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Asthma morbidity and treatment in children with sickle cell
Samuel O Anim1, Robert C Strunk2, and Michael R DeBaun3,†
1Division of Pediatric Hematology and Oncology, Department of Pediatrics, Washington
University School of Medicine, Saint Louis, MO, USA
2Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington
University School of Medicine, Saint Louis, MO, USA
3Vanderbilt University, Division of Pediatric Hematology Oncology, Department of Pediatrics,
2200 Children's Way, 11206 Doctor's Office Tower, Nashville, TN 37232, USA
Children with sickle cell disease (SCD) and a comorbid condition of asthma have increased
numbers of vaso-occlusive pain and acute chest syndrome episodes, and all-cause mortality. When
assessed systematically, asthma prevalence is probably similar among children with SCD when
compared with the general African–American population. With increasing recognition of the
importance of asthma in the management of SCD, hematologists must become familiar with
asthma and develop a multidisciplinary approach, including early recognition, appropriate
management and referral to asthma specialists.
acute chest syndrome; asthma; bronchial hyper-reactivity; bronchodilator response; pulmonary
function tests; sickle cell disease; sickle cell pain
Sickle cell disease (SCD) is one of the common hemoglobinopathies worldwide and is
inherited as an autosomal recessive disorder by mendalian genetics [1,2]. Hemoglobin SS
(SCD-SS) and sickle cell-β0 thalassemia (SCD-S β0thal) are the most severe phenotypes,
occurring in approximately 60% of individuals with SCD in North America. Other
compound heterozygote phenotypes, including hemoglobin SC (SCD-SC) and sickle cell-β+
thalassemia (SCD-Sβ+ thal) occur in approximately 9–12% and 1%, respectively, based on
data from newborn cohort studies [3–5]. The underlying defect in SCD-SS is a single
nucleotide substitution, which results in a hemoglobin molecule that has substitution of
glutamic acid with valine at position 6 of the β-globin molecule [6]. SCD-SC occurs from
single nucleotide exchange resulting in the substitution of glutamic acid with lysine also at
position 6 of the hemoglobin molecule. These amino acid switches change the net electrical
charge of the hemoglobin molecule making it easily susceptible to polymerization under
© 2011 Expert Reviews Ltd
†Author for correspondence: Tel.: +1 615 875 3040, Fax: +1 615 875 3055, email@example.com.
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Financial & competing interests disclosure
Michael DeBaun has received funding from the National Heart, Lung, and Blood Institute (grant number RO1-HL079937-05). The
authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
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Published in final edited form as:
Expert Rev Respir Med. 2011 October ; 5(5): 635–645. doi:10.1586/ers.11.64.
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states of low oxygen tension and stress [7]. SCD-Sβ+ thal and SCD-Sβ0thal phenotypes are
due to impaired production of β-hemoglobin chains resulting from gene deletions or
mutations in the presence of the sickle cell mutation in the other β-globin allele. SCD-Sβ+
thal is characterized by decreased production, and SCD-Sβ0thal by complete absence, of the
β-chain. Atopic asthma, a chronic disorder of the airways, is characterized by recurrent
episodes of airway narrowing from inflammation, mucus plugging and bronchoconstriction
culminating in airway remodeling [8,9]. Similar to SCD, asthma exhibits significant
heterogeneity in clinical presentation in children. Diagnosis of asthma is primarily based on
symptoms and clinical findings, and can be supported by pulmonary function tests, such as
the presence of airway obstruction and bronchodilator response on spirometry, which may
also be useful in monitoring effectiveness of treatment. Supporting laboratory tests include
elevation of total serum IgE levels, peripheral blood eosinophilia and specific allergen
sensitivity. Despite being supportive for the diagnosis of asthma, the use of laboratory or
pulmonary function studies alone are not indicative of an asthma diagnosis. In our clinical
experience, in the setting of acute asthma exacerbation, many patients with SCD will not
have decreased oxygen saturation [10] and will not have any audible wheezing; however,
when spirometry is performed there is evidence of airway reversibility that correlates with
the current symptoms.
Epidemiology of asthma & SCD
Newborn screening data between 1990 and 1999 reported an incidence of SCD of one in
2474 of live births [11]. All 50 states and the District of Colombia currently have active
screening programmes for hemoglobinopathies [12]. In the USA, SCD population estimates
ranged from 104,000 to 138,900 based on birth cohort disease prevalence, but from 72,000
to 98,000 when corrected for early mortality [13].
The past 20 years have seen a doubling in the incidence of asthma, with about 34 million
people affected [14]. Between 2006 and 2008, asthma prevalence was 9.3% amongst
children under the age of 17 years, with prevalence in African–Americans at 14.6% and
multiracial children, 13.6%, when compared with Caucasians, 8.2% [15]. Unlike children,
the prevalence of asthma in African–Americans adults is 7.8%, similar to the general
population prevalence of 7.3% [15]. These prevalence estimates for asthma were based on
eliciting a positive response by an adult member of a family to the question 'have you ever
been told by a doctor or other health care professional that you have asthma?' and 'do you
still have asthma?' [15]. When the prevalence of asthma in SCD is compared with the
general African–American population, there appears to be a similar or slightly higher
prevalence of asthma, only one study was designed to address prevalence in the same
geographic area (Table 1) [16]. Variation in asthma prevalence in SCD (Table 1) is as a
result of different definitions used in the diagnosis of asthma. Less stringent definitions of
asthma as well as a selection bias towards individuals with underlying lung disease results in
a higher prevalence of asthma. However, in Saint Louis (MO, USA) where children with
SCD have been assessed for asthma using standardized clinical and pulmonary function
criteria, the prevalence of asthma in SCD is similar to that seen in the Saint Louis city
elementary schools where the racial mixture is similar to that in the SCD clinic [17].
Rationale for article
Asthma is a distinct, common comorbid condition in SCD; associated with an increase in
SCD-related morbidity and premature mortality. Despite the well recognized clinical entity
of asthma, particularly in children, nuances of asthma diagnosis in children with SCD are
challenging with common symptoms of asthma such as cough, wheeze, chest pain and
exercise intolerance attributed to infection or SCD instead of asthma. Further compounding
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the diagnosis is the fact that while positive test results for airway lability, such as
methacholine challenge test and bronchodilator response, are strong predictors for asthma in
the general population, their association with asthma in SCD is far less clear. In children
with SCD, a physician diagnosis of asthma remains the primary basis of children at risk for
pain and acute chest syndrome [18,19]. Among all children with SCD, evaluation for asthma
risk factors should be carried out routinely and repeatedly, but the results of these tests
should not supersede the physician diagnosis of asthma. Understanding the nuances of
diagnosis of asthma, particularly in children with SCD, is critical because a physician
diagnosis of asthma is one of the few established risk factors associated with SCD-related
Optimal management of asthma in children with SCD has not been established, but practical
approaches to care can be gleaned from asthma management in the general population. Until
more asthma specific studies on therapy in SCD are available, asthma in children and adults
with SCD should be recognized early and managed according to National Heart, Lung and
Blood Institute (NHLBI) guidelines for asthma therapy in the general population [20]. This
article will highlight challenges in diagnosis and management of asthma among individuals
with SCD.
Asthma & sickle cell pain
Vaso-occlusive pain is the leading cause of admissions to hospital, and even in a state of
relative good health, a significant number of children have some amount of pain. In the
multi-institutional study, Cooperative Study of Sickle Cell Disease (CSSCD), a prospective
cohort of 291 infants was followed for a mean length of 11 years and 4062-patient-years. Of
these children, 16.8% had a diagnosis of asthma. An increased incidence of painful episodes
(1.39 vs 0.47 events per patient-year; p < 0.001) was noted in children with asthma
compared with those without asthma [18]. In a second cohort study of 1016 children from
the Silent Cerebral Infarct Multi-Center Clinical (SIT) trial, a diagnosis of asthma occurred
in 22% of the cohort and was associated with an increased rate of vaso-occlusive pain
episodes that resulted in hospitalization and acute chest syndrome (ACS) episodes [19].
After final adjustment for age, hemoglobin F and baseline hemoglobin levels, vaso-
occlusive pain rates were 73 and 57 episodes per 100 patient-years among children with and
without an asthma diagnosis respectively (p = 0.0176) [19]. However, a single institution
retrospective cohort study from France did not find an impact of asthma on pain episodes. A
total of 297 children with sickle cell anemia were enrolled, 25 with a history of asthma and
272 without a history of asthma, with follow-up at 7 and 6 years, respectively, for a total of
1805 patient-years. No association existed between asthma and the rate of vaso-occlusive
pain episodes (72 and 60 pain episodes per 100 patient-years; p = 0.53). This lack of
association between asthma and SCD-related pain might be attributed to: the sample size, as
the absolute rate of pain for patients with and without asthma were similar to that obtained
in the CSSCD; differences in management of pain within France [21]; or the inherent
limitations of a single-center study when compared with a multicentered study that did find
a significant relationship between vaso-occlusive pain and asthma.
Lower airway obstruction (LAO) is a common risk indicator of asthma. Using spirometry in
a single institutional study with LAO defined as forced expiratory volume in 1 s (FEV1)/
forced vital capacity ratio (FVC) < 95% CI and adjusted for age and gender [22], children
with LAO had more than twofold the admission rates for either pain or ACS compared with
children with normal lung function when assessed prospectively from time of pulmonary
function test (PFT) [23]. In this review of PFT records of 102 children with SCD, children
with LAO had twice the rate of morbidity when compared with children with normal lung
function (2.5 vs 1.2 hospitalizations for pain or ACS per patient-year; p = 0.003; risk ratio:
2.0; 95% CI: 1.3–3.3). Children with restriction did not have different rates of future
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morbidity compared with children with normal lung function (1.4 vs 1.2 hospitalizations for
pain or ACS per patient-year; p = 0.68; rate ratio: 1.1; 95% CI: 0.6–2.1). LAO was also
associated with increased risk of morbidity, even in those children without a diagnosis of
asthma. Several limitations exist in this study, including but not limited to referral bias of a
hospital based cohort that had to receive spirometry evaluation for inclusion and a small
sample size that is sensitive to outliers. As a single institution study with several limitations,
the study results require repeating before significant confidence can be placed in the
association between LAO- and SCD-related morbidity.
Asthma & acute chest syndrome
Acute chest syndrome is the leading cause of death and admissions to the pediatric intensive
care unit in children and adolescents, and the second most common cause of admission after
vaso-occlusive pain episodes in children [24]. Multiple ACS definitions have been
proposed; although significant differences exist in terms of clinical symptoms needed, it is
accepted that an infiltrate or new radiodensity on imaging is an important criterion that
needs to be fulfilled. Other clinical features include hypoxemia, respiratory distress, fever,
need for blood transfusion and rapid deterioration in clinical status [25,26]. Differentiating
between an acute asthma exacerbation and ACS is a challenge clinically as they can present
with similar symptoms. Wheezing and cough, a common clinical presentation of asthma, are
also common findings of ACS, and a new radiodensity on chest x-ray may represent either
atelectasis or infiltrate. One usually needs to treat for both asthma and ACS in the setting of
a previous doctor diagnosis of asthma. In the CSSCD infant cohort, asthma was associated
with more frequent ACS episodes, 0.39 versus 0.20 events per patient-year (p < 0.001) [18],
and a similar twofold rate of ACS per patient-year (0.31 vs 0.16 events/patient; p = 0.03)
was found in the French study [21]. Recurrent ACS episodes are associated with abnormal
lung function among children with SCD [27]. Also, the proportion of children with a
physician diagnosis of asthma increases linearly as the number of ACS episodes increase
Given, the intrinsic limitations of the study design of most SCD studies, where careful
delineation of asthma was not part of the original purpose of the study, we are unable to
determine whether ACS predisposes to asthma or vice versa. However, children with ACS
are diagnosed with asthma at a younger age compared with those without ACS [29],
suggesting that asthma is a predictor of the occurrence of ACS. In the SIT trial, involving
1016 children with SCD, An et al. also confirmed that a doctor diagnosis of asthma was
associated with increased incidence rates of ACS [19]. In this large study, after final
adjustment for age, hemoglobin F and baseline hemoglobin levels, ACS incidence rates
were 22 and 12 episodes per 100 patient-years among children with and without an asthma
diagnosis, respectively (p < 0.0001) [19]. Severe recurrent wheezing is associated with
increased rates of hospitalization for ACS, risk ratio = 2 (95% CI: 1.2–3.4; p = 0.005) [30].
In a retrospective study, by Knight-Madden et al. children with recurrent episodes of ACS
were more likely to have atopic asthma and bronchial hyper-reactivity compared with those
with only a single ACS event, 53 versus 8% (Odds ratio [OR]: 8.1; 95% CI: 2.3–28.6; p <
0.001) [16]. While the results of these studies do not demonstrate causality, they show a
close association between ACS and asthma, suggesting that a diagnosis of asthma
predisposes to future ACS episodes.
The diagnosis of asthma at different ages is a challenge particularly in younger children; our
group follows the premise that asthma is a lifelong condition, as demonstrated by
progressive decline in lung function over 15 years in persons who gave a self report of
asthma [31] and at 28 years in children with frequent wheezing [32]. Probably the most
compelling support that a diagnosis of asthma precedes ACS is based on the observation that
in the CSSCD, children with a diagnosis of asthma presented with ACS at 2.4 years
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compared with 4.6 years in children without asthma (hazard ratio: 1.64; 95% CI: 1.13–2.39;
p = 0.01) [18]. Additionally, results from two retrospective studies, suggest, but do not
confirm, that a previous diagnosis of asthma is associated with future ACS episodes. In the
first study a history of asthma and home use of inhaled β adrenergic agonists were
associated with increased readmission within 14 days of discharge for an ACS episode, OR
= 3.8 (95% CI: 0.9–15; p = 0.06) and OR = 6 (95% CI: 1.2–3; p < 0.05), respectively [33].
In the second study, Boyd et al. reviewed medical records of children admitted for pain of
children with asthma (cases), 35% developed ACS in hospital compared with 12% in
children without asthma (controls) [34]. Children with a physician diagnosis of asthma were
about four-times more likely to develop ACS and also had longer hospitalizations for ACS,
5.6 compared with 2.6 days (p = 0.01) [34]. The association between asthma and SCD is not
limited to patients with hemoglobin SS. In a retrospective study, a greater proportion of
children with SCD-SC had a prior history of asthma or wheezing than those with SCD-SS,
50.7 versus 33.8% (p = 0.04) [35].
Asthma & mortality
Life expectancy in SCD has improved over the past 20–30 years and is partially dependent
on SCD phenotype. In a prospective study that followed 3764 individuals from birth to 66
years of age, the median age at death for males and females were 42 and 48 years of age for
SCD-SS and SCD-Sβ0thal, but 60 and 68 years of age for SCD-SC, respectively (p < 0.001)
[36], much lower than the general population. Pulmonary findings on autopsy may include
findings consistent with acute asthma exacerbation and or pulmonary hypertension [37–39].
A risk for premature death among those with SCD-SS and asthma was demonstrated in the
CSSCD prospective cohort of 138 individuals with asthma and 1825 individuals without
asthma [40]. Individuals were identified at a mean age of 9.7 and 14.2 years (p < 0.001),
respectively, and followed for a total of 18,495 patient-years. Hazard ratio for the comorbid
condition of asthma was 2.36 (95% CI: 1.21–4.62; p = 0.01) [40]. Although result of this
study does not establish a cause and effect relationship between asthma and premature
mortality, it provides compelling support of at least a strong association.
A causal link between the presence of asthma and premature death is suggested by the report
of Field et al. of two adolescents with histories of severe persistent asthma in addition to
SCD [37]. Both individuals were prescribed appropriate treatment for their asthma and had
recently received medical care from a pediatric asthma specialist; however, both adolescents
died suddenly in the midst of increased respiratory symptoms consistent with asthma
exacerbation, where post mortem findings were consistent with asthma [37]. Taken together,
these data underscore the importance of not only diagnosing asthma in children and adults
with SCD, but also understanding the optimal management for this vulnerable population.
SCD is associated with airway hyper-responsiveness & bronchodilator
Airway hyper-responsiveness (AHR) and increased bronchodilator reactivity (BDR) are
measures of airway lability. Tests for AHR and BDR are often used as evidence to support a
diagnosis of asthma in children without SCD; however, asthma is ultimately a clinical
diagnosis and individuals with asthma may not have either a positive AHR or increased
Measurement of AHR can be done either with methacholine, cold air or exercise challenge
tests, and BDR is measured with administration of inhaled short-acting β-adrenergic agonist.
Reported prevalence of airway lability in children with SCD is variable with rates between
14 and 75% [41–44]. In part, the large range of airway lability is related to the different
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definitions of a positive result as well as the methodology used. Several studies have
documented that both AHR and increased BDR in SCD are higher than the prevalence of
asthma in the cohort, indicating that a high false positive rate is likely to arise if these tests
are used as a diagnostic criterion (Tables 2 & 3).
American Thoracic Society criterion for positive BDR response requires an increase in
FEV1 ≥ 12% predicted after bronchodilator administration, and among adults an increase in
FEV1 of at least 200 ml [45]. Leong et al. compared 40 children with SCD, aged 6–19 years
with 14 healthy controls made up of siblings of patients with SCD, but no family history of
asthma. Reactive airway disease (RAD) was defined in this cohort as a recurrent wheezing
responsive to bronchodilator [44]. Airway lability was defined as either a positive cold air
challenge or an increase in FEV1 of at least 12% if the initial FEV1 was too low to allow the
cold air challenge. Prevalence of airway lability was 64% in the whole SCD population and
73% in the children with RAD, which was not statistically different from those without
RAD (p = 0.2) [44]. One postulate is that ACS increases airway sensitivity, and as such,
children with a history of ACS are more likely to have airway lability. This temporal
relationship of ACS and increased airway lability has not been established and the opposite
could as easily be true, namely that airway lability is associated with an increase rate of ACS
episodes. Sylvester et al. did not see any difference in the prevalence of AHR defined using
cold air and exercise challenge tests among children with a history of ACS compared with
those without a history of ACS [41]. Further, Knight-Madden et al. did not find a significant
association between airway lability and recurrent ACS. In this retrospective study, the
investigators compared 80 children with SCD to an equal number of appropriately matched
controls without SCD [16]. Prevalence of airway lability, defined as hyper-responsiveness
with a decrease in FEV1 of at least 10% with exercise test or BDR of ≥12%, was 14 versus
6% in children with SCD and healthy controls, respectively (p = 0.12). In the group with
recurrent ACS compared with a single ACS episode, the proportion of children with airway
lability, 71 versus 39%, was also not statistically significant (p = 0.133) [16]. Further
prospective and more complete lung studies are needed to determine the relationship
between airway lability and the incidence of ACS. If such a relationship is established, then
perhaps targeted therapeutic interventions can be introduced in a clinical trial.
As part of a prospective NIH-funded study, Field et al. explored the relationship between
methacholine responsiveness, asthma diagnosis, determinants of atopy, and a measure of
hemolysis in a multicenter prospective study involving 99 children aged between 5.6 and
19.9 years, all with SCD-SS [43]. Using the outcome of the methacholine challenge of
provocative concentration that causes a decrease in FEV1 by 20% from baseline (PC20), 2
mg of methacholine/ml was needed in 42% (41 out of 98) of the cohort for a positive
methacholine challenge test. Despite the well established relationship between methcholine
and asthma in the general population, no such association exists in children with SCD (p =
0.986). However, methacholine responsiveness was associated with elevated IgE levels (p <
0.009), younger age (p < 0.001) and elevated lactate dehydrogenase (LDH) levels (p =
0.005). The observation that an elevated LDH level, a marker of increased hemolysis, was
associated with PC20 levels suggest that chronic hemolysis in children with SCD may play a
role in the pathogenesis of AHR [43]. AHR testing appears to be safe in children without
SCD; however, in children with SCD, no additional data appears to be obtained that will
change the clinical management of the patient and there is a possibility that adverse side
affects due to the administration of methacholine may occur [46]. Similarly, the utility of the
cold air challenge is also in question because cold air used in the cold air challenge test can
trigger sickle cell pain and wheezing among children with SCD [44].
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Role of IgE levels as a predictor of asthma
Elevated total or specific IgE levels are involved in the pathogenesis of atopy and asthma. In
the general population these tests can be used as a predictor of asthma. Burrows et al.
examined the relationship between IgE levels and the self report of asthma among the
general population [47]. Diagnosis of asthma was closely associated with IgE levels
standardized for age and gender (p < 0.0001). Of the 177 individuals with the lowest levels
of IgE, there were no reports of asthma, in contrast to a prevalence of approximately 40% in
those with high IgE levels [47]. A similar association between elevated IgE levels and
physician diagnosis of asthma in SCD exists [19]. In the SIT trial cohort, approximately,
50% (261 of 521) of the population had a total IgE level greater than the 90th percentile
when compared with the general population; whereas, only 10% would have been expected
to exceed the 90th percentile. Furthermore, 25% of children with SCD had an IgE level
above the 98th percentile. In this cohort, children with higher IgE levels had a higher odds
of a diagnosis of asthma [19]. Higher IgE levels were documented in a second study,
involving children with SCD in which a relationship between IgE levels and asthma was
found [48]. In 297 children evaluated for asthma, the mean total IgE level, adjusted for age
was higher in children with SCD compared with the general population 234.8 versus 62 IU/
ml, respectively [48]. Comparison of total IgE levels in children with SCD with and without
a physician diagnosis of asthma also showed a statistical difference of 623 versus 207 IU/ml,
respectively (p = 0.005). In this same study, children with a physician diagnosis of asthma
were more likely to be sensitized to aeroallergens using a skin test (79 vs 43%; p = 0.03).
Thus different reference ranges, which have not yet been established, are required when
considering use of IgE levels in predicting asthma in children with SCD.
In addition to total IgE levels being associated with asthma in SCD, total IgE levels are
associated with ACS rates. In the SIT trial wherein, 1003 patients with over 3000 patient-
years An et al. again demonstrated that IgE levels were associated with ACS (p = 0.048) but
not pain episodes (p = 0.28) [19]. The biological basis for this association is unclear, but
most likely is related to the strong relationship between IgE levels and asthma in SCD and
IgE levels and the relationship between asthma as well as ACS in SCD [19].
Lung function abnormality & SCD
Restrictive lung function is the predominant lung function abnormality in adults, with a
reported prevalence of 74% [49]. By contrast, lower airway obstruction is the predominant
lung function abnormality in children [50]. Onset of abnormal lung function is prior to the
development of overt SCD-related morbidity and most prevalent in children with severe
phenotypes such as SCD-SS [50,51]. Valid lung function assessment by either spirometry or
lung volumes are dependent on the effort of subjects. As such, pulmonary function tests
should only be conducted when children with SCD are in their steady state or at least 2
weeks after discharge from hospital for a vaso-occlusive pain episode, ACS or other
complications of SCD and conducted by technicians skilled in obtaining repeatable efforts
from children. Appropriate reference ranges should be used in the interpretation of results
and appropriately adjusted for age, ethnicity, gender and height, as these factors influence
lung function. Optimal interval for PFT has not been determined, but should be at least
annually and even more frequently in the setting of clinical symptoms of lung disease, or
previous findings of LAO or restriction.
Asthma management in SCD
Early recognition and prevention of acute asthma exacerbation, SCD-related pain and ACS
will decrease the effects of both asthma and SCD on the lungs, ultimately improving quality
of life and survival. One of the barriers to effective management of children with respiratory
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symptoms is failure to appropriately recognize asthma in these children [52]. In children
with SCD, cough is likely to be interpreted as the presence of infection, while chest pain or
tightness are likely to be interpreted as sickle cell pain requiring analgesics rather than as a
sign of asthma. The misclassification of these symptoms may result in worsening asthma. In
addition, significant heterogeneity exists in how physicians diagnose asthma in children with
SCD. In a survey of clinicians on the important factors required in establishing an initial
diagnosis of asthma, only 60% of physicians surveyed correctly identified wheeze,
symptomatic improvement with bronchodilator, recurrent cough, exclusion of other
diagnosis and peak flow measurements [53]. A significant number of physicians are
reluctant to use systemic corticosteroids in these children because of side effects (see next
section). In the absence of specific guidelines for this cohort, it is important that physicians
familiarize themselves with the NHLBI recommendations for both prevention of asthma and
treatment of acute asthma exacerbation (Box 1) [20].
Box 1
National Heart, Lung and Blood Institute recommendations for treatment of
acute asthma
Early recognition of worsening asthma symptoms by patient and physicians are
important in the management that takes place in the acute care setting such as
the emergency department, physician's office or urgent care.
Oxygen to relieve hypoxemia in moderate or severe exacerbations.
SABA to relieve airflow obstruction.
Addition of inhaled ipratropium bromide in severe exacerbations.
Systemic corticosteroids to decrease airway inflammation in moderate or severe
exacerbations for patients who fail to respond promptly and completely to a
Consideration of adjunct treatments, such as intravenous magnesium sulfate or
heliox, in severe exacerbations that are unresponsive to the initial treatments
listed above.
Monitoring response to therapy with serial measurements of lung function.
Preventing relapse of the exacerbation, or recurrence of another exacerbation by
providing: referral to follow-up asthma care within 1–4 weeks; an ED asthma
discharge plan with instructions for medications prescribed at discharge,
increased medications or advice to seek medical care if asthma worsens; review
of inhaler techniques whenever possible; and consideration of initiating inhaled
ED: Emergency department; SABA: Short-acting β-agonsit.
Reproduced with permission from [20].
Typical chest x-ray findings of asthma include hyperinflation of the lungs with flattening of
the diaphragm, increased bronchial markings and atelectasis from mucus plugging [54].
These findings can easily be mistaken for and managed as an infiltrate associated with ACS,
instead of an acute asthma exacerbation.
Treatment to reduce asthma-related morbidity requires that asthma severity be classified
based on frequency of symptoms and history of exacerbation. Additionally, attempts should
be made to recognize exercise-induced symptoms because the majority of these children
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may not be very active in sports and might have difficulty with activities of daily living,
such as coughing or wheezing while walking or climbing up stairs.
Bronchodilators are one of the most commonly prescribed medications for the management
of asthma particularly in the setting of an acute exacerbation. These may be in the form of
albuterol or other β adrenergic agonists. To date, no randomized controlled studies have
been done examining the specific effects of inhaled bronchodilators in children with SCD
[55]. In the setting of ACS, however, bronchodilator use improves oxygenation, clinical
outcome and is associated with a mean improvement in FEV1 of about 27% [56,57]. As
such, in children with ACS where symptoms overlap with asthma, bronchodilator use may
improve both asthma and ACS.
Leukotrienes are metabolites of arachidonic acid which, are released during inflammation.
These metabolites have effects on both the vasculature as well as airways leading to vaso-
and broncho-constriction, and may be important mediators in both SCD and asthma.
Individuals with SCD have higher levels of urinary cysteinyl leukotrienes E4 at baseline and
significantly increased levels during periods of sickle cell pain and ACS [58–60], making it
particularly attractive as a future targeted treatment. No studies however have been done
looking at the role of leukotriene modifiers in the treatment of asthma in this cohort.
Inhaled or systemic corticosteroids are the cornerstone of maintenance and acute
management in children with asthma. However, guidelines for use of this class of
medication for children with SCD are unclear. Inhaled corticosteroids were found to be
superior to leukotriene modifiers in persistent asthma with the end points of decreased use of
albuterol as rescue medication, lower asthma symptoms score, decreased night time cough
and awakenings, as well as increased percentage of asthma symptom-free days [61].
Systemic corticosteroids can be used in the treatment of children with SCD to hasten
recovery. Beneficial effect of systemic dexamethasone was demonstrated in a randomized
controlled trial of 43 children with SCD and ACS, with a median age of 6.7 years. Duration
of hospitalization was lower in children who received dexamethasone, at time intervals of 47
versus 80 h (p = 0.005) [62]. Other variables such as need for blood transfusions, mean
duration of oxygen, analgesic therapy and duration of fever were also lower in the
dexamethasone group. However, readmission rate within 72 h after discharge was increased
in those who received dexamethasone, although not statistically significant between the two
groups (27 vs 4.7%; p = 0.095). A significant weakness in the trial was the observation that
participants were not evaluated for the presence of pre-existing asthma, as children with
asthma have a higher rate of ACS [62]. Perhaps the beneficial effect of the corticosteroid
treatment group when compared with the nontreatment group was related to being treated
for an unrecognized asthma exacerbation.
The high readmission rate associated with steroid administration in SCD was supported in a
large multi-institutional retrospective study consisting of 3090 individuals with 5247
hospital admissions for ACS, of which 874 (17%) were associated with corticosteroid use
[63]. Using propensity score analysis to adjust for confounding factors, systemic
corticosteroid use was associated with a comorbid asthma diagnosis (OR: 3.9; 95% CI: 3.2–
4.8), increased length of stay (OR: 25; 95% CI: 14–38%) and readmission rates within 72 h
of discharge (OR: 2.3; 95% CI: 1.6–3.4).
In addition to hospital readmission, systemic corticosteroid use in individuals with SCD is
associated with cerebral hemorrhage and fat emboli. Strousse et al. identified systemic
corticosteroid administration as a possible cause of life threatening problems [64]. In this
retrospective case–control study looking for risk factors for hemorrhagic strokes in SCD,
hemorrhagic stroke was associated with use of systemic corticosteroids within 14 days prior
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to event (OR: 20; 95% CI: 2.9–217; p < 0.0005) [64]. While the exact mechanism for this
association is not fully understood, the use of corticosteroid is associated with hypertension
which is a well-established factor for stroke in patients without SCD [65]. Johnson et al. also
reported a fatal case of methylprednisone used in the management of acute asthma
exacerbation in a 25 year old male with history of SCD-Sβ+ thal [66]. Although asthma
responded to treatment with corticosteroid the patient deteriorated 18 h after discontinuation
of the corticosteroid with severe pain similar to his known vaso-occlusive pain. Autopsy
findings were consistent with fat embolism in the lungs, multiple scattered foci of necrosis
in the bone marrow as well as a decrease in the amount of fat in the bone marrow for his age
Not all studies demonstrate adverse effects of corticosteroid in patients with SCD. In a
retrospective chart review of 63 children aged 17 months to 20 years admitted for ACS who
received prednisone as part of their treatment regimen, Kumar et al. did not find an
increased rate of hospital readmission [67]. Although this difference is unclear, the most
likely explanation is the exceeding small size of the study when compared with
aforementioned hospital study, the lack of a prospective data collection with careful entry
criteria, as was the case for the randomized trial and the possible difference between
dexamethasone and prednisone, with the former having a longer half-life.
In summary, given the importance of corticosteroids in the management of an asthma
exacerbation, corticosteroids should be used with caution, but not withheld when patients
with SCD have asthma exacerbations. The optimal dosing schedule for systemic
corticosteroids has not been established for individuals with SCD and asthma, but
minimizing the exposure to corticosteroids in SCD while not eliminating its benefits is a
solid strategy to undertake, until evidence-based guidelines are developed.
Expert commentary
Asthma is a distinct comorbid condition in SCD with inflammation being an integral part of
both conditions [68–70]. Despite of advances in pulmonary medicine, asthma still remains a
clinical diagnosis. In children with multiple admissions for vaso-occlusive pain and ACS
episodes, as well as those with early presentation of ACS, asthma should be strongly
considered as a potentially modifiable risk factor. In such cases, evaluation needs to include
a thorough family history of asthma, clinical history with attention to asthma risk factors,
such as environmental tobacco smoke exposure either in utero or in the first years of life,
history of allergic rhinitis, eczema and history of food allergies. While there exists a
relationship between other risk factors of atopy such as elevated IgE levels, peripheral blood
eosinophilia and tests for airway lability, interpretation of positive results should be done
with caution and only used to support a clinical diagnosis, rather than used as the sole
diagnostic criterion. Exacerbation of asthma in children with SCD would be defined same as
in children without underlying SCD, as wheeze that is not responsive to bronchodilators and
associated with worsening over time. A multidisciplinary approach is required in the
management and prevention of asthma involving a pulmonologist and other supporting
services, as well as adoption of asthma prevention strategies such as environmental controls,
the use of asthma coaches and scheduled hospital follow-up following admission for SCD-
related vaso-occlusive or asthma exacerbation. Children with SCD and asthma should
receive comprehensive care that includes at least a biannual visit to the pulmonologist and
hematologist as well as an annual PFT.
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Five-year view
The future of SCD research will focus on treatment strategies geared towards identifying
optimal modalities of treatment. Leukotriene modifiers, an effective adjuvant therapy for the
treatment of asthma, offer such targeted therapy and need to be studied in randomized
control trials, perhaps comparing effectiveness to other asthma medications such as inhaled
corticosteroids. Price et al. recently published a multi-institutional parallel study in
individuals with asthma but without SCD to evaluate the real-world effectiveness of
leukotriene inhibitors in comparison to inhaled corticosteroids as first-line therapy or a long-
acting β2 agonist as add-on therapy in individuals already receiving inhaled corticosteroids
as first-line therapy had different results [71]. At 2 months, leukotriene inhibitors were
equivalent to inhaled corticosteroids and to long acting β2 agonist as add-on therapy to
inhaled corticosteroids with respect to mini asthma quality-of-life questionnaire scores but
resulted in lower scores at 2 years [71]. Median adherence to medications was better in the
leukotriene group compared with the inhaled corticosteroid group, especially when
medication adherence is of particular importance in individuals with SCD. Another area of
research is the role of early viral infections in later outcomes of SCD, first in terms of
asthma development and abnormal lung function. As early viral infection has been deemed
important for the pathogenesis of asthma in the general population understanding the
implications of the same infection may prove to be critical in the management of SCD. For
example, rhinovirus infection in childhood is associated with about ten-times increased risk
of wheezing at 3 years of age and wheezing at 3 years of age is also associated with a
diagnosis of asthma at 6 years (OR: 25.6) [72,73]. Understanding the implications for the
pathogenesis in lung disease related to SCD is critical for identifying modifiable treatment
strategies. Chronic lung disease is associated with increased mortality in SCD [74]. As such,
identification of patient factors that are associated with development of abnormal lung
function will go a long way in stratifying patients to determine those at risk of increased
mortality. This will lead to treatment strategies aimed at halting this process. Other areas for
future study include the relationship between early infections and other markers of
inflammation as well as the progression of lung function from childhood to adulthood
through prospective longitudinal studies. In children with asthma but without SCD, nitric
oxide synthase does play a role in AHR [75]. However, this has not been studied fully in
children with SCD. We do know that a positive methacholine challenge test is associated
with elevated LDH a marker of hemolysis which corresponds to nitric oxide depletion.
Although Field et al. did not find any association between exhaled nitric oxide and AHR
[43], future studies further exploring the effects of exhaled nitric oxide will aid in our
understanding of AHR in this cohort.
Papers of special note have been highlighted as:
• of interest
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text:
I repeat... Unschooling is NOT for the lazy parent!! Rules and force are easy for a parent, but at what cost to the child and the relationship? Permissive parenting and non-involvement is NOT what I am promoting here... This Unschooling life is very involved, connected and takes time to find ways to ensure the child's rights and freedoms … [Read more...]
Radical Unschooling: The Unlazy Parenting Revolution
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The Philosophy Behind Radical Unschooling
"Dayna, I've semi-followed you and your work for a long time, but I have to say this interview gave me a new-found deep respect and fondness for you, and your philosophy. You were absolutely tapped in and flowing mad truth, with such perfect clarity, grace and undeniable integrity and consistency. You even brought tears to my eyes a … [Read more...]
Our Radical Unschooling Life – The Video!
Here is a video of our family where I share why we choose to live the life we do with our children. I explain the philosophy of Radical Unschooling in detail and Joe shares his views. Please comment below and share why you choose to parent the way you do. Are you Unschooling? Do you wish you could? What is holding you back from living the … [Read more...]

subset: commoncrawl


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A rural Park Rapids, Minn., man made his first appearance Wednesday in Becker County District Court on 11 felony counts of possession of child pornography.
Gregory Hubert Dirkes, 45, of 36318 Co. Rd. 127, Park Rapids, was charged as the result of an undercover investigation conducted by a Minneapolis police officer in the fall of 2008.
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antique toys© canicula - See portfolio
|Size (?)
|Pixel / Inches
|Add to cart
|Direct Download
|Standard XS
|346 x 346 (0.1 MP)4.8 '' x 4.8 '' (72 dpi)
|1 credit
|Standard S
|693 x 693 (0.5 MP)9.6 '' x 9.6 '' (72 dpi)
|3 credits
|Standard M
|1378 x 1378 (1.9 MP)4.6 '' x 4.6 '' (300 dpi)
|6 credits
|Standard L
|1924 x 1924 (3.7 MP)6.4 '' x 6.4 '' (300 dpi)
|8 credits
|Standard XL
|2793 x 2793 (7.8 MP)9.3 '' x 9.3 '' (300 dpi)
|10 credits
|Standard XXL
|3873 x 3873 (15.0 MP)12.9 '' x 12.9 '' (300 dpi)
|12 credits
|Vector V
|Fits any dimensionFits any dimension
|6 credits
|Extended XV
|Fits any dimensionFits any dimension
|40 credits
|caniculaSee portfolio
|Image reference
|Czech Republic
|Descriptive Category
|Objects Games/Leisure/Sports Old Toy
|Lifestyles Youth Childhood
["animal","antique","bear","brown","buggy","child","childhood","cute","design","doll","dolly","drawing","duck","fluffy","fur","furry","gift","girl","hand-drawn","happy","horse","icon","illustration","image","isolated","kid","life","little","love","old","pillow","play","pram","puppet","puppy","retro","rock","rocking horse","romantic","set","small","soft","stuffed","sweet","teddy","toy","vector","vintage","web"]animal antique bear brown buggy child childhood cute design doll dolly drawing duck fluffy fur furry gift girl hand-drawn happy horse icon illustration image isolated kid life little love old pillow play pram puppet puppy retro rock rocking horse romantic set small soft stuffed sweet teddy toy vector vintage web See all keywords
The vector illustration "antique toys" from canicula is available on Fotolia under a Royalty Free license from 1 credit (Credit from $0.74).
Available in AI/EPS and JPEG formats, this vector file may be downloaded for all kinds of professional uses. The V and XV files are delivered in AI/EPS. To modify this file, vector editing software such as Adobe Illustrator, Freehand, or CorelDRAW is required. JPEG files are available in different resolutions (up to 3,873 x 3,873 pixels in 300 DPI).
The author of this picture, canicula also has 24 images in the same series.
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CBS Pushes 'Extant' to 10 p.m.
The Halle Berry drama, which has been soft in live-plus-same-day ratings, will now have a lead-in from a "Criminal Minds" repeat on Wednesday.
CBS is hoping Extant will fare better in a later time slot. Three weeks into its freshman season, the network has decided to shift its pricey Halle Berry drama from 9 to 10 p.m. on Wednesdays.
The later hour has been good for fellow summer drama Under the Dome, albeit less so this season, but the current Big Brother lead-in has clearly not been doing Extant any favors. After a strong debut with total viewers (9.6 million) and a relatively soft showing with adults 18-49 (a 1.6 rating), its latest episode clocked just a 1.1 rating in the key demo and 6.5 million viewers. That's roughly half of Big Brother's rating.
PHOTOS Halle Berry's Career in Pictures
Extant was intended to be CBS' marquee debut after last summer's surprise success Under the Dome. The show has recouped some viewers in live-plus-3 returns, averaging 2.2 million, and just over half of a point in growth in the demo, and the first round of live-plus-7 has the premiere growing by 50 percent.
The measure of success for Extant is even more skewed by CBS' partnership with Amazon Prime to stream the episodes four days after their broadcast premiere. That data is not publicly available, though CBS Entertainment chairman Nina Tassler recently said that it was the top-performing show for Amazon U.K.
Swapping Unforgettable and Reckless on Sunday nights has worked well for Unforgettable, lifting it 43 percent. Its freshman neighbor was stabilized by the shift.
Extant's move is immediate, going into effect this Wednesday, July 30.
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Taken in Dunrobin, Ont, Canada with Canon 40D and 70-200 f4 L lens
viewed 896 as of Apr 21/11
favourites 51 as of Apr 21/11
Featured in
Canon DSLR
TERRIFIC! Love this! What an amazing action shot and what perfection in focus and clarity!
Exceptional!!!!! Incredible moment captured!
Will you come and get me and take me to where you are so I can see some of this beauty? Fabulous Jim!!!
EXTRAORDINARY!!! shot. It must have been such a rewarding day for you…Jules
Superb image Jim, great work!
Great shot Jim. What a stunning bird!!
Extraordinary shot!!!
A truly FABULOUS capture … well done!! Take Care ~ Rick & Deb ~ ☺
Absolutely stunning and amazing. Well done Jim.—Steve


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fuckin lv her April 18, 2011
would love to fuck that huge pussy
@ katja April 14, 2011
kannste haben
Analyzer July 2, 2011
I wish she had taken that in her ass...I've seen her take a fairly large guy in her ass and she's tight as a crab shell! Moaning and barking the whole time!!!
Fucker May 19, 2012
dan June 8, 2012
now this bitch can take a mean cock.....
kkoj April 12, 2011
WKJR April 9, 2011
DAAAAMM THATgall needs more loobb
Jay April 6, 2011
Oww turbo
gabyzucker April 6, 2011
etwas creme ?
alex April 6, 2011
wow that was bad did not enjoy it at all
katja April 6, 2011
so einen dicken grossen schwanz haette ich auch gerne mal in meiner moese
so good April 8, 2011
that was fantastic luv it
bigdick April 6, 2011
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Central Idaho Cabin Rentals with Cable TV(11)
11 Results
Central Idaho
Recent Central Idaho Reviews
Such a fun cabin!
We rented this cabin with a group of friends and had the best time. It is clean, in a nice location and has everything we needed. The game room was very entertaining and all of us had fun. We are going back this winter with our family.
Gorgeous retreat!
Located in the beautiful, pristine mountains near Salmon, Idaho, this home is a perfect get-away from the stress of everyday life. Picturesque views from every window, as well as a deck to soak up the sun allow you to connect with nature. The cabin has been updated with all modern conveniences, such as wifi, to help you keep up while escaping at the same time. Truly a restful respite awaits you at this spectacular mountain home.


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The difference in oils?
msalex28aSeptember 10, 2008
Is there a difference in candle fragrance oil than reed diffuser fragrance oil
The diffuser oil is the same thing as perfumers oil. You can actually use "Everclear" (the alcohol you drink) in place of diffuser oil. Really, you can use anything that is 95proof or more. Denatured alcohol from the hardware store has the same proof as everclear and perfumers oil but they add the bad smelling stuff to it so you can't drink it.
For my diffusers I use everclear and whatever scent I use for candles. They turn out good for me. When I started making diffusers, I couldn't find diffuser oils so I did a little research. That's why I use everclear. It was the cheapest.


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This is one time the Healthy Skeptic wasn't skeptical enough. Whom you choose to interview, and what personal choices you let them describe, can overwhelm the rest of the story's message.
In contrast with the last LA Times piece we reviewed, this Healthy Skeptic column addressed all of our criteria.
The Healthy Skeptic column does its usual fine job evaluating claims – this time about probiotic products.
Although the overall tone of the column displayed appropriate healthy skepticism, we feel it dropped the ball in a number of key areas. If you're going to delve into these anti-aging claims, we look for more.
The Healthy Skeptic column can usually be counted on to drive home to consumers the need for evidence to back up health care product claims. It succeeded in that once again this time.
We almost always applaud the LA Times' Healthy Skeptic column, although sometimes it just pushes us to push the paper to do more with it. We give it a 5-star score but it could have easily been even better.
The LA Times' Healthy Skeptic column clears up some fuzzy claims about an approach to dyslexia.
The column attempted to evaluate the quality of the evidence but relied on a dueling quotes approach that did not actually provide readers with much analysis. Because so much of the story is spent on the herbal remedy makers' claims, the story needed to either present the actual evidence used to make these claims or use other evidence to knock these claims down.
This was a report on a Finnish study about the potential cardiovascular benefits of frequent sauna use. Read our review before you commit to a daily sit in the sweat lodge.
Another entry in the solid "Healthy Skeptic" series in the LA Times. Good job exploring the claims about an allergy product called Allergen Block – stating that there is no evidence it works.
There are multiple ways to search our reviews. You may search by keyword, news source or review rating.


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Ahmed Ben Bella, Revolutionary Who Led Algeria After Independence, Dies at 93
Ahmed Ben Bella, a farmer's son who fought for France in World War II, turned against it in the brutal struggle for Algerian independence and rose to become Algeria's first elected president, has died at his home in Algiers, the capital. He was 93.
The state news agency announced his death on Wednesday morning.
Tall, athletic, handsome and charismatic, Mr. Ben Bella was known for his quick mind, courage and political cunning, traits that became tools of survival in a turbulent life. He faced heavy combat in wartime France and Italy, escaped French assassination attempts as well as a prison, then survived the murderous intrigues of political rivals as he struggled to impose socialism on his sprawling, divided country in the anarchy that followed independence in 1962....
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- A grandmother's trove of Civil War photos goes to Library of Congress
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- Stanford historian looks to the U.S. Postal Service to map the boom and bust of 19th-century American West
- U.S. historian denounces Japanese scholars' statement over wartime sexual slavery
- Timothy V Johnson Named Head of Tamiment Library


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Byron Smith pleads not guilty
LITTLE FALLS — Accused murderer Byron Smith entered a plea of not guilty Thursday.
Smith, 65, faces two counts of first-degree murder in the Thanksgiving Day 2012 shooting deaths of Haile Kifer, 18, and her cousin Nicholas Brady, 16.
Smith's attorney Steven Meshbesher entered the plea before Judge Douglas Anderson in Morrison County District Court in Little Falls.
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hienschDecember 1, 2012
does water go everywhere with the showerhead / half door?
Mike Strutt Design
Short answer is yes, do expect some water to escape onto the floor, but not much. Many clients like the clean look of no door, especially in a tub/shower combo. I always plan ahead and install blocking in the other wall in the event clients wish to add a glass door later on. I've built more than a half dozen half glass showers like this now. Checking in with clients months later, they've all found that they are happy with their choice and are not bothered by the minimal amount of water that does escape. None have opted to have the extra glass door installed. A floor mat and/or heated floors do help. It all depends on your comfort level.


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Thomaspaul - Goldfinch Wool Pile Rug Chocolate/Red
Thomas concept is simple. The design concept is to mix unrelated historic design styles -- art nouveau, 60s pop art, 70s minimalism, 18th century baroque -- and reinterpret these disparate periods into a unique style with a coordinated color palette that works with todays interiors. Price points are accessible to attract a stylish and design driven youth.
Product Specifications
- Sold By
- Category
- Rugs
- Style
- Contemporary


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The first time we stay here and not the last!!!!! It is clean, everything function as it has to be,Frigde, microwave and tv. Beds are good, ery important! Wifi in room is fast It is neat and very central located motel.
Friendly staff at the reception we did meet.
The price is very good.
- Official Description (provided by the hotel):
- The Golden Link Motel is a double-diamond AAA rated property located just 4 miles east of Disney on the shores of Lake Cecile. We offer free continental breakfast daily with coffee, orange juice and assorted danish. Our swimming pool is heated year-round to 86F degrees. All rooms come with a free refrigerator, microwave, safe, and free wireless internet. Our guests enjoy a coin laundry complete with irons. Come enjoy our peaceful lakefront with fishing dock, barbeque grill, and picnic area. ... more less
- Reservation Options:
- TripAdvisor is proud to partner with Expedia, Booking.com, Travelocity, TripOnline SA, Orbitz, Hotels.com, Odigeo and Tingo so you can book your Golden Link Motel reservations with confidence. We help millions of travelers each month to find the perfect hotel for both vacation and business trips, always with the best discounts and special offers.
- Also Known As:
- Golden Link Hotel Kissimmee
- Hampton Inn Kissimmee


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News and insight: all headlines
Compact Media Group, which is backed by Lyceum Capital, has signed an exclusive contract with Revolution Studios to manage the financial administration of its intellectual property rights.
Lyceum Capital has exited its investment in international clinical trial research firm Synexus in an £83m secondary buyout backed by private equity in
Lyceum Capital has hired Geoff Neville as Operations and Development Partner
Compact Media Group wins Dreamworks deal
Compact Media Group, which is backed by Lyceum Capital, has signed an exclusive contract with DreamWorks Animation to ensure the studio receives the maximum financial value from its contract rights.
Lyceum Capital exits Access Group
Lyceum Capital has exited its investment in Access Technology Group after a period of sustained growth at the software company.
Access Group, the business management software firm backed by Lyceum Capital, has acquired cloud hosting specialist StratoGen.
CuroCare becomes Sequence Care Group
Lyceum Capital-backed specialist care provider CuroCare has announced that it is changing its name to Sequence Care Group.


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2003 Dodge Durango • 75,050 miles
I have a engine ticki.G sou.D coming from cylinder 8 so I got the codes and it came up with random misfire codes so I had all plugs changed and replaced the coil on #8 and it did nothing and the only light on my dash is the emmisions light one mechanic said I had a vacum problem and that the problem was. Internal have u ever had this problem I dont know what to do next can u help.
January 2, 2013.
January 2, 2013.
Check out the related content below while we wait for the question to be answered by a professional mechanic.
What would be compatible to use for a replacement engine in my Breeze? I am just looking to get something that would work with it to get it up and running. Can I use a different model ...
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If i took out my 91 toyota carolla engine what other cars would it be compatible with?
4 answers • 1991 Toyota Corolla
We have two Jeeps that we need to replace the 4.0 engines on. a 1996 2 wheel drive and a 1998 4 wheel drive. We have found a 1994 2 wheel drive engine that we are planning on putting ...
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1990 Toyota Camry mileage: 150,000. 1. The oil warning light is on. 2. There are four quarts of oil in the car. 3. The oil filter is dry. 4. The engine sounds rough. 5. There is noise ...
3 answers • 1990 Toyota Camry • 150,000 miles


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Minneapolis, MNUSA
June 2, 2013
About us…
Help support your Meetup
Twin Cities (Minneapolis and St Paul and surrounding area in Minnesota) Visualization group focuses on creating a community around visually telling stories (most often with computer technology and data). The group arose out of the desire of a handful people that wanted to discuss visualization across sectors, such as non-profits, journalism, museums, academia, arts, and the private sector. We welcome everyone; mostly likely you work with visualization technologies, work closely with people that do, or are interested in getting started.
We regularly meet on the Third Tuesday of each month at Clockwork (but do check the schedule to make sure as sometimes this can shift).
Clockwork hosts our meetings and provides pizza and drinks.
The Eyeo Festival donated a ticket to their 2013 event to raffle.
Providing drinks at Hack Day.
115 Art Coders
249 collaborators
423 IoT Pioneers
186 Innovators
207 Cassandra Ringers
796 Google Developers
Meetup members, Log in
By clicking "Sign up" or "Sign up using Facebook", you confirm that you accept our Terms of Service & Privacy Policy


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Wayne State Interview Questions
Interview Experience
Interview Experience
Getting an Interview
Getting an Interview
Interview Difficulty
Interviews for Top Jobs at Wayne State
- Research Assistant (4)
- Research Associate (1)
- Resident Advisor (1)
- Developer (1)
- Technician (1)
- Manager (1)
- Applications Specialist II (1)
- Early Intervention Specialist (1)
- Institutional Research Analyst (1)
- Research Assistant/Research Study Coordinator (1)
- Student Assistant/Office Assistant (1)
- Peer Mentor (1)
- Adjunct (1)
- Assistant Professor (1)
- Student (1)
- Student Assistant (1)
- Engineering (1)
3 Candidate Interview Reviews Back to all InterviewsSort: Popular Date Difficulty
- Application Details
I applied online – interviewed at Wayne State.Interview Details
Interview was very smooth. Secretary was very helpful in scheduling the time back and forth. Most questions were focused on the job descriptions, like former experience, skills, etc. Not many out-of-box questions in the process. Interview team was very nice and warm. Definitely a great place to begin your career.Interview Questions
No OfferPositive ExperienceAverage Interview
- Do you think you are over qualified for this position given your former experience? Answer Question
- Application Details
I applied online. The process took a day – interviewed at Wayne State in March 2009.Interview Details
Applying for any job begins online. I received a telephone to call to set up the interview. The interview consisted of a one to one meeting with a supervisor (unsure of exact title), and two weeks later, I was informed that the position had been filled by someone other than myself.Interview Questions
No OfferPositive ExperienceAverage Interview
- What would you say is your biggest weakness? View Answer
- Application Details
I applied through an employee referral. The process took 2 weeks – interviewed at Wayne State.Interview Details
I was notified of an available position by a friend and told who to contact. I sent an email with resume attached and a brief cover letter. I also left a message with the point of contact simply stating i had been given his name by a friend and told to email and call. My email was returned rather quickly and i received a call to set up an interview. The interview was professional but not tense. The interviewer was polite and it was more like a discussion of what the job would entail and how my education and work experience might suit their needs.Interview Questions
No OfferPositive ExperienceAverage Interview
- None of the cliche "what is your worst quality?" questions. Probably the most difficult question related to how i would overcome my lack of a financial background if i were to receive the job. Answer Question


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Dozens of Future Shop stores have been closed across Canada, its parent company Best Buy Canada Ltd. announced Saturday. The company said it was shutting down 66 Future Shop stores effective immediately. Meanwhile, another 65 stores will be closed for ...Read More »
UN staff, diplomats flee Yemen's capital amid Saudi air campaign
Saudi Arabia's navy evacuated dozens of diplomats from Yemen and the United Nations pulled out international staff on Saturday after a third night of Saudi-led air strikes trying to stem advances by Iranian-allied Houthi fighters. Residents reported heavy clashes between ...Read More »
Montenegro soccer fans blamed for violence in Euro qualifier
Montenegrin soccer fans who keep causing trouble and forced Friday's Euro 2016 qualifier against Russia to be abandoned are hypocrites and barbarians, the general secretary of the Adriatic republic's football association said. The Group G match ended midway through the ...Read More »
Al-Shabaab hotel attack in Somalia leaves 24 dead
Blood spattered utensils, bullet-pocked walls and overturned chairs mark the reception area of a prominent hotel in the Somali capital following an attack by Islamic extremists that killed at least 24, including six attackers. Somali special forces stood over three ...Read More »
Former federal minister John Baird to advise mining giant Barrick Gold
Former foreign affairs minister John Baird has a new job as an adviser to global mining giant Barrick Gold, the corporation has confirmed. In its annual report, the company listed Baird and former U.S. lawmaker Newt Gingrich as members of its ...Read More »
Employees, customers react to country-wide Future Shop closures
Reaction poured in from across Canada over news that dozens of Future Shop locations will be closed. Future Shop's parent company Best Buy Canada Ltd. said it was shutting down 66 Future Shop stores effective immediately. Meanwhile, another 65 stores will ...Read More »
Are selfies a boon or blight to museums?
Visitors to the Royal Ontario Museum during the first Museum Week organized by Twitter are there not just to see, but to be seen – in the selfie photos they snap in front of their favourite pieces of art or archeological ...Read More »
Canada's Nguyen 5th in men's event at figure skating worlds
An aggressive approach by Nam Nguyen paid off Saturday, but didn't result in a podium finish for the Toronto figure skater. The 16-year-old landed his quadruple jump to climb from ninth place to finish fifth after the men's free skate at ...Read More »
Officials to provide update on Toronto fire that killed 10-year-old boy
A 10-year-old boy is dead after an early morning fire at a townhouse in Scarborough, Ont., that also left five other members of the boy's family in hospital. The mother of the family and one daughter are in serious condition, while ...Read More »
Historic St. John's mansion gets makeover, listed for $1.4M
A St. John's man is investing millions of dollars to restore a historic home in the centre of the city — a home that isn't protected by heritage status. Bruce Blackwood and his partner are revamping the 12,000 square foot mansion at 55 ...Read More »


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Violin Concerto In E Minor - Violin/Piano
Detailed Description
Violin Concerto In E Minor - Violin/Piano (Set of performance parts). Composed by Pietro Nardini (1722-1793). Edited by S Franko. For Orchestra, Piano, Violin (Violin). String Solo. 12 pages. G. Schirmer #LB934. Published by G. Schirmer (HL.50257040).
For violin and piano.


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Latest Technology Content
Jenkins J10 Black Earphones Review - $3 can go a long way
This random bargain bin store pick-up blew us away - here's why these earphones are so great at only $3.00 AUD retail pricing.
This random bargain bin store pick-up blew us away - here's why these earphones are so great at only $3.00 AUD retail pricing.
It shouldn't come as much of a surprise, but Nintendo has announced that it has delayed The Legend of Zelda for the Wii U into 2016. Nintendo's producer on the game, Eiji Aonuma explained: "We are not longer making a 2015 release our number one priority".
Aonuma continues, saying that "we have discovered several new possibilities for this game" which sounds quite exciting. Nintendo needs The Legend of Zelda for the Wii U to be perfect, but maybe we're seeing it delayed for something new coming out in the coming months? A next-gen console, possibly?
The marketing campaign for the eagerly awaited follow up to the last James Bond film; 2012's 'Skyfall' kicks into overdrive today, with the release of the first trailer for 'Spectre'.
'Skyfall' moved the Bond franchise slightly closer to it's historical roots, with many elements having been eschewed as old-fashioned having now back in fashion. In the latest entry, the villainous terrorist group SPECTRE (Special Executive for Counter-intelligence, Terrorism, Revenge and Extortion) makes a return to the franchise for the first time since 1981's 'For Your Eyes Only'.
'Spectre' is set to be released on October 23rd, 2015.
Continue reading 'James Bond's 'Spectre' teased in first trailer' (full post)
The business communication platform Slack confirmed a data breach which left users vulnerable - with usernames, email addresses, passwords, phone numbers, Skype logins, and other information compromised.
It's unknown if the cybercriminals actually decrypted any of the passwords, with no payment information accessed. "We are very aware that our service is essential to many teams," Slack said in a blog post. "We deeply regret this incident and apologize to you, and to everyone who relies on Slack, for the inconvenience."
Slack has added two-factor authentication today, and users will need to enter a verification code along with their traditional password. It's recommended all users begin using it immediately.
Continue reading 'Slack rolling out two-factor authentication after data breach' (full post)
Hotels are finding a number of different uses for radio-frequency identification (RFID) technology, with a specific note of inventory and mobile check-in solutions. Implementing RFID solutions is becoming more cost-affordable, and there is great upside if it is done well, hardware supporters believe.
"That is going to be a revolution in the future," said Steve Waldron, CIO of the Grange Hotels based in London, in a statement published by Skift. "Basically everything that has value and enhances guest experience will have an RFID chip in it for housekeeping to instantly room check to a tablet - bathrobes, duvets, blankets and so on."
RFIDs are extremely valuable in warehouses, stores, and other locations that need to keep accurate tracking of inventory. Hotels are able to instantly track supplies that can be used in guest rooms, along with food items in restaurants.
Grand Theft Auto V PC will be released worldwide on April 14 - and after multiple delays - Rockstar Games wants to show the world that it'll be worth the wait. Here are some pictures in beautiful 4K resolution. The game studio will also release a new game trailer next week.
Continue reading 'Rockstar Games makes us drool with more GTA 5 PC images in 4K' (full post)
Drones are being embraced by Hollywood directors, as the small unmanned aircraft are able to capture photographs and video footage from unique angles. Drones also are being tasked with live news footage, as they can be rapidly deployed and are relatively inexpensive.
However, there is some concern related to drone safety due to the ease in which drones can be utilized - experience isn't really a necessity before flying a drone. It can become even more dangerous on a film set, which tend to be high-pressure and fast-moving.
"Whenever you have a tool at your disposal that allows you to tell the story more efficiently and more poignantly, you use it," said Pieter Jan Brugge, executive producer of "Bosch," in a statement published by the Wall Street Journal. "The shot tells the story."
Continue reading 'Drones are being enjoyed by Hollywood, filming unique shots' (full post)
A growing number of mobile users in the United States are relying on smartphones and tablets to access their bank accounts, using apps and mobile websites.
Thirty nine percent of mobile phone owners are using mobile banking in 2014, a slight increase from 29 percent in 2012 and 33 percent in 2013, according to a survey from the Federal Reserve.
If you have a bank account, chances are very good that your bank has a mobile app that you can utilize to check your balance, recent transactions, and other typical activities. Regional and national banks are pushing users towards mobile banking - and it's becoming a major selling point - as 26 percent of respondents noted they switched banks in the past year because of a more enjoyable mobile experience elsewhere.
Nine Inch Nails frontman Trent Reznor will be tasked with leading the Beats Music evolution, with Apple hoping the service could one day compete with Spotify. The Silicon Valley company dished out $3 billion for the company known for trendy headphones and earbuds - and a lot of people wondered what would happen to Beats Music.
Apple reportedly failed in its efforts to get music labels to lower licensing costs, as Apple wanted to sell a subscription to Beats Music for just $8 per month - $2 less than Spotify's $10 per month service. However, Apple - which once held great influence in the music industry - must adapt to changing times, with more users turning to streaming services over paid music downloads.
"They're used to being a shaper rather than a responder," said Toni Sacconaghi, financial analyst at Sanford C. Bernstein, in a statement to the New York Times. "This is one of the few times where Apple is playing catch-up and not necessarily coming from a position of strength."
Gamers interested in picking up a console bundle likely won't see as many deals in 2015, GameStop said during a financial call. GameStop actually may have lost up to $250 million in physical game title sales because of increased bundles in 2014, according to a study from The NPD Group.
"Based on our discussions with publishers and platform holders, these pack-in programs will be significantly reduced in 2015," said Tony Bartel, COO of GameStop, during a recent post-earnings financial call.
To help generate sales in 2014, especially leading up towards the holidays, there were plenty of Sony PlayStation 4 and Microsoft Xbox One console bundles available. Xbox One gamers saw bundles with Assassin's Creed Unity, Black Flag, Sunset Overdrive and Call of Duty: Advanced Warfare. Meanwhile, PS4 bundles included Destiny, The Last of Us and other select choices.
Despite South Korea blaming North Korea for hacking its nuclear power operator, officials in Pyongyang have denied their involvement. In a data breach in late 2014, hackers were able to steal employee personal information, physical designs and manuals of the Korea Hydro and Nuclear Power Co.
The Korean Central News Agency said Seoul fabricated evidence saying Internet protocol addresses were linked to the north - even though the recent data breaches were "believed to have been caused by an [unidentified] group of North Korean hackers."
North Korea is believed to have a budding cyberespionage program, with most of its efforts targeted at South Korean banks and other critical infrastructure.


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Dora The Explorer Party
Age Group
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Apparel Size
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"Your child's big day is almost here, and that calls for an adventure!
Your little explorer can join up with Dora and Boots to solve problems and save the day with Dora's Flower Adventure decorations and supplies. Just like Dora's friend Backpack, BirthdayExpress.com has everything you need. You'll find the essentials, like plates, cups and napkins, but there are fun novelty items, too. Your child will feel fabulous with Dora's Flower Adventure bracelets and hair brushes, and can even dress up like the cartoon hero with a wig and Dora costume. You'll find all the gear you want to throw a party your child will love. By putting everything you need in one spot, BirthdayExpress.com simplifies party planning. Running around town looking for decorations is not a fun adventure. Dora's Flower Adventure supplies remove the hassle. A pre-designed party-in-a-box makes planning a birthday even easier. You'll get just what you want at BirthdayExpress.com. Dora and Boots are ready for an adventure. Your little one can join them as you celebrate with officially licensed Dora's Flower Adventure supplies and decorations from BirthdayExpress.com. Your child will feel like just like an explorer when they play with Dora and her friends. "