailability of dietary supplements
(0.6–4 g/day) is 15% to 20% (11,12). Unabsorbed
L-carnitine is degraded by microorganisms in the large intestine.
Major metabolites identified are trimethylamine
oxide in urine and -butyrobetaine in feces (11,12).
Bioavailability of oral acetyl-L-carnitine has not been studied
in normal healthy humans.
Distribution in Tissues, Fluids, and Cells
L-Carnitine and acylcarnitine esters are present in all tissues.
In most tissues and cells, they are present in higher
concentration than in the circulation. For example, in human
skeletal muscle and liver, respectively, nonesterified
L-carnitine is concentrated 76-fold and 50-fold from that
in serum (estimated from data in Ref. 13).
Tissue Accumulation
L-Carnitine and acetyl-L-carnitine are concentrated in
most tissues via high-affinity, Na+-dependent organic
cation transporter OCTN2 (14). Kt for L-carnitine binding
is 3 to 5 M; OCTN2 binds acetyl-L-carnitine and
propionyl-L-carnitine with comparable affinity. This protein
is highly expressed in heart, placenta, skeletal muscle,
kidney, pancreas, testis, and epididymis and weakly
expressed in brain, lung, and liver. L-Carnitine entry
into the liver occurs via a low-affinity (Kt = 5 mM)
transporter, probably distinct from OCTN2. Several other
L-carnitine transporters have been identified, including
OCTN1, OCTN3, and ATB0,+, and Oat9S (2,15). Specific
roles for these transporters in carnitine metabolism in humans
have not been determined.
Homeostasis, Renal Reabsorption, and Excretion
Circulating L-carnitine concentrations are maintained
at a fairly constant level of around 50 M, predominantly
through efficient reabsorption by the kidney
(11). At a filtered load of 50 mol/L, the efficiency of
L-carnitine and acylcarnitine ester reabsorption is 90% to
98%. However, as the filtered load of L-carnitine increases,
for example, after consumption of a dietary supplement
or after intravenous infusion, the efficiency of reabsorption
declines rapidly. Physiologically, the efficiency of
L-carnitine reabsorption is sensitive to the amount in the
diet as well as the differences in the macronutrient content
of the diet. Clearance of acylcarnitine esters is often
higher than that of nonesterified L-carnitine. Experimental
110 Rebouche
studies have shown that in rats and humans, kidneys
are able to synthesize acetyl-L-carnitine from L-carnitine
and either acetoacetate or -hydroxybutyrate, and that
L-carnitine, acetyl-L-carnitine, and -butyrobetaine (also
synthesized in human kidneys) are secreted from mucosal
cells into the tubular lumen (11). Because the kinetics of
transport of these metabolites by the sodium-dependent
L-carnitine transporter are not different, the relative proportions
appearing in urine reflect not only those in the
glomerular filtrate but also those in the renal tubular epithelium
that are secreted into the lumen. Thus, under
conditions of rapid intracellular synthesis of acylcarnitine
esters or direct accumulation from the circulation, secretion
of these species will lead to a higher proportion of
acylcarnitine esters in urine compared to that in the circulation.
By inference, kidneys may be substantially involved
in the regulation of circulating acylcarnitine ester
concentrations (11).
L-Carnitine deficiency is defined biochemically as abnormally
low concentration (<20 M) of nonesterified
L-carnitine in plasma (2). A concentration ratio of acylcarnitine
esters/nonesterified L-carnitine of 0.4 or greater
in plasma is also considered abnormal. Nutritional
L-carnitine deficiency has not been shown to occur in the
absence of other mitigating factors (2).
Primary L-carnitine deficiency occurs as a result of
defects in the gene coding for the plasma membrane
L-carnitine transporter OCTN2 (16). Characteristic features
of this disease are cardiomyopathy, hypoketotic hypoglycemia,
and muscle weakness. Secondary carnitine
deficiency occurs in association with genetic diseases of
organic acid metabolism and in genetic diseases involving
defects in fatty acid oxidation. Secondary carnitine deficiency
has been described in patients with end-stage renal
disease requiring maintenance hemodialysis. Secondary
carnitine deficiency has been observed during chronic use
of drugs, including valproic acid, cisplatin, ifosfamide, zidovudine,
and pivalic acid-containing prodrugs (17–20).
L-Carnitine, acetyl-L-carnitine, and/or propionyl-Lcarnitine
may be used for replacement therapy to
restore normal carnitine concentrations and/or abnormal
nonesterified-to-esterified carnitine ratio. They may be
used as supplements to increase the carnitine load of
the body and/or increase the flux of carnitine among
compartments. In some conditions, both replacement
therapy and supplementation are appropriate. For primary
and some secondary carnitine deficiencies (see
earlier), L-carnitine is used for replacement therapy.
L-Carnitine Supplementation in Neonatal Nutrition
L-Carnitine has been described as a conditionally essential
nutrient for infants. For the last 25 years, commercial
enteral infant formula products have included L-carnitine,
where necessary, to achieve an L-carnitine concentration
similar to that in human milk (∼60 mol/L). Bovine milkbased
formulas typically contain a higher concentration
of L-carnitine than does human milk. On the other hand,
premature infant formulas, both enteral and parenteral,
typically do not include L-carnitine at the time of manufacture,
but are sometimes supplemented at the time of
use. The rationale for supplementation is twofold: Infants
utilize lipids as a primary source for energy and growth after
birth, requiring a high rate of mitochondrial oxidation,
and the concentration of L-carnitine in infant circulation
and tissues typically is lower without supplementation
than in infants fed human milk or formulas containing
carnitine. Studies in premature infants typically have focused
on the effect of L-carnitine supplements on growth
rate and morbidity, with mixed results. In one doubleblind,
placebo-controlled, randomized trial of L-carnitine
supplementation in premature infants 28 to 34 gestational
weeks of age at birth, no differences in two-week
weight gain over 8 weeks were observed between supplemented
and nonsupplemented infants (21). More recently,
in another prospective, randomized, placebo-controlled,
double-blinded study, 29 premature neonates received
carnitine supplementation (20 mg/kg body weight/day)
or placebo for up to eight weeks. Supplemented neonates
regained their birth weight more rapidly than placebo
group neonates, indicating that L-carnitine supplementation
may promote more rapid catch-up growth (22). An
extensive review of these and many more relevant studies
has been published (23). For infants expected to be on
parenteral nutrition for seven days or longer, supplementation
with L-carnitine 10 to 20 mg/kg body weight/day,
given intravenously or orally, is recommended (23).
L-Carnitine Replacement Therapy and Supplementation
in End-Stage Renal Disease
Regular L-carnitine supplementation in hemodialysis patients
can improve lipid metabolism, antioxidant status,
and anemia requiring erythropoietin and may reduce incidence
of intradialytic muscle cramps, hypotension, asthenia,
muscle weakness, and cardiomyopathy (24,25). The
recommended dosage is 50 mg/kg body weight/day, to a
maximum of 3 g/day.
L-Carnitine and Propionyl-L-Carnitine Supplementation
for Cardiac Ischemia, Congestive Heart Failure,
Cardiomyopathy, and Peripheral Arterial Disease
Experimental studies have shown L-carnitine to be an
effective antianginal agent that reduces ST-segment depression
and left ventricular end-diastolic pressure during
stress in patients with coronary artery disease (25). Cardioprotective
effects of L-carnitine have been observed following
aortocoronary bypass grafting and following acute
myocardial infarction. Carnitine administration initiated
early after acute myocardial infarction attenuated left ventricular
dilation and resulted in smaller left ventricular
volumes (25).
L-Carnitine deficiency syndromes sometimes
present with dilated cardiomyopathy and are often
effectively treated with L-carnitine (26). Thus, it was suggested
that cardiomyopathy progressing to congestive
heart failure but not associated with inherited L-carnitine
deficiency might respond to L-carnitine supplementation.
A large-scale clinical trial of L-carnitine supplementation
L-Carnitine, Acetyl-L-Carnitine, and Propionyl-L-Carnitine 111
versus placebo in 574 patients with heart failure produced
promising results with regard to improvement in maximum
duration of exercise, but other endpoints, including
death and hospital admissions during the follow-up
period, were not different between treatment groups
(26). Utility of L-carnitine supplements for congestive
heart failure not associated with inherited L-carnitine
deficiency remains debatable (26,27).
Peripheral arterial disease is a common manifestation
of atherosclerosis and is associated with reduced arterial
circulation in the lower extremities. In five large, randomized,
double-blind, placebo-controlled studies, with
long duration of therapy, and three short-duration studies,
propionyl-L-carnitine supplementation (1–3 g/day,
orally) for up to one year improved initial claudication
distance (distance walked before muscular symptoms appeared)
and absolute claudication distance (distance at
which patient stopped walking due to muscular cramps)
(28). Quality of life outcomes were also improved with
propionyl-L-carnitine treatment relative to placebo. Experimental
and clinical studies suggest that the improvements
observed in clinical trials are due to protection
by propionyl-L-carnitine from the effects of oxidative
stress and inflammation in ischemic tissue endothelium
(28), as well as due to increased blood flow resulting
from endothelium-dependent vasodilation elicited by
propionyl-L-carnitine (29).
L-Carnitine Supplementation for Exercise Performance
and Weight Reduction
L-Carnitine supplementation has been suggested to improve
exercise performance in healthy humans. Proposed
mechanisms include enhanced muscle fatty acid oxidation,
altered glucose homeostasis, enhanced acylcarnitine
production, modification of training responses, and altered
muscle fatigue resistance (30).Areview of published
studies has led to the conclusion that L-carnitine supplements
do not improve exercise performance in healthy humans
(30–33). On the other hand, in conditions where the
nonesterified L-carnitine concentration of skeletal muscle
may be significantly reduced, such as in peripheral arterial
disease and end-stage renal disease, L-carnitine supplementation
has afforded some benefit to muscle function
and exercise performance (33).
In a double-blind, placebo-controlled, crossover design
clinical trial, oral administration of 4.5 g of propionyl-
L-carnitine (as glycine propionyl-L-carnitine) to trained
athletes significantly enhanced peak power production
in resistance-trained males with significantly lower lactate
accumulation (34). The incremental differences in
power production were modest and were observed only
after repeated short-durationWingate cycle sprints. However,
it is noted that, particularly for elite athletes, modest
enhancement in performance can be highly significant
in outcomes in competitive sports. Propionyl-L-carnitine
may be more effective in enhancement of exercise performance
than L-carnitine, because of its ability to increase
nitric oxide production and vasodilation.Moreover,
propionyl-L-carnitine may enhance citric acid cycle activity
by providing propionyl units that can be converted to
Because of its role in facilitating fatty acid oxidation,
L-carnitine has been suggested to aid in weight loss
regimes. Two facts argue against this. First, there is no
evidence that it facilitates, directly or indirectly, mobilization
of fatty acids from adipose tissue. Second, in normal
humans, the intracellular concentration of L-carnitine is
not rate-limiting for transesterification of fatty acids by
CPT I. Adding an increment of L-carnitine will not increase
the rate at which this reaction occurs. There is no
scientific evidence that L-carnitine supplements facilitate
weight loss in humans.
L-Carnitine and Acetyl-L-Carnitine Replacement Therapy
and Supplementation for Chronic Fatigue
L-Carnitine may improve symptoms of fatigue in humans.
Use of the cancer chemotherapeutic agents cisplatin and
ifosfamide is associated with fatigue. In a prospective,
open-label study, improvement of symptoms of fatigue
was observed in 50 nonanemic patients following
L-carnitine supplementation to the chemotherapeutic
regimen of cisplatin or ifosfamide (35). However, in a subsequent
randomized, double-blind, placebo-controlled
trial, no improvement in measures of fatigue was observed
as a result of L-carnitine supplementation (36).
The study included an open-label phase, in which fatigue
symptoms did show some improvement with L-carnitine
Chronic fatigue syndrome (CFS) in humans was
found to be associated with low circulating acetyl-Lcarnitine
concentration and decreased accumulation in
several brain regions (37). It has been suggested that
acetyl-L-carnitine helps maintain neuronal metabolic activity
by promoting glucose and lactate uptake and utilization
through its role as a precursor of glutamate in
neurons (38). In a randomized, open-label study of 30
patients with CFS, acetyl-L-carnitine and propionyl-Lcarnitine
showed beneficial effects on fatigue and attention
concentration (39).
Acetyl-L-Carnitine Supplementation for Depression and
Cognitive Function in the Elderly
Acetyl-L-carnitine appears to have specific and perhaps
unique roles in brain metabolism. Animal studies and
in vitro experiments suggest that this agent has promise
in slowing or reversing memory and cognition decline
as well as the decline in physical performance that normally
occurs in the process of aging. In studies of the
elderly, patients with depressive syndrome scored significantly
lower on the Hamilton Rating Scale for Depression
(modified for the elderly) following supplementation with
acetyl-L-carnitine (40). Older subjects with mild mental
impairment had improved scores on cognitive performance
tests following such supplementation (41).Ametaanalysis
of the efficacy of acetyl-L-carnitine in mild cognitive
impairment and mild Alzheimer disease included
all identified double-blind, placebo-controlled, prospective,
parallel-group studies using treatment doses of 1.5
to 3.0 g/day of acetyl-L-carnitine that were conducted between
1983 and 2000 (42). This analysis showed a significant
advantage for acetyl-L-carnitine compared to placebo,
with beneficial effects observed on both clinical scales and
psychometric tests. The benefit of supplement use was
112 Rebouche
observed for three months, and it was found to increase
over time. The typical usage recommended by vendors is
1 to 3 g/day.
L-Carnitine Supplementation in Liver Dysfunction with
Hyperammonemia occurs in some inborn errors of
metabolism and as a result of drug- or toxicant-induced
hepatotoxicity. Mortality and metabolic consequences
of acute ammonium intoxication in mice are reduced
by pharmacologic administration of L-carnitine (6). The
mechanism for this effect may have two components.
L-Carnitine administration normalizes the redox state
of the brain (perhaps by increasing the availability of
-hydroxybutyrate and/or acetyl-L-carnitine to the brain),
and it increases the rate of urea synthesis in the liver,
perhaps, in part, by activation of the glucocorticoid receptor.
At least part of the protective effect is associated
with flux through the carnitine acyltransferases, as
analogs of L-carnitine that are competitive inhibitors of
carnitine acyltransferases enhance the toxicity of acute
ammonium administration (6). Thus, it has been proposed
that L-carnitine increases urea synthesis in the liver by facilitating
fatty acid entry into mitochondria, leading to increased
flux through the -oxidation pathway, an increase
of intramitochondrial reducing equivalents, and enhancement
of ATP production (6). Carnitine supplementation
may benefit individuals with hepatic dysfunction due to
inborn errors of metabolism or chemical intoxication.
L-Carnitine and Acetyl-L-Carnitine Replacement Therapy
and Supplementation in Diabetes
L-Carnitine infusion improves insulin sensitivity in
insulin-resistant diabetic patients (43). Glucose oxidation
is increased during L-carnitine administration, concurrent
with lower plasma concentration of lactate. These
observations suggest that L-carnitine activates normally
depressed pyruvate dehydrogenase activity in insulinresistant
patients (43). Intravenous administration of
acetyl-L-carnitine increases glucose disposal in Type 2 diabetic
patients (44). Such administration appears to promote
storage of glucose as glycogen, rather than increase
in glucose oxidation (44).
L-Carnitine and Acetyl-L-Carnitine Replacement Therapy
and Supplementation in HIV Infection
L-Carnitine and acetyl-L-carnitine ester concentrations are
below normal in some human immunodeficiency virus
(HIV)-infected patients undergoing antiretroviral therapy
(45). L-Carnitine administration as part of antiretroviral
therapy with either zidovudine or didanosine reduced
lymphocyte apoptosis and oxidant stress compared to the
antiretroviral regimens without L-carnitine (46).
L-Carnitine and Acetyl-L-Carnitine Supplementation in
Male Reproductive Dysfunction
L-Carnitine and/or acetyl-L-carnitine supplementation
may be beneficial in men with oligoasthenospermia, a condition
in which low sperm count is associated with low
sperm motility. Epididymal fluid contains the highest concentration
of L-carnitine in the human body. L-Carnitine is
secreted from the epithelium into epididymal plasma via
a testis-specific carnitine transporter (47). The very high
concentration of L-carnitine in epididymal fluid provides
for passive diffusion of L-carnitine into spermatozoa during
transit and maturation through the epididymis. Mature
spermatozoa acetylate L-carnitine to generate a pool
of intracellular acetyl-L-carnitine (48). In semen obtained
from 101 men with normal or abnormal spermiograms,
concentrations of L-carnitine and acetyl-L-carnitine correlated
positively with the number of spermatozoa, the
percentage of motile spermatozoa, and the percentage of
normal cells (49). A meta-analysis comparing L-carnitine
and/or acetyl-L-carnitine to placebo treatment and including
nine randomized, controlled clinical trials revealed
significant improvements in pregnancy rate, total sperm
motility, forward sperm motility, and presence of atypical
sperm cells (50). The benefits of L-carnitine and acetyl-Lcarnitine
may be due to increased mitochondrial fatty acid
oxidation, resulting in improvement in motility epididymal
sperm, as well as due to the putative antiapoptotic
effect(s) of carnitine in the testes (51).
Transient diarrhea, nausea, vomiting, abdominal cramps,
and/or "fish-odor syndrome" have been noted in rare
cases after consumption of 2 to 6 g of L-carnitine (52).
L-Carnitine is approved as a pharmaceutical by the U.S.
Food and Drug Administration for treatment of primary
systemic carnitine deficiency, as well as for acute
and chronic treatment of patients with inborn errors
of metabolism that result in secondary carnitine deficiency
(e.g., medium-chain acyl-CoA dehydrogenase deficiency,
glutaric aciduria, Type 2 diabetes, methylmalonic
aciduria, and propionic acidemia) (52). L-Carnitine is also
approved, by the U.S. Food and Drug Administration, as
a pharmaceutical for the prevention and treatment of carnitine
deficiency in patients with end-stage renal disease
who are undergoing dialysis (52).
L-Carnitine and esters of L-carnitine have a proven, essential
role in cellular fatty acid metabolism. Beyond that,
numerous other functions have been suggested by physiological
and pharmacological studies in experimental animals
and in humans. These include, but are not limited
to, antioxidant and antiapoptotic properties, a role
in membrane lipid remodeling, and modulation of gene
expression. Identification of and evidence for these putative
functions have led to hypotheses concerning a role for
L-carnitine and its esters in promotion of physiological
function (e.g., exercise performance), in prevention,
slowing, or attenuation of progressive alteration or loss
of physiological function (e.g., cognitive function in aging,
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L-Carnitine, Acetyl-L-Carnitine, and Propionyl-L-Carnitine 113
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text:
MONTGOMERY, Ala. – The Birmingham-Southern men's basketball team dropped its road game at Huntingdon College on Thursday afternoon, falling to the Hawks 70-55.
Three Panthers scored in double digits in the loss with freshman Troy Stephens (Atlanta, Ga./St. Pius X Catholic HS) leading the way with 11 points. Senior Zachary Allison (Pelham, Ala./Wallace State CC) and junior Kaden Moore (Gadsden, Ala./Hokes Bluff HS) each finished with 10 points.
Moore also recorded 11 rebounds to earn his first double-double of the season.
The Panthers and Hawks battled closely for much of the game, but BSC could not manage to find a lead at any point in regulation.
With the loss, BSC drops to 6-4 on the season.
Birmingham-Southern's next game will be on New Year's Day when the Panthers open Southern Athletic Association play at Millsaps College. Tipoff is set for 3 p.m.
JOIN THE B-FUND TODAY – Support BSC Athletics today by joining the B-Fund. Gifts to the B-Fund help support all of our 22 sports teams, coaches, and 450+ student-athletes. Used as the common funding source for championship rings, championship banners, facility upgrades, new transportation, and more, the B-Fund allows the department to enhance the athletic experience of every student-athlete at Birmingham-Southern.
Click HERE to join the B-Fund today


text:
So the core system works. That still leaves a lot of testing for the error cases, etc. And then all the additional logic used in the Kiosk context and not in PayCash.
But, considering the amount of *real* time I've been able to spend porting, I'm very pleased with myself.
I am: accomplished
Current Media: office cleaners


text:
Where to Watch Tomorrow's Super Blue Blood Moon, In and Around Metro Manila
We're getting a blue moon, a total lunar eclipse, and a supermoon all at once!
January may have been a crazy month, but at least it's ending with something cool—a super blue blood moon. If this sounds like a mouthful, it's because it's a combination of three lunar events happening at once: A supermoon, a blood moon, and a blue moon.
A supermoon occurs when the moon is at its perigee, or the point in its orbit that is closest to the Earth. According to Space.com, a super moon can "appear up to 14 percent larger and 30 percent brighter than usual."
When a full moon occurs two times within a month, that's called a blue moon—hence the common expression "Once in a blue moon." A blood moon, as its name suggests, happens when the moon takes on a striking orange or red tint during a lunar eclipse. While the moon is completely covered by the Earth's shadow, light from the Earth's sunrise and sunset shines on the surface of the moon, giving it its reddish appearance.
PAGASA says this rare sight will grace Philippine skies on January 31, from 6:49 p.m. to 12:09 a.m. The Philippine Astronomical Society has compiled a list of observation stations all over the country, which you can see below:
Philippine Astronomical Society, Inc.
Luneta, Rizal Park
Open to all from 6 p.m. to 12 a.m., walk-ins allowed.
Bedan Society of Young Astronomers
San Beda College, Manila
Details: https://goo.gl/tFk6XC
Open to all from 6 p.m. to 10 p.m.
Manila Street Astronomers
SM North EDSA
Details: https://goo.gl/t6KVeV
Open to all from 7 p.m. onwards, walk-ins allowed.
UP Astronomical Society
PAGASA Astronomical Observatory UP Diliman
Open to all from 6 p.m. to 12:10 a.m., walk-ins allowed.
Cutting Edge Trinoma
Trinoma Park
Details: https://goo.gl/K4jHj3
Open to all from 6:30 p.m. to 9 p.m.
Manila Street Astronomers
Pinaglabanan Shrine, San Juan City
Open to all from 6 p.m. to 12 a.m., walk-ins allowed.
Astronomical League of the Philippines, Inc.
SM by the Bay Central Park, SM Mall of Asia
Open to all from 6 p.m. to 12 a.m., walk-ins allowed.
Manila Street Astronomers
Alabang Town Center
Open to all from 6 p.m. to 12 a.m., walk-ins allowed.
Astronomy and Physics Society of St. Edward Integrated School
SunTech iPark Lancaster Sqaure New City, Imus, Cavite
Details: https://goo.gl/WQK7Ji
Open to all from 7 p.m. to 10 p.m., walk-ins allowed.
Philippine Astronomical Society
Sampaloc Lake Park, Bonifacio Statue, San Pablo City, Laguna
Open to all from 7:30 p.m. to 10 p.m., walk-ins allowed.
UPLB Astronomical Society
Carabao Park, UP Los Baños
Open to all from 7 p.m. to 10 p.m.
Kapusod in cooperation with Philippine Astronomical Society
Lakefront, Kapusod, Kinalaglagan, Mataasnakahoy, Batangas
Note: Public commute at night is not available
Open to all from 7 p.m. to 11 p.m., walk-ins allowed.
IAU Astronomical Society
Indiana Aerospace University Sports Arena
Open to all from 7 p.m. to 12 a.m., walk-ins allowed.
Davao Stargazers
Abreeza Ayala Mall, Davao City
Open to all from 7 p.m. to 10 p.m., walk-ins allowed.
This story originally appeared on Esquiremag.ph. Minor edits have been made by the Spot.ph editors.


text:
Managed to squeeze in some scrapbooking (and more cards!) during a long, but full weekend!! And I also did some reading of the final Harry Potter book--it's so funny because I couldn't put it down! I even brought it with me to a party! Such a dork!!
The first two are cards made from Label Tulip 'Chardonnay' Kit. The next two lay-outs are made from the August SOML kit, and the last two are from the Cocoa Daisy August kit. Thanks for looking!!
Monday, August 13, 2007
1 comment:
- jo said...
Very cool! You got a lot done! :)
- August 15, 2007 at 9:31 AM
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text:
Monday through Friday
8:00 a.m.-6:00 p.m.
1703 North Beauregard St.
Alexandria, VA 22311-1714
Complete Customer Service Details
by Carol Ann Tomlinson
Table of Contents
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Strachota, B. (1996). On their side: Helping children take charge of their learning. Greenfield, MA: Northeast Foundation for Children.
Stronge, J. (2002). Qualities of effective teachers. Alexandria, VA: ASCD.
Sylwester, R. (1995). A celebration of neurons: An educator's guide to the human brain. Alexandria, VA: ASCD.
Thomas, L. (1983). Late night thoughts on listening to Mahler's ninth symphony. New York: Bantam Books.
Tieso, C. (2002). The effects of grouping and curricular practices on intermediate students' math achievement. Hartford: National Research Center on the Gifted and Talented, University of Connecticut.
Tomlinson, C. (2003). Fulfilling the promise of the differentiated classroom. Alexandria, VA: ASCD.
Tomlinson, C. (2004). How to differentiate instruction in mixed-ability classrooms (2nd ed.). Alexandria, VA: ASCD.
Tomlinson, C., Brimijoin, K., & Narvaez, L. (2008). The differentiated school: Making revolutionary changes in teaching and learning. Alexandria, VA: ASCD.
Tomlinson, C., Callahan, C., Moon, T., Tomchin, E., Landrum, M., Imbeau, M., … Eiss, N. (1995). Preservice teacher preparation in meeting the needs of gifted and other academically diverse students. Charlottesville: National Research Center on the Gifted and Talented, University of Virginia.
Tomlinson, C., Callahan, C., Tomchin, C., Eiss, N., Imbeau, M., & Landrum, M. (1997). Becoming architects of communities of learning: Addressing academic diversity in contemporary classrooms. Exceptional Children, 63, 269–282.
Tomlinson, C., & Imbeau, M. (2010). Leading and managing a differentiated classroom. Alexandria, VA: ASCD.
Tomlinson, C., & McTighe, J. (2006). Integrating differentiated instruction and understanding by design: Connecting content and kids. Alexandria, VA: ASCD.
Tomlinson, C., & Moon, T. (2013). Assessment in a differentiated classroom: A guide for student success. Alexandria, VA: ASCD.
van Manen, M. (1991). The tact of teaching: Toward a pedagogy of thoughtfulness. Albany: State University of New York.
van Manen, M. (2003). The tone of teaching. New York: Scholastic.
Vygotsky, L. (1978). Mind in society: The development of higher psychological processes (M. Cole, V. John-Steiner, S. Scribner, & E. Souberman, Eds.). Cambridge, MA: Harvard University Press.
Vygotsky, L. (1986). Thought and language (A. Kozulin, Ed. & Trans.). Cambridge, MA: The MIT Press. (Original work published 1934.)
Watanabe, M. (2012). "Heterogenius" classrooms: Detracking math and science. New York: Teachers College Press.
Wiggins, G., & McTighe, J. (2005). Understanding by design (2nd ed.). Alexandria, VA: ASCD.
Williamson, M. (1992). A return to love. New York: HarperCollins
Willis, J. (2006). Research-based strategies to ignite student learning. Alexandria, VA: ASCD.
Willis, J. (2010). The current impact of neuroscience on teaching and learning. In D. Sousa (Ed.), Mind, brain, and education: Neuroscience implications for the classroom (pp. 44–66). Bloomington, IN: Solution Tree.
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After receiving complaints from industry members about how difficult their business site was to use (to be fair, it was built in the late 1980s), the United States Postal Service commissioned a redesign of RIBBS, the Rapid Information Bulletin Board System. Over the course of two years, I led the team in a multi-phase, iterative redesign using Agile methodology. Highly collaborative and lean, we designed and developed in two-week sprints with user goals as our shared focal point.
The first stage of the project involved an analysis of the existing site, both its content and its context. In order to understand the problem we were solving, it was necessary to see the picture in its entirety.
Three primary user groups surfaced during my research: developers looking for software release information, business mailers staying up-to-date with important policy and mailing requirements, and USPS employees. Each of these groups had different vocabularies and different levels of familiarity with RIBBS, the legacy site. Figuring out how to totally overhaul the site without alienating former power users was a major challenge. Ultimately we arrived at a solution through a series of iterations and testing.
User Flows
Analyzing how personas accomplish key goals on the legacy site brought pitfalls and pain points to the fore. Disjointed menus, poor search functionality, unreliable navigation, and an overwhelming amount of technical jargon were flagged as major issues.
Information Architecture
Using card sorting techniques, I looked for commonalities in the users' mental models of the content. How were they classifying and grouping different information on the site? What were they calling it and where did they expect to find it? What should live near it? We used this data to start reorganizing the sitemap and navigation.
As soon as I had gotten the content audit under control and we'd mapped out which features and templates we'd need, we started wireframing and visual prototyping. We embraced a fail-fast approach, testing and validating concepts with stakeholders and users early and often. When we arrived at our skinned beta-ready designs, we coded the templates and implemented them in the CMS.
After three months of research, design, and development, we launched the beta for the 2016 National Postal Forum. We used the initial release as an opportunity to continue refining the design, capturing feedback from users and monitoring analytics to improve the experience.


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Monday, July 28, 2008
Where did you go on Vacation?
I have all 50 States For $1 each that are shadowed. Need a different size or color I can do that for you. Just call in advance and I will get it ready for you. The ones I have ready are white on black and mostly 2' high. Some are 1 3/4' because they otherwise would not fit across 12x12. Order yours today.
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text: Horse Riding Hat Bag - Green Waterproof/Navy Fleece Lining £10.00 Quantity: at £10.00 each Add To Basket 1 in stock. Hat bag made from green waterproof nylon lined with navy blue polar fleece. Zip fastening with a loop handle for carrying/hanging. Great for keeping your hat clean and for keeping your gloves in for everyday use or travelling to competitions.


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Heritage Polarstretch Gloves
The Polarstretch Fleece glove offers a warm, comfortable custom fit with our soft stretchable Fleece design. Read more...
Made with exclusive Heritage breathable "Polarstretch" soft fleece material, which features stretch in all directions. The palm is made with durable nylon stretch fleece with grip pattern to help keep control on the reins. Touchscreen friendly. Black.
Customer Service
At Dressage Extensions, our goal is your complete satisfaction. We want you to receive all items exactly as you anticipated. If you are not satisfied for any reason, you are invited to return the unused item for an exchange or complete refund within 30 days (undergarments are not returnable). Just follow the return instructions on the back of the invoice that accompanies your order. Call us if you have any questions.
Our Customer Service Department is committed to answering your questions. Our expert dressage staff is available by e-mail or by phone at 800-303-7849. The Customer Service department's hours of operation are from 8:00 a.m. to 5:00 p.m., Monday through Friday and 9 a.m. to 5:00 p.m., Saturday, Pacific time.
If you encounter any difficulties with our website, please contact our web administrator Here.
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New York Fashion Week
As a stylist and blogger, attending New York's Fashion Week is a must. This is where I can absorb the creativity and vibrancy of the fashion world and be renewed. The imagination and hard work of designers, models and everyone who puts together a show is tremendous. I can't help feeling part of something bigger.
For fall fashion 2018, expect to see bright colors, fun plaids, oversized coats, furs of all colors, embellishments like crystals, and pink, pink and more pink. Check out my videos of NYFW in live action for inspiration!
One standout runway show was by Chromat, Autumn/Winter 2018: Wavvy. It's more than a trend now to embrace our identities in culture, race, gender identity, and different body types. Chromat's collection in swimwear and ready-to-wear is a hot, bold, energetic example of what's great about being a real woman in 2018.
Photographs 1-3 credited to Luca Tombolini / Indigital.tv Voque. Photographs 4-9 credited to Amanda Bantham


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When you're injured, your only concern should be how to get your life back together as quickly as possible, or how you can help your loved one to recover. You don't need the added anxiety of looking for a lawyer and worrying if the one you've found has the right skills and experience to represent you.
AJN attorneys are all trial lawyers themselves. We know which questions to ask when looking for a lawyer. Our court room experience coupled with our huge database of attorneys is what guides us in choosing the best lawyer for you. Let us save you the time, money and energy you need for other things.
It's entirely possible that an AJN lawyer who is certified for handling failure to diagnose cancer cases may not be certified for handling design defect or construction cases. This practice—unique among legal information services—assures you of an objective, unbiased match with a qualified attorney.
Sometimes, after talking with clients, we find that their situation can best be handled without a lawyer. When that happens, we'll provide you with information about other agencies or organizations that can be of help.
IMPORTANT: You are never locked-in to any lawyer that we recommend for you. If, for any reason, you are not satisfied with the lawyer we have selected, we'll find you another one. At AJN, we're not satisfied unless you are. This personal touch is the hallmark of our service, and we stand by it one hundred percent.
We are your Liaison. In our over 25 years of practicing law, one of the main complaints we have heard from clients is that lawyers do not return calls. At American Justice Network, we help connect you to the lawyer best suited for your case and we stay actively involved from beginning to end. If your calls are not being answered, you can contact us and we will get in touch with your lawyer. We have the ability to bypass secretaries and paralegals and get directly to your attorney.
In addition, we ask all lawyers we work with to give us regular updates on all files subject to clients' consent. This is an added benefit that American Justice Network provides. Often the trial lawyers who represent the catastrophically injured are very busy preparing for trial and may not always have the time to return all telephone calls and handle other administrative duties. If that happens, we will make sure you are kept up-to-date.
Fees - AJN works for you free of charge. You pay us nothing, ever. When you meet with the attorney we refer you to, you will agree on a fee to handle your case. Most personal injury cases are accepted on a contingent fee basis. This means that you do not pay your lawyers any upfront costs. Your lawyer will bear the risk of any out-of-pocket costs associated with trying your case and will get paid only if you win. It's important to understand that your lawyer is spending their own money and time to try your case. You should feel confident that the work being done is to the best of their ability, as they want you to recover as much as possible. The more you win, the more they earn.
AJN has already established fee arrangements with all the attorneys in our network. If your case is successful, you will receive a settlement and your lawyer will be paid the amount you both agreed on. We, in turn, will be paid by your lawyer. Our fee is never deducted from your sum. This is a business practice between lawyers. It helps ensure that the right lawyers handle the right cases and don't take them strictly for the money.


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Our global presence continually grows across many diverse markets. Between 'own buy' and franchise stores you can shop KM worldwide from Monoco to Moscow.
Our roles explained
Our Store and Assistant Managers are responsible for:
- Maximising sales and profit, and delivering against targets
- Ensuring that sales and service performance is monitored through KPIs
- Maintaining visual merchandising standards
- Recruiting, training, coaching and developing team members
- Leading, motivating & inspiring team members to deliver excellent customer service
- Managing the store operations
Our Supervisors are responsible for:
- Leading and managing the store team, supporting the management team
- Implementing commercial decisions set out by the management team
- Monitoring and driving store teams to reach targets, as well as achieving their own
- Maintaining high visual merchandising and store standards
- Assisting management in training and developing team members
Our in-store Stylists are responsible for:
- Constantly delivering fun, informed and indulgent service to clients
- Achieving store targets (eg: sales and account cards)
- Living the Brand Values
- Demonstrating professional and effective communication with team members and clients
- Ensuring the product is displayed at its best


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Do you like to ski? If so, get out there and enjoy it while you can. Dryer and warmer weather is shortening the ski season and reducing the number of resorts that will have enough snow to remain in business.
Within the next 20 years, the number of days at or below freezing in some of the most popular ski towns in the United States will decline by weeks or even a month, according to a new report by the Climate Impact Lab. In Park City, Utah, for example, an average of 194 days each year between 1981 and 2010 were at or below freezing, but that figure could be cut in half by late century if emissions continue to rise at the current rate.
In the Alps, the eight-nation mountain range that accounts for 40 percent of the world's skier-days, resorts are facing the loss of up to 70 percent of their snow cover by the end of the century, and the snow line will be a kilometer higher – above the base of most ski areas. Even in the best-case scenarios, global warming is likely to cause snowfall to be replaced by rain across the Alps, according to a report in the European Geosciences Union journal Cryosphere.
If you're a skier, you've seen the evidence already. "From 1960 to 2017, the Alpine snow season shortened by 38 days—starting an average of 12 days later and ending 26 days earlier than normal," Jeffrey Kluger wrote in Time magazine. Europe experienced its warmest-ever winter in the 2015–16 season, with snow cover in the southern French Alps just 20 percent of its typical depth.
Problems from the Northeast to Alaska
For skiers in the northeastern United States, Daniel Scott, who directs the University of Waterloo's Interdisciplinary Centre on Climate Change in Ontario, has similar news: Even under the most optimistic climate change models, ski areas in southern New England will no longer be economically viable by 2040.
Lower-altitude resorts are most vulnerable. By Scott's account, as reported by Maine Public's Fred Bever, low-snow casualties will include Mohawk in Connecticut, Blue Hills outside of Boston, and some bigger places, such as Jiminy Peak in western Massachusetts. Creeping into the northern tier, New Hampshire's Attitash is in the climate change crosshairs, as is Maine's Shawnee Peak -- the starter hill for many Portland families.
In just the past decade — the warmest in Earth's recorded history — the snow line rose between 1,200 and 1,500 feet in the northern Sierra Nevada. "The storms are not pushing over the crest like they used to. They don't have the same intensity any more," said Jamie Shectman, a founder of the Mountain Rider's Alliance, which strives to establish healthy and profitable local ski areas.
Alyeska Resort in Alaska typically posts one of the world's biggest snowfall totals by the end of each ski season, but in August 2017 announced that it was delaying its planned opening date by three weeks. Traditionally, Alyeska opened for the long Thanksgiving weekend. The resort ultimately was able to open on December 9.
Marketing Director Eric Fullerton said the decision to delay was based on "shifting weather patterns," meaning that snow cover was unpredictable early in the season, despite the investment of millions of dollars in snowmaking in recent years. "Sometimes we'll get the inversion where there's rain on the bottom and there's a lot of snow on top, and it makes it difficult to ski all the way to the bottom. Or it flip flops, and there's not enough snow on the top and we got snow on the bottom," he told local media. Fullerton added that it was difficult to get a return on investment when the ski area could not guarantee top-to-bottom skiing.
Over the past 60 years, Alaska has warmed more than twice as rapidly as the rest of the United States. The statewide average annual air temperature has increased by 3°F and average winter temperature by 6°F. The lack of snow in Anchorage has forced organizers of the famous Iditarod dogsled race to alter the course twice in recent years.
Canary in the coal mine
If nothing is done to stop global warming and our planet continues to burn greenhouse gases as we do now, the ski industry will be a shadow of what it is today, according to a 2017 study titled "Projected climate change impacts on skiing and snowmobiling: A case study of the United States" and published by Global Environmental Change. As summarized by Powder Magazine, the study found: "Climate change will scrape weeks off both sides of the season at ski resorts from California to Maine, and the losses will be so much that even population growth won't be enough to sustain business in skiing. Ski resorts at lower elevations--especially in the Northeast and Upper Midwest, but also in the Pacific Northwest and towns like Park City, Utah--will suffer the most, some places seeing their season cut by upwards of 80 percent."
The ski industry is seen a bit like the canary in the coal mine of climatology, wrote John Branch in The New York Times. Sensing this, the industry was among the first to push for awareness of the threat of global warming, long before the turn of the century, led by resorts like Aspen, in Colorado. The National Ski Area Association adopted a climate-change policy in 2000. In 2007, the snowboarder Jeremy Jones founded Protect Our Winters to further rally the winter-sports community.
Globally, the ski industry generates up to $70 billion per year. In Colorado, downhill skiing accounts for $4.6 billion in economic activity and 45,000 jobs.
Snow-making helps, but it is no panacea. "We may have reached a sort of peak season era in the 2000s when we had a lot of snow-making penetration," Scott told Maine Public's Bever. "And it's still growing in different markets, but now the climate has shifted just that much that, in these last five years anyway, the average season-length has tipped down for the first time in over 30 years.
"And adding snow-making capacity isn't necessarily the answer," Scott said. "We've seen that in the last couple of years, where it's just too warm to even make it, or even when you do make it and it just melts so quickly so you're throwing money out the door. So yeah, they'll have to look at how to diversify their revenues, and not every ski area is able to do that."
Scott, along with Robert Steiger of the University of Innsbruck and others, have looked at future warming in the context of the cities chosen to host the Winter Olympics, from Chamonix in 1924 to Pyeongchang in South Korea and Beijing in 2022. Even if emissions are cut enough to meet the target of the Paris climate agreement, only 13 of the 21 look certain to be cold enough to host snow-sports in the 2050s. With high emissions, the number would drop to just eight in the 2080s.
As The Economist summed it up in a January article, "The sight of helicopters rushing snow to Olympic sites in Vancouver in 2010 may be a harbinger of the future."


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Seven terror suspects were in custody in Belgium and France Friday as under-fire European authorities stepped up the fight against extremist networks following triple bombings in Brussels claimed by ISIS.
Six people were being held after raids across the Belgian capital Thursday, two days after airport and metro suicide blasts that left 31 people dead and 300 injured.
And in the Paris suburbs, police arrested a man accused of plotting an attack in France that was "in the advanced stages" and found a small stash of explosives.
In Brussels, families faced an agonizing wait after forensic experts warned it could take weeks to identify fatalities.
U.S. Secretary of State John Kerry arrived for talks with the Belgian authorities, who have faced heavy criticism over how the Brussels attackers – at least three of whom were known to authorities – slipped through the net.
Tags: arrests; Brussels attacks; EU; ISIS; terror suspects; terrorism


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Dr. Sabari Girish, Consultant – Orthopaedics & Spine Surgery
Posted on Wednesday, May 31, 2017
Back pain is a very, very uncommon problem in children as their spines are relatively flexible compared to that of adults.
So if your child complains of back pain or any related symptoms – especially if it aggravates after any physical or sports activity, make sure you seek immediate medical help.
It is very important that the cause of back pain be identified and treated/ managed early to ensure the best possible outcome. The optimal course of treatment will be decided after a detailed evaluation of the condition, which may include haematological and radiological investigations like CT or MRI. Remember, not treating the child on time can lead to several potential complications, including disabilities.
Common causes of backache in children
Of the 24 state-of-the-art operating theatres, 12 are already functional. The first totally integrated OTs in Kerala, these spacious theatres provide modern technology that facilitates collaborative work.
You'll have access to the most advanced technology, ranging from blood work to imaging services, ensuring a distinct advantage when it comes to diagnosis and treatment.


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|Up a level
- National Library of Medicine Listing (5470)
- WB Practice of Medicine (489)
- WB 102.5 Clinical medicine - evidence-based practice (7)
- WB Practice of Medicine (489)
Blakey, John, Brown, M., Pinchin, J., Barley, M. and Sharples, S. (2015) 'PRO: confronting resistance to rule-based medicine is essential to improving outcomes'. Thorax, Vol 70, Issue 2, pp. 110-111.
Mavhu, Webster ORCID: https://orcid.org/0000-0003-1881-4398, Willis, Nicola, Mufuka, Juliet, Mangenah, Collin, Mvududu, Kudzanayi, Bernays, Sarah, Mangezi, Walter, Apollo, Tsitsi, Araya, Ricardo, Weiss, Helen A and Cowan, Frances ORCID: https://orcid.org/0000-0003-3087-4422 (2017) 'Evaluating a multi-component, community-based program to improve adherence and retention in care among adolescents living with HIV in Zimbabwe: study protocol for a cluster randomized controlled trial.'. Trials, Vol 18, Issue 1, p. 478.
Nagpal, Sukrti, Sinclair, David and Garner, Paul ORCID: https://orcid.org/0000-0002-0607-6941 (2013) 'Has the NTD Community Neglected Evidence-Based Policy?'. PLoS Neglected Tropical Diseases, Vol 7, Issue 7, e2238.
Opiyo, Newton, Molyneux, Elizabeth, Sinclair, David, Garner, Paul ORCID: https://orcid.org/0000-0002-0607-6941 and English, Mike (2014) 'Immediate fluid management of children with severe febrile illness and signs of impaired circulation in low-income settings: a contextualised systematic review'. BMJ Open, Vol 4, Issue 4, e004934.
Rohwer, Anke, Garner, Paul ORCID: https://orcid.org/0000-0002-0607-6941 and Young, Taryn (2014) 'Reading systematic reviews to answer clinical questions'. Clinical Epidemiology and Global Health, Vol 2, Issue 1, pp. 39-46.
von Elm, Erik, Ravaud, Philippe, MacLehose, Harriet, Mbuagbaw, Lawrence, Garner, Paul ORCID: https://orcid.org/0000-0002-0607-6941, Ried, Juliane and Bonfill, Xavier (2013) 'Translating Cochrane Reviews to Ensure that Healthcare Decision-Making is Informed by High-Quality Research Evidence'. PLoS Medicine, Vol 10, Issue 9, e1001516.
Wakeham, Katie, Harding, Richard, Levin, Jonathan, Parkes-Ratanshi, Rosalind, Kamali, Anatoli and Lalloo, David ORCID: https://orcid.org/0000-0001-7680-2200 (2017) 'The impact of antiretroviral therapy on symptom burden among HIV outpatients with low CD4 count in rural Uganda: nested longitudinal cohort study.'. BMC Palliative Care, Vol 17, Issue 1, p. 8.


text:
- $39,000 price
- 5855343 listing id
- Neighborhood: Golden Vista RV Resort
- Status: Active
Come experience the finest in resort style living in Golden Vista Resort. Fabulous 55+, gated, active adult community with amenities and activities galore. Plus you OWN the Land! This lot features a full concrete pad w/stamped concrete design, 10x12 shed, all RV hook ups and gorgeous views of the Superstition Mountains. Fun, active, community street. This lot is adjacent to and can only be sold with park model/AZ room #681. Ideal for your RV site, move in a new park model or park your RV and live in unit 681. Please call today for more information and to schedule a showing.
Courtesy of: Century 21-Towne & Country
Office Phone: (480) 335-1400
Copyright Arizona Regional Multiple Listing Service, Inc. All rights reserved. Information is deemed reliable but not guaranteed.
Updated: 22nd September, 2019 7:26 PM.
3710 S GOLDFIELD Road Apache Junction, AZ


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Do you need coffee every morning? Catch everyones attention with this perfect mug! 11oz and 15oz versions available.
Hurry! Only 12 left in stock.
Arguing With A Teacher Is Like Wrestling A Pig In Mud Sooner Or Later You Realize That They Like It
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Western Visions is the National Museum of Wildlife Art's largest and longest running fundraiser, with a variety of exciting events. This year's show will run from September 9th to October 9th, 2016 and features a wide selection of art for sale. Wild 100 painters and sculptors participate in the art portion of the show and sale and as many as 2,000 people attend the events.
Back to All Events
Earlier Event: August 20America's Horse in Art
Later Event: September 8Raise the Roof for the Russells


text: NSPI's outstanding career opportunities are just the beginning. Round Rock is part of the high tech community of Austin, Texas. Known as the "Live Music Capital of the World", Austin, as the state capital of Texas, is both politically charged and culturally rich. The surrounding hill country and area lakes offer many forms of outdoor recreation. There are very few places in the United States where you can enjoy the superior climate and pristine surroundings of such a beautiful region, while still benefiting from everything that a world-class employer can offer. Please click here for information about Austin, Texas.


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45 Reviews
The shadow has it.
Bringing constant refinement to the 11-speed XT drivetrain, the Shimano XT RD-M8000 Rear Derailleur offers improved chain retention when you're riding across jarring, rock-strewn trails. Benefiting from trickle-down technology from the XTR group, Shadow RD+ technology keeps the chain from bouncing around with its handy stabilizer switch. The Shadow design is optimized for increased stability with its slanted position, allowing for silky-smooth shifting in every gear.
The XT's robust aluminum construction takes a serious beating without fuss, equating to worry-free confidence when you're rallying across technical terrain. In conjunction with a low-friction shift cable, Shimano claims shifting requires 20% less effort. Other key features include an easy-to-adjust chain stabilizer for effortless fine-tuning, as well as Direct Mount attachment with compatible frames for a stronger and lighter mount interface. As a bonus for riders with older frames not compatible with Direct Mount, the included link attaches in a conventional manner.
- The ultimate racing workhorse for mountain derailleurs
- Durable aluminum construction withstands trail abuse
- Shadow RD+ with stabilizer switch prevents dropped chains
- Direct-mount option with compatible frames (without link)
- Compatible with conventional derailleur attachment (with link)
- 11-speed rear derailleur: gs/medium 1x11/2x11, sgs/long 3x11
- Item #SHI008G
Tech Specs
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- Reviews
What do you think about this product?
Have questions about this product?
Best value for your money
reliable, smooth shifting. Paired with a 11-46 10spd cassette and a goatlink and never had any problems.
You don't need the X
- Familiarity: I've put it through the wringer
In the name of your bike grouppo to get great shifting and light weight. Did I mention inexpensive? XT does everything that its racing big brother does and leaves a little green in your wallet for a good macro brew.
- Familiarity: I've put it through the wringer
I got this derailleur after bending my XTR derailleur for what I thought would be temporary. However, I decided XT is all I need. It's cheaper, works well, and is more durable in my opinion. Don't get me wrong, I loved my XTR setup - especially when I was racing. But now, I want durability for those long days in the saddle (with the occasional race).
Dependable XT & near XTR Performance
- Familiarity: I've put it through the wringer
I've ridden the XTR 11spd groupset, and decided that at half the cost, using the same design with heavier materials, it would be worth trying the XT derailleur and cassette (XTR shifter). Boy was I happy! It was nearly impossible to tell the difference in the XTR full groupset I rode vs my XT with XTR shifter. Shifts like butter, no stutter or interrupt mid spin, no hard clunks, and adjustable clutch is a huge +. You can't adjust clutch strength on SRAM comparable models, leaving them with a lot of chain slap - Never had an issue with my XT chainslapping.
Also - VERY DURABLE. Took a minor hit to the derailleur by clipping a tree mid-air. Bent the hanger... picked up a new hanger and was good as new! was super worried the derailleur would have issues, but it was completely fine!
Go to for rear derailleur
XT is a go to for drivetrain if running Shimano, or thinking of converting from SRAM. Cant beet the quality for the price, and a great pair with e13 9-46 cassette - better range than eagle for a lot less.
- Familiarity: I've used it several times
XT stuff is the real deal. With the latest update, XT honestly feels like XTR. Don't get caught up in the status race. Unless you're a really serious racer, it's hard to make an argument for XTR from a value perspective.
- Familiarity: I've put it through the wringer
XT is the MTB'er group. The shifting is so close the XTR I doubt anyone will notice. I've used this derailleur with an XT 11-42 cassette and a 1x 30t chainring and it shifts great. It is plenty durable enough you might end up putting it on a couple different bikes.
MTB standard
- Familiarity: I've put it through the wringer
Even if it's Shimano's 2nd tier, XT will always be my gold standard. The crispest shifting on the market- the combo of the XT derailleur and shifter leave nothing to be desired. I've used this setup with an XT 11-42 cassette, E*13 9-44 cassette and SRAM 10-42 cassette. Shifts great on all, but with the E*13 you'll want the long cage. Durable enough to take a season or two of smashing into rocks.
Great product
- Familiarity: I've used it several times
The xt derailleur is amazing for the price really nice shifting durable strong I really recommend , I was using sram x9 groupset it works really similar so don't be afraid to try it.....
Amazing for the price
- Familiarity: I've put it through the wringer
This derailleur is one of the best I have ever owned. The clutch is great, the shifting is instantaneous, and it is lighter weight than my 10 speed SLX derailleur.
One sturdy derailleur
- Familiarity: I've put it through the wringer
I think that the XT groupset is one of the best you can buy at this point. They are fairly light, very reliable, and will last forever. Not to mention, it's super affordable! Easy to install and also really easy to maintain. Might not be the ultra light race set up you want, but is just flat out reliable.
Loving it
I just put my first XT groupo on a build and I'm loving the clean shifting of this derailleur. The chain retention stabilizer switch is cool once you realize you have it and lock it instead of wondering why things are rattling so much on a descent.... but that's just my bad
Great Set Up
- Familiarity: I've used it several times
This was one part of my 1 x 11 set up for a Surly Krampus. Great value and quality. Another outstanding product from Shimano. If you have questions on set ups for your bike make sure you call in to talk to a bike Gearhead.
My, what a long cage you have.
- Familiarity: I've put it through the wringer
With the advent of 1x and the huge big cog, derailleurs have had to keep up with long cages. XT the best working, everyman components on the market. Shifts well and never needs adjustments.
Best combo price/quality
- Familiarity: I've put it through the wringer
Great value, super durable, shifts really well. What more can you ask for?
XT is the everyman groupo
- Familiarity: I've put it through the wringer
No, it's not XTR, but mechanically it is the same, and only a little heavier, but a good bit cheaper. I love XT and see no reason to go with anything else. XTR is for the racers with sponsors, XT is for the rest of us
Works great for my 1x11 build on a new Yeti SB6 custom build. Very smooth, cant wait for spring to get ripping!
Big bang for your buck
- Familiarity: I've put it through the wringer
The XT rear derailleur's does shift cleaner than other XT products in the past. The clear advantage is Shimano's new clutch design to provide chain retention, so you can run a 1X configuration with a 11-46 cassette. If you have any questions on this product, I will be happy to help you out.
Do you need the long cage to run the 11-46 on a 1x11?
I'm going to get a SRAM 11-42 cassette, will this LONG cage work on my 1x11?
Smooth operator!
- Familiarity: I've put it through the wringer
I bought this after Shae( She is great) from the bike dept at backcountry recommend it as part of the parts ( Race Face Narrow Wide Chainring, Shimano CN-HG600 11-Speed Chain,Shimano XT CS-M8000 Cassette, Shimano XT SL-M8000 RapidFire Trigger) to convert my baby (2016 Santa Cruz Heckler) to a 1 x 11. After a 100 miles the the derailleur is still smooth and is tougher that it looks. I had a couple of bad crashes that had me fearing the worst, however it is still going. I could not be happier; all done at a very reasonable price. My only regret is that i did not changed sooner to a 1 x11
Great. Consider adding Goat Link
- Familiarity: I've put it through the wringer
I use this on a 11 x 46t XT cassette. It is crisp, however it does take a while to dial in. I added the Goat Link 11 and it made the derailleur perform incrementally better.
Based on your experience with the 11-46, would you recommend doing the 11-42 or the 11-46 with the xt8000?
46 tooth hands down. I would much rather have a bunch of gearing the back and if I needed to gear it up a little, just change a front chain ring.
Now, if I use a 1x11 with a 9-46 cassette,
should I use the medium cage or the long cage
You'll want the long cage for that E*13 cassette.
With a 34T oval should I go for the med or long derailleur? I have not decided on the cassette yet. probably stick to 42 and get in shape.
Hey The Chad - If you are sticking with a 11-42 cassette then the medium cage will work fine for your set-up. Give me a shout with any additional questions.
What cassette size will this handle? Or the longcage version? I need 11-42, but would like to upgrade to 11-46.
Kevin, this derailleur will accommodate 11-46 in a 1x11 drivetrain or 11-42 in a 2x11 setup.
Can I use this RD with a Shimano Saint 10sp shifter and Shimano XT 10sp cassette? I need to replace my Saint derailleur and would like to use this RD-M8000 if it's compatible with my current 1x10 setup.
Hi John! The m8000 derailleur will not work with your 10 speed set up, but the m786 will. Check it out below:
With apologies to Virginia, it is possible to run a Shimano XT M8000 rear derailleur with a 10-speed cassette and shifter. I did so for some 1,500 miles of the 2,000 miles I put on my bike last year and plan to carry over the same setup (Sunrace MX3 11-42T 10-speed cassette with Saint 10-speed shifter) this season. Shifting was smooth, precise, and immediate through the full range.
I chose the M8000 after reading up on other experiences at MTBR.com, and because it offers an upgrade path to 11-speed and can better accommodate a wide-range cassette than the M786.
Only criticism to date is having to replace the jockey wheels as the bearing for the tension pulley seized up.
So I can use the medium length RD with the 11-42 cassette if I'm running it 1x11, right? The long cage is only required for the triple, right?
Hey Zachary,
A medium cage would work fine for 1x11 with an 11-42 cassette.


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For those of you who have been paying attention, it's been one month since I submitted the first three chapters of my novel, To Katie with Love, to the agent who requested it. With the passage of time my excitement has quieted, but hardly disappeared. Getting past the query letter is a big deal. The first step. Maybe not an open door, but certainly a turn of the knob. I haven't heard anything yet, but as they say in the business…no news is good news.
Then again…
In other news, while I was waiting, I did get another rejection. Oh, I've had rejection before. It's never fun, but it's always important to personal growth. It's how we learn…how we get stronger…what drives us to keep going…
Honestly, all I could think of was, what do you mean you don't love me? Haven't you read my blog? Everyone loves me! I'm clever, funny, sarcastic…and I can blog about anything. Even leprechauns…Godzilla…cheese! I never skip a day, even when I'm sick. And I can identify at least ten different kinds of cow! I'll prove it. Line them up!
Ok…so maybe a cow line up on a Monday night isn't the way to go.
The simple truth of it is this…not everyone will love you. No matter how good you are. No matter how many people swear you're the next Ernest Hemingway, Jane Austen, or Erma Bombeck. Just as many people won't quite "get" you. But if you have the "voices" in you…the stories begging you to let them out…you have to keep going. That's what I'm doing.
I know I'm good. If this agent doesn't think so, I'll just query another one. And another one after that.
Hey, I'm a writer…it's what we do.


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Adoption Form
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