bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Program Environment Scale: Assessing Client Perceptions of Community‐Based Programs for the Severely Mentally Ill
Authors: Burt Martha R. , Duke Amy-Ellen , Hargreaves William A. 
Published: March 2003

AbstractThe Program Environment Scale (PES) was developed for use with clients of community‐based programs for the severely mentally ill. It is intended to fill the gap in available tools for assessing clients' perceptions of program functioning as it affects their “quality of life” in a program. Formal pretests were conducted with 121 clients at 12 randomly selected programs near Washington, DC. The final field test used a revised form (29 domains; 129 items) with 221 clients in 22 programs selected randomly throughout the U.S., including Clubhouse, day treatment, psychosocial rehabilitation, and social club programs. Twenty‐three subscales met at least five of eight psychometric criteria for internal consistency and discriminant validity. A 24th subscale was retained because of its substantive importance. Successful subscales cover program atmosphere and interactions (program cares about me, energy level, friendliness, openness, staff‐client and client‐client respect, reasonable rules, availability of positive physical contact, protection from bad touch, staff investment in their jobs, and confidentiality), client empowerment/staff‐client equality (program and treatment empowerment, egalitarian space use), and service components (support for paid work, work importance, emergency access, family activities, housing, public benefits, community activities, medications, substance abuse, and continuity). Subscale validity is indicated by associations of specific service offerings with scores on scales measuring client perceptions of those services, and by an ability to differentiate among program models (i.e., Clubhouses, day treatment programs, and psychosocial rehabilitation programs look different from each other). Subscale scores were not influenced by client characteristics (gender, race, age, diagnosis, number of hospitalizations, length of time in program). The final scale has 97 items and takes about 25 minutes to complete. The PES succeeds in measuring different aspects of programs as clients perceive them. In the programs we visited, directors felt the PES covers the important things they want to know about how clients perceive their program. The PES should become a useful tool both for researchers interested in how client responses to programs may influence their therapeutic outcomes, and for practitioners interested in improving their clients' program experiences and/or increasing convergence of staff and client views of their program.
Adolescent Development and Juvenile Justice
Authors: Reppucci N. Dickon 
Published: March 2003

AbstractThe central question examined in this address is, “Do children's crimes make them adults?” I begin by focusing on the concept and history of adolescence in our society, I then examine the development and philosophy of the juvenile justice system. Adolescent development and juvenile justice are brought together around the concepts of maturity, judgment, and competence, followed by a brief introduction to some current research that we are engaged in regarding the issues of adjudicatory and culpability competence. I conclude with suggested directions for future work.
The Identification of Early Risk Factors for Severe Emotional Disturbances and Emotional Handicaps: An Epidemiological Approach
Authors: Mason Craig A. , Chapman Derek A. , Scott Keith G. 
Published: March 2003

AbstractEpidemiological methodology is used to examine the relationship between early childhood risk factors and future identification as having a Severe Emotional Disturbance or as having an Emotional Handicap (SED/EH) at age 13. Data were obtained from 1979/1980 Florida birth records that were electronically linked with 1992/1993 Florida school records. An epidemiological perspective was chosen due to its ability to model both individual and community‐level risk. In regards to increasing an individual's risk of SED/EH, two factors, gender (being male) and low maternal education (mother not completing high school at the time of the child's birth), were found to have particularly strong effects. When examining effects of these risk factors upon overall rates of SED/EH in the community, maternal education and marital status (being unmarried at the time of the child's birth) were associated with a large proportion of the cases. Health/biological markers were moderately associated with SED/EH on the individual level, but were related to a relatively small percentage of cases in the population. In addition, effects varied based upon ethnic/cultural heritage. Researchers are encouraged to consider using an epidemiological perspective and its potential utility in the field of community psychology and public policy is discussed.
“Nothing About Me, Without Me”: Participatory Action Research with Self‐Help/Mutual Aid Organizations for Psychiatric Consumer/Survivors
Authors: Nelson Geoffrey , Ochocka Joanna , Griffin Kara , Lord John 
Published: March 2003

AbstractParticipatory action research with self‐help/mutual aid organizations for psychiatric consumer/survivors is reviewed. We begin by tracing the origins of and defining both participatory action research and self‐help/mutual aid. In so doing, the degree of correspondence between the assumptions/values of participatory action research and those of self‐help/mutual aid for psychiatric consumer/survivors is examined. We argue that participatory action research and self‐help/mutual aid share four values in common: (a) empowerment, (b) supportive relationships, (c) social change, and (d) learning as an ongoing process. Next, selected examples of participatory action research with psychiatric consumer/survivor‐controlled self‐help/mutual aid organizations which illustrate these shared values are provided. We conclude with recommendations of how the key values can be promoted in both the methodological and substantive aspects of future participatory action research with self‐help/mutual aid organizations for psychiatric consumer/survivors.
Fixed points of commuting holomorphic mappings other than the Wolff point
Authors: Bracci Filippo 
Published: March 2003

Let

Δ
\Delta

be the unit disc of

C

\mathbb C

and let

f
,
g
∈

H
o
l

(
Δ
,
Δ
)

f,g \in \mathrm {Hol}(\Delta ,\Delta )

be such that

f
∘
g
=
g
∘
f

f \circ g = g \circ f

. For

A
>
1

A>1

, let

F
i
x

A

(
f
)
:=
{
p
∈
∂
Δ
∣

lim

r
→
1

f
(
r
p
)
=
p
,

lim

r
→
1

|

f
′

(
r
p
)

|

≤
A
}

\mathrm {Fix}_A (f):=\{p \in \partial \Delta \mid \lim _{r \to 1}f(rp)=p, \lim _{r \to 1}|f’(rp)|\leq A \}

. We study the behavior of

g
g

on

F
i
x

A

(
f
)

\mathrm {Fix}_A (f)

. In particular, we prove that

g
(

F
i
x

A

(
f
)
)
⊆

F
i
x

A

(
f
)

g(\mathrm {Fix}_A (f))\subseteq \mathrm {Fix}_A (f)

. As a consequence, besides conditions for

F
i
x

A

(
f
)
∩

F
i
x

A

(
g
)
≠
∅

\mathrm {Fix}_A(f) \cap \mathrm {Fix}_A(g) \neq \emptyset

, we prove a conjecture of C. Cowen in case

f
f

and

g
g

are univalent mappings.
In Vivo Pharmacodynamics of HMR 3270, a Glucan Synthase Inhibitor, in a Murine Candidiasis Model
Authors: Andes D. , Marchillo K. , Lowther J. , Bryskier A. , Stamstad T. , Conklin R. 
Published: March 2003

ABSTRACT

In vivo pharmacokinetic/pharmacodynamic characterization for numerous antibacterial compounds has had a significant impact upon optimal dosing regimen design and the development of in vivo susceptibility breakpoints. More recently, similar characterization has been undertaken for antifungal drug classes. Very little is known of these pharmacodynamic relationships for the new echinocandin class of compounds. We utilized a neutropenic murine model of disseminated candidiasis to describe the time course antifungal activity of HMR 3270, a new glucan synthase inhibitor. Single-dose in vivo time kill studies with four 16-fold escalating doses demonstrated concentration-dependent killing when drug levels in serum were more than four times the MIC. Postantifungal effects were dose dependent, ranging from 8 to 80 h duration. Multiple dosing regimen studies utilized six total doses, four dosing intervals, and a treatment duration of 6 days. Shortening the dosing interval from every 144 h (q144h) to q36h resulted in a fourfold rise in the dose necessary to achieve a net fungistatic effect. The peak/MIC ratio most strongly correlated with treatment outcomes (peak/MIC ratio,
R
2
= 98%; ratio of the area under the concentration-time curve from 0 to 24 h to the MIC,
R
2
= 79%, percentage of time above the MIC,
R
2
= 61%). Studies were also conducted with five additional
Candida albicans
isolates to determine if a similar peak/MIC ratio was associated with efficacy. In vivo concentration-dependent killing was similarly observed in studies with each of the additional isolates. The peak/MIC ratio necessary to produce efficacy was relatively similar among the strains studied (
P
= 0.42). The peak/MIC ratio (mean ± standard deviation) necessary to achieve a fungistatic effect was 3.72 ± 1.84, and the ratio necessary to achieve maximal killing was near 10.
In Vivo Pharmacodynamics of a New Triazole, Ravuconazole, in a Murine Candidiasis Model
Authors: Andes D. , Marchillo K. , Stamstad T. , Conklin R. 
Published: March 2003

ABSTRACT

In vivo studies have characterized the pharmacodynamic characteristics of the triazole fluconazole. These investigations demonstrated that the ratio of the area under the concentration-time curve from 0 to 24 h to the MIC (24-h AUC/MIC ratio) is the critical pharmacokinetic/pharmacodynamic (PK/PD) parameter associated with treatment efficacy. Further analysis demonstrated that a fluconazole 24-h AUC/MIC ratio of 20 to 25 was predictive of treatment success in both experimental models and clinical trials. We used a neutropenic murine model of disseminated
Candida albicans
infection to similarly characterize the time course activity of the new triazole ravuconazole. The PK/PD parameters (percent time above the MIC, AUC/MIC ratio, and peak level in serum/MIC ratio) were correlated with in vivo efficacy, as measured by organism number in kidney cultures after 24 and 72 h of therapy. Ravuconazole kinetics and protein binding were performed in neutropenic infected mice. Peak/dose and AUC/dose values ranged from 0.03 to 0.04 and 0.30 to 0.34, respectively. Serum elimination half-life ranged from 3.9 to 4.8 h. Protein binding was 95.8%. Single-dose postantifungal effect studies demonstrated prolonged suppression of organism regrowth after serum ravuconazole levels had fallen below the MIC. Treatment efficacies with the five dosing intervals studied were similar, supporting the argument for the AUC/MIC ratio as the PK/PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (AUC/MIC ratio,
R
2
= 91%; peak/MIC ratio,
R
2
= 85%; percent time above the MIC,
R
2
= 47 to 65%). Similar studies were conducted with seven additional
C. albicans
isolates with various ravuconazole susceptibilities (MIC, 0.016 to 0.12 μg/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The ravuconazole free-drug AUC/MIC ratios were similar for all of the organisms studied (10 to 36; mean ± SD = 20.3 ± 8.2;
P
= 0.43). These free-drug AUC/MIC ratios are similar to those observed for fluconazole in this model.
Sublethal Injury and Resuscitation of
Candida albicans
after Amphotericin B Treatment
Authors: Liao Robert S. , Rennie Robert P. , Talbot James A. 
Published: March 2003

ABSTRACT

Amphotericin B treatment was previously shown to inhibit
Candida albicans
reproduction and reduce the fluorescence of vitality-specific dyes without causing a corresponding increase in the fluorescence of the mortality-specific dyes bis-(1,3-dibutylbarbituric acid)trimethine oxonol and SYBR Green Ι. In the present study, we have confirmed these results and have shown that the numbers of CFU are reduced by 99.9% by treatment with 0.5 μg of amphotericin B per ml for 10 h at 35°C. This reduction was not due to fungal cell death. First, the level of reduction of the tetrazolium salt 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2
H
-tetrazolium hydroxide increased in the presence of concentrations of amphotericin B that caused greater than 90% reductions in the numbers of CFU. Second, fungal cells treated with amphotericin B at a concentration of 0.5 μg/ml were resuscitated by further incubation at 22°C for 15 h in the continued presence of amphotericin B. Third, recovery of the ability to replicate was prevented by sequential treatment with 20 μg of miconazole per ml, which also increased the fluorescence of mortality-specific dyes to near the maximal levels achieved with 0.9 μg of amphotericin B per ml. Sequential treatment with fluconazole and flucytosine did not increase the levels of staining with the mortality-specific dyes. Itraconazole was less effective than ketoconazole, which was less effective than miconazole. The practice of equating the loss of the capacity of
C. albicans
to form colonies with fungal cell death may give incorrect results in assays with amphotericin B, and the results of assays with caution with other antifungal agents that are lipophilic or that possess significant postantifungal effects may need to be interpreted.
Drug Resistance Is Not Directly Affected by Mating Type Locus Zygosity in
Candida albicans
Authors: Pujol Claude , Messer Shawn A. , Pfaller Michael , Soll David R. 
Published: March 2003

ABSTRACT

Recently, evidence was presented that in a collection of fluconazole-resistant strains of
Candida albicans
there was a much higher proportion of homozygotes for the mating type locus (
MTL
) than in a collection of fluconazole-sensitive isolates, suggesting the possibility that when cells become
MTL
homozygous they acquire intrinsic drug resistance. To investigate this possibility, an opposite strategy was employed. First, drug susceptibility was measured in a collection of isolates selected for
MTL
homozygosity. The majority of these isolates had not been exposed to antifungal drugs. Second, the level of drug susceptibility was compared between spontaneously generated
MTL
-homozygous progeny and their
MTL
-heterozygous parent strains which had not been exposed to antifungal drugs. The results demonstrate that naturally occurring
MTL
-homozygous strains are not intrinsically more drug resistant, supporting the hypotheses that either the higher incidence of
MTL
homozygosity previously demonstrated among fluconazole-resistant isolates involved associated homozygosity of a drug resistance gene linked to the
MTL
locus, or that
MTL
-homozygous strains may be better at developing drug resistance upon exposure to the drug than
MTL
-heterozygous strains. Furthermore, the results demonstrate that a switch by an
MTL
-homozygous strain from the white to opaque phenotype, the latter functioning as the facilitator of mating, does not notably alter drug susceptibility.
Genetic Basis for Differential Activities of Fluconazole and Voriconazole against
Candida krusei
Authors: Fukuoka Takashi , Johnston Douglas A. , Winslow Carol A. , de Groot Marcel J. , Burt Catherine , Hitchcock Christopher A. , Filler Scott G. 
Published: March 2003

ABSTRACT

Invasive infections caused by
Candida krusei
are a significant concern because this organism is intrinsically resistant to fluconazole. Voriconazole is more active than fluconazole against
C. krusei
in vitro. One mechanism of fluconazole resistance in
C. krusei
is diminished sensitivity of the target enzyme, cytochrome P450 sterol 14α-demethylase (CYP51), to inhibition by this drug. We investigated the interactions of fluconazole and voriconazole with the CYP51s of
C. krusei
(ckCYP51) and fluconazole-susceptible
Candida albicans
(caCYP51). We found that voriconazole was a more potent inhibitor of both ckCYP51 and caCYP51 in cell extracts than was fluconazole. Also, the ckCYP51 was less sensitive to inhibition by both drugs than was caCYP51. These results were confirmed by expressing the
CYP51
genes from
C. krusei
and
C. albicans
in
Saccharomyces cerevisiae
and determining the susceptibility of the transformants to voriconazole and fluconazole. We constructed homology models of the CYP51s of
C. albicans
and
C. krusei
based on the crystal structure of CYP51 from
Mycobacterium tuberculosis
. These models predicted that voriconazole is a more potent inhibitor of both caCYP51 and ckCYP51 than is fluconazole, because the extra methyl group of voriconazole results in a stronger hydrophobic interaction with the aromatic amino acids in the substrate binding site and more extensive filling of this site. Although there are multiple differences in the predicted amino acid sequence of caCYP51 and ckCYP51, the models of the two enzymes were quite similar and the mechanism for the relative resistance of ckCYP51 to the azoles was not apparent.
Genome-Wide Expression Profile Analysis Reveals Coordinately Regulated Genes Associated with Stepwise Acquisition of Azole Resistance in
Candida albicans
Clinical Isolates
Authors: Rogers P. David , Barker Katherine S. 
Published: March 2003

ABSTRACT

Candida albicans
is an opportunistic human fungal pathogen and a causative agent of oropharyngeal candidiasis (OPC), the most frequent opportunistic infection among patients with AIDS. Fluconazole and other azole antifungal agents have proven effective in the management of OPC; however, with increased use of these agents treatment failures have occurred. Such failures have been associated with the emergence of azole-resistant strains of
C. albicans
. In the present study we examined changes in the genome-wide gene expression profile of a series of
C. albicans
clinical isolates representing the stepwise acquisition of azole resistance. In addition to genes previously associated with azole resistance, we identified many genes whose differential expression was for the first time associated with this phenotype. Furthermore, the expression of these genes was correlated with that of the known resistance genes
CDR1
,
CDR2
, and
CaMDR1
. Genes coordinately regulated with the up-regulation of
CDR1
and
CDR2
included the up-regulation of
GPX1
and
RTA3
and the down-regulation of
EBP1
. Genes coordinately regulated with the up-regulation of
CaMDR1
included the up-regulation of
IFD1
,
IFD4
,
IFD5
,
IFD7
,
GRP2
,
DPP1
,
CRD2
, and
INO1
and the down-regulation of
FET34
,
OPI3
, and
IPF1222
. Several of these appeared to be coordinately regulated with both the CDR genes and
CaMDR1
. Many of these genes are involved in the oxidative stress response, suggesting that reduced susceptibility to oxidative damage may contribute to azole resistance. Further evaluation of the role these genes and their respective gene products play in azole antifungal resistance is warranted.
Isolation of Three
Mycobacterium ulcerans
Strains Resistant to Rifampin after Experimental Chemotherapy of Mice
Authors: Marsollier Laurent , Honoré Nadine , Legras Pierre , Manceau Anne Lise , Kouakou Henri , Carbonnelle Bernard , Cole Stewart T. 
Published: March 2003

ABSTRACT

By use of a murine model for Buruli ulcer,
Mycobacterium ulcerans
was found to be susceptible to rifampin, with the MIC being 0.5 to 1 μg/ml. Three mutants were isolated after rifampin monotherapy. Two were resistant to rifampin at 8 μg/ml, and one was resistant to rifampin at 32 μg/ml. The mutants harbored Ser416Phe mutations and His420Tyr mutations in the
rpoB
gene, and these mutations have also been found to be responsible for rifampin resistance in the leprosy and tubercle bacilli. The results indicate that while rifampin may be active against
M. ulcerans
, it should never be used as monotherapy in humans.
In Vivo Antiretroviral Activity of Stampidine in Chronically Feline Immunodeficiency Virus-Infected Cats
Authors: Uckun Fatih M. , Chen Chun-Lin , Samuel Peter , Pendergrass Sharon , Venkatachalam T. K. , Waurzyniak Barbara , Qazi Sanjive 
Published: March 2003

ABSTRACT
Here we report the antiretroviral activity of the experimental nucleoside reverse transcriptase inhibitor (NRTI) compound stampidine in cats chronically infected with feline immunodeficiency virus (FIV). Notably, a single oral bolus dose of 50 or 100 mg of stampidine per kg resulted in a transient ≥1-log decrease in the FIV load of circulating peripheral blood mononuclear cells in five of six FIV-infected cats and no side effects. A 4-week stampidine treatment course with twice-daily administration of hard gelatin capsules containing 25 to 100 mg of stampidine per kg was also very well tolerated by cats at cumulative dose levels as high as 8.4 g/kg and exhibited a dose-dependent antiretroviral effect. One of three cats treated at the 25-mg/kg dose level, three of three cats treated at the 50-mg/kg dose level, and three of three cats treated at the 100-mg/kg dose level (but none of three control cats treated with placebo pills) showed a therapeutic response, as evidenced by a ≥1-log reduction in the FIV load in peripheral blood mononuclear cells within 2 weeks. The previously documented in vitro and in vivo antiretroviral activity of stampidine against primary clinical human immunodeficiency virus type 1 isolates with genotypic and/or phenotypic NRTI resistance, together with its favorable animal toxicity profile, pharmacokinetics, and in vivo antiretroviral activity in FIV-infected cats, warrants further development of this promising new NRTI compound.
Single Nucleotide Polymorphisms in Genes Associated with Isoniazid Resistance in
Mycobacterium tuberculosis
Authors: Ramaswamy Srinivas V. , Reich Robert , Dou Shu-Jun , Jasperse Linda , Pan Xi , Wanger Audrey , Quitugua Teresa , Graviss Edward A. 
Published: March 2003

ABSTRACT

Isoniazid (INH) is a central component of drug regimens used worldwide to treat tuberculosis. Previous studies have identified resistance-associated mutations in
katG
,
inhA
,
kasA
,
ndh
, and the
oxyR-ahpC
intergenic region. DNA microarray-based experiments have shown that INH induces several genes in
Mycobacterium tuberculosis
that encode proteins physiologically relevant to the drug's mode of action. To gain further insight into the molecular genetic basis of INH resistance, 20 genes implicated in INH resistance were sequenced for INH resistance-associated mutations. Thirty-eight INH-monoresistant clinical isolates and 86 INH-susceptible isolates of
M. tuberculosis
were obtained from the Texas Department of Health and the Houston Tuberculosis Initiative. Epidemiologic independence was established for all isolates by IS
6110
restriction fragment length polymorphism analysis. Susceptible isolates were matched with resistant isolates by molecular genetic group and IS
6110
profiles. Spoligotyping was done with isolates with five or fewer IS
6110
copies. A major genetic group was established on the basis of the polymorphisms in
katG
codon 463 and
gyrA
codon 95. MICs were determined by the E-test. Semiquantitative catalase assays were performed with isolates with mutations in the
katG
gene. When the 20 genes were sequenced, it was found that 17 (44.7%) INH-resistant isolates had a single-locus, resistance-associated mutation in the
katG
,
mabA
, or
Rv1772
gene. Seventeen (44.7%) INH-resistant isolates had resistance-associated mutations in two or more genes, and 76% of all INH-resistant isolates had a mutation in the
katG
gene. Mutations were also identified in the
fadE24
,
Rv1592c
,
Rv1772
,
Rv0340
, and
iniBAC
genes, recently shown by DNA-based microarray experiments to be upregulated in response to INH. In general, the MICs were higher for isolates with mutations in
katG
and the isolates had reduced catalase activities. The results show that a variety of single nucleotide polymorphisms in multiple genes are found exclusively in INH-resistant clinical isolates. These genes either are involved in mycolic acid biosynthesis or are overexpressed as a response to the buildup or cellular toxicity of INH.