Investigation of slowing down and charge-exchange of nickel and uranium ions in gases and solids in the energy range (60 - 200) MeV/u

In this thesis new slowing down and charge-state measurements will be presented in the energy range of (60 - 200) MeV/u. These measurements were done using the Fragment Separator (FRS) facility at GSI in Darmstadt. The presented data were taken during two experimental runs. The experiments were divided into two parts. In the first part a 200 MeV/u Ni27+ beam was used. The evolution of charge states as a function of the target thickness was investigated covering both the non-equilibrium and equilibrium region. This was done with various mono-atomic materials (Z2 = 6, 7, 10, 13, 18, 22) and compound materials (ethylene, polyethylene and polypropylene). From the measured charge-state distributions the one-electron ionization and capture cross sections have been extracted. A 40 % gas-solid difference is observed in the ionization cross sections for the mono-atomic materials. In the compound materials a 30 % difference is observed between ethylene and the polymers. The experimental cross sections for the mono-atomic materials have been compared with theoretical calculations [1, 2]. The theoretical ionization cross sections agree quite well with the corresponding experimental ionization cross sections. In the gaseous targets the agreement between experiment and theory is better than 3 %. For the capture cross sections the agreement between experiment and theory is also very good for the lighter target materials (Z2 <= 7). For the heavier targets large deviations up to one order of magnitude are observed. These deviations are due to the increasing importance of the non-radiative capture channel in heavier target materials which is quite difficult to calculate accurately. The results motivate for further refinement of the theory in this energy region. In the second part 3 different uranium beams were used with initial energies of 61 MeV/u (U86+ incident), 85 MeV/u (U73+ incoming) and 200 MeV/u (U81+ incident) to measure the evolution of the charge states again and the energy loss as a function of the target thickness in the same materials as used in the first part plus some additional mono-atomic materials Z2 = 29, 36, 47, 54. From the measured charge-state distributions and energy losses the mean charges and stopping forces have been extracted. At 61 MeV/u we observe a gas-solid difference in the mean charge of up to 4 charge states for the mono-atomic materials. The corresponding stopping powers (forces) at the same specific energy only show a gas-solid difference for light materials (Z2 <= 7). The stopping forces are compared with calculations done with the PASS code [3, 4], ATIMA code [5] and the Hubert et al. tables [6]. The agreement is quite good between experiment and theory. The PASS code predicts by using the experimental mean charges a gas-solid difference in the stopping force for the heavier target materials. In the data at 200 MeV/u there is a gas-solid difference in the ionization rate for U81+ ions similar to the Ni27+ results.In dieser Dissertation werden neue Ladungsverteilungen und Energieverlustmessungen präsentiert. Diese Messungen wurden am Fragment Separator (FRS) bei der GSI in Darmstadt durchgeführt. Die Daten, die hier vorgestellt werden, wurden in zwei Experimenten aufgenommen. Die Experimente bestanden aus zwei Teilen. Im ersten Teil wurde mit einem 200 MeV/u Ni27+ Strahl gemessen. Ziel dieser Messung war die Entwicklung der Ladungsverteilung als Funktion der Targetdicke vom Nichtgleichgewicht bis Gleichgewicht zu untersuchen. Dies wurde mit verschiedenen Targets gemacht (Z2 = 6, 7, 10, 13, 18, 22, Äthylen, Polyäthylen und Polypropylen). Von den gemessenen Ladungsverteilung konnten die Umladungsquerrschnitte für Elektroneneinfang und -verlust extrahiert werden. Ein Gas-Festkörper Effekt von 40 % wurde im Ionizationsquerrschnitt für die monoatomaren (reinen Elemente) Targets gemessen. Im Äthylen und den Polymeren (Polyäthylen und Polypropylen) war ein Effekt von 30 % zu sehen. Die experimentellen Umladungsquerrschnitte für die monoatomaren Targets wurden mit theoretischen Rechnungen von A. Surzhykov und S. Fritzsche [1] und V. P. Shevelko [2] verglichen. In der Ionization stimmen die theoretischen Rechnungen mit den experimentellen Werten gut überein. In den Gastargets ist die Übereinstimmung besser als 3 %. Im Elektroneneinfang gibt es gute Übereinstimmung zwischen Experiment und Theorie bei den leichten Targets (Z2 <= 7), bei den schweren Targets gibt es grosse Abweichungen bis zu einer Grössenordnung. Diese Abweichung kommt zustande, weil der nicht-radiative Querrschnitt einen grösseren Anteil hat bei den schweren Targets und dieser Teil sehr schwer theoretisch zu rechnen ist. Die Ergebnisse sind eine Motivation für Verbesserungen in der Theorie im diesen Energiebereich. Im zweiten Teil wurde ein Uranstrahl bei drei verschiedenen Energien benutzt, diese waren 61 MeV/u mit 86+ als Eingangsladungszustand, 85 MeV/u mit 73+ als Eingangsladungszustand und 200 MeV/u mit 81+ als Eingangsladungszustand. Ziel dieser Messung war es wiederum, die Entwicklung der Ladungsverteilung zu untersuchen und auch Energieverluste zu messen. Dieselben Targets wurden benutzt und zusätzlich wurden folgende Targets vermessen Z2 = 29, 36, 47, 54. Von den gemessenen Ladungsverteilungen und Energieverlusten wurde die mittlere Ladung und das Bremsvermögen bestimmt. Bei 61 MeV/u ist ein Gas-Festkörper Effekt in der mittleren Ladung bei den monoatomaren Targets zu sehen. Der Effekt hat eine Grösse von fast 4 Ladungen. Das dazu gehörige Bremsvermögen zeigt nur einen Gas-Festkörper Effekt bei den leichteren Targets (Z2 <= 7). Die experimentellen Werte wurden mit dem PASS Programm [3, 4], dem ATIMA Programm [5] und den Hubert et al. Tabellen [6] verglichen. Die theoretischen Rechnungen von den Programmen stimmen mit den experimentellen Werten gut überein. PASS sagt einen Gas-Festkörper Effekt bei den schwereren Targets voraus, weil experimentelle Ladungen als Eingangsparameter benutzt wurden. Bei der 200 MeV/u Messung wurde ein Gas-Festkörper Unterschied in der Ionizationsrate in der Entwicklung des U81+ Ladungszustand beobachtet, ähnlich wie in der Ni27+ Messung

Bloodstream infections in community hospitals in the 21st century: A multicenter cohort study

Background: While the majority of healthcare in the US is provided in community hospitals, the epidemiology and treatment of bloodstream infections in this setting is unknown. Methods and Findings: We undertook this multicenter, retrospective cohort study to 1) describe the epidemiology of bloodstream infections (BSI) in a network of community hospitals and 2) determine risk factors for inappropriate therapy for bloodstream infections in community hospitals. 1,470 patients were identified as having a BSI in 9 community hospitals in the southeastern US from 2003 through 2006. The majority of BSIs were community-onset, healthcare associated (n = 823, 56%); 432 (29%) patients had community-acquired BSI, and 215 (15%) had hospital-onset, healthcare-associated BSI. BSIs due to multidrug-resistant pathogens occurred in 340 patients (23%). Overall, the three most common pathogens were S. aureus (n = 428, 28%), E. coli (n = 359, 24%), coagulase-negative Staphylococci (n = 148, 10%), though type of infecting orgaism varied by location of acquisition (e.g., community-acquired). Inappropriate empiric antimicrobial therapy was given to 542 (38%) patients. Proportions of inappropriate therapy varied by hospital (median = 33%, range 21-71%). Multivariate logistic regression identified the following factors independently associated with failure to receive appropriate empiric antimicrobial therapy: hospital where the patient received care (p,0.001), assistance with $3 ADLs (p = 0.005), Charlson score (p = 0.05), community-onset, healthcare-associated infection (p = 0.01), and hospital-onset, healthcareassociated infection (p = 0.02). Important interaction was observed between Charlson score and location of acquisition. Conclusions: Our large, multicenter study provides the most complete picture of BSIs in community hospitals in the US to date. The epidemiology of BSIs in community hospitals has changed: community-onset, healthcare-associated BSI is most common, S. aureus is the most common cause, and 1 of 3 patients with a SI receives inappropriate empiric antimicrobial therapy. Our data suggest that appropriateness of empiric antimicrobial therapy is an important and needed performance metric for physicians and hospital stewardship programs in community hospitals

Carbapenemase-Encoding Gene Copy Number Estimator (CCNE): a Tool for Carbapenemase Gene Copy Number Estimation

Carbapenemase production is one of the leading mechanisms of carbapenem resistance in Gram-negative bacteria. An increase in carbapenemase gene (blaCarb) copies is an important mechanism of carbapenem resistance. No currently available bioinformatics tools allow for reliable detection and reporting of carbapenemase gene copy numbers. Here, we describe the carbapenemase-encoding gene copy number estimator (CCNE), a ready-to-use bioinformatics tool that was developed to estimate blaCarb copy numbers from whole-genome sequencing data. Its performance on Klebsiella pneumoniae carbapenemase gene (blaKPC) copy number estimation was evaluated by simulation and quantitative PCR (qPCR), and the results were compared with available algorithms. CCNE has two components, CCNE-acc and CCNE-fast. CCNE-acc detects blaCarb copy number in a comprehensive and high-accuracy way, while CCNE-fast rapidly screens blaCarb copy numbers. CCNE-acc achieved the best accuracy (100%) and the lowest root mean squared error (RMSE; 0.07) in simulated noise data sets, compared to the assembly-based method (23.4% accuracy, 1.697 RMSE) and the OrthologsBased method (78.9% accuracy, 0.395 RMSE). In the qPCR validation, a high consistency was observed between the blaKPC copy number determined by qPCR and that determined with CCNE. Reverse transcription-qPCR transcriptional analysis of 40 isolates showed that blaKPC expression was positively correlated with the blaKPC copy numbers detected by CCNE (P, 0.001). An association study of 357 KPC-producing K. pneumoniae isolates and their antimicrobial susceptibility identified a significant association between the estimated blaKPC copy number and MICs of imipenem (P, 0.001) and ceftazidime-avibactam (P, 0.001). Overall, CCNE is a useful genomic tool for the analysis of antimicrobial resistance genes copy number; it is available at https://github.com/biojiang/ccne

Positive follow-up blood cultures identify high mortality risk among patients with Gram-negative bacteraemia

Objectives: The role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk. Methods: An observational study with a prospectively enrolled cohort of adult inpatients with GNB was conducted at Duke University Health System from 2002 to 2015. FUBCs were defined as blood cultures performed from 24 hours to 7 days from initial positive blood culture. Results: Among 1702 patients with GNB, 1164 (68%) had FUBCs performed. When performed, FUBCs were positive in 20% (228/1113) of cases. FUBC acquisition was associated with lower all-cause in-hospital mortality (108/538, 20%, vs. 176/1164, 15%; p 0.01) and attributable in-hospital mortality (78/538, 15%, vs. 98/1164, 8%; p < 0.0001). Propensity score–weighted Cox proportional hazards models revealed that obtaining FUBCs was associated with reductions in all-cause (hazard ratio (HR) 0.629; 95% confidence interval (CI), 0.511–0.772; p < 0.0001) and attributable mortality (HR 0.628; 95% CI, 0.480–0.820; p 0.0007). Positive FUBCs were associated with increased all-cause mortality (49/228, 21%, vs. 110/885, 11%; p 0.0005) and attributable mortality (27/228, 12%, vs. 61/885, 7%; p 0.01) relative to negative FUBCs. Propensity score–weighted Cox proportional hazards models revealed that positive FUBCs were associated with increased all-cause (HR 2.099; 95% CI, 1.567–2.811; p < 0.0001) and attributable mortality (HR 1.800; 95% CI, 1.245–2.603; p 0.002). In a calibration analysis, a scoring system accurately identified patients at high risk of positive FUBCs. Conclusions: Rates of positive FUBCs were high and identified patients at increased risk for mortality. Clinical variables can identify patients at high risk for positive FUBCs. FUBCs should be considered in the management of GNB

Global differences in the management of Staphylococcus aureus bacteremia: no international standard of care

BackgroundDespite being the leading cause of mortality from bloodstream infections worldwide, little is known about regional variation in treatment practices for Staphylococcus aureus bacteremia (SAB). The aim of this study was to identify global variation in management, diagnostics, and definitions of SAB.MethodsDuring a 20-day period in 2022, physicians throughout the world were surveyed on SAB treatment practices. The survey was distributed through listservs, e-mails, and social media.ResultsIn total, 2031 physicians from 71 different countries on 6 continents (North America [701, 35%], Europe [573, 28%], Asia [409, 20%], Oceania [182, 9%], South America [124, 6%], and Africa [42, 2%]) completed the survey. Management-based responses differed significantly by continent for preferred treatment of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) bacteremia, use of adjunctive rifampin for prosthetic material infection, and use of oral antibiotics (P P –4 days of positive blood cultures, responses ranged from 2 days in 31% of European respondents to 7 days in 38% of Asian respondents (P ConclusionsLarge practice variations for SAB exist throughout the world, reflecting the paucity of high-quality data and the absence of an international standard of care for the management of SAB.Immunogenetics and cellular immunology of bacterial infectious disease

The association of female sex with management and mortality in patients with Staphylococcus aureus bacteraemia

Objectives: The association of biological female sex with outcome in patients with Staphylococcus aureus bacteraemia remains unresolved. The aim of this study was to determine the independent association of female sex with management and mortality in patients with S. aureus bacteraemia.Methods: This is a post hoc analysis of prospectively collected data from the S. aureus Bacteraemia Group Prospective Cohort Study. Adult patients with monomicrobial S. aureus bacteraemia at Duke University Medical Center were enrolled from 1994 to 2020. Univariable and multivariable Cox regression analyses were performed to assess differences in management and mortality between females and males.Results: Among 3384 patients with S. aureus bacteraemia, 1431 (42%) were women. Women were, as compared with men, more often Black (581/1431 [41%] vs. 620/1953 [32%], p < 0.001), haemodialysis dependent (309/1424 [22%] vs. 334/1940 [17%], p 0.001) and more likely to be infected with methicillinresistant S. aureus (MRSA) (697/1410 [49%] MRSA in women vs. 840/1925 [44%] MRSA in men, p 0.001). Women received shorter durations of antimicrobial treatment (median 24 [interquartile range 14-42] vs. 28 [interquartile range 14-45] days, p 0.005), and were less likely to undergo transesophageal echocardiography as compared with men (495/1430 [35%] vs. 802/1952 [41%], p < 0.001). Despite these differences, female sex was not associated with 90-day mortality in either univariable (388/1431 [27%] in women vs. 491/1953 [25%] in men, p 0.204) or multivariable analysis (adjusted hazard ratio for women 0.98 [95% CI, 0.85-1.13]).Discussion: Despite significant differences in patient characteristics, disease characteristics, and management, women and men with S. aureus bacteraemia have a similar mortality risk. Annette C. Westgeest, Clin Microbiol Infect 2023;29:1182Immunogenetics and cellular immunology of bacterial infectious disease

Influence of Vancomycin Minimum Inhibitory Concentration on the Outcome of Methicillin-Susceptible Staphylococcus aureus Left-Sided Infective Endocarditis Treated with Anti-staphylococcal Beta-Lactam Antibiotics; a Prospective Cohort Study by the International Collaboration on Endocarditis

Objectives: Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is ≥1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (≥1.5 mg/L) phenotype. Methods: All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal β-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (≥1.5 mg/L) or low (<1.5 mg/L). Isolates underwent spa typing to infer clonal complexes and multiplex PCR for identifying virulence genes. Univariate analysis was performed to evaluate the association between in-hospital and 1-year mortality, and vancomycin MIC phenotype. Results: Sixty-two cases met the inclusion criteria. Vancomycin MIC was low in 28 cases (45%) and high in 34 cases (55%). No significant differences in patient demographic data or characteristics of infection were observed between patients with infective endocarditis due to high and low vancomycin MIC isolates. Isolates with high and low vancomycin MIC had similar distributions of virulence genes and clonal lineages. In-hospital and 1-year mortality did not differ significantly between the two groups (32% (9/28) vs. 27% (9/34), p 0.780; and 43% (12/28) vs. 29% (10/34), p 0.298, for low and high vancomycin MIC respectively). Conclusions: In this international cohort of patients with left-sided MSSA endocarditis treated with antistaphylococcal β-lactams, vancomycin MIC phenotype was not associated with patient demographics, clinical outcome or virulence gene repertoire

China-United States Research Collaborations in Antimicrobial Resistance

A strong synergy can result from China-US antimicrobial resistance (AMR) collaborations given similarities and differences between their respective healthcare systems and research infrastructures. The Antibacterial Resistance Leadership Group has employed a model of realistic growth, starting with a feasible, relatively low-resource observational study in a critical priority pathogen. This and other observational studies will provide vital scientific information required for the rational design of future interventional trials. In addition, it provides a mutual, low-risk opportunity for determining the strengths and opportunities of the research collaboration. Issues identified during the observational studies can be addressed prior to the initiation of high-resource interventional studies. Collaborative clinical AMR studies between China and the United States have tremendous potential to decrease AMR rates, improve responsible antibiotic use, and ultimately improve the lives of patients in both countries

The Pitt Bacteremia Score Predicts Mortality in Nonbacteremic Infections

Background. Predicting mortality risk in patients is important in research settings. The Pitt bacteremia score (PBS) is commonly used as a predictor of early mortality risk in patients with bloodstream infections (BSIs). We determined whether the PBS predicts 14-day inpatient mortality in nonbacteremia carbapenem-resistant Enterobacteriaceae (CRE) infections. Methods. Patients were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and Other Enterobacteriaceae, a prospective, multicenter, observational study. We estimated risk ratios to analyze the predictive ability of the PBS overall and each of its components individually. We analyzed each component of the PBS in the prediction of mortality, assessed the appropriate cutoff value for the dichotomized score, and compared the predictive ability of the qPitt score to that of the PBS. Results. In a cohort of 475 patients with CRE infections, a PBS 4 was associated with mortality in patients with nonbacteremia infections (risk ratio [RR], 21.9 95% confidence interval [CI], 7.0, 68.8) and with BSIs (RR, 6.0 95% CI, 2.5, 14.4). In multivariable analysis, the hypotension, mechanical ventilation, mental status, and cardiac arrest parameters of the PBS were independent risk factors for 14-day all-cause inpatient mortality. The temperature parameter as originally calculated for the PBS was not independently associated with mortality. However, a temperature < 36.0° C vs 36° C was independently associated with mortality. A qPitt score 2 had similar discrimination as a PBS 4 in nonbacteremia infections. Conclusions. Here, we validated that the PBS and qPitt score can be used as reliable predictors of mortality in nonbacteremia CRE infections