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Comparisons of O- and K-antigenic types and serum sensitivity were carried out with 149 strains of Escherichia coli isolated from adults with bacteremia and 46 strains from neonates with bacteremia. O-antigenic types O6, O4, O2, O16, O18, and O7 were observed most frequently, but their relative prevalence did not differ materially between adult and neonatal bacteremias, A greater proportion of strains from neonatal bacteremia contained K1 antigen and were autoagglutinable compared with strains from adult bacteremia, although K1 was the most frequent K antigen found in strains from adults. K-antigen-containing strains did not appear to be associated with enhanced severity of bacteremia, but nontypable strains, autoagglutinable strains, and strains of O-antigenic types O4, O6, and O8 were associated with a greater frequency of shock and fatal outcome in adults. No differences could be detected between the serum sensitivities of E. coli isolated from adult bacteremia and those from neonatal bacteremia. K antigen did not affect serum sensitivity, but E. coli strains of O types O18, O2, O4, and O7 were more serum-resistant than other E. coli. Bacteremia caused by serum-sensitive E. coli was less often associated with shock and death than bacteremia caused by serum-resistant E. coli.

The antibody response to the infecting Escherichia coli strain, as well as the protective effect of antibodies to the O, K, and H antigens, was analyzed in rabbits with experimental hematogenous pyelonephritis. The rabbits were infected by intravenous injection of E. coli O6:K13:H1 after ligature of the left ureter for 24 hr. By hyperimmunization of different rabbits with E. coli O6:K2a,2c:H1, E. coli O22:K13:H1, and E. coli O2:K2ab:H1, it was possible to show that antibodies to O6 and K13 antigens, but not H1 antibodies, protected against the hematogenous pyelonephritis. By the indirect hemagglutination technique a marked antibody response to O6 after challenge was shown in all of the rabbits not pre-immunized with an O6-containing strain. Only a moderate antibody response to K13 (in some rabbits no response at all), was noted. The latter might be due to inadequate antigenic stimulation or to induction of tolerance in the rabbits.

Experimental, ascending acute pyelonephritis in rats was produced by injecting 0 x 5 ml of 10(9) bacteria/ml into the urinary bladder via the urethra. No traumatic manipulation of the ureters of kidneys was necessary. A grading system for kidney lesions based on macro- and microscopical examination was used. The capacity of different Escherichia coli and proteus strains to induce acute pyelonephritis was tested, and the E. coli 06K13H1 strain and the Proteus mirabilis 03H1 strain were especially capable of causing urinary tract infection. For the P. mirabilis 03H1 strain, a dominance of right kidney lesions was noted in contrast to the E. coli 06K13H1 strain which did not show any side preference.

Acute pyelonephritis (but not cystitis or “asymptomatic” bacteriuria) due to Escherichia coli induces serum antibodies to 0- but rarely to K-antigens, especially not to the most common antigen, Kl. Locally produced secretory IgA and IgG antibodies to 0- and K-antigens appear in urine during most infections. The E. coli in urine of patients with asymptomatic bacteriuria are different from those in patients with acute pyelonephritis and cystitis and undergo continuous changes, presumably caused by the local antibody response. The E. coli become less virulent and are less able to attach to uroepithelial cells than E. coli causing acute symptomatic infections. Antibodies in urine prevent epithelial adherence. Parenteral and intravesicular injections of killed bacteria can protect against ascending pyelonephritis in rats. A few K-antigens dominate among E. coli that cause urinary tract infections. Vaccination of problem cases is a possibility because of the protective nature of K-antibodies. The mechanism of renal scarring that appears in some patients with urinary tract infections is unknown. Autoantibodies to the Tamm-Horsfall protein that increase after acute pyelonephritis or the cross-reactions noted between certain E. coli and antigens on the kidney may be involved.

The properties of 709 strains of Escherichia coli isolated from feces of healthy schoolchildren were compared with those of 115 strains from the urine of girls with asymptomatic bacteriuria (ABU) detected in a screening program. These fecal strains were also compared with 45 strains that caused asymptomatic reinfections and 10 that caused symptomatic reinfections in the same group of girls. Typing of O antigen was done by direct bacterial agglutination, and K typing was done with a serum agar technique. Hemolytic capacity was assessed in solid medium. Sensitivity to the bactericidal effect of normal serum and minimal inhibitory concentrations of ampicillin were also determined. The strains isolated from girls who had reinfections of ABU were found to be a random sample of the fecal flora, but the strains from children with symptomatic reinfection were not. Strains from index patients with ABU differed from the other groups in a way that was indicative of adaptive changes in the structure of cell envelopes.

This chapter contains section titled: Methods Relations between Attachment in Vitro and Severity of UTI in Vivo Bacterial Adherence Properties Epithelial Cell Receptors Glycolipid Receptors Susceptibility to Urinary Tract Infection Antibacterial Agents and Attachment Conclusions References Discussion References

Emerging treatment options for hemophilia, including gene therapy, modified factor products, antibody‐based products, and other nonreplacement therapies, are in development or on their way to marketing authorization. For proof of efficacy, annual bleeding rates (ABRs) have become an increasingly important endpoint in hemophilia trials. We hypothesized that ABR analyses differ substantially between and within medicinal product classes and that the ABR observation period constitutes a major bias. For ABR characterization, an internal factor VIII (FVIII) treatment database has been built based on confidential clinical trial data submitted to the Paul‐Ehrlich‐Institut (PEI). Furthermore, anonymized data from 46 trial protocols submitted for review to the PEI were analyzed (FVIII replacement, n = 27; antibody‐based, n = 12; and gene therapy, n = 7) for methodology. Definitions of bleeding episodes and ABR observational periods differed substantially in clinical trials. In the initial observation phase, individual ABRs of patients, treated prophylactically for 1 year, vary by about 40% (P < 0.001), which finally led to a significant reduction of the ABR group mean by 20% (P < 0.05). Furthermore, the high variance in ABRs constitutes a major challenge in statistical analyses. In conclusion, considerable heterogeneity and bias in the ABR estimation in clinical trials was identified, which makes it substantially more difficult to compare the efficacy of different treatment regimens and products. Thus, awareness of the important pitfalls when using ABR as a clinical outcome is needed in the evaluation of hemophilia therapies for patients, physicians, regulators, and health technology assessment agencies.

The explosion of a type Ia supernova could be triggered either by accretion from a companion—which should be indicated by brightening caused by interaction of supernova ejecta with the companion—or by a merger with a white dwarf or other small star; here observations by the Kepler mission of three type Ia supernovae reveal no such brightening, leading to the conclusion that they were triggered by a merger. Type Ia supernovae are thought to be the result of a thermonuclear runaway in carbon/oxygen white dwarfs, but it is uncertain whether the explosion is triggered by accretion from a non-degenerate companion star or by a merger with another white dwarf. Observations of a supernova immediately following the explosion provide unique information on the distribution of ejected material 1 and the progenitor system. Models predict 2 that the interaction of supernova ejecta with a companion star or circumstellar debris lead to a sudden brightening lasting from hours to days. Here we present data for three supernovae that are likely to be type Ia observed during the Kepler mission 3 with a time resolution of 30 minutes. We find no signatures of the supernova ejecta interacting with nearby companions. The lack of observable interaction signatures is consistent with the idea that these three supernovae resulted from the merger of binary white dwarfs or other compact stars such as helium stars.

Shared decision-making (SDM) involves patients in choosing their treatment or care options. SDM enhances patient engagement and treatment satisfaction. SDM has proved difficult to implement and sustain in routine clinical practice, hence a supportive tool is needed. This quality improvement study focuses on the development of a generic tool, labeled SDM:KOMPASS, which is intended to support hospital settings by facilitating the visualization of their formative progress and the setting of goals for the SDM implementation into routine clinical practice. The main objective of the present paper is to describe the development of this generic tool. A six-step development process was performed to develop a tool and investigate the tool’s overall perceived usability. Qualitative methods, such as observations, individual and focus group interviews, provided insights. A 10-item quantitative survey gauged informants’ immediate attitudes towards the tool. Purposefully sampled informants (N = 20), including healthcare professionals and patients, contributed diverse perspectives regarding; 1) The tool’s readability and clarity, 2) the construct’s domains and content, and 3) the tool’s perceived usability. In alignment with real-world challenges, SDM:KOMPASS emerges as a potentially valuable resource for healthcare organizations embedding SDM. The six-step development process revealed how the tool SDM:KOMPASS has potential to enhance SDM implementation’s manageability, goal-setting, and focus. Professionals engaged in strategic implementation within somatic and mental hospital departments find the tool potentially beneficial and feasible. The tool shows promise and usability but requires careful attention due to its comprehensiveness. The next step is to alpha test the tool in clinical practice.

Shared decision-making (SDM) refers to the collaboration between patients and their healthcare providers to make clinical decisions based on evidence and patient preferences, often supported by patient decision aids (PDAs). This study explored practitioner experiences of SDM in a context where SDM has been successfully implemented. Specifically, we focused on practitioners' perceptions of SDM as a paradigm, factors influencing implementation success, and outcomes. We used a qualitative approach to examine the experiences and perceptions of 10 Danish practitioners at a cancer hospital experienced in SDM implementation. A semi-structured interview format was used and interviews were audio-recorded and transcribed. Data was analyzed through thematic analysis. Prior to SDM implementation, participants had a range of attitudes from skeptical to receptive. Those with more direct long-term contact with patients (such as nurses) were more positive about the need for SDM. We identified four main factors that influenced SDM implementation success: raising awareness of SDM behaviors among clinicians through concrete measurements, supporting the formation of new habits through reinforcement mechanisms, increasing the flexibility of PDA delivery, and strong leadership. According to our participants, these factors were instrumental in overcoming initial skepticism and solidifying new SDM behaviors. Improvements to the clinical process were reported. Sustaining and transferring the knowledge gained to other contexts will require adapting measurement tools. Applying SDM in clinical practice represents a major shift in mindset for clinicians. Designing SDM initiatives with an understanding of the underlying behavioral mechanisms may increase the probability of successful and sustained implementation.