bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Faced’ with responsibility: Levinasian ethics and the challenges of responsibility in Norwegian public health nursing
Authors: Clancy Anne , Svensson Tommy
Published: June 2007

Abstract  This paper is concerned with aspects of responsibility in Norwegian public health nursing. Public health nursing is an expansive profession with diffuse boundaries. The Norwegian public health nurse does not perform ‘hands on’ nursing, but focuses on the prevention of illness, injury, or disability, and the promotion of health. What is the essence of ethical responsibility in public health nursing? The aim of this article is to explore the phenomenon based on the ethics of responsibility as reflected upon by the philosopher Emanuel Levinas (1906–1995). From an ethical point of view, responsibility is about our duty towards the Other, a duty we have not always chosen, are prepared for, or can fully explain; but it is nevertheless a demand we have to live with. Interviews with five experienced Norwegian nurses provide the empirical base for reflection and interpretation. The nurses share stories from their practice. In interpreting the nurses’ stories, the following themes emerge: personal responsibility; boundaries; temporality; worry, fear, and uncertainty; and a sense of satisfaction. As the themes are developed further, it becomes apparent that, despite their diversity, they are all interrelated aspects of ethical responsibility. Responsibility for the Other cannot be avoided, ignored, or transferred. The nurses’ responsibility is personal and infinite. Levinasian ethics can help nurses understand the importance of accepting that being a responsive carer can involve not only contentment in the predictable, but also the fear, worry, and uncertainty of the unpredictable.
Nursing involvement in euthanasia: how sound is the philosophical support?
Authors: McCabe Helen
Published: June 2007

Abstract  Preference utilitarians are concerned to maximize the autonomous choices of individuals; for this reason, they argue that nurses ought to advocate for those patients who desire assistance with ending their lives. This approach prompts us to consider, then, the moral validity of nursing involvement in measures intended to end the lives of patients. In this article, the terms of preference utilitarianism are set out and considered in order to determine whether this approach offers sufficient philosophical support for sanctioning a role for nursing in euthanasia. Ultimately, it is found that preference utilitarianism is lacking in this respect, as well as in its fitness for guiding nursing activity in general. In particular, it is found that nurses are required to exchange a handmaiden relationship with the medical profession for an equally undignified relationship with patients. If nursing involvement in measures intended to end the lives of patients is to find sufficient philosophical support, then we need to look elsewhere.
The sensitivity and precision of search terms in Phases I, II and III of the Cochrane Highly Sensitive Search Strategy for identifying reports of randomized trials in medline in a specific area of health care—HIV/AIDS prevention and treatment interventions
Authors: Eisinga Anne , Siegfried Nandi , Clarke Mike
Published: June 2007

Objectives:  To detect term(s) in the Cochrane Highly Sensitive Search Strategy (HSSS) that retain high sensitivity but improve precision in retrieving reports of trials in the PubMed version of medline.

Methods:  Individual terms from the PubMed version of the HSSS were added, term by term, to an African HIV/AIDS strategy to identify reports of trials in medline using PubMed. The titles and abstracts of the records retrieved were read by two handsearchers and checked by a clinical epidemiologist. The sensitivity and precision of each term in the three phases of the HSSS were calculated.

Results:  Of 7719 records retrieved, 285 were identified as reports of trials [204 randomized (RCTs); 81 possibly randomized or quasi‐randomized (CCTs)]. Phase III had the highest sensitivity (92%). Overall, precision was very low (3.7%). One term, ‘random*[tw]’, retrieved all RCTs found by our search and improved precision to 29%. The least sensitive terms, yielding no records, were ‘(doubl* AND mask*)[tw]’ and terms containing ‘trebl*’ or ‘tripl*’, except for ‘(tripl* AND blind*)[tw]’. The highest precision per term was for ‘Double‐blind Method [MeSH]’ (76%).

Conclusions:  To retrieve all RCTs and CCTs found by our search, seven terms are needed but precision remains low (4.3%). Developments in the methods of search strategy design may help to improve precision while retaining high levels of sensitivity by identifying term(s) which occur frequently in relevant records and are the most efficient at discriminating between different study designs.
The information‐seeking behaviour of doctors: a review of the evidence
Authors: Davies Karen
Published: June 2007

This paper provides a narrative review of the available literature from the past 10 years (1996–2006) that focus on the information seeking behaviour of doctors. The review considers the literature in three sub‐themes: Theme 1, the Information Needs of Doctors includes information need, frequency of doctors’ questions and types of information needs; Theme 2, Information Seeking by Doctors embraces pattern of information resource use, time spent searching, barriers to information searching and information searching skills; Theme 3, Information Sources Utilized by Doctors comprises the number of sources utilized, comparison of information sources consulted, computer usage, ranking of information resources, printed resource use, personal digital assistant (PDA) use, electronic database use and the Internet. The review is wide ranging. It would seem that the traditional methods of face‐to‐face communication and use of hard‐copy evidence still prevail amongst qualified medical staff in the clinical setting. The use of new technologies embracing the new digital age in information provision may influence this in the future. However, for now, it would seem that there is still research to be undertaken to uncover the most effective methods of encouraging clinicians to use the best evidence in everyday practice.
Applying Psychology to Help Save the World: Reflections on a Career in Psychology
Authors: Oskamp Stuart
Published: June 2007

This reflective personal account traces phases of the author's career where he saw psychology as relevant to major world problems. Chronologically, these problems included issues of international conflict, waste of energy and natural resources, human behaviors that caused environmental destruction, and the paramount threat of global climate change. Psychologists can make valuable contributions to describing, evaluating, and resolving these problems, and their vital importance should motivate the research and teaching of many psychologists. Our generation's success in achieving sustainable patterns of living on the Earth will determine whether the Earth will retain a livable environment for future generations. Brief suggestions are offered for approaches that may lead to more effective research and advocacy on crucial social issues.
Elder Abuse: Disparities Between Older People's Disclosure of Abuse, Evident Signs of Abuse, and High Risk of Abuse
Authors: Cohen Miri , Levin Sarah Halevy , Gagin Roni , Friedman Gideon
Published: June 2007

OBJECTIVES: To assess and compare three types of assessment tools for identifying elder abuse: direct questions to elicit disclosure of abuse if it exists, identification of evident signs of abuse, and assessment of high risk for abuse.

DESIGN: Cross‐sectional.

SETTING: Rambam and Hadassah medical centers, Israel.

PARTICIPANTS: Seven hundred thirty persons aged 70 and older hospitalized in general hospitals in 2004/05 and their principal caregivers.

MEASUREMENTS: Expanded indicator of abuse (E‐IOA) tool, questionnaires looking for evident signs of abuse, and direct experience of abusive behavior.

RESULTS: Although 5.9% of respondents disclosed experiencing abusive behaviors, 21.4% were identified with evident signs of abuse, and 32.6% were classified as being at high risk for abuse. More than 70% of those who disclosed abuse were identified with evident signs and were at high risk for abuse. Those who disclosed being abused suffered particularly from physical and sexual abuse. According to logistic regression, higher caregiver subjective burden was a predictor of disclosure (odds ratio (OR)=1.81, 95% confidence interval (CI)=1.19–2.74), evident signs of abuse (OR=1.86, 95% CI=1.45–2.35), and high risk of abuse (OR=1.55, 95% CI=1.27–1.88); heavier objective caregiver load was a predictor of evident signs of abuse (OR=1.14, 95% CI=1.05–1.24) and of high risk (OR=1.18, 95% CI=1.06–1.38) only; and respondent functional status was a predictor of evident signs of abuse (OR=1.88, 95% CI=1.70–2.37).

CONCLUSION: The use of the three assessment tools is needed for optimal identification of abuse, whereas assessment for high risk proved an efficient method in the absence of respondent disclosure or professional detection of signs of abuse. Hospitalization provides an excellent opportunity for identifying elderly persons at risk of abuse.
A Brief Risk Stratification Tool to Predict Functional Decline in Older Adults Discharged from Emergency Departments
Authors: Hustey Fredric M. , Mion Lorraine C. , Connor Jason T. , Emerman Charles L. , Campbell James , Palmer Robert M.
Published: June 2007

OBJECTIVES: To determine the effectiveness of the six‐item Triage Risk Screening Tool (TRST) to assess baseline functional status and predict subsequent functional decline in older community‐dwelling adults discharged home from the emergency department (ED).

DESIGN: Secondary data analysis of a randomized, controlled trial.

SETTING: EDs of two urban academic hospitals.

PARTICIPANTS: Six hundred fifty community‐dwelling adults aged 65 and older presenting to the ED and discharged home. Patients were categorized a priori as “high risk” if they had cognitive impairment or two or more risk factors on the TRST.

MEASUREMENTS: Functional status: summed activity of daily living (ADL) and instrumental activity of daily living (IADL) scores at baseline, 30 days, and 120 days. Self‐perceived physical health: standardized physical health component of the Medical Outcomes Study 36‐Item Short‐Form Health Survey (SF‐36). Functional decline: loss of one or more ADLs and one or more IADLs from ED baseline at 30 and 120 days. Decline in self‐perceived physical health: follow‐up SF‐36 standardized physical health component scores four or more points lower than baseline.

RESULTS: TRST scores correlated with baseline ADL impairments, IADL impairments, and self‐perceived physical health at all endpoints (P<.001). A TRST score of two or more was moderately predictive of decline in ADLs or IADLs (30‐day ADL area under the receiver operating characteristic curve (AUC)=0.64; 95% confidence interval (CI)=0.56–0.72; 120‐day ADL AUC=0.66; 95% CI=0.58–0.74) but not perceived physical health.

CONCLUSION: The TRST identifies baseline functional impairment in older ED patients and is moderately predictive of subsequent functional decline after an initial ED visit. The TRST provides a valid proxy measure for assessing functional status in the ED and may be useful in identifying high‐risk patients who would benefit from referrals for further evaluation or surveillance upon ED discharge.
The Etiology of the Occurrence of En Banc Review in the U.S. Court of Appeals
Authors: Giles Micheal W. , Hettinger Virginia A. , Zorn Christopher , Peppers Todd C.
Published: June 2007

The U.S. Courts of Appeals, working principally through three‐judge panels, constitute important final arbiters of the meaning of the federal constitution, laws, and regulations and, hence, significant policymakers within the federal system. En banc rehearing—reconsideration of the decision of a three‐judge panel by the full complement of judges appointed to the circuit—is an institutional device that ensures circuit decisions are in line with the established preferences of the circuit. The use of en banc varies in frequency across circuits and within circuits over time. Drawing on legal, attitudinal, and strategic perspectives of judicial behavior, we develop and test a set of integrated expectations regarding the causes of this variation. Our analysis finds support for the operation of all three models and suggests that the influence of ideology on the use of en banc in the recent era is not unique but part of a long‐standing pattern.
Strategic Party Government: Party Influence in Congress, 1789–2000
Authors: Lebo Matthew J. , McGlynn Adam J. , Koger Gregory
Published: June 2007

Why does the influence of Congressional parties fluctuate over time? Building on prevailing answers, we develop a model, Strategic Party Government, which highlights the electoral motives of legislative parties and the strategic interaction between parties. We test this theory using the entire range of House and Senate party behavior from 1789 to 2000 and find that the strategic behavior of parties complements members' preferences as an explanation for variation in party influence. Specifically, the strongest predictors of one party's voting unity are the unity of the opposing party and the difference between the parties in the preceding year. Moreover, we find strong links between party behavior in Congress and electoral outcomes: an increase in partisan influence on legislative voting has adverse electoral costs, while winning contested votes has electoral benefits.
Elections and Activist Coalitions in the United States
Authors: Schofield Norman , Miller Gary
Published: June 2007

Formal models of voting have emphasizd the mean voter theorem, that all parties should rationally adopt identical positions at the electoral mean. The lack of evidence for this assertion is a paradox or contradiction in need of resolution. This article attempts to resolve this paradox by considering an electoral model that includes “valence” or nonpolicy judgements by voters of party leaders. The theorem is used to suggest that Republican success depends on balancing the opposed demands of economic and social conservatives. Democrat success in future elections resides in overcoming the policy demands of economic liberals and gaining support from cosmopolitans—the socially liberal but economically conservative potential supporters of the party.
Disputes, Democracies, and Dependencies: A Reexamination of the Kantian Peace
Authors: Ward Michael D. , Siverson Randolph M. , Cao Xun
Published: June 2007

Militarized interstate disputes are widely thought to be less likely among democratic countries that have high levels of trade and extensive participation in international organizations. We reexamine this broad finding of the Kantian peace literature in the context of a model that incorporates the high degree of dependency among countries. Based on in‐sample statistical tests, as well as out‐of‐sample, predictive cross‐validation, we find that results frequently cited in the literature are plagued by overfitting and cannot be characterized as identifying the underlying structure through which international conflict is influenced by democracy, trade, and international governmental organizations. We conclude that much of the statistical association typically reported in this literature apparently stems from three components: (1) geographical proximity, (2) dependence among militarized interstate disputes with the same initiator or target, and (3) the higher‐order dependencies in these dyadic data. Once these are incorporated, covariates associated with the Kantian peace tripod lose most of their statistical power. We do find that higher levels of joint democracy are associated with lower probabilities of militarized interstate dispute involvement. We find that despite high statistical significance and putative substantive importance, none of the variables representing the Kantian tripod is associated with any substantial degree of predictive power.
Region, Local Context, and Voting at the 1997 General Election in England
Authors: Johnston Ron , Jones Kelvyn , Propper Carol , Burgess Simon
Published: June 2007

There has been considerable debate in recent work on voting patterns in Great Britain regarding the importance of regional effects: are these “real” or are they simply statistical artifacts of decision‐making processes at smaller spatial scales which are aggregated up to the regional scale if not incorporated directly into any modeling? Using a multilevel model design, this article reports on analyses of survey data for the 1997 general election in England which allows tests of whether regional variations are no more than aggregation effects. Individual voters are nested within households, neighborhoods, constituencies, and regions and when all of the smaller‐scale spatial levels are included in the model, the observed regional effects are statistically insignificant. At the 1997 general election, at least, regional variations within England in support for the three main parties—basically, a north‐south divide—are aggregation effects.
An Experimental Template for Case Study Research
Authors: Gerring John , McDermott Rose
Published: June 2007

Methods are usually classified as either “experimental” or “observational,” a dichotomy that has governed social science research for centuries. By implication, this dichotomization precludes a consideration of experimental strategies in case study work. Yet, we argue that one gains purchase on the tasks of research design by integrating the criteria traditionally applied to experimental work to all research in the social sciences—including case study work, the focus of this article. Experimental research designs aim to achieve variation through time and across space while maintaining ceteris paribus assumptions, thus maximizing leverage into the fundamental problem of causal inference. We propose to capture these multiple criteria in a four‐fold typology: (1) A Dynamic comparison mirrors laboratory experimentation through the use of both temporal and spatial variation; (2) A Longitudinal comparison employs temporal variation; (3) A Spatial comparison exploits variation through space; and (4) A Counterfactual comparison relies on imagined comparison. All comparison case study research designs can be slotted into one of these four categories. Moreover, the typology illustrates in a concise fashion the ways in which case study research designs attempt to mimic the virtues of experimental design and the degree to which they succeed. The classic experiment, with manipulated treatment and randomized control, thus provides a useful template for discussion about methodological issues in experimental and observational contexts.
Roles of P-Glycoprotein, Bcrp, and Mrp2 in Biliary Excretion of Spiramycin in Mice
Authors: Tian Xianbin , Li Jun , Zamek-Gliszczynski Maciej J. , Bridges Arlene S. , Zhang Peijin , Patel Nita J. , Raub Thomas J. , Pollack Gary M. , Brouwer Kim L. R.
Published: June 2007

The multidrug resistance proteins P-glycoprotein (P-gp), breast cancer resistance protein (Bcrp), and multidrug resistance-associated protein 2 (Mrp2) are the three major canalicular transport proteins responsible for the biliary excretion of most drugs and metabolites. Previous in vitro studies demonstrated that P-gp transported macrolide antibiotics, including spiramycin, which is eliminated primarily by biliary excretion. Bcrp was proposed to be the primary pathway for spiramycin secretion into breast milk. In the present study, the contributions of P-gp, Bcrp, and Mrp2 to the biliary excretion of spiramycin were examined in single-pass perfused livers of male C57BL/6 wild-type, Bcrp-knockout, and Mrp2-knockout mice in the presence or absence of GF120918 (GW918), a P-gp and Bcrp inhibitor. Spiramycin was infused to achieve steady-state conditions, followed by a washout period, and parameters governing spiramycin hepatobiliary disposition were recovered by using pharmacokinetic modeling. In the absence of GW918, the rate constant governing spiramycin biliary excretion was decreased in Mrp2
−
knockout mice (0.0013 ± 0.0009 min
−1
) relative to wild-type mice (0.0124 ± 0.0096 min
−1
). These data are consistent with the ∼8-fold decrease in the recovery of spiramycin in the bile of Mrp2-knockout mice and suggest that Mrp2 is the major canalicular transport protein responsible for spiramycin biliary excretion. Interestingly, biliary recovery of spiramycin in Bcrp-knockout mice was increased in both the absence and presence of GW918 compared to wild-type mice. GW918 significantly decreased the rate constant for spiramycin biliary excretion and the rate constant for basolateral efflux of spiramycin. In conclusion, the biliary excretion of spiramycin in mice is mediated primarily by Mrp2 with a modest P-gp component.
In Vitro Selection and Characterization of Human Immunodeficiency Virus Type 2 with Decreased Susceptibility to Lopinavir
Authors: Masse Sherie , Lu Xiaozhi , Dekhtyar Tatyana , Lu Liangjun , Koev Gennadiy , Gao Feng , Mo Hongmei , Kempf Dale , Bernstein Barry , Hanna George J. , Molla Akhteruzzaman
Published: June 2007

Lopinavir (LPV)-ritonavir has demonstrated durable antiviral activity in human immunodeficiency virus type 1 (HIV-1)-infected antiretroviral-naïve and protease inhibitor (PI)-experienced patients. However, information on LPV activity against HIV-2 and the patterns of mutations in HIV-2 in response to selection by LPV is limited. The activity of LPV against three strains of HIV-2 was assessed and compared to activity against a reference HIV-1 strain. LPV demonstrated activity similar to that observed against HIV-1 in two HIV-2 strains (HIV-2MSand HIV-2CBL-23) tested. On the other hand, approximately 10-fold-reduced susceptibility was observed with the third HIV-2 strain, HIV-2CDC310319. Passage of HIV-2MSwith increasing concentrations of LPV selected mutations V47A and D17N in the HIV-2 protease gene. The introduction of both 17N and 47A either individually or together into HIV-2RODmolecular infectious clones showed that the single V47A substitution in HIV-2 resulted in a substantial reduction in susceptibility to LPV. In contrast, this mutant retained wild-type susceptibility to other PIs and appeared to be hypersusceptible to atazanavir and saquinavir.
Tetracyclines as an Oral Treatment Option for Patients with Community Onset Skin and Soft Tissue Infections Caused by Methicillin-ResistantStaphylococcus aureus
Authors: Ruhe Jörg J. , Menon Anupama
Published: June 2007

Few data exist on the clinical utility of the expanded-spectrum tetracyclines doxycycline and minocycline for the treatment of community-associated methicillin-resistantStaphylococcus aureus(MRSA) skin and soft tissue infections (SSTI). We performed a retrospective cohort study of 276 patients who presented with 282 episodes of MRSA SSTI to the emergency room or outpatient clinic at two tertiary medical centers between October 2002 and February 2007. The median percentage of patients infected with MRSA strains that were susceptible to tetracycline was 95%. Time zero was defined as the time of the first incision and drainage procedure or, if none was performed, the time of the first positive wound culture. The median patient age was 48 years. Abscesses constituted the majority of clinical presentations (75%), followed by furuncles or carbuncles (13%) and cellulitis originating from a purulent focus of infection (12%). A total of 225 patients (80%) underwent incision and drainage. Doxycycline or minocycline was administered in 90 episodes (32%); the other 192 SSTI were treated with β-lactams. Treatment failure, defined as the need for a second incision and drainage procedure and/or admission to the hospital within at least 2 days after time zero, was diagnosed in 28 episodes (10%) at a median of 3 days after time zero. On logistic regression analysis, receipt of a β-lactam agent was the only clinical characteristic associated with treatment failure (adjusted odds ratio, 3.94; 95% confidence interval, 1.28 to 12.15;P= 0.02). The expanded-spectrum tetracyclines appear to be a reasonable oral treatment option for patients with community onset MRSA SSTI in areas where MRSA strains are susceptible to the tetracyclines.
Differential Fungicidal Activities of Amphotericin B and Voriconazole against
Aspergillus
Species Determined by Microbroth Methodology
Authors: Meletiadis Joseph , Antachopoulos Charalampos , Stergiopoulou Theodouli , Pournaras Spyros , Roilides Emmanuel , Walsh Thomas J.
Published: June 2007

Antifungal agents may differ in their fungicidal activities against
Aspergillus
spp. In order to compare the fungicidal activities of voriconazole and amphotericin B against 40 isolates of
Aspergillus fumigatus
,
A. flavus
, and
A. terreus
, we developed a new microbroth colorimetric method for assessing fungicidal activities and determining minimal fungicidal concentrations (MFCs). This methodology follows the antifungal susceptibility testing reference method M-38A for MIC determination. After drug removal and addition of fresh medium, growth of viable conidia adhering to the bottoms of the microtitration wells was assessed by a colorimetric assay of metabolic activity after 24 h of incubation. The new method was faster (six times), reproducible (92 to 97%), and in agreement with culture-based MFCs (91 to 100%). Differential fungicidal activities of voriconazole and amphotericin B were found among the three
Aspergillus
species, with
A. fumigatus
and
A. flavus
having the lowest (1 and 2 mg/liter, respectively) and
A. terreus
the highest (>16 mg/liter) median amphotericin B MFCs;
A. flavus
had a lower median voriconazole MFC (4 mg/liter) than the other species (>8 mg/liter;
P
< 0.05). Amphotericin B was fungicidal (MFC/MIC ≤ 4) against all
A. fumigatus
and
A. flavus
isolates but no
A. terreus
isolates, whereas voriconazole was fungicidal against 82% of
A. flavus
isolates and fungistatic (MFC/MIC > 4) against 94% of
A. fumigatus
and 84% of
A. terreus
isolates. The new methodology revealed a concentration-dependent sigmoid pattern of fungicidal effects, indicating that fungicidal activity is not an all-or-nothing phenomenon and that some degree of fungicidal action can be found even for agents considered fungistatic based on the MFC/MIC ratio.
Safety and Pharmacokinetics of Bevirimat (PA-457), a Novel Inhibitor of Human Immunodeficiency Virus Maturation, in Healthy Volunteers
Authors: Martin David E. , Blum Robert , Wilton John , Doto Judy , Galbraith Hal , Burgess Gina L. , Smith Philip C. , Ballow Charles
Published: June 2007

Bevirimat (BVM; formerly known as PA-457) is a novel inhibitor of human immunodeficiency virus (HIV) maturation that is being developed for the treatment of HIV infection. The pharmacokinetics of this agent in healthy male volunteers were studied in a randomized, double-blind study in which the participants received single oral doses of placebo (
n
= 8) or escalating doses of BVM at 25, 50, 100, or 250 mg (
n
= 6 per dose); escalation was performed only after the pharmacokinetics and safety of the preceding dose had been evaluated. Plasma was collected over 480 h after dosing and urine was collected over 48 h after dosing for determination of the values of pharmacokinetic parameters. BVM was well absorbed after oral administration, with peak plasma concentrations being achieved 1 to 3 h after dosing. The half-life was 60 to 80 h. The exposure assessed by determination of the peak concentration and the area under the concentration-time curve was dose proportional. Single oral doses of BVM were well tolerated: there were no dose-limiting toxicities, and no serious adverse events were reported. These findings suggest that that BVM offers a favorable pharmacokinetic profile, with predictable pharmacokinetics following the oral administration of single doses. The long half-life of BVM may facilitate once-daily dosing.
Colistin Methanesulfonate against Multidrug-Resistant
Acinetobacter baumannii
in an In Vitro Pharmacodynamic Model
Authors: Kroeger Lisa A. , Hovde Laurie B. , Mitropoulos Isaac F. , Schafer Jeremy , Rotschafer John C.
Published: June 2007

Using an in vitro pharmacodynamic model, a multidrug-resistant strain of
Acinetobacter baumannii
was exposed to colistin methanesulfonate alone and in combination with ceftazidime. Pre- and postexposure colistin sulfate MICs were determined. A single daily dose of colistin methanesulfonate combined with continuous-infusion ceftazidime prevented regrowth and postexposure MIC increases.
In Vivo Efficacy of Moxifloxacin Compared with Cloxacillin and Vancomycin in a
Staphylococcus aureus
Rabbit Arthritis Experimental Model
Authors: Grossi Olivier , Caillon Jocelyne , Arvieux Cedric , Jacqueline Cedric , Bugnon Denis , Potel Gilles , Hamel Antoine
Published: June 2007

We investigated the efficacies of moxifloxacin, cloxacillin, and vancomycin in a rabbit model of
Staphylococcus aureus
arthritis. No significant difference between therapeutic regimens was observed after a 7-day treatment. Oral moxifloxacin could be a suitable alternative to standard parenteral therapy for
S. aureus
arthritis.
Pharmacokinetics of Aztreonam in Healthy Subjects and Patients with Cystic Fibrosis and Evaluation of Dose-Exposure Relationships Using Monte Carlo Simulation
Authors: Vinks Alexander A. , van Rossem Ronald N. , Mathôt Ron A. A. , Heijerman Harry G. M. , Mouton Johan W.
Published: June 2007

Aztreonam (AZM) is a monobactam antibiotic with a high level of activity against gram-negative micro-organisms, including
Pseudomonas aeruginosa
. We evaluated AZM pharmacokinetics and pharmacokinetic-pharmacodynamic relationships in patients with cystic fibrosis (CF) and healthy subjects. Pharmacokinetic data in eight CF patients and healthy subjects that were matched for age, gender, weight, and height were obtained and analyzed by using the nonparametric adaptive grid algorithm. Probabilities of target attainment using percentages of time of unbound concentration above the MIC (
f
T>MIC) were obtained by using a Monte Carlo simulation. AZM total body clearance was significantly higher in CF patients (100.1 ± 17.1 versus 76.2 ± 7.4 ml/min in healthy subjects;
P
< 0.01). The pharmacokinetic parameter estimates for terminal half-life (1.54 ± 0.17 h [mean ± the standard deviation]) and volume of distribution (0.20 ± 0.02 liters/kg in patients with CF patients were not different from those in healthy subjects. Monte Carlo simulations with a target of a
f
T>MIC of 50 to 60% at a dose of 1,000 mg every 8 h indicated a clinical breakpoint of 4 mg/liter and 1 to 2 mg/liter for healthy subjects and CF patients, respectively. This study using matched controls showed that AZM total body clearance and not the volume of distribution is higher in CF patients as a result of increased renal clearance. Pharmacokinetic parameter estimates in healthy subjects resulted in a clinical susceptibility breakpoint of ≤4 mg/liter for a dose of 1,000 mg every 8 h. Patients suspected of having high clearance rates, such as CF patients, should be monitored closely, with dosing regimens adjusted accordingly.
Concentration-Effect Relationship of Ceftazidime Explains Why the Time above the MIC Is 40 Percent for a Static Effect In Vivo
Authors: Mouton Johan W. , Punt Nieko , Vinks Alexander A.
Published: June 2007

Growth-kill dynamics were characterized in vitro, and the parameter estimates were used to simulate bacterial growth and kill in vivo using both mouse and human pharmacokinetics. The parameter estimates obtained in vitro predicted a time above the MIC of between 35 and 38% for a static effect in mice after 24 h of treatment.
Molecular Characterization of
Staphylococcus aureus
Isolates from a 2005 Clinical Trial of Uncomplicated Skin and Skin Structure Infections
Authors: Jones Ronald N. , Nilius Angela M. , Akinlade Bolanle K. , Deshpande Lalitagauri M. , Notario Gerard F.
Published: June 2007

A clinical trial of uncomplicated skin and skin structure infections (39 locations in 19 states) observed that community-associated or community-onset methicillin-resistant
Staphylococcus aureus
(CO-MRSA) represented 23% of all pathogens at baseline culture and 53% of 190
S. aureus
isolates. CO-MRSA strains typically were Panton-Valentine leukocidin (PVL) positive (95%), contained staphylococcal cassette chromosome
mec
type IVa (99%), were USA300 or USA400 clones (92%), and exhibited minimal coresistances (macrolides and/or fluoroquinolones). Clinical results remained identical (89% cures) regardless of the antimicrobial used or CO-MRSA molecular patterns, PVL production, or antimicrobial susceptibility profiles.
Identification and Characterization of Small Molecules That Inhibit Intracellular Toxin Transport
Authors: Saenz Jose B. , Doggett Teresa A. , Haslam David B.
Published: June 2007

Shiga toxin (Stx), cholera toxin (Ctx), and the plant toxin ricin are among several toxins that reach their intracellular destinations via a complex route. Following endocytosis, these toxins travel in a retrograde direction through the endosomal system to the
trans
-Golgi network, Golgi apparatus, and endoplasmic reticulum (ER). There the toxins are transported across the ER membrane to the cytosol, where they carry out their toxic effects. Transport via the ER from the cell surface to the cytosol is apparently unique to pathogenic toxins, raising the possibility that various stages in the transport pathway can be therapeutically targeted. We have applied a luciferase-based high-throughput screen to a chemical library of small-molecule compounds in order to identify inhibitors of Stx. We report two novel compounds that protect against Stx and ricin inhibition of protein synthesis, and we demonstrate that these compounds reversibly inhibit bacterial transport at various stages in the endocytic pathway. One compound (compound 75) inhibited transport at an early stage of Stx and Ctx transport and also provided protection against diphtheria toxin, which enters the cytosol from early endosomes. In contrast, compound 134 inhibited transport from recycling endosomes through the Golgi apparatus and protected only against toxins that access the ER. Small-molecule compounds such as these will provide insight into the mechanism of toxin transport and lead to the identification of compounds with therapeutic potential against toxins routed through the ER.
Transcriptional Regulation of the Heme Binding Protein Gene Family of
Bartonella quintana
Is Accomplished by a Novel Promoter Element and Iron Response Regulator
Authors: Battisti James M. , Smitherman Laura S. , Sappington Kate N. , Parrow Nermi L. , Raghavan Rahul , Minnick Michael F.
Published: June 2007

We previously identified a five-member family of hemin-binding proteins (Hbp's) of
Bartonella quintana
that bind hemin on the outer surface but share no homology with known bacterial heme receptors. Subsequently, we demonstrated that expression of the
hbp
family is significantly influenced by oxygen, heme, and temperature conditions encountered by the pathogen in the human host and the body louse vector; e.g., we observed a dramatic (>100-fold) increase in
hbpC
transcript levels in response to the “louse-like” temperature of 30°C. The goal of the present study was to identify a transcription factor(s) involved in the coordinated and differential regulation of the
hbp
family. First, we used quantitative real-time PCR (qRT-PCR) to show that the same environmental conditions generate parallels in the transcript profiles of four candidate transcriptional regulators (Irr, Fur, RirA, and BatR) described in the order
Rhizobiales
, with the greatest overall change in the transcription of
irr
(a >5-fold decrease) at a “louse-like” temperature, suggesting that Irr may function as an
hbpC
repressor. Second, a
B. quintana
strain hyperexpressing Irr was constructed; it exhibits a “bloodstream-like”
hbp
transcript profile in the absence of an environmental stimulus (i.e.,
hbpC
is repressed and
hbpA
,
hbpD
, and
hbpE
mRNAs are relatively abundant). Furthermore, when this strain is grown at a “louse-like” temperature, an inversion of the transcript profile occurs, where derepression of
hbpC
and repression of
hbpA
,
hbpD
, and
hbpE
are readily evident, strongly suggesting that Irr and temperature influence
hbp
family expression. Third, electrophoretic mobility shift analyses show that recombinant Irr binds specifically to the
hbpC
promoter region at a sequence that is highly conserved in
Bartonella hbp
genes, which we designated the
hbp
family box, or “H-box.” Fourth, we used the H-box to search the
B. quintana
genome and discovered a number of intriguing open reading frames, e.g., five members of a six-member family of cohemolysin autotransporters. Finally, qRT-PCR data regarding the effects of Fur and RirA overexpression on the
hbp
family are provided; they show that Fur's effect on the
hbp
family is relatively minor but RirA generates a “bloodstream-like”
hbp
transcript profile in the absence of an environmental stimulus, as observed for the Irr-hyperexpressing strain.
SalY of theStreptococcus pyogenesLantibiotic Locus Is Required for Full Virulence and Intracellular Survival in Macrophages
Authors: Phelps Hilary A. , Neely Melody N.
Published: June 2007

Streptococcus pyogenesutilizes numerous mechanisms for evading the host immune response but has only recently been found to survive in the intracellular environment. In this study, we demonstrate the requirement of a putative ABC transporter permease for intracellular survival in macrophages. The highly attenuatedS. pyogenesmutant, SalY, was identified from a transposon mutagenesis screen, with over 200-fold attenuation in virulence in a zebrafish invasive-disease model. Sequencing of the region surrounding the insertion identified a locus that is highly conserved in otherS. pyogenesgenomes and is homologous to an operon involved in lantibiotic production. In vitro analysis demonstrated that the SalY mutant is deficient in intracellular survival in murine macrophages, a phenotype also observed in zebrafish macrophages in vivo. Macrophage crude cell lysates added to bacterial cultures resulted in the death of the SalY mutant but only growth inhibition of the wild-type strain. Specific depletion of zebrafish macrophages in vivo restored the ability of the SalY mutant to cause disease to wild-type levels. The SalY-infected, macrophage-depleted zebrafish exhibit large lesions and invasive dissemination at a rate and level similar to those of the wild type. In contrast, an M protein mutant with a degree of attenuation similar to that of the SalY mutant did not regain full virulence by in vivo depletion of macrophages. The putative SalY ABC transporter may be an example of the ability ofS. pyogenesto adapt and evolve new survival strategies that allow dissemination and growth in previously uninhabitable sites.
Lipid A Modification Systems in Gram-Negative Bacteria
Authors: Raetz Christian R.H. , Reynolds C. Michael , Trent M. Stephen , Bishop Russell E.
Published: June 2007

The lipid A moiety of lipopolysaccharide forms the outer monolayer of the outer membrane of most gram-negative bacteria. Escherichia coli lipid A is synthesized on the cytoplasmic surface of the inner membrane by a conserved pathway of nine constitutive enzymes. Following attachment of the core oligosaccharide, nascent core-lipid A is flipped to the outer surface of the inner membrane by the ABC transporter MsbA, where the O-antigen polymer is attached. Diverse covalent modifications of the lipid A moiety may occur during its transit from the outer surface of the inner membrane to the outer membrane. Lipid A modification enzymes are reporters for lipopolysaccharide trafficking within the bacterial envelope. Modification systems are variable and often regulated by environmental conditions. Although not required for growth, the modification enzymes modulate virulence of some gram-negative pathogens. Heterologous expression of lipid A modification enzymes may enable the development of new vaccines.
Subcutaneous adipose tissue exerts proinflammatory cytokines after minimal trauma in humans
Authors: Pachler Christoph , Ikeoka Dimas , Plank Johannes , Weinhandl Heinz , Suppan Maria , Mader Julia K. , Bodenlenz Manfred , Regittnig Werner , Mangge Harald , Pieber Thomas R. , Ellmerer Martin
Published: June 2007

Inflammatory cytokines released from adipose tissue play an important role in different pathological processes. In the present study, we investigated the inflammatory cytokine response of human subcutaneous adipose tissue (SAT) by applying the open-flow microperfusion technique. Four standard 18-gauge microperfusion catheters were inserted into periumbilical SAT of eight healthy male volunteers [29 ± 3 yr, BMI 24.3 ± 1.9 (mean ± SD)]. SAT probe effluents were collected at 60-min intervals for 8 h after catheter insertion. Different perfusion fluids were used to measure the local effect of insulin and/or glucose on the cytokine response. SAT probe effluents were analyzed for IL-1β, IL-6, CXCL8 (IL-8), and TNF-α. SAT concentrations of IL-1β increased 100-fold from 1.0 ± 0.2 pg/ml (mean ± SE) to 101.5 ± 23.2 pg/ml ( P < 0.001) after 8 h. A 130-fold increase was observed for CXCL8, from 49 ± 29 to 6,554 ± 1,713 pg/ml ( P < 0.001). Furthermore, a 20-fold increase of IL-6 was observed within the first 5 h (from 159 ± 123 to 3,554 ± 394 pg/ml; P < 0.001), and a significant decline to 2,154 ± 216 pg/ml ( P < 0.01) was seen thereafter. Finally, TNF-α increased from 1.4 ± 0.6 to 2.5 ± 0.5 pg/ml ( P < 0.05) in hour 2 and remained stable thereafter. Local administration of insulin exerted a stimulatory effect on the inflammatory response of IL-6. In conclusion, SAT exerts a highly reproducible and consistent proinflammatory cytokine response after minimally invasive trauma caused by the insertion of a catheter in humans.
Statistical Convergence of Double Sequences on Probabilistic Normed Spaces
Authors: Karakus S. , Demırcı K.
Published: June 2007

The concept of statistical convergence was presented by Steinhaus in 1951. This concept was extended to the double sequences by Mursaleen and Edely in 2003. Karakus has recently introduced the concept of statistical convergence of ordinary (single) sequence on probabilistic normed spaces. In this paper, we define statistical analogues of convergence and Cauchy for double sequences on probabilistic normed spaces. Then we display an exampl e such that our method of convergence is stronger than usual convergence on probabilistic normed spaces. Also we give a useful characterization for statistically convergent double sequences.
Model‐Based Reconstructive Elasticity Imaging Using Ultrasound
Authors: Aglyamov Salavat R. , Skovoroda Andrei R. , Xie Hua , Kim Kang , Rubin Jonathan M. , O′Donnell Matthew , Wakefield Thomas W. , Myers Daniel , Emelianov Stanislav Y.
Published: June 2007

Elasticity imaging is a reconstructive imaging technique where tissue motion in response to mechanical excitation is measured using modern imaging systems, and the estimated displacements are then used to reconstruct the spatial distribution of Young′s modulus. Here we present an ultrasound elasticity imaging method that utilizes the model‐based technique for Young′s modulus reconstruction. Based on the geometry of the imaged object, only one axial component of the strain tensor is used. The numerical implementation of the method is highly efficient because the reconstruction is based on an analytic solution of the forward elastic problem. The model‐based approach is illustrated using two potential clinical applications: differentiation of liver hemangioma and staging of deep venous thrombosis. Overall, these studies demonstrate that model‐based reconstructive elasticity imaging can be used in applications where the geometry of the object and the surrounding tissue is somewhat known and certain assumptions about the pathology can be made.
General Symmetric Starter of Orthogonal Double Covers of Complete Bipartite Graph
Authors: El-Shanawany R. A. , Higazy M. Sh.
Published: June 2007

An orthogonal double cover (ODC) of the complete graph is a collection of graphs such that every two of them share exactly one edge and every edge of the complete graph belongs to exactly two of the graphs. In this paper, we consider the case where the graph to be covered twice is the complete bipartite graphKmn,mn(for any values ofm,n) and all graphs in the collection are isomorphic to certain spanning subgraphs. Furthermore, the ODCs ofKn,nby certain disjoint stars are constructed.
Quality Evaluation in Flexible Manufacturing Systems: A Markovian Approach
Authors: Li Jingshan , Huang Ningjian
Published: June 2007

The flexible manufacturing system (FMS) has attracted substantial amount of research effort during the last twenty years. Most of the studies address the issues of flexibility, productivity, cost, and so forth. The impact of flexible lines on product quality is less studied. This paper intends to address this issue by applying a Markov model to evaluate quality performance of a flexible manufacturing system. Closed expressions to calculate good part probability are derived and discussions to maintain high product quality are carried out. An example of flexible fixture in machining system is provided to illustrate the applicability of the method. The results of this study suggest a possible approach to investigate the impact of flexibility on product quality and, finally, with extensions and enrichment of the model, may lead to provide production engineers and managers a better understanding of the quality implications and to summarize some general guidelines of operation management in flexible manufacturing systems.
The Use of Cerami Sequences in Critical Point Theory
Authors: Schechter Martin
Published: June 2007

The concept of linking was developed to produce Palais-Smale (PS) sequencesG(uk)→a,G'(uk)→0forC1functionalsGthat separate linking sets. These sequences produce critical points if they have convergent subsequences (i.e., ifGsatisfies the PS condition). In the past, we have shown that PS sequences can be obtained even when linking does not exist. We now show that such situations produce more useful sequences. They not only produce PS sequences, but also Cerami sequences satisfyingG(uk)→a,(1+||uk||)G'(uk)→ 0as well. A Cerami sequence can produce a critical point even when a PS sequence does not. In this situation, it is no longer necessary to show thatGsatisfies the PS condition, but only that it satisfies the easier Cerami condition (i.e., that Cerami sequences have convergent subsequences). We provide examples and applications. We also give generalizations to situations when the separating criterion is violated.