From Indifference to Entrapment: The Netherlands and the Yugoslav Crisis, 1990-1995

A detailed analysis of the response to the Yugoslav crisis by one of America's key allies in NATO. The author focuses on the question of how a Western bureaucracy faced up to the most complex foreign policy challenge of the 1990s. The Netherlands, as a 'pocket-sized medium power', is an interesting case study. While the margins for Dutch foreign policy are limited, fate had it that the Netherlands occupied the European presidency during the second half of 1991, when the recognition issue divided the West and the parameters for the subsequent international intervention in the Balkans were set. By July 1995, the involvement of the Netherlands had deepened to the extent that Dutch troops who found themselves trapped in the UN safe area of Srebrenica together with the local Muslim population were unable to prevent the worst massacre in Europe since the Second World War. This study is based on interviews with all the major players, including two former Defence Ministers and two former Ministers of Foreign Affairs, and on documents from the Netherlands Ministry of Foreign Affairs, made available under the country's own 'freedom of information act'

From Indifference to Entrapment

A detailed analysis of the response to the Yugoslav crisis by one of America's key allies in NATO. The author focuses on the question of how a Western bureaucracy faced up to the most complex foreign policy challenge of the 1990s. The Netherlands, as a 'pocket-sized medium power', is an interesting case study. While the margins for Dutch foreign policy are limited, fate had it that the Netherlands occupied the European presidency during the second half of 1991, when the recognition issue divided the West and the parameters for the subsequent international intervention in the Balkans were set. By July 1995, the involvement of the Netherlands had deepened to the extent that Dutch troops who found themselves trapped in the UN safe area of Srebrenica together with the local Muslim population were unable to prevent the worst massacre in Europe since the Second World War. This study is based on interviews with all the major players, including two former Defence Ministers and two former Ministers of Foreign Affairs, and on documents from the Netherlands Ministry of Foreign Affairs, made available under the country's own 'freedom of information act'

Dynamic controlled atmosphere: A review of methods for monitoring fruit responses to low oxygen

The storage of fruit at minimum oxygen condition is crucial for optimal fruit quality maintenance. However, the optimal oxygen partial pressure of fruit varies according to several factors such as species, cultivar, harvest maturity, temperature, growing season and storage period. Based on these factors, storage technologies were developed that allow for the detection of the lower oxygen limit (LOL) and the storage of fruit under the lowest optimal oxygen partial pressure. One emerging technology is known as dynamic controlled atmosphere (DCA). Commercially, there are four DCA systems used: [1] DCA based on ethanol production and accumulation (DCA-Eth); [2] DCA based on chlorophyll fluorescence (DCA-CF); DCA based on the respiratory quotient (DCA-RQ) and [4] DCA based solely on CO2 production (DCA-CD). This reviews the recent developments of these DCA systems and their effect on fruit quality. Generally, the storage of fruit under DCA has a positive effect on the overall fruit quality, with regards to reduced physiological disorders and higher flesh firmness maintenance, when compared to controlled atmosphere (CA). Evidence also shows that storing fruit under DCA-RQ and DCA-CD allowed higher volatile compound emission and concentration, which can contribute positively to fruit flavor. The DCA systems are “green storage technologies” because the system enables the increase of storage temperature and thereby saving electrical energy. Storage of apples under DCA maintains an overall fruit quality similar to CA combined with the ripening inhibitor 1-Methylcyclopropen (1-MCP), which is an interesting option for organic fruit storage. Dynamic controlled atmosphere is a recently developed storage technique and is in constant improvement. The latest developed DCA techniques (DCA-RQ and DCA-CD), in contrast to DCA-CF, allow the use of extremely low oxygen levels. In the future, new and multi-sensor DCA systems are under development, which might not just control O2 partial pressure but also temperature and other parameters to allow for more energy efficient but high quality fruit storage systems

Antimicrobial Use in Pediatric Oncology and Hematology: Protocol for a Multicenter Point-Prevalence Study With Qualitative Expert Panel Assessment

Background: Because infections are a major driver of morbidity and mortality in children with hematologic or oncologic diseases, antimicrobials are frequently prescribed in pediatric oncology practice. However, excess or inappropriate use of antimicrobials is directly linked to the emergence of antimicrobial resistance. Although point-prevalence studies have examined the extent of antimicrobial use, a comprehensive qualitative evaluation of individual antimicrobial prescriptions remains lacking. Objective: The aim of this study is to identify appropriate versus inappropriate antimicrobial use among pediatric cancer patients in a point-prevalence study, followed by an expert panel adjudication process and a subsequent report of these findings to participating centers. This study also aims to improve the quality of patient care by informing centers about discrepancies between internal standards of care and national guidelines. Methods: Our point-prevalence study is performed at pediatric cancer centers in Germany and Austria. All patients under 18 years old who are hospitalized at the time of the study are included. As a supplement to the point-prevalence study, an expert panel is qualitatively assessing each of the antimicrobial prescriptions at the participating centers to review local guidelines and compare them with national guidelines. Results: As of December 2021, the point-prevalence survey has been conducted at 30 sites and expert panel adjudication for qualitative assessment of each antimicrobial use is ongoing. Results of the study are expected in 2022. Conclusions: This is the first point-prevalence study conducted among pediatric cancer centers with an integrated, multistep, qualitative approach that assesses each antimicrobial prescription. The results of this study will inform possible interventions for internal guidelines and antimicrobial stewardship programs implemented at pediatric cancer centers. In addition, local guidelines will be compared with national guidelines. Furthermore, this study will contribute to the overall integration of antimicrobial stewardship principles and initiatives in pediatric oncology and hematology, thereby improving safety and quality of care for children and adolescents with cancer and blood disorders

Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy

Background: The analysis of phenotypic characteristics on Mycobacterium tuberculosis (MTB)-specific T cells is a promising approach for the diagnosis of active tuberculosis (aTB) and for monitoring treatment success. We therefore studied phenotypic changes on MTB-specific CD4 T cells upon anti-tuberculosis treatment initiation in relation to the treatment response as determined by sputum culture.Methods: Peripheral blood mononuclear cells from subjects with latent MTB infection (n = 16) and aTB (n = 39) at baseline, weeks 9, 12, and 26 (end of treatment) were analyzed after intracellular interferon gamma staining and overnight stimulation with tuberculin. Liquid sputum cultures were performed weekly until week 12 and during 4 visits until week 26.Results: T cell activation marker expression on MTB-specific CD4 T cells differed significantly between subjects with aTB and latent MTB infection with no overlap for the frequencies of CD38pos and Ki67pos cells (both p < 0.0001). At 9 weeks after anti-TB treatment initiation the frequencies of activation marker (CD38, HLA-DR, Ki67) positive MTB-specific, but not total CD4 T cells, were significantly reduced (p < 0.0001). Treatment induced phenotypic changes from baseline until week 9 and until week 12 differed substantially between individual aTB patients and correlated with an individual's time to stable sputum culture conversion for expression of CD38 and HLA-DR (both p < 0.05). In contrast, the frequencies of maturation marker CD27 positive MTB-specific CD4 T cells remained largely unchanged until week 26 and significantly differed between subjects with treated TB disease and latent MTB infection (p = 0.0003).Discussion: Phenotypic changes of MTB-specific T cells are potential surrogate markers for tuberculosis treatment efficacy and can help to discriminate between aTB (profile: CD38pos, CD27low), treated TB (CD38neg, CD27low), and latent MTB infection (CD38neg, CD27high)

Cross-sectional seroprevalence surveys of SARS-CoV-2 antibodies in children in Germany, June 2020 to May 2021

The rate of SARS-CoV-2 infections in children remains unclear due to many asymptomatic cases. We present a study of cross-sectional seroprevalence surveys of anti-SARS-CoV-2 IgG in 10,358 children recruited in paediatric hospitals across Germany from June 2020 to May 2021. Seropositivity increased from 2.0% (95% CI 1.6, 2.5) to 10.8% (95% CI 8.7, 12.9) in March 2021 with little change up to May 2021. Rates increased by migrant background (2.8%, 4.4% and 7.8% for no, one and two parents born outside Germany). Children under three were initially 3.6 (95% CI 2.3, 5.7) times more likely to be seropositive with levels equalising later. The ratio of seropositive cases per recalled infection decreased from 8.6 to 2.8. Since seropositivity exceeds the rate of recalled infections considerably, serologic testing may provide a more valid estimate of infections, which is required to assess both the spread and the risk for severe outcomes of SARS-CoV-2 infections

Antimicrobial use in pediatric oncology and hematology in Germany and Austria, 2020/2021: a cross-sectional, multi-center point-prevalence study with a multi-step qualitative adjudication process

Background Due to the high risk of severe infection among pediatric hematology and oncology patients, antimicrobial use is particularly high. With our study, we quantitatively and qualitatively evaluated, based on institutional standards and national guidelines, antimicrobial usage by employing a point-prevalence survey with a multi-step, expert panel approach. We analyzed reasons for inappropriate antimicrobial usage. Methods This cross-sectional study was conducted at 30 pediatric hematology and oncology centers in 2020 and 2021. Centers affiliated to the German Society for Pediatric Oncology and Hematology were invited to join, and an existing institutional standard was a prerequisite to participate. We included hematologic/oncologic inpatients under 19 years old, who had a systemic antimicrobial treatment on the day of the point prevalence survey. In addition to a one-day, point-prevalence survey, external experts individually assessed the appropriateness of each therapy. This step was followed by an expert panel adjudication based upon the participating centers’ institutional standards, as well as upon national guidelines. We analyzed antimicrobial prevalence rate, along with the rate of appropriate, inappropriate, and indeterminate antimicrobial therapies with regard to institutional and national guidelines. We compared the results of academic and non-academic centers, and performed a multinomial logistic regression using center- and patient-related data to identify variables that predict inappropriate therapy. Findings At the time of the study, a total of 342 patients were hospitalized at 30 hospitals, of whom 320 were included for the calculation of the antimicrobial prevalence rate. The overall antimicrobial prevalence rate was 44.4% (142/320; range 11.1–78.6%) with a median antimicrobial prevalence rate per center of 44.5% (95% confidence interval [CI] 35.9–49.9). Antimicrobial prevalence rate was significantly higher (p < 0.001) at academic centers (median 50.0%; 95% CI 41.2–55.2) compared to non-academic centers (median 20.0%; 95% CI 11.0–32.4). After expert panel adjudication, 33.8% (48/142) of all therapies were labelled inappropriate based upon institutional standards, with a higher rate (47.9% [68/142]) when national guidelines were taken into consideration. The most frequent reasons for inappropriate therapy were incorrect dosage (26.2% [37/141]) and (de-)escalation/spectrum-related errors (20.6% [29/141]). Multinomial, logistic regression yielded the number of antimicrobial drugs (odds ratio, OR, 3.13, 95% CI 1.76–5.54, p < 0.001), the diagnosis febrile neutropenia (OR 0.18, 95% CI 0.06–0.51, p = 0.0015), and an existing pediatric antimicrobial stewardship program (OR 0.35, 95% CI 0.15–0.84, p = 0.019) as predictors of inappropriate therapy. Our analysis revealed no evidence of a difference between academic and non-academic centers regarding appropriate usage. Interpretation Our study revealed there to be high levels of antimicrobial usage at German and Austrian pediatric oncology and hematology centers with a significant higher number at academic centers. Incorrect dosing was shown to be the most frequent reason for inappropriate usage. Diagnosis of febrile neutropenia and antimicrobial stewardship programs were associated with a lower likelihood of inappropriate therapy. These findings suggest the importance of febrile neutropenia guidelines and guidelines compliance, as well as the need for regular antibiotic stewardship counselling at pediatric oncology and hematology centers. Funding European Society of Clinical Microbiology and Infectious Diseases, Deutsche Gesellschaft für Pädiatrische Infektiologie, Deutsche Gesellschaft für Krankenhaushygiene, Stiftung Kreissparkasse Saarbrücken

Phenotypic changes on Mycobacterium tuberculosis-specific CD4 T cells as surrogate markers for tuberculosis treatment efficacy

This work was supported by the European & Developing Countries Clinical Trials Partnership (EDCTP) (PanACEA, grant numbers IP.2007.32011.011, IP.2007.32011.012, IP.2007.32011.013), by the German Ministry for Education and Research (BMBF; Grant No. 01KA0901) by the European Commission, DG XII, INCO-DC (grant ICA-CT-2002-10048) and by the German Center for Infection Research (DZIF).Background: The analysis of phenotypic characteristics on Mycobacterium tuberculosis (MTB)-specific T cells is a promising approach for the diagnosis of active tuberculosis (aTB) and for monitoring treatment success. We therefore studied phenotypic changes on MTB-specific CD4 T cells upon anti-tuberculosis treatment initiation in relation to the treatment response as determined by sputum culture. Methods: Peripheral blood mononuclear cells from subjects with latent MTB infection (n=16) and aTB (n=39) at baseline, week 9, 12 and 26 (end of treatment) were analyzed after intracellular interferon gamma staining and overnight stimulation with tuberculin. Liquid sputum cultures were performed weekly until week 12 and during 4 visits until week 26. Results: T cell activation marker expression on MTB-specific CD4 T cells differed significantly between subjects with aTB and latent MTB infection with no overlap for the frequencies of CD38pos and Ki67pos cells (both p < 0.0001). At 9 weeks after anti-TB treatment initiation the frequencies of activation marker (CD38, HLA-DR, Ki67) positive MTB-specific, but not total CD4 T cells, were significantly reduced (p < 0.0001). Treatment induced phenotypic changes from baseline until week 9 and until week 12 differed substantially between individual aTB patients and correlated with an individual's time to stable sputum culture conversion for expression of CD38 and HLA-DR (both p < 0.05). In contrast, the frequencies of maturation marker CD27 positive MTB-specific CD4 T cells remained largely unchanged until week 26 and significantly differed between subjects with treated TB disease and latent MTB infection (p = 0.0003). Discussion: Phenotypic changes of MTB-specific T cells are potential surrogate markers for tuberculosis treatment efficacy and can help to discriminate between aTB (profile: CD38pos, CD27low), treated TB (CD38neg, CD27low), and latent MTB infection (CD38neg, CD27high).Publisher PDFPeer reviewe

From Indifference to Entrapment : The Netherlands and the Yugoslav Crisis, 1990-1995

A detailed analysis of the response to the Yugoslav crisis by one of America's key allies in NATO. The author focuses on the question of how a Western bureaucracy faced up to the most complex foreign policy challenge of the 1990s. The Netherlands, as a 'pocket-sized medium power', is an interesting case study. While the margins for Dutch foreign policy are limited, fate had it that the Netherlands occupied the European presidency during the second half of 1991, when the recognition issue divided the West and the parameters for the subsequent international intervention in the Balkans were set. By July 1995, the involvement of the Netherlands had deepened to the extent that Dutch troops who found themselves trapped in the UN safe area of Srebrenica together with the local Muslim population were unable to prevent the worst massacre in Europe since the Second World War. This study is based on interviews with all the major players, including two former Defence Ministers and two former Ministers of Foreign Affairs, and on documents from the Netherlands Ministry of Foreign Affairs, made available under the country's own 'freedom of information act'