text:
West SEH, Zeng L, Lee BL, Kosorok MR, Laxova A, Rock MJ, Splaingard MJ, Farrell PM. Respiratory Infections With Pseudomonas aeruginosa in Children With Cystic FibrosisEarly Detection by Serology and Assessment of Risk Factors. JAMA. 2002;287(22):2958-2967. doi:10.1001/jama.287.22.2958
© 2017
Author Affiliations: Department of Pathobiological Sciences and School of Veterinary Medicine (Dr West), Departments of Pediatrics (Drs Kosorok, Rock, and Farrell, and Mss Laxova and Zeng) and Biostatistics and Medical Informatics (Drs Lee and Kosorok and Ms Zeng), Medical School, University of Wisconsin, Madison; and Department of Pediatrics, Medical College of Wisconsin, Milwaukee (Dr Splaingard).
Context Patients with cystic fibrosis (CF) are susceptible to lower respiratory
tract infections with Pseudomonas aeruginosa and
typically acquire this organism in early childhood. Once P aeruginosa infection is established, eradication may be impossible,
and progressive lung disease often aggravates morbidity and mortality risks.
The ability to diagnose CF by genetic testing at birth makes it possible to
determine the temporal sequence of events that result in P aeruginosa–associated pulmonary infections.
Objective To evaluate the longitudinal relationship between the production of
an antibody response against P aeruginosa and clinical
factors associated with P aeruginosa pulmonary infections
in patients with CF diagnosed in early life.
Design, Setting, and Patients Serum samples and oropharyngeal cultures (protocol cultures) were obtained
at 6-month intervals from April 15, 1985, to April 15, 2000 (or for up to
180 months depending on their enrollment date) from 68 patients at 2 centers
in Madison and Milwaukee, Wis, diagnosed through the Wisconsin CF Neonatal
Screening Project, a longitudinal cohort study. Additional cultures were obtained
at examining physicians' discretion (all cultures).
Main Outcome Measures Time to serum IgG, IgA, and IgM antibody titer of at least 1:256 against P aeruginosa, assessed by enzyme-linked immunosorbent assay
using cell lysate, exotoxin A, and elastase as antigens; time to organism
isolation from respiratory samples; time to Wisconsin Cystic Fibrosis Radiograph
(WCXR) score of 5 or more.
Results The median time to an antibody titer of at least 1:256 was 17.8, 24.2,
and 70.9 months for cell lysate, exotoxin A, and elastase, respectively. The
rise of anti–cell lysate and anti–exotoxin A titers to 1:256 or
more occurred a mean of 11.9 (P<.001) and 5.6
(P = .04) months, respectively, before the isolation
of P aeruginosa for all cultures and 18.2 (P<.001) and 11.9 (P = .006)
months, respectively, before protocol cultures. There was no significant difference
between the rise of anti–cell lysate and anti–exotoxin A titer
and a WCXR score of 5 or more (P = .24 and .32, respectively).
Treatment with long-term, non-Pseudomonas oral antibiotics
and integration of CF infants with older, chronically infected patients were
associated with a significantly increased risk of P aeruginosa pulmonary infection.
Conclusions In CF patients diagnosed through neonatal screening, P aeruginosa pulmonary infections occurred 6 to 12 months before the
organism was isolated from respiratory secretions. The longitudinal monitoring
of P aeruginosa antibody titers, in concert with
WCXR score, should facilitate diagnosis and treatment of P aeruginosa pulmonary infections in young children with CF.
Cystic fibrosis (CF) is an autosomal recessive disease characterized
by malnutrition due to pancreatic insufficiency and chronic obstructive pulmonary
disease with recurrent respiratory tract infections.1
In most patients, the characteristic lung disease eventually becomes the predominant
problem. Studies of the epidemiology of Pseudomonas aeruginosa in CF have demonstrated the prevalence of2,3
and morbidity caused by3,4 this
respiratory pathogen and have provided some insights regarding the timing5 and risk factors6- 10
in P aeruginosa–associated pulmonary infections.
Previous research on the acquisition of P aeruginosa–associated pulmonary disease in patients with CF has been cross-sectional
in design,2,11- 14
did not evaluate the antibody response to P aeruginosa,2,12,15- 18
or concentrated on older patients.15,19- 28
With the ability to diagnose CF by genetic testing at birth, it is now possible
to determine the temporal sequence of events that result in P aeruginosa–associated pulmonary infections. More precise and
reliable knowledge of these events could be valuable for the development of
optimal therapeutic regimens for the treatment of these infections, which
account for much of the morbidity associated with CF,4
even though drugs29 are now available for treatment
and potential eradication. This approach has been successful in preventing
the malnutrition associated with CF.1,30
As part of the Wisconsin CF Neonatal Screening Project,7,31
we have studied the longitudinal relationship between clinical indicators
of P aeruginosa–associated pulmonary infection,
the detection of P aeruginosa by oropharyngeal cultures,
and the production of an antibody response in 68 patients who were diagnosed
with CF through newborn screening. Our investigation differs from other longitudinal
studies correlating the acquisition of P aeruginosa
with the production of an antibody response against this organism20- 28
in that our patients were young children who were free of pulmonary disease
at the time of diagnosis with CF through newborn screening.1,30
Thus, in our study, a rise in serum antibodies against specific P aeruginosa antigens should be indicative of the initial infection.
Our patients were also well nourished throughout the assessment period because
of the early nutritional assessment and supplementation.1,32
In addition we characterized the antibody response using a statistical model.
Using these methods, we have been able to extend our previous assessment of
risk factors associated with acquisition of P aeruginosa infections in CF.9
The Wisconsin CF Neonatal Screening Project is a longitudinal investigation
designed to assess the potential benefits and risks of newborn screening for
CF and is described in detail elsewhere.1,7,31
The 2 CF centers and their treatment regimens were described previously.9 This study consisted of 63 patients diagnosed with
CF before age 12 weeks and 5 patients who were diagnosed at ages 13.0, 13.3,
14.4, 20.7, and 280.9 weeks; 13 patients had meconium ileus. To screen for
CF, an immunotrypsinogen assay was used from April 15, 1985, to June 30, 1991,
and used in combination with DNA analysis for the ΔF508CFTR mutation from July 1, 1991, to June 30, 1994. The presumptive
diagnosis of CF was confirmed with a positive sweat test revealing a chloride
level at or above 60 mEq/L. After consent for participation was obtained from
their parents, patients were enrolled at either the Madison or Milwaukee CF
Centers (referred to as centers A and B, respectively), and were followed
up in an evaluation and treatment protocol31
that prevented malnutrition.1,30
The Wisconsin CF Neonatal Screening Project was approved by the Human Subjects
Committee at the University of Wisconsin-Madison and the Research and Publications
Committee/Human Rights Board at Children's Hospital of Wisconsin, Milwaukee.
Samples of oropharyngeal secretions were obtained and cultured for P aeruginosa every 6 months from April 15, 1985, to April
15, 2000, as part of the longitudinal evaluation protocol.31
Additional samples were obtained as needed at the request of the examining
physician. For each infant or young child who could not cough on instruction,
a research nurse depressed the child's tongue and aggressively swabbed the
oropharynx (swab: BD Culturette collection and transport system, Becton Dickinson
and Co, Franklin Lakes, NJ) until the child gagged. For children who could
cough on instruction, the child was asked to cough and the nurse vigorously
swabbed the oropharynx until the child gagged. Expectorated sputum samples
(<10% of the specimens) were obtained from patients who could produce such
samples. Bacteriological culture methods were similar at the 2 centers. The
amounts of P aeruginosa recovered on the initial
isolation plates were categorized: x, no colonies; 0, a few colonies to light
growth; 1, moderate growth; 2, heavy growth. These groups reflect the approximate
number of organisms present in the oropharyngeal or sputum samples and vary
by orders of magnitude.
Serum specimens were obtained at intervals of approximately 6 months,
were stored at –80°C, and were then analyzed as coded samples, thus
keeping the laboratory workers blinded to the clinical identification. A total
of 2134 antibody titers were determined. An antibody capture immunoassay with
antigen excess33 was used to determine the
levels of anti-Pseudomonas antibodies. The antigens
used were a cell lysate derived from P aeruginosa
strains PAO1,34 FRD,35
and UWP100 (isolated from a patient with CF at the University of Wisconsin
Hospital and Clinics), purified exotoxin A (List Biological Laboratories Inc,
Campbell, Calif), and an elastase toxoid36
prepared from purified elastase (Nagase and Co Ltd, Tokyo, Japan).
The antigens were diluted in 100 mM of sodium carbonate and 0.02% sodium
azide, pH 9.6, for a final protein concentration of 100 ng/well and bound
to Costar flat-bottom, high-binding polystyrene enzyme immunosorbent assay/radioimmunoassay
96-well microtiter plates (Corning Inc, Corning, NY) at 37°C for 2 hours.
The plates were washed 3 times in BBS-T (100 mM of boric acid, 150 mM of NaCl,
and 0.05% Tween 20, pH 8.5). To saturate excess antigen-binding sites, the
plates were blocked with 1% fish gelatin in BBS-T for 16 hours at room temperature.
Two-fold dilutions (1:4 to 1:8192) of the patient sera in 1% fish gelatin
in BBS-T were incubated in the blocked plates for 2 hours at 37°C. The
plates were then washed 3 times in BBS-T. Alkaline phosphatase–conjugated
ImmunoPure goat anti–human IgG + IgA + IgM (H + L) (Pierce Chemical
Co, Rockford, Ill) was used as the secondary antibody and P-nitrophenylphosphate (Pierce) in 10 mM of diethanolamine and 0.5
mM of MgCl2, pH 9.5, was used as the substrate for alkaline phosphatase.
The degree of color development was read at 405 nM using an EL312 Microplate
reader and was analyzed using KC3 software (Bio-Tek Instruments, Winooski,
Two-fold dilutions of sera from an adult male without CF (a physician
with 30 years of exposure to P aeruginosa through
pediatric pulmonology practice) were included on each plate as a positive
control. To control for interfering color that may be present in the lower
dilutions of sera, 2-fold dilutions (1:4 to 1:512) of pooled normal human
serum from more than 50 Midwestern adults (Sigma Chemical Co, St Louis, Mo)
in the absence of antigen were included on each plate. Controls lacking either
patient serum or the secondary antibody were also included on each plate.
The anti-cell lysate, anti–exotoxin A, or anti-elastase titer was determined
as the highest dilution in which the OD405 (optical density) reading
was at least 0.2 units. To eliminate any interference due to the color of
serum at the lower dilutions, the OD405 reading also had to be
0.1 units above the corresponding dilution of pooled normal human serum in
the absence of antigen. For the statistical and graphical analyses, the titer
values were expressed as log2.
Chest radiographs were obtained at 6-month intervals up to age 3 years
and once per year for children aged 4 years and older, as previously described,5 and were scored using the Wisconsin Cystic Fibrosis
Radiograph (WCXR) Scoring system.37 This system
provides a sensitive, objective method for longitudinal and quantitative chest
radiology in children with CF. Our analyses show that, with this scoring system,37 very mild, reversible abnormalities are distinguished
as scores less than 5. Additional radiographs were obtained at the discretion
of the patient's physician. Data on the presence and magnitude of cough, other
signs of respiratory infection, and the use of antibiotics were obtained at
all protocol visits; oral antibiotics given routinely included trimethoprim-sulfamethoxazole
and cephalosporins. Cough severity was assessed by parents and reported to
investigators at visits according to 4 categories: 0, no cough; 1, rare cough;
2, cough in the morning or with postural drainage; or 3, frequent (>10 times
per day), productive, or paroxysmal cough.
To characterize the shape and timing of the antibody response directed
against P aeruginosa, we used least-squares isotonic
regressions38 to fit a monotone increasing,
decreasing, or flat curve to the titer level as a function of age. The significance
of the nonflatness of each curve was assessed by comparing the R2 value based on a nonparametric bootstrap under the null
hypothesis of flatness and assuming Gaussian errors. We then used an exact
binomial test to evaluate whether the number of increasing or decreasing curves
was significantly greater than what would be expected under the flat null
hypothesis. We then performed a piecewise linear regression of the antibody
titers (cell lysate, exotoxin A, and elastase) on age for each patient. The
regression function was constrained to be nondecreasing and to consist of
at most 3 phases: an initial plateau, a linear rise, and a final plateau.
The number of phases and the boundary points between the phases were not determined
a priori but were estimated from the data. This estimation was accomplished
by converting the regression model into a linear complementarity problem and
solving using the Lemke method, which is a pivoting algorithm similar to the
Simplex algorithm for linear programming.39
To determine the longitudinal relationships between P aeruginosa infection and antibody response, the distribution of the
times to first antibody titer 1:256 or higher (cell lysate, exotoxin A, and
elastase), time to first culture positive for P aeruginosa (with infection severity of 0, 1, or 2), and time to first significant
clinical event (coughing, WCXR score ≥5) were summarized with Kaplan-Meier
estimates of the cumulative distribution function to account for right-censoring
of the data.40 Comparisons between the time-to-event
distributions were made with a paired log-rank test41
using a robust variance estimate since many individuals typically experienced
both events being compared.
To assess the association between antibody response and patient characteristics
and risk factors, the effects of risk factors on the time when antibody titers
(cell lysate, exotoxin A, and elastase) were first 1:256 or greater was evaluated
with the Andersen-Gill proportional hazards model42
to account for baseline and time-dependent covariates. Eleven baseline covariates
(treatment received at CF centers A or B, population per square mile according
to ZIP code, mother's education in years beyond high school, genotype [homozygous ΔF508vs other genotypes and heterozygous ΔF508vs other genotypes], estimated median annual income [in
units of $10 000] based on ZIP code of parents' residence, marital status
of mother, meconium ileus status, definite or probable pancreatic sufficiency
vs definite or probable pancreatic insufficiency, sex, and residence in an
urbanized area) were considered in this model. Also considered were 8 time-dependent
covariates (use or nonuse of long-term [>30 days] non-Pseudomonas oral antibiotics, total number of days hospitalized, total duration
of infections in days, total count of antibiotic prescriptions for infections,
first-degree relatives with CF [parents and siblings] vs no first-degree relatives
with CF, total number of upper respiratory tract [presumably viral] infections,
treatment at center B old hospital prior to June 1, 1990, and treatment by
the single physician at center B prior to June 1, 1990).
The effect of life history covariates on the time to the first titer
of 1:256 or greater was assumed to occur in the interval between the first
titer of 1:256 or greater and the most recent prior titer less than 1:256.
A step-down regression selection procedure was performed beginning with a
full model consisting of all potentially significant covariates. The least
significant covariates were removed 1 at a time until the remaining covariates
were significant at the .10 level. The proportionality assumption for the
Andersen-Gill model was assessed by looking at the smoothed plot of the Martingale
residuals vs time.43 For these statistical
analyses we used SAS version 6.12 (SAS Institute, Cary, NC) and S-Plus version
3.4 (Mathsoft Inc, Seattle, Wash) software packages.
Table 1 summarizes the baseline
characteristics of the study population. When the presumptive diagnosis of
CF was confirmed with a positive sweat test result, the median age at diagnosis
was 6.8 weeks. Four patients had a false-negative newborn screening result
and were diagnosed at ages 6.9, 7.9, 20.7, and 280.9 weeks on the basis of
family history or clinical symptoms. Chest radiographs were obtained for 57
patients within 1 week of diagnosis; 30% of these had WCXR scores of less
than 2.0 (indicating a normal appearance or minimal changes), 40% had a score
of 2.0 to less than 5.0 (indicating reversible, mild abnormalities), and 30%
had a score of 5.0 or greater (indicating irreversible lung damage). For all
patients, the initial chest radiographs showed median and mean (SD) WCXR scores
of 3.36 and 4.32 (3.7), respectively. These scores indicate that the majority
of patients had no irreversible lung damage when they entered the study. None
of the patients received antimicrobial agents specific for P aeruginosa (ie, ciprofloxacin, parenteral anti-Pseudomonas drugs, or aerosolized tobramycin) before the organism was
isolated from an oropharyngeal culture.
Sufficiently complete data for least-squares isotonic regression were
available for 52 (cell lysate), 51 (exotoxin A), and 51 (elastase) patients.
The numbers of patients with significantly increasing curves were 41 (cell
lysate), 42 (exotoxin A), and 34 (elastase). This number was significantly
larger than the 2.5% expected under the flat null hypothesis (P<.001 for all 3 antigens). In contrast, the numbers of patients
with significantly decreasing curves were 3 (cell lysate), 3 (exotoxin A),
and 2 (elastase). None of these numbers was significantly larger than the
2.5% expected under the flat null hypothesis (P =
.14 for cell lysate; P = .14 for exotoxin A; and P = .37 for elastase). Thus the curves are significantly
monotone increasing. Representative responses are shown in Figure 1 and the characteristics of the response for each antigen
are given in Table 2. Most responses
were characterized by an initial plateau, rise, and final plateau (51%, 56%,
and 55% of patients for cell lysate, exotoxin A, and elastase, respectively).
Distinct differences were noted in the response to the 3 antigens. The midpoint
of the responses to the cell lysate preparation and exotoxin A occurred approximately
10 months before the midpoint of the elastase response and 11 to 14 months,
respectively, before the beginning of the final plateau of the elastase response.
The magnitude of the cell lysate and exotoxin A responses was approximately
2 doubling dilutions greater than the response to elastase. In 5 patients,
the cell lysate and exotoxin A titers rose to 1:256 or greater before age
9 months; however, this response was not due to the presence of maternal antibody
against P aeruginosa, because each of these patients
had earlier titers ranging from 1:8 to 1:32.
To assess the longitudinal relationship of the different events associated
with acquisition of P aeruginosa–associated
pulmonary infections, we plotted the percentage of patients with a specific
event vs the time of first acquisition of that event using Kaplan-Meier analysis
(Figure 2). All 68 were used in
each Kaplan-Meier plot. We studied as potential early indicators the first
report of significant cough (category ≥2) during the day as reported by
the parents, the first pulmonary infection or course of antibiotics, a WCXR
score of 5 or greater, the first report of a significant antibody response
against the cell lysate, exotoxin A, and elastase antigens, and the first
isolation of P aeruginosa from an oropharyngeal culture.
A category 2 cough was defined as cough occurring in the morning or with postural
drainage. A significant antibody response was defined as a titer of 1:256
or greater and was considered indicative of an infection caused by P aeruginosa; for the majority of our patients this represented a 64-fold
increase in titer over the initial titer obtained at the time of CF diagnosis.
The median time to a cough of category 2 or greater was 4.33 months
and for a WCXR score greater than or equal to 5 was 24.02 months. The median
times to a titer of 1:256 or greater were 17.8, 24.2, and 70.9 months for
cell lysate, exotoxin A, and elastase, respectively. The median time to the
first colony (magnitude categories ≥0, ≥1, or ≥2) was 29.8, 101.6,
and 132.7 months, respectively, for all cultures and 36.3, 102, and 135 months,
respectively, for the protocol-only cultures. One culture-positive patient
did not develop a titer of 1:256 or greater to cell lysate, 3 did not develop
a titer of 1:256 or greater to exotoxin A, and 11 did not develop a titer
of 1:256 or greater to elastase. Sixteen patients remained culture negative
throughout the study but titers of 1:256 or greater were detected for cell
lysate in 14 of these patients, for exotoxin A in 11 patients, and for elastase
in 7 patients.
As shown in Figure 3, a significant
difference was observed between the first detection of a titer of 1:256 or
greater for P aeruginosa antigens and the first isolation
of the organism from an oropharyngeal culture at a magnitude of 0 or greater
(all cultures). Titers to cell lysate and exotoxin A were detected a mean
of 11.9 and 5.6 months before the first isolation of P aeruginosa (P<.001 and P
= .04, respectively). In contrast, the titer to elastase was detected a mean
of 41.1 months after the first isolation of the organism (P = .003). For the protocol-only cultures, the titers to cell lysate
and exotoxin A were detected 18.2 and 11.9 months, respectively, before the
first isolation of the organism (P<.001 for cell
lysate and P = .006 for exotoxin A). The rise of
anti–cell lysate and anti–exotoxin A titers occurred before, or
coincided with, the first isolation of P aeruginosa
in 63% and 54% of the patients, respectively.
We also compared the difference in timing of a WCXR score greater than
or equal to 5 and the first detection of a titer of 1:256 or higher for cell
lysate and exotoxin A and the first isolation of P aeruginosa. There was no significant difference between these outcomes for cell
lysate and exotoxin A (P = .24 and P = .32, respectively). However, like the detection of a titer of 1:256
or higher for cell lysate and exotoxin A, the WCXR score greater than or equal
to 5 first occurred 5.8 months before the first isolation of P aeruginosa (P<.001). These observations
indicate that radiographic evidence of irreversible lung damage occurred before P aeruginosa was first isolated by culture and that the
radiographic detection of lung pathology coincided in time with the production
of an antibody response directed against cell lysate and exotoxin A.
Our previous assessment of risk factors for acquisition of P aeruginosa–associated pulmonary disease9
revealed that treatment at an integrated CF clinic and increased use of aerosols
were significant risks while the maternal level of education provided a beneficial
effect. For our assessment of risk factors associated with production of anti–P aeruginosa antibodies, we used life history information
to evaluate the relationship between the development of an antibody titer
greater than or equal to 1:256 and the baseline characteristics (eg, genotype)
and longitudinal health care experience of the study patients. This analysis
was limited to development of cell lysate and exotoxin A titers greater than
or equal to 1:256 because these titers correlated well with clinical indicators
of pulmonary disease.
The final results from a stepdown regression model selection are presented
in Table 3. Martingale residual
plots indicated that the proportionality assumption was valid. Patients followed
up in center B had a significantly higher risk of developing titers greater
than or equal to 1:256 for cell lysate and exotoxin A than patients followed
up at center A. Long-term (>30 days) use of oral non-Pseudomonas antibiotics was also associated with a higher risk of developing titers
greater than or equal to 1:256 for cell lysate and exotoxin A. We also found
that as the parents' income increased, the risk of developing an exotoxin
A titer greater than or equal to 1:256 decreased; this beneficial effect was
not associated with developing a titer greater than or equal to 1:256 against
cell lysate. The apparently mild decreased risk of developing a titer greater
than or equal to 1:256 for cell lysate associated with an increased number
of viral respiratory tract infections is likely to be a confounding covariate
rather that a beneficial risk factor. Similarly, the apparent relationship
of cell lysate and exotoxin A titers to "original physician" (1985-1990) in
center B may reflect a confounding effect.5
The other variables that were considered, as listed in the "Statistical Analysis"
section, did not show any significant relationships with acquisition of a
high titer.
Recognizing the importance of P aeruginosa
in the morbidity and mortality4 of CF as well
as the new opportunities for presymptomatic diagnosis through neonatal screening,1 we have focused on methods for improved detection
of P aeruginosa–associated respiratory tract
infections. Our studies are being pursued under the assumption that early
identification of P aeruginosa is essential to achieve
success in treating or eradicating this organism before irreversible lung
disease occurs. It has been especially advantageous to evaluate our study
patients longitudinally with a systematic protocol for collecting data prospectively.1,31 Since our patients were generally
diagnosed with CF through newborn screening (median age of confirmed diagnosis
= 6.8 weeks) and the majority had negative P aeruginosa cultures and WCXR scores less than 5 at the time of entry into the
study, they were considered to be free of detectable P aeruginosa at that time. The observation that the mean magnitude of the titers
for the initial plateau for cell lysate, exotoxin A, and elastase of 1:16
or less confirms this assumption and conclusion (Table 2). Thus, this investigation differs significantly from previous
longitudinal studies assessing P aeruginosa acquisition
and production of an anti–P aeruginosa antibody
in which the patients were investigated after a CF diagnosis based on clinical
indicators or were followed up for a short time. Additionally, as a result
of newborn screening and early nutritional intervention, the patients in our
study were well nourished.1,30
We characterized the production of serum antibodies directed against P aeruginosa in patients with CF and detected a temporal
hierarchy in the development of antibodies against specific P aeruginosa antigens: exotoxin A before cell lysate before elastase.
Similarly, Hollsing et al27 observed that antibodies
against exotoxin A and phospholipase C were produced before antibodies against
elastase and alkaline protease. This temporal difference in antibody response
to specific antigens could reflect the ability of the tested antigens to act
as immunogens or alternatively represents a sequential production of these
antigens during the establishment of P aeruginosa–associated pulmonary infections.45- 48
Specifically, P aeruginosa converts from a nonmucoid
to a mucoid state, modifies the composition of lipopolysaccharide, produces
decreased amounts of elastase, and loses the ability to produce flagella during
the establishment of a P aeruginosa–associated
pulmonary infection in CF patients.45- 48
In a previous study, we showed that the magnitude of the elastase response
is predictive of a more advanced infection.5
Thus, this temporal hierarchy in development of antibodies to specific P aeruginosa antigens may reflect the development of lung
disease. It is noteworthy that patients with CF younger than 9 months developed
cell lysate and exotoxin A titers of 1:256 or higher before P aeruginosa was isolated from an oropharyngeal culture. This finding
agrees with recent observations on the early development of P aeruginosa–associated pulmonary infections from serial bronchoscopy
Comparing the temporal relationships of several clinical indicators
of P aeruginosa–associated pulmonary infections
revealed that a rise in antibody titers to 1:256 or greater directed against
exotoxin A and cell lysate occurred after the first report of significant
cough and correlated with a WCXR score greater than or equal to 5. Even though P aeruginosa frequently had not been isolated from an oropharyngeal
culture at this time, the combination of a rise in antibody titer to 1:256
or greater and these clinical indicators of pulmonary infection indicates
the presence of the organism. Because of their noninvasive nature, oropharyngeal
cultures have been recommended and are routinely used for diagnosis of P aeruginosa–associated respiratory tract disease.49 However, because conflicting results have been obtained
regarding the predictability of oropharyngeal cultures in the diagnosis of P aeruginosa–associated disease,12,14,18,25
the ability to detect an antibody titer against exotoxin A and cell lysate
suggests that an enzyme-linked immunosorbent assay to detect antibodies directed
against specific P aeruginosa antigens, in conjunction
with a WCXR score greater than or equal to 5, could be used to diagnose P aeruginosa–associated pulmonary infections in young
patients with CF.
The diagnostic strategy of longitudinal antibody titer monitoring would
be better for children than recurrent bronchoscopies. Additionally, the diagnosis
of P aeruginosa–pulmonary infection could be
made 6 to 12 months before the organism is isolated from oropharyngeal and
perhaps bronchoalveolar lavage cultures in a majority of patients. Other investigators
have suggested the utility of serum antibody titers against the organism for
the diagnosis of P aeruginosa–associated pulmonary
infections.24,25 The potential
presence of P aeruginosa in lower respiratory tract
infections has implications for both the time at which treatment is begun
and also for the choice of antimicrobial agents that are used. For example,
treatment with non–P aeruginosa antibiotics
could either predispose a patient to a P aeruginosa
lung infection, as our data suggest (Table
3), or could exacerbate an undiagnosed lung infection caused by
the organism. In support of this conclusion, Høiby and colleagues44,50,51 have shown that early
intervention with appropriate antibiotics can eradicate nonmucoid P aeruginosa from the lungs of patients with CF.
Assessment of factors that can potentially increase the risk of P aeruginosa–associated pulmonary infection was possible
in this study because we have available in our database life history information
collected prospectively from the date of CF diagnosis. Our previous evaluations
of potential risk factors for P aeruginosa–associated
pulmonary disease9 were based solely on positive
cultures and were limited by the sensitivity of isolation of the organism
from oropharyngeal secretions. In addition, it is obvious from the data reported
herein that the organism may not be isolated until after respiratory disease
supervenes. Therefore, our current evaluation of covariates using titers greater
than or equal to 1:256 as the outcome event is much better than our earlier
studies using only oropharyngeal cultures as the outcome event. Our previous
research, however, identified 20 potential factors that we focused on with
respect to P aeruginosa–associated pulmonary
infection risk.
The results of the stepwise regression model used in this study confirm
the previous finding of a center effect: from 1985 to 1990 (when half the
screened patients were diagnosed), center B used an old clinic setting with
a small waiting room that mixed young patients diagnosed through screening
with older infected patients with CF, as described in detail previously9; also, there was only 1 physician and limited handwashing
facilities. In contrast, center A employed a segregated clinic with isolated
waiting areas and 3 physicians. Our finding in this study of a strong center
effect with significantly more risk of P aeruginosa–associated
pulmonary infection among the patients followed up in an integrated clinic
provides more evidence for the concept of cross-infection, ie, person-to-person
transmission of the organism, and the potential value of segregated clinics.
This strategy of care is used with good results in Denmark52
and should be considered by every region embarking on neonatal CF screening
programs. Indeed, clinics dedicated specifically to infants and young children
with CF offer many advantages as an integral component of the follow-up system
needed for a successful newborn screening program.1
Both nutritional and pulmonary care can be delivered in a highly effective
fashion when very specialized treatment plans are provided to young children
with CF, rather than integrating them with older patients.1
Communication and psychosocial advantages also emerge in such a setting.53
The other significant risk factor we found was long-term (>30 days)
non-Pseudomonas antibiotic administration taken orally
as a prophylactic measure in a manner that has become common for many CF centers.29,54- 56 Other
studies with less precise outcome measures have also suggested this risk.57 In addition, a recent controlled trial58
involving 209 children (average age <15 months), 119 of whom completed
continuous therapy (either daily cephalexin or placebo), demonstrated a significantly
increased risk of cultures positive for P aeruginosa.
Our study also shows that long-term use of non-Pseudomonas antibiotics is an especially significant risk for young CF patients.
Indeed this is the first epidemiologic investigation, to our knowledge, to
link the oral antibiotic risk factor directly to P aeruginosa–associated pulmonary infection, as opposed to colonization by the organism
identified by culturing respiratory secretions. Because the risk of long-term,
non-Pseudomonas oral antibiotics in young children
with CF might outweigh the potential benefits, we recommend a more prudent
approach based on a careful comprehensive determination of each patient's
respiratory status, especially in the care of infants and young children with
CF. The longitudinal monitoring of P aeruginosa antibody
titers should be helpful in this ongoing assessment.
The implications of the Wisconsin CF Neonatal Screening Project1 are profound for the treatment of young children with
this genetic disorder. Early diagnosis through neonatal screening provides
an opportunity for a transformation in treatment strategy. Instead of hospitalizations
and medical interventions for sick patients who experience delayed diagnosis,
screening allows presymptomatic identification of most patients with CF and
the potential for prospective evaluation and preventive care. It has been
demonstrated conclusively that malnutrition can be prevented in association
with screening.1,30,59
Similarly, since the CF lung is free of pathology at birth, early diagnosis
coupled with careful follow-up of the respiratory symptoms (especially cough),
infection status, and chest radiographs could provide better outcomes, as
already suggested by some observational studies.59
We recommend that longitudinal P aeruginosa serology
also become part of the respiratory care follow-up, especially using exotoxin
A titers. In addition, therapeutic trials with anti-Pseudomonas antibiotics are needed in young children with CF when they first show
an increased anti–P aeruginosa antibody titer.


text:
An Investment Opinion
Companies in every industry use different measures. For example, AT&T (NYSE: T), the Father Time of telecommunications, reports operational earnings, operational cash earnings, operational EBITDA, EBITDA, EBIT, and operational EBIT. Good grief.
What are investors supposed to do with this alphabet soup? To keep today's story under 15,000 words, let's focus on EBITDA (earnings before interest, taxes, depreciation, and amortization), often called cash flow, since it's used so often.
Is EBITDA a valuable measure of cash flow, shenanigans to make unprofitable or marginally profitable companies look sharp, or something in between?
My take is that EBITDA is worth a look in some cases but should never be used as a valuation tool. I came to this brilliant conclusion after a reader chewed up a story I'd written on casino operator Harrah's Entertainment (NYSE: HET).
In this article, I said gaming company investors often focus on EBITDA as a way of glimpsing a firm's true earnings power before certain charges. This is the party line on EBITDA -- that capital intensive companies report EBITDA to give investors a feel for cash flow before debt payments, taxes, depreciation, and amortization charges reduce the income statement to ashes. Problem is, EBITDA leaves out so much that its usefulness is very limited.
Now, companies that report EBITDA aren't doing anything wrong. It's just that when an analyst advises valuing shares on an EBITDA or cash flow basis you better sharpen your pencil.
First we need an example of what EBITDA does, because it can be handy. Say you're six years old and want to open an Orangina stand, hoping Coca-Cola (NYSE: KO) will eventually figure out a way to buy your operation. You have no money so mom and dad front the capital equipment costs: $30 for oranges, cups, sugar, water, and signage (not signs, signage).
At the end of the day, mom and dad want to know how much money you made. They don't want a figure that's been adjusted for interest payments on the debt you owe them, taxes, and depreciation of the fixed assets -- at least I hope not. That's the idea behind EBITDA, to give investors a sense how much money a young or fast-growing company is generating before it shells it all out to creditors, Uncle Sam, etc.
Look at wireless firm Nextel (Nasdaq: NXTL), which is spending a fortune to build a global communications network. Last year it reported a net loss of $1.5 billion. This bottom-line figure doesn't tell investors anything about the money Nextel generated from business, so it also reported EBITDA of $698 million. That's somewhat useful when compared to the company's EBITDA loss of $99 million in 1998. Investors see the company is making fast progress -- that people are aggressively buying its services.
EBITDA is really like looking at profits after deducting the cost of goods sold, and sales, general, and administrative expenses.
The problem is twofold: First, EBITDA leaves out so many expenses that to think of it as a measure of profitability is a huge mistake. Second, it's way off base to think of EBITDA as cash flow, or even a proxy for cash flow, since it doesn't measure actual cash flowing into a company.
Specifically, EBITDA neglects the following considerations:
Since this story is getting really boring, let's pick one item -- capital expenditures -- and focus on that. These expenses are a critical, ongoing outlay for almost every company. AT&T reported $18.2 billion in 1999 EBITDA. Wow. That's a nice improvement from 1998 when it reported $13.4 billion in EBITDA. But this measure disregards the company's sky-high capital expenditures.
Last year alone AT&T spent $13.5 billion on capital equipment, and it will continue spending billions annually to upgrade and build out its networks. Expenditures such as this will always be a big part of the mix for AT&T, as it will for gaming, cable television, satellite communications, and many other companies in industries that like to focus on EBITDA.
Since capital expenditures aren't part of the EBITDA mix, it's worse than useless for investors to start basing a company's valuation upon it. See, that $18.2 billion isn't available to AT&T investors. The company will consume a big chunk of it to generate expected cash flows in the future. Investor and businessman Warren Buffett talks about cash flow and capital expenditures in detail at the end of his 1986 annual report. Buffett doesn't look at cash flow anyway, but strongly advises backing out capital spending costs for those who do.
EBITDA also falls short as a measure of cash flow, which makes it especially confusing since companies often use the terms interchangeably. EBITDA doesn't really measure cash flow at all since it neglects the balance sheet.
For example, Nextel reported $698 million in EBITDA last year. Does that mean $698 million in cash actually flowed through the company's coffers? No. Look at the company's cash flow statement and you'll see it reported $324 million in cash from operations after adjusting for accounts receivable, and other costs like inventory. There's a big difference between these two numbers -- and the lower of the two is what measures cash actually provided by operations.
Is there a better way to evaluate cash flow? Sure, just look at cash flow from operations. If you want to go a step further, look at free cash flow (FCF). In its simplest form, FCF is simply cash from operations minus capital expenditures. This has the advantage of capturing at least three items EBITDA leaves out: Receivables, inventory, and capital expenditures (property, plant and equipment).
It's not a cure-all since it omits the cost of debt. Also, many terrific companies are cash flow negative in their formative stages. Wal-Mart reported negative free cash flow for years while handily beating its cost of capital and building its retail empire. Focusing on FCF alone could lead investors to miss opportunities.
There isn't any silver bullet when it comes to examining profitability. Smart investing involves taking the time to get familiar with a company, its industry, and the way it reports earnings.
Have a great day.

subset: commoncrawl


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Rosanne Cash, 'Sleeping in Paris' (Exclusive Live Performance)
The Boot's week-long presentation of exclusive live performances from Rosanne Cash continues with a song from her 1993 album, 'The Wheel,' 'Sleeping in Paris.' 'The Wheel' was Rosanne's first album written and recorded after the break-up of her marriage to Rodney Crowell. Much of the album reflected the singer-songwriter's feelings of carefully embarking on a new relationship with producer and future husband John Leventhal.
Interestingly, one of the lines in 'Sleeping in Paris,' "the lonely road is a bodyguard," was penned by Rosanne for a seventh-grade writing project. It was also the closing line in her 2010 memoir, 'Composed.'
All of this week's live performances were recorded in the living room of Rosanne and husband John Leventhal's New York apartment. Each of the songs was chosen from fan requests via the singer's Twitter page. Come back tomorrow for another exclusive live performance!
Legacy Recordings/MasonJarMusic
More Rosanne Cash Live Performances:


text:
WASHINGTON -- Some days Mitt Romney must wonder how he got involved with this crew. Here he's trying to talk about jobs, jobs, jobs -- and his political colleagues keep changing the subject to a topic about which an alarming few seem to know anything at all: women.
Specifically, women's plumbing.
Introductions are no longer necessary for the formerly obscure Missouri congressman, Todd Akin, who had hoped to snatch Democrat Claire McCaskill's Senate seat. For those who didn't pay their cable bill, Akin recently assured Americans that in cases of "legitimate rape," women don't get pregnant because "the female body has ways to try to shut that whole thing down."
To think we've overlooked this fail-safe method of birth control. More legitimate rape; fewer unwanted children. It has a certain Talibanesque ring to it.
All Hades broke loose, one is grateful to note, despite Akin's lame attempts at penitence. From Romney to Karl Rove, condemnation of Akin's remarks was stern, with many calling for him to step out of the race. Yet even Akin's apology and self-correction were mealy-mouthed and lacking in, shall we say, remorse born of clarity.
In a hastily constructed ad released Tuesday, Akin tried to organize his thoughts: "Rape is an evil act," he said, apparently appealing to those who still weren't sure. "I used the wrong words in the wrong way and for that I apologize. ... I have a compassionate heart for the victims of sexual assault. I pray for them."
Of course words were never the problem. The "thinking" was the problem. Akin's belief that legitimate rape so scrambles the female's signals that even biology is thwarted was born of conversations he says he had with doctors. Akin at least should surrender the names of those doctors so that they can be removed from the practice of medicine. For those still confused, raped women do get pregnant, which is why many who are strongly pro-life nevertheless allow abortion exceptions for rape victims. Even so, the Republican Party platform calls for a "human life" amendment to the Constitution that, strictly applied, likely would prohibit any abortion under any circumstances.
Akin's gift to Democrats wasn't just a probable campaign killer for him personally. It also reminded critics that Akin once co-sponsored legislation with Paul Ryan re-defining rape as "forcible" versus, what, voluntary? To be fair, there is a difference between morning-after remorse that some call "rape" and rape as most understand it. But for these purposes, as President Obama said, "Rape is rape." Does a raped woman need bruises to qualify for an abortion?
More broadly, Akin's comments furthered the perception that Republicans are waging a war on women.
The gender gap exists for a reason.
Whether mandating transvaginal probes prior to abortion under "informed consent" logic or misunderstanding basic biology, Republicans have managed to alienate a fair portion of the female population. Even pro-life women will have a hard time standing by men who are so willfully ignorant.
These episodes not only are embarrassing, but they shift debate from the profound to the ridiculous.
One Catholic strategist close to GOP anti-abortion discussions put it this way to me: "Any politician is an idiot if he cannot speak eloquently on the tragedy of abortion, with compassion for women and a sense of recognition also for the life of the child. ... Akin does a disservice to the cause of educating Americans about the humanity of the unborn child. Honestly, though, he is the exception."
Perhaps so, but the cumulative effect of Republican actions aimed at limiting women's access to abortion rather than seeking remedy through education poses an existential threat to the GOP. You don't change people's hearts by insulting their minds.
As GOP convention planners consider platforms and pledges, they might also contemplate a seminar for Republican men about how the fairer sex works. Recognizing that attendance could be humiliating, they could put a brown wrapper around it (note to Akin supporters: this is a metaphor) and call it something deceptively innocuous, such as: "Golf and Skinny-Dipping, from the Sea of Galilee to the Gulf of Mexico."
Once attendees are seated, Condoleezza Rice and Darla Moore, recently named the first women members of Augusta National Golf Club, could conduct a PowerPoint presentation of the female reproductive system.
Given the likelihood of a large audience, the GOP might need a bigger tent than usual.
Kathleen Parker's email address is firstname.lastname@example.com.
Gov. Terry E. Branstad - Jwood....Thanks, buddy.... I'm a hands-on-man,too. . . .PBS just had Senate Minority leader, Mitch McConnell, most hated man in Congress.....Mark Shields just did a number on him.... LOL.....There's no love lost between those two...Fun to watch ole turtle-neck McConnell squirm.
Equalizer, that clown was the governor of Iowa. If I'd been one of the PBS commentators I'd have bodily thrown him out of the room before beating the pulp out of him with my 3-wood. I'm totally convinced that's the only way to shut these lying bastards up.
Clarification: I watched the RNC on PBS.....it was during 'guest' appearance by the (R)Governor of Puerto Rico and another (R) 'gentleman'. Spot was hosted by Gwen Iffle and Judy Woodruff. The 'gentleman' became quite hostile despite Ms Woodruff's fact checked point. - - - - -Never let it be said the GOP allows 'truths' to get in the way when power is the goal.
Reminded that fact checking found the claim by RW that Obama gutted the 'work for welfare' was untrue: The dude got hostile saying he didn't care what 'they' said. - - - - One thing for sure: The GOP is sticking by their lies.
"We're not going to let our campaign be dictated by fact-checkers," Romney pollster Neil Newhouse said at a panel organized by ABC News.
anonymous_4064 - Religious RW extremists believe in Creationalism - NOT FACTS.
Think someone from planned-parenthood could go to the GOP convention and give these people a sex-education course.


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10b Chestnut Plaza Westfield Stratford City Montfichet Road, Olympic Park London, E20 1GL United Kingdom
Staybridge Suites London - Stratford City
Modern suite hotel with complimentary WiFi and breakfast in East London's buzzing Westfield Stratford City
The Staybridge Suites® London – Stratford City hotel provides a home from home, apartment-style accommodation in the modern Westfield Stratford City shopping and leisure complex. The pubs, galleries and markets of London's dynamic East End are within strolling distance. Stratford International Station and Tube station are a five-minute walk away for national rail, London Underground and DLR trains across the city.
The City of London financial district, Canary Wharf and London City airport (LCY) are a short Tube-ride away. The hotel's cosy, casual meeting space, The Den, can be configured boardroom-style for up to 16 people and complimentary WiFi is available throughout.
You're a five-minute walk from Queen Elizabeth Park and within strolling distance of the East End's Old Spitalfields Market. Hop on the Tube for an exhibition at ExCeL London or concert at the 02 Arena.
Stock up on groceries from The Pantry, open 24 hours, and prepare dinner in your suite's fully equipped kitchen. Start your day with a complimentary breakfast featuring hot items and coffee to go. Unwind with drinks and snacks and meet other guests at social receptions three evenings a week. Take advantage of the free laundry service and work out in the Fitness Room with views over the Olympic Park.
Quick Info
- Check In: 3:00 PM
- Check Out: 12:00 PM
- Minimum Check-In Age: 18
- Self Parking Fee: 9.5 GBP
- Print Fact sheet
- Chat Online
- Important Update
Hotel Highlights
- On-site Guest Self-Laundry Facilities
- Complimentary Breakfast Buffet
- Standard Wireless Internet service is free for all members
- On-Site Fitness Center Available
Guest Reviews
Overall Experience
London Nähe Olympiacenter
24 June 2017
Ich war im Juni für 5 Nächte in London und kann das Hotel empfehlen. Die Lage direkt am großen Einkaufszentrum und an der Tube ist ideal. Doppelbetten für zwei große Personen etwas ungünstig da wären Einzelbetten besser gewesen
Great location and impeccable customer service
21 June 2017
We stayed while attending a concert at the Queen Elizabeth Olympic Park and the location couldn't have been any better - especially with being next to the Stratford Westfield and transport links.
The thing that made the visit though was the attitude and helpfulness of the staff. Absolutely 5 star service throughout and couldn't do enough to make a stay an amazing one.
Suite was prefect too, all the facilities we could want, spotlessly clean and well laid out.
Wonderful stay thankyou!
Wonderful home from home experience
20 June 2017
Stayed at Staybridge Stratford in June while attending a concert. We were greated by friendly concierge and shown to lifts to get to reception. The staff member who checked us in was lovely. She was warm and friendly and always had a smile. The pantry and social areas were clean and very welcoming. Our room was perfect. Confortable beds, toiletries, a well equipped kitchen and everythinh was very clean and well layed out. The breakfast was brilliant. Had lots of choices and i loved the fact you could take it away or bring back to the room. All staff we had contact with were friendly and professional and could not of done anything more for us. Staying above a shopping centre was a great experience and although busy, we found our room to be very quiet. Would def reccommend and will def return for another visit. We normally stay im central london, but Stratford centre is brilliant, easy to get to via tube or DLR. Hope to return again soon.
A great east London option
19 June 2017
Large rooms by London standards and the property is newer and very clean and well-kept. Spire status was rewarded, even on an award stay, and breakfast was good. Only complaint was the slightly confusing lighting- lots of different overhead bulbs and lamps, and yet the key main bathroom switch was blocked from view if I had the wardrobe door open. But overall, this is a great option if you don't mind being a little bit further out from the city core.


text:
Well, this shouldn't surprise us.
The always objective ABC World News Tonight:rolleyes: ran an alarmist piece this evening on the violent crime wave that's "sweeping" the country, complete with the obligatory sound bites from the DC Police Chief, the Mayor of Philadelphia, and others.
The cause: easy access to guns by juveniles and gangs.
Nary a mention, of course, of all the gun laws that are being broken by these juvie gangs.


text:
(1) Absinthe (AKA The Green Fairy) - Obviously, I have to start with this one as it is my favorite! Being extremely high in alcohol content and the color green, this is my drink of choice! Drinking absinthe is not simple. You cannot just simply unscrew the bottle and pour the booze in a glass (or if you are a classy gal like me, drink straight from the bottle.) How do you drink absinthe? Well, you would need to first pour a very small amount into a glass. Afterwards, you will need a special spoon that is perforated to be placed over the glass. Take a sugar cube and then place it on the spoon. Pour water over it. The water dissolves the sugar into the glass. This not only dilutes the drink but makes it sweeter. With the high alcohol content, you need to dilute this in order to be able to drink it easily. It smells and tastes like licorice!
|image source
|Image source
(3) Mead - It is made from fermented honey and water. Sometimes fruit or hopps are added and according to Wikipedia, it is known as the "ancestor of all fermented drinks." Here in Montreal, we can find mead at the local SAAQ (liquor store) as well as at the Jean-Talon Market. Sometimes, if I am lucky, I can find a fruit-flavored mead. https://en.wikipedia.org/wiki/Mead
|image source
(4) Bloody Mary - A couple of my friends will order this drink while we are out. I guess they order it due to the title and because it most probably resembles blood. Personally, this is not my drink of choice as one of it's main ingredients is tomato juice (yuck!).
(5) Sangria - One of my personal favorites. This cocktail reminds me of summertime, where one could find me in my backyard or on a terrace somewhere sharing a pitcher of this drink. In fact, this is definitely my go-to beverage during the summer months. According to Wikipedia, Sangria is from Ireland, Spain, and Portugal. It normally consists of red wine, chopped fruit, and brandy. I chose this beverage to add to my list because of the name. In french, the word "sang" means blood and well the drink is a dark red color. I was not too far off the mark there because according to Wikipedia, the drink was named after the Spanish and Portuguese word for bleeding!
This is it. I am pretty sure there maybe beers out there that could be considered a Gothic drink but I am not a beer fan, personally. When I do go out, I like a nice glass of red wine, sangria (obviously) or I order a flavored Martini.I prefer hard liquor!


text:
Patrick Yam: Quantitative Easing - Re-Leveraging of a Nation
Quantitative Easing: Re-Leveraging of a Nation
This program is sold out
Patrick Yam, CEO, Sensei Partners; Macro-Economist; Academician; Investor; Author
Why are today's headlines highlighting the current Fed monetary policy of quantitative easing – and is this Fed policy a curse or blessing? Will the increase in monetary supply break the national debt ceiling and heighten inflation? Gain a clear understanding of these issues and what they mean to you, as Professor Yam brings transparency to understanding quantitative easing in his presentation of "Odyssey to Optimism through Knowledge."
MLF: Business & Leadership
Location: SF Club Office
Time: 11:30 a.m. check-in, noon program
Cost: $20 standard, MEMBERS FREE, $7 students (with valid ID)
Program Organizer: Kevin O'Malley


text:
German Shepherd Dog Forums (http://www.germanshepherds.com/forum/)
- General Behavior (http://www.germanshepherds.com/forum/general-behavior/)
- - Sudden fights between dogs (http://www.germanshepherds.com/forum/general-behavior/439337-sudden-fights-between-dogs.html)
Sudden fights between dogs
hey guys, my friend whos has 3 dogs, Rex(11 month Male GSD), Kale (10 month Male rot) and Athena 1 year ( Female GSD)
A few weeks back Rex started showing signs of aggressive such as toy aggression. Now it has become worst to the point where Rex just randomly come forward to Kale/Athena and will start a fight. Kale and Rex fight more for some reason and they have scars and such. It strange because they grew up together. My friend is thinking of re-homing rex because of this issue.
Any help to solve this problem would be great!
Rex and Kale: Not netrued
Athena : is spayed
234 Attachment(s)
Without knowing more info, your friend has two intact male dogs of strong working backgrounds. They are going through "puberty" becoming adults. Fights are not surprising at all. In fact this sounds like a situation that is bound to have a horrific outcome.
Sent from Petguide.com Free App
Two or More Dogs
Leerburg Dog Training | Dealing with the Dominant Dog
He'll need this if he can't get the above worked out:
Leerburg | How to Break Up a Dog Fight Without Getting Hurt!
Best solution is to rehome one of the males. The fact that he has these three dogs this close in age says alot and none of it is good!
They need to understand the info in the links and 'then" hire a trainer or rehome some dogs..not looking good here!
Yupp, dump the one with the problems. That will solve it, for the owner anyway.
Three young dogs, too bad there wasn't any planning involved, and the dogs are the ones that will suffer.
It is probably better to rehome the troublemaker soon. If he keeps him, then he will probably have drop three senior dogs at the shelter in quick succession, when they start being troublesome with their vet bills.
If people want to keep multiple young dogs, they have to be a leader, and be prepared to train them, and manage them. Usually male/female is fine, and usually male/male is fine, but male/male/female (spayed or not), or female/female can be very tricky.
I am not sure how you can help your friend. If he has asked for advice, then I think maybe the best thing to do is to point him to training classes, NILIF to improve his leadership, discuss managing the dogs better, and maybe neutering both boys. It usually won't help behavioral issues, but it can take some of the male-male crap because they will now not be producing all that testosterone.
Alright, thanks for your replies, I am learning this myself. I'll talk to him to bringing to a trainer and as last resort to rehome Rex.
Good move and good luck to all involved. :)
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text:
[Date Index]
[Thread Index]
[Author Index]
Re: Run[] in background (NT)?
On 29 Sep 2000, Tom Aldenberg wrote:
> I run a batch shell script from Mathematica:
> Run["c:\acsl\math\amath.exe (+options)"]. How can I do that in the
> background under NT without the acslmath program taken over the
> screen?
Under its current implementation, there is no way to suppress the console
window produced by invoking Run[].
P.J. Hinton
User Interface Programmer paulh at wolfram.com
Wolfram Research, Inc.
Disclaimer: Opinions expressed herein are those of the author alone.


text:
Though some were apprehensive about the future of Mitsubishi in Australia when it ceased local production and discontinued the Mitsubishi 380, the Japanese marque continues to thrive here.
Mitsubishi Lancer has filled the slot left by the 380, and the Mitsubishi Magna before it, and though smaller than them, frequently meets the needs of those downsizing their family cars. Unless the kids are large teenagers Lancer owners tell us their cars are large enough suit their needs.
Lancer's body styling steers clear of the mainstream in this class and the Mitsubishi stylists have given it a heavily sculpted nose that slants forwards rather than backwards.
A neat lower air dam and bold bonnet creases that flow into the A-pillars give it a neat and purposeful look. The angles of the tail-lights add to the stance. The squared off shape of the rear bumper and the way it tapers around visually shortens the overhang.
Inside, the double-domed binnacle and deep dial cluster work well both from an aesthetic and ergonomic point of view. The dash trim has a soft touch that gives it a feeling of substance, again making it feel like a larger more upmarket car than it really is. Which is another feature that received positive comments from owners and backs up their statements that the Lancer can be used as a replacement for the Mitsubishi 380.
The cabin has plenty of stowage areas for the bottles, mobile phones and assorted bits and pieces we all tend to carry around these days.
The Lancer VRX that was our test car for the last week has the convenience of has Bluetooth, steering wheel controls and a smart key.
The boot can take a handy amount of luggage and it can be expanded by flipping down the split-fold rear seats. These are fitted across the complete Lancer range. As well as the sedan we tested, Mitsubishi Lancer is also offered as a stylish hatchback. Though the hatch works well, many buyers are opting for the sedan.
Stability and traction controls were specified by Mitsubishi Australia as standard in the Lancer for quite some time before they became mandatory in this country.
Typically the Lancer's engine will use about seven to nine litres per hundred kilometres on motorways and in gentle cruising on flattish roads. Around town this is likely to rise to nine to eleven litres per hundred. These are good numbers for a mid-sized family car with good interior volume.
The manual gearbox felt a bit on the notchy side at first, but we found that we soon settled into its way of doing things and liked the sporting feeling. There's also the option of a continuously variable transmission (CVT). The latter can be an acquired taste, but once you're used to its different operation most owners soon cease to notice its peculiarities.
The Lancer sits confidently flat when you drive it around corners with a bit of verve. However, there is a less than compliant ride at times when you hit rough bush roads. The firmish suspension won't please everybody so try to take one for a decent test drive on suitable roads to see what you think.
Steering is well-weighted and responsive and driving enthusiasts will enjoy the experience in what is after all a practical family sedan.
Those who love to drive will appreciate the control the suspension offers and, while you really wouldn't call it a sports sedan, it comes closer than you might expect.
Mitsubishi's Lancer is built to a high quality in Japan and has earned a well deserved reputation for flawless running for year after year. While not the most exciting car on the road it fills the needs of family car drivers. It is well priced and in this hard fought segment of the market it holds its own nicely.
ES 2.0-litre four-door sedan: $21,690 (manual), $24,190 (CVT)
VR 2.0-litre four-door sedan: $26,390 (manual), $28,890 (CVT)
VRX 2.4-litre four-door sedan: $30,990 (manual), $33,490 (CVT)
Aspire 2.4-litre four-door sedan: $34,690 (CVT)
Ralliart 2.0-litre four-door sedan: $44,490 (DSG)
ES Sportback 2.0-litre five-door hatch: $21,690 (manual), $24,190 (CVT)
VR Sportback 2.0-litre five-door hatch: $26,390 (manual), $28,890 (CVT)
VRX Sportback 2.4-litre five-door hatch: $30,990 (manual), $33,490 (CVT)
Ralliart Sportback 2.0-litre four-door sedan: $44,490 (DSG)
Note: These prices do not include government or dealer delivery charges. Contact your local Mitsubishi dealer for driveaway prices.
ABS Brakes: Standard in all models
Automatic Transmission: CVT standard in Aspire, optional in all other models, DSG standard in Ralliart
Cruise Control: Standard in all models
Dual Front Airbags: Standard in all models
Front Side Airbags: Standard in all models
Electronic Stability Program: Standard in all models
Rear Parking Sensors: Not offered in ES, standard in all models
Reversing Camera: Not offered in ES, standard in all models
USB/Auxiliary Audio Inputs: Standard in all models
Bluetooth: Not offered in ES, standard in all models
Steering Wheel Mounted Controls: Not offered in ES, standard in all models
SPECIFICATIONS (Mitsubishi Lancer ES 2.0-litre four-door sedan)
Capacity: 1.998 litres
Configuration: Four cylinders in line
Head Design: SOHC, four valves per cylinder
Compression Ratio: 10.0:1
Bore/Stroke: 86.0 mm x 86.0 mm
Maximum Power: 110 kW @ 6000 rpm
Maximum Torque: 197 Nm @ 4250 rpm
Driven Wheels: Front
Manual Transmission: Five-speed
Automatic Transmission: CVT
Final Drive Ratio: 4.235:1
Dimensions, weight and capacity
Length: 4570 mm
Wheelbase: 2635 mm
Width: 1760 mm
Height: 1490 mm
Turning Circle: NA
Kerb Mass: 1285 kg
Fuel Tank Capacity: 59 litres
Towing Ability: 550 kg (1000 kg)
Boot Capacity: 400 litres
Suspension and brakes
Front Suspension: Independent, MacPherson struts, coil springs, anti-roll bar
Rear Suspension: Independent, multi-link,coil springs, anti-roll bar
Front Brakes: Ventilated disc
Rear Brakes: Disc
Fuel Consumption
Type: Petrol 91RON
Combined Cycle (ADR 81/02): 6.9 L/100km
Green vehicle guide ratings
Greenhouse Rating: 7/10
Air Pollution Rating: 6.5/10
Standard Warranty
Five years/130,000 km


text:
|Thread Tools
I was wondering if anyone has filled the Consular Report of Birth Abroad before in the EU or EU country? I have only heard horror stories online from expats in Asian countries about terrible interviews, tons of needed paperwork and DNA samples..
I am just wondering what to expect the process to be like in the EU
DS1 Dec 2009 DZ Twins July 2012
My understanding is that there will be less questions if both parents are already US Citizens. Also, there is some benefit to making the application sooner rather then later; there is more room for questions about parentage if the application isn't made soon after the birth. We had to get our birth certificate & other supporting documentation translated from the local language to English by a translator authorized by the embassy.
The drive over, getting through security and waiting in line was the worst part.
The interview consisted of one question, "Can I have all your paperwork?"
We were both military though so that might have made it easier.
DS1 Dec 2009 DZ Twins July 2012
As a PP said, the waiting-in-line and going through security was the hard part. That, and getting a good passport photo of a 2-month old baby!
We ended up applying for the SSN card, passport and birth report all at once since the consulate is a 6 hour drive for us.
In total it took about 30 minutes. We basically just gave the women a big stack of paperwork, passport photos, the money for the applications, and she looked through it to make sure she had everything she needed, made photocopies, told us how cute our DS was.. then we signed the passport and birth certificate documents in front of the consulate. There was no interview and everyone was very friendly and nice. She spent the most time explaining to us how the dual citizenship works for him and when to use what passports..
They asked nothing about our intention to immigrate to the US (I was worried about the immigration aspect since my DH isn't US and we have no intention of moving back, I had heard him not having a green card could be an issue-- it wasn't). I had also heard that having your DH/DW be non-US and you being US could cause some sort of problems but they seemed to care less and asked nothing about any of it. All they cared about was that we filled things out right and that DS had his eyes open in his photos
Once the women was sure they had all our paperwork she smiled and said expect to have everything in about a week.. so I am hoping this means DS is 'approved'
Overall it was a painless and fast process (so far) at least compared to getting his EU stuff (which took much much longer and many more appointments).
DS1 Dec 2009 DZ Twins July 2012
We got his consulate birth report certificate thingie and passport about 4-5 days after filing them at the consulate!
DS1 Dec 2009 DZ Twins July 2012
Hi thereWe did this in costa rica and it was a peice of cake. just toook the paper work and wen in, it was ready again in just a few days. If anyone needs more info just feel free to contact me in a PM
Glad it all went ok.
For future reference for anyone else that needs passports/birth reports etc from the Embassy - you are allowed to bring a self-addressed, stamped Special Delivery envelope (or send one with our application) for them to send your stuff back to you. Here in the UK it costs less than £6 compared to the £14 courier service they offer at the Embassy.
I thought I'd just add my little story in here, but I did it in Moscow, Russia in 2005. I am a US citizen, my husband is not. We were moving from Siberia to the Middle East though and just passing through Moscow, but they gave us the birth certificate and a temporary passport for our daughter and we were on our way. I just filled out a little paperwork. I actually felt it sounded a lot more complicated than it ended up being. I remember I was really worried about the domicile issue, because I had spent so much time out of the US and according to their descriptions I really felt as if I wasn't qualified.
Mama to a lively DD (10/05) and DS (06/23) !
Is there a time limit to doing this?
They can only get a certificate of birth abroad under the age of 18. We are procrastinators and didn't fill out the paperwork for our 4.5 year old until he was 3. She asked me why we were doing it now, but other than that no issues.
Mom to:
Three big girls (10) + (almost 9!);
One little boy (6) and a full on toddler (8/12) born with TAPVR (repaired at 6 days old).
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"The Coolest Guy…Uh, Girl Know" Episode #3 – Gretchin Irons
So now that we have a cool 103GBF You Tube Channel, which we'd love for you to subscribe to, I thought I'd start a new feature and post videos of me interviewing the "Coolest Guy (or Girl) I Know". Episode #3 features Gretchin Irons, the host of the web series "The Best Day Ever – Evansville". Her show highlights the attributes of our great city. We find out a little bit more about this cool chick as I ask some very hard-hitting, probing questions. (Not Really!)
Check out "The Best Day Ever – Evansville" website here to see Gretchin in action!


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Revision history of "CircuitCo:CircuitCo/BeagleBone Battery"
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Glendale (GNIS FID: 612750) is a populated place LOCATED WITHIN the City of Everett. In turn, the City of Everett is located within Middlesex County.
Glendale is located at latitude 42.414 and longitude -71.048. The elevation of Glendale is 79 feet above mean sea level.
Since Glendale is located within the City of Everett, all of the census and demographic data for residents of Glendale are included as part of the information reported for City of Everett in the "Data" tab above.
In similar fashion, ALL OF THE NAVIGATION TABS ABOVE ARE FOR THE City of Everett Community Profile.
Middlesex County: Subdivisions (MCDs) | Cities & Towns | ZIP Codes | Features (airports, churches, hospitals, etc.)
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Data Source - USGS GNIS FID: 612750
BOUNDARY MAPS: City of Everett | Middlesex County
Everett, MA
(< 0.1 mile)
Malden, MA (1.4 miles NW)
Chelsea, MA (1.9 miles SSE)
Revere, MA (1.9 miles ESE)
Medford, MA (3.1 miles W)
Somerville, MA
(3.1 miles SW)
Melrose, MA (3.4 miles NNW)
Cambridge, MA (3.9 miles SW)
Boston, MA (3.9 miles S)
Saugus, MA (4.1 miles NNE)
West Everett, MA
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Malden Centre, MA (1.4 miles NW)
Admirals Hill, MA (1.4 miles S)
Hendersonville, MA (1.4 miles SW)
Linden, MA (1.4 miles NNE)
Maplewood, MA
(1.4 miles N)
Edgeworth, MA (1.4 miles WNW)
Faulkner, MA (1.4 miles NNW)
Wellington, MA (1.9 miles W)
Oak Grove, MA (1.9 miles NW)


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Results 1 to 15 of 22
Thread: Bath Salts Underway
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Bath Salts Underway
Last night I finally got myself in gear for the bath salt gift production. I had purchased everything earlier and just couldn't seem to get myself going but last night it finally kicked in. I used cute glass Christmas jars that I found at yard sales. They were mostly clear but did have a small holiday design on them. I used Epsom salts, baking soda, food coloring and stress relief essential oil which contains eucalyptus and mint. I went with 3 cups Epsom salts, 1 cup baking soda, 20 drops oil and 3 small drops each of blue, green and yellow food coloring. I added the blue and stirred like crazy, then added the green and stirred and finally added the yellow and stirred until my arm wanted to fall off. It gave it a speckled aqua look with each of the colors showing up a bit. I did the recipe twice and filled 2 jars and I had a little bit left over......
Yep I put that in a nice warm bath for myself. It smelled wonderful.
Tonight I will make some more to give as gifts.
They sound so nice!!!! I'm sure that everyone will love them.11-12-2004, 02:28 PM #3
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It's amazing what putting a simple gift in a nice container will do to make it look expensive. Those bath salts in the stores are in small containers and are so expensive. These containers hold almost a quart and they will look pretty sitting out in their bathroom. Next year they can reuse them for something as well.
I get 1/2 gallon of salts for $2, 1 box of baking soda for .50, food coloring is just pennys for the dabs I use and the essential oil was less than $5 and will do tons of jars. It's really a gift for next to nothing. Just stick on a nice bow and a card and it's done.Sponsored Links Remove Advertisements12-03-2004, 11:15 AM #4
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Pic of our Bath Salts
Here is a pic of the bath salts that dd and I are giving as Christmas gifts. They are made of epsom salts, baking soda and glycerin. The green ones are stress relief scent (eucalyptus and mint) and the pink ones are romantic scent (jasmine and chamomile). I used some Christmas jars and other jars that I had found at yard sales and I did have a few of the mason jars already on hand. They are really a cheap gift but I do think they have nice eye appeal.12-03-2004, 12:11 PM #512-03-2004, 12:18 PM #6
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Very nice Pat.12-03-2004, 12:52 PM #7
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They look so pretty. They are going to love them! I think it's so wonderful that you and dd made all these gifts together.12-03-2004, 01:27 PM #8
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Yes making them together was the best part. I will treasure memory and hope that when she grows up she'll look back on it and smile.12-03-2004, 01:29 PM #912-03-2004, 02:29 PM #10
They are beautiful! I'm sure that everyone will love them!12-03-2004, 08:59 PM #11
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how cute !!12-03-2004, 09:47 PM #1212-03-2004, 10:25 PM #13
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I bet everyone is going to love them. I love the way you decorated the jars or where they already made with the Christmas theme?~*Michelle*~~Wife to Rick since Dec. 19, 1986~~Mother to Richard, 27, Chris, 24, and Dakota, 21~~Special Education Teacher~12-05-2004, 07:57 AM #14
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Some of them already had a Christmas pic on them. For the others I just bought red lids and added the rafia in Christmas colors.12-05-2004, 09:26 AM #15
Those are great PAt!!!
Similar Threads
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BMA's Advertising and Promotions Articles, Vol. I HTML version
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Navigation & Other Stuff
2010 Jeep Grand Cherokee Limited 5.7. New to me.
System will not retain my home address. Voice Recognition seems to not be working either. I have requested new software from Chrysler.
Should the new updated software solve these issues? All other functions on Radio/Nav systems seems to be okay. Also, are there better graphics in newer system - maps and such?
Thanks, Dusty :)
Re: Navigation & Other Stuff
Software won't update graphics. As for the hardware not retaining your address, it's either a memory problem, or the backup battery. The unit should retain all of that info even when you disconnect the battery, which means it's probably in RAM, backed up by a watch battery.
Re: Navigation & Other Stuff
After much research, it seems my U Connect RER radio may nave a hard drive failure. Any thoughts if this can be fixed/replaced rather than the whole unit?
All seems okay except entering home address, other addresses and phone book.
Any thoughts?
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Governance Factors Affecting Internal Auditors' Ethical Decision Making: An Exploratory Study
Stewart, Jenny & O'Leary, Conor (2007) Governance Factors Affecting Internal Auditors' Ethical Decision Making: An Exploratory Study. Managerial Auditing Journal, 22(8), pp. 787-808.
This paper explores the ethical decision making of internal auditors and the impact of corporate governance mechanisms thereon. It also explores whether ethical decision making is influenced by years of experience in internal auditing.
Sixty-six internal auditors were presented with five ethical dilemmas. For each scenario, a key element of corporate governance was manipulated to assess its impact on ethical decision making. These were audit committee support; management integrity regarding accounting policies; management integrity regarding pressure on internal audit; external auditor characteristics; and organisational code of conduct.
Findings Participants were generally sensitive to ethical dilemmas but were not always confident that their peers would act ethically. A higher quality external audit function was positively associated with internal auditors' ethical decision making. However, the strength of other governance mechanisms did not appear to influence ethical decision making. Finally, more experienced internal auditors adopted a more ethical stance in some cases. Research limitations/implications Our sample was self-selected and may not be representative of internal auditors in general. Our lack of significant results may be due to insufficient variability in our manipulations and/or an oversimplification of reality in our scenarios.
Practical implications The study has implications for the internal audit profession with respect to training and the provision of support mechanisms to strengthen the ability of internal auditors to withstand pressure when dealing with ethical dilemmas. Originality/value This paper is the first to study whether the strength of other governance mechanisms influence internal auditors' ethical decision making.
Impact and interest:
Citation counts are sourced monthly from Scopus and Web of Science® citation databases.
These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.
Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.
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|internal audit, ethics, corporate governance, external audit, years of experience
|Australian and New Zealand Standard Research Classification > COMMERCE MANAGEMENT TOURISM AND SERVICES (150000) > ACCOUNTING AUDITING AND ACCOUNTABILITY (150100)
|Current > QUT Faculties and Divisions > QUT Business School
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|Copyright 2007 Emerald Publishing
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Erase una vez un padre (original 1998; edition 1998)
by Nick Hornby
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About a Boy by Nick Hornby (1998)
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This was one of my favorite movies growing up, and so I'm glad I finally read the source material. I grew up with a mother who was very unstable. Hornby's portrayal of life as a depressive's child is really spot on. As an angsty teenager, I really felt like Nick Hornby got me. That this still has the same emotional resonance for me years later is really a testament to the writing.
I absolutely loved the film of this novel, watched it many, many times, so thought it time to read the novel and compare. The first half of the film is practically word for word the same; but then the film and the book gradually diverge with different storylines - although the outcome is the same, they all live happily ever after.
Not sure what I'd have thought of the book if I didn't know the film so well...
As things stand I liked the book, but preferred the film.
I don't remember it very well, but I did recommend it to my husband, who normally reads mystery/thrillers and sci-fi, so it must be pretty good.
Even better than the movie -- and I LOVED the movie!
I've been meaning to read this for a while since I've loved the film. I really enjoy the dynamic of each chapter being told from the point of view of one of the 2 main characters. Maybe the this theme is nothing new an adult who has no clue how to act like one and a kid that just doesn't function like one. I've had my share on this matter, but I really loved how things worked, how they interact with each other, how they make you feel with them and sometimes laugh at them. Another great book by Nick Hornby.
A follow-up to High Fidelity, British writer Hornby's superb 1996 novel about pop-music obsession, About A Boy (the film rights to which have reportedly been sold for $3 million) is an acerbic, emotionally richer yet no less funny tale. Will (36, single, lonely, in search of a girlfriend and a life) meets Marcus (12, lonely, in search of happiness for himself and his suicidal mother). At first, befriending Marcus is merely an attempt to assuage a guilty conscience brought about by a life of leisure.
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Amazon.com Amazon.com Review (ISBN 0141007338, Paperback)Will Lightman is a Peter Pan for the 1990s. At 36, the terminally hip North Londoner is unmarried, hyper-concerned with his coolness quotient, and blithely living off his father's novelty-song royalties. Will sees himself as entirely lacking in hidden depths--and he's proud of it! The only trouble is, his friends are succumbing to responsibilities and children, and he's increasingly left out in the cold. How can someone brilliantly equipped for meaningless relationships ensure that he'll continue to meet beautiful Julie Christie-like women and ensure that they'll throw him over before things get too profound? A brief encounter with a single mother sets Will off on his new career, that of "serial nice guy." As far as he's concerned--and remember, concern isn't his strong suit--he's the perfect catch for the young mother on the go. After an interlude of sexual bliss, she'll realize that her child isn't ready for a man in their life and Will can ride off into the Highgate sunset, where more damsels apparently await. The only catch is that the best way to meet these women is at single-parent get-togethers. In one of Nick Hornby's many hilarious (and embarrassing) scenes, Will falls into some serious misrepresentation at SPAT ("Single Parents--Alone Together"), passing himself off as a bereft single dad: "There was, he thought, an emotional truth here somewhere, and he could see now that his role-playing had a previously unsuspected artistic element to it. He was acting, yes, but in the noblest, most profound sense of the word."
What interferes with Will's career arc, of course, is reality--in the shape of a 12-year-old boy who is in many ways his polar opposite. For Marcus, cool isn't even a possibility, let alone an issue. For starters, he's a victim at his new school. Things at home are pretty awful, too, since his musical therapist mother seems increasingly in need of therapy herself. All Marcus can do is cobble together information with a mixture of incomprehension, innocence, self-blame, and unfettered clear sight. As fans of Fever Pitch and High Fidelity already know, Hornby's insight into laddishness magically combines the serious and the hilarious. About a Boy continues his singular examination of masculine wish-fulfillment and fear. This time, though, the author lets women and children onto the playing field, forcing his feckless hero to leap over an entirely new--and entirely welcome--set of emotional hurdles.
(retrieved from Amazon Thu, 12 Mar 2015 18:18:43 -0400)
A comedy on a bachelor in London who specializes in affairs with single mothers. To improve his chances, he joins a single parents' association and gets a boy to pretend he is his son.
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Oregon Historical County Records Guide
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This antique steam-powered tractor is one of many examples of logging, road, and farm equipment at the Collier Memorial State Park Logging Museum. (Photo No. klaDA0089a)
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Let the light of faith shine throughout your life as it does on the faces of these little ones in the presence of Jesus. The beautiful Into His Arms Faith Based Rug will reinforce to children and all who see it the message of God's love.
Size: 7'8" x 10'9" Rectangle
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Manufactured in the U.S.A. by Joy Carpets
SensoryEdge specializes in waiting room toys, classroom rugs, children's furniture, and sensory based products. In addition to a great selection, we have many great reasons to buy from us. We have been the leader in this industry for more than a decade. A customer-centered shopping experience has always been our goal and we pride ourselves in giving you a great experience from start to finish. Shop with us today and see the SensoryEdge difference.
Here are just a few of the reason why you should buy from us:


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3 Recommendations
pinkeye's recommendation
pocky chocolate = love <333
palacinka's recommendation
Whenever we are in Japan we buy tons of these! It makes us feel like we are 5 again, but gives a grown up chocolate fix! They are also available at the bigger Asian supermarkets in big cities like New York, where there's a nice one near Astor place.
Yournewbestfriend's recommendation
So good. Pocky chocolate makes me so happy. Skinny biscuits dipped in creamy milk chocolate. Yum.


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Fish IP Law LLP is a premier intellectual property (IP) law firm providing strategic services of only the highest caliber to help make clients' dreams come true. Holistically guiding clients through the patent process, Fish uses a three-pronged approach – identifying, procuring, and shepherding – to provide the best legal counsel possible and help turn IP visions into realities.
The team at Fish IP Law serves as both legal advisers and trusted business advisers. The firm's experts help clarify the complexities of IP law so clients can make sound business decisions aligned with their business goals. For more than 20 years, Fish's quest to "make dreams come true" has been driven by the focus of a talented staff and embodied in the impactful work performed for clients. FULL DESCRIPTION


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Does anyone know the kinds of vinegar and oil is used at Subway on their sandwiches?
Sandie from Marysville, WA
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I mix my olive oil with red wine vinager in a bottle and voila just like subway, years ago I managed a subway and thats all it was
I know they use red wine vinegar and blended olive oil (canola oil blended with extra virgin olive oil) but if your looking for a brand I don't have any idea. Hope this helps.
My daughter used to work at Subway and if you are talking about the original Subway sauce, all it is, is regular Italian dressing!!
I too do not have the exact oils. However at work recently we got 6 foot sub and they sent along packages of condiments with the huge sandwich. Red wine vinergar and olive/canol oil combo were in the goodie bag. So don't make the mix just ask for a couple extra packets when you find yourself at the sub shop. I hope this helps.
I too love subway, and though I don't know what kind of sauces they use for those I would like to know if anyone has a recipe for their Sweet Onion Sauce. I've looked at CopyKat and can't find it.
Subway oil is 90% canola oil, and 10% extra virgin olive oil. yikes.
1/2 cup light corn syrup
1 Tablespoon white minced onion
1 Tablespoon red wine vinegar
2 teaspoons white vinegar
1 teaspoon balsamic vinegar
1 teaspoon brown sugar
1 teaspoon buttermilk powder
1/4 teaspoon lemon juice
1/8 teaspoon poppy seeds
1/8 teaspoon salt
pinch of cracked pepper
pinch of garlic powder
combine all in microwave bowl..heat on high for 1-2 min until it boils rapidly...whisk well, cover and cool. makes about 2/3 of a cup...hope this helps
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