Neutrophils seeking new neighbors: radiotherapy affects the cellular framework and the spatial organization in a murine breast cancer model.

Neutrophils are known to contribute in many aspects of tumor progression and metastasis. The presence of neutrophils or neutrophil-derived mediators in the tumor microenvironment has been associated with poor prognosis in several types of solid tumors. However, the effects of classical cancer treatments such as radiation therapy on neutrophils are poorly understood. Furthermore, the cellular composition and distribution of immune cells in the tumor is of increasing interest in cancer research and new imaging technologies allow to perform more complex spatial analyses within tumor tissues. Therefore, we aim to offer novel insight into intra-tumoral formation of cellular neighborhoods and communities in murine breast cancer. To address this question, we performed image mass cytometry on tumors of the TS/A breast cancer tumor model, performed spatial neighborhood analyses of the tumor microenvironment and quantified neutrophil-extracellular trap degradation products in serum of the mice. We show that irradiation with 2 × 8 Gy significantly alters the cellular composition and spatial organization in the tumor, especially regarding neutrophils and other cells of the myeloid lineage. Locally applied radiotherapy further affects neutrophils in a systemic manner by decreasing the serum neutrophil extracellular trap concentrations which correlates positively with survival. In addition, the intercellular cohesion is maintained due to radiotherapy as shown by E-Cadherin expression. Radiotherapy, therefore, might affect the epithelial-mesenchymal plasticity in tumors and thus prevent metastasis. Our findings underscore the growing importance of the spatial organization of the tumor microenvironment, particularly with respect to radiotherapy, and provide insight into potential mechanisms by which radiotherapy affects epithelial-mesenchymal plasticity and tumor metastasis.

No increase in compliance before aseptic procedures in German hospitals. A longitudinal study with data from the national surveillance system over four years.

BACKGROUND: Hand hygiene plays a crucial role in the prevention of healthcare-associated infections and transmission of pathogens. In 2008 the national campaign 'Aktion Saubere Hände' was launched in Germany. It is based on the World Health Organization (WHO) 'Clean Care is Safer Care' initiative. Direct observation and feedback of the results are key components in the improvement of hand hygiene compliance. In 2014 a voluntary national surveillance electronic tool for the documentation of directly observed compliance to hand hygiene was introduced. AIM: Description and evaluation of compliance with the WHO model 'my 5 moments' in German hospitals after implementation. METHODS: Direct observation was performed in the participating hospitals by trained local staff according to the WHO recommendations. We evaluated wards that reported annually at least 150 hand hygiene opportunities (HHOs) of hand hygiene per observation period from January 1st, 2015 until December 31st, 2018. FINDINGS: In all, 1,485,622 HHOs observed on 3337 wards in 525 hospitals were included into analysis. Overall compliance increased from 72% (interquartile range: 61-82) to 76% (66-84). Compliance significantly increased for all individual moments of the WHO model except moment 2. In the multivariate logistic regression analysis the following parameters were independently associated with a high compliance in hand hygiene: intensive care unit, nurse, opportunity observed in 2017 or 2018, as well as all moments except moment 2. CONCLUSION: Overall compliance in German hospitals increased over time. To improve HH compliance 'before aseptic procedures' appears to be difficult and should be addressed explicitly. Underlying reasons need to be the focus of future investigations.

Internal Delensing of Cosmic Microwave Background Polarization B-Modes with the POLARBEAR Experiment.

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

Detection of CMB-Cluster Lensing using Polarization Data from SPTpol.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500 deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M_{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

Use of ventilator utilization ratio for stratifying alcohol-based hand-rub consumption data to improve surveillance on intensive care units.

BACKGROUND: Germany has established a nationwide surveillance system of alcohol-based hand-rub consumption (AHC) per patient-day in hospital settings as a surrogate parameter for hand hygiene (HH) compliance. Analysis of AHC data in intensive care units (ICUs) shows not only a wide range of consumption between units of different specialties, but also within units of one specialty. This seems to reflect variation in the number of HH opportunities per patient-day between ICUs due to variation in complexity of care. AIM: To investigate whether ventilator utilization ratio (VUR) might be a good surrogate for describing complexity and intensity of care on ICUs and whether stratification by VUR works as a new method of setting benchmarks for AHC data. METHODS: Data from 365 ICUs participating in the German national nosocomial infection surveillance system (KISS) were used. VUR was calculated by dividing the number of ventilator-days per unit by the number of patient-days per unit. AHC was stratified according to VUR in quartiles. FINDINGS: The median AHC was 107mL/patient-day [interquartile range (IQR): 86-134] and the median VUR was 33% (IQR: 22-45%). The Spearman rank correlation coefficient was 0.28 (P<0.0001). After stratifying AHC according to VUR, the AHC in quartile I was significantly lower compared to quartile IV. There was also significant difference between quartile I and quartiles II and III. CONCLUSION: Stratification of AHC data according to VUR is suggested to improve the quality of benchmark parameters based on AHC data as surrogate parameter for HH compliance in ICUs.

Three years of national hand hygiene campaign in Germany: what are the key conclusions for clinical practice?

The World Health Organization (WHO) started the 'Clean Care is Safer Care' campaign in 2005. Since then, more than 120 countries have pledged to improve hand hygiene as a keystone of their national or subnational healthcare-associated infection prevention programmes. Thirty-eight countries have implemented national campaigns. Germany started a national campaign to improve hand hygiene compliance on 1 January 2008. The campaign, 'AKTION Saubere Hände', is funded by the German Ministry of Health and was initiated by the National Reference Centre for the Surveillance of Nosocomial Infections, the Society for Quality Management in Health Care and the German Coalition for Patient Safety. The campaign is designed as a multi-modal campaign based on the WHO implementation strategy. Since the end of 2010, more than 700 healthcare institutions have been actively participating in the campaign, among which are 28 university hospitals. Voluntarily participating hospitals have to implement the following measures: active support by hospital administrators of local campaign implementation, participation in a one-day introductory course, education of healthcare workers at least once a year, measurement of alcohol-based hand-rub consumption (AHC) and feedback on resulting data, implementation of the WHO 'My Five Moments for Hand Hygiene' model, increase in hand-rub availability, participation in national hand hygiene day at least every two years, and participation in national campaign network workshops at least once every two years. Observational studies to measure hand hygiene compliance are optional. Overall, there has been a significant increase of 11% in hand hygiene compliance in 62 hospitals that observed compliance before and after intervention. A total of 129 hospitals provided AHC data for three years and achieved an overall increase of 30.7%. The availability of alcohol-based hand rub increased from 86.8% to > 100% in intensive care units and from 63.6% to 91.3% in non-intensive care units. Overall, the implementation of a national campaign using the WHO multi-modal intervention strategy has led to improved hand hygiene compliance and hand-rub availability in participating settings.

Invited article: millimeter-wave bolometer array receiver for the Atacama pathfinder experiment Sunyaev-Zel'dovich (APEX-SZ) instrument.

The Atacama pathfinder experiment Sunyaev-Zel'dovich (APEX-SZ) instrument is a millimeter-wave cryogenic receiver designed to observe galaxy clusters via the Sunyaev-Zel'dovich effect from the 12 m APEX telescope on the Atacama plateau in Chile. The receiver contains a focal plane of 280 superconducting transition-edge sensor (TES) bolometers instrumented with a frequency-domain multiplexed readout system. The bolometers are cooled to 280 mK via a three-stage helium sorption refrigerator and a mechanical pulse-tube cooler. Three warm mirrors, two 4 K lenses, and a horn array couple the TES bolometers to the telescope. APEX-SZ observes in a single frequency band at 150 GHz with 1' angular resolution and a 22' field-of-view, all well suited for cluster mapping. The APEX-SZ receiver has played a key role in the introduction of several new technologies including TES bolometers, the frequency-domain multiplexed readout, and the use of a pulse-tube cooler with bolometers. As a result of these new technologies, the instrument has a higher instantaneous sensitivity and covers a larger field-of-view than earlier generations of Sunyaev-Zel'dovich instruments. The TES bolometers have a median sensitivity of 890 µK(CMB)√s (NEy of 3.5 × 10(-4) √s). We have also demonstrated upgraded detectors with improved sensitivity of 530 µK(CMB)√s (NEy of 2.2 × 10(-4) √s). Since its commissioning in April 2007, APEX-SZ has been used to map 48 clusters. We describe the design of the receiver and its performance when installed on the APEX telescope.

[Quality management for preventing healthcare-acquired infections. The importance of surveillance]. / Qualitätsmanagement zur Infektionsprävention im Krankenhaus. Die Bedeutung der Surveillance.

Healthcare acquired (nosocomial) infections are one of the most frequent complications of medical care. The management to prevent such nosocomial infections is a typical example of the use of the general principles of quality management in healthcare institutions: each institution should compare their own nosocomial infection rates for defined patient risk groups with reference data and identify problems concerning specific infection types or units/departments. This comparison should stimulate a careful analysis of the process of care and the options to improve the situation. Structured interventions, such as the introduction of bundles of infection control measures or checklists, are very helpful to increase compliance with infection control measures and to decrease nosocomial infection rates. However, often only interventions individually designed according to the specific needs in a particular unit/department are successful to improve infection rates. Therefore, the employment of experienced infection control personnel and surveillance strategies designed according to the specific needs of the institution are key elements of a good infection control management within healthcare institutions.

Costs of nosocomial pneumonia caused by meticillin-resistant Staphylococcus aureus.

Nosocomial infections with meticillin-resistant Staphylococcus aureus (MRSA) lead to increased health and economic costs. The purpose of this study was to determine costs for nosocomial MRSA pneumonia compared with meticillin-susceptible S. aureus (MSSA) pneumonia. A case-control study was conducted with patients who acquired nosocomial pneumonia with either MRSA or MSSA between January 2005 and December 2007. Patients were matched for age, severity of underlying disease, stay on intensive care units and non-intensive care units, admission and discharge within the same year, and in-hospital stay at least as long as that of cases before MRSA pneumonia. Our analysis includes 82 patients (41 cases, 41 controls). The overall costs for patients with nosocomial MRSA pneumonia were significantly higher than for patients with MSSA pneumonia (€60,684 vs €38,731; P=0.01). The attributable costs for MRSA pneumonia per patient were €17,282 (P<0.001). The financial loss was higher for patients with MRSA pneumonia than for patients with MSSA pneumonia (€11,704 vs €2,662; P=0.002). More cases died than controls while in the hospital (13 vs 1 death, P<0.001). Hospital personnel should be aware of the attributable costs of MRSA pneumonia, and should implement control measures to prevent MRSA transmission.

Pathways to clean hands: highlights of successful hand hygiene implementation strategies in Europe.

Hand hygiene is the most effective way to stop the spread of microorganisms and to prevent healthcare-associated infections (HAI). The World Health Organization launched the First Global Patient Safety Challenge - Clean Care is Safer Care - in 2005 with the goal to prevent HAI globally. This year, on 5 May, the WHO s initiative SAVE LIVES: Clean Your Hands, which focuses on increasing awareness of and improving compliance with hand hygiene practices, celebrated its second global day. In this article, four Member States of the European Union describe strategies that were implemented as part of their national hand hygiene campaigns and were found to be noteworthy. The strategies were: governmental support, the use of indicators for hand hygiene benchmarking, developing national surveillance systems for auditing alcohol-based hand rub consumption, ensuring seamless coordination of processes between health regions in countries with regionalised healthcare systems, implementing the WHO's My Five Moments for Hand Hygiene, and auditing of hand hygiene compliance.

[Clean Hands Campaign. No chance for hospital infections!]. / "AKTION Saubere Hände". Keine Chance den Krankenhausinfektionen!

There are approximately 500,000 hospital acquired infections per year in Germany of which about 20-30% (100,000-150,000) could be prevented. Hospital acquired infections are associated with increased mortality and prolonged hospital stay. Based on approximately 4 additional days of hospital stay, nosocomial infections cause additional 2 million hospital days per year. In other words, 6 hospitals each with 1,000 beds would be caring solely for patients with nosocomial infections for 1 year in Germany. Experts agree that careful hand hygiene is the single most effective measure to prevent transmission of pathogens. The rate of nosocomial infections can be reduced by improved compliance of hand hygiene as demonstrated in the literature. The ''AKTION Saubere Hände'' (Clean Hands Campaign) is a national campaign by the National Reference Centre for the Surveillance of Nosocomial Infections, the Society for Quality Management in the Health System and the Action Alliance Patient Safety aimed at the sustained improvement of hand hygiene behaviour in German hospitals.

Clonal diversity in episodes with multiple coagulase-negative Staphylococcus bloodstream isolates suggesting frequent contamination.

BACKGROUND: Coagulase-negative Staphylococci (CoNS) are frequently recovered from blood cultures, which may indicate contamination or true bacteremia. PATIENTS AND METHODS: CoNS isolates recovered from patients with episodes of two or more blood cultures positive for CoNS within 24 h were typed by both pulsed-field gel electrophoresis (PFGE) and speciation. RESULTS: PFGE typing of 94 CoNS isolates recovered from episodes with two or more positive blood cultures for CoNS within 24 h discriminated 35 strain clusters. The CoNS isolates were unrelated in 15 (39%) of 38 episodes, suggesting contamination. Sensitivity and specificity of CoNS speciation compared to PFGE was 96% and 67%, respectively. Clonal and species diversity differed between hospital areas. CONCLUSION: Contamination may frequently be present even in the setting of the recovery of CoNS from two or more blood culture sets within 24 h. Speciation of CoNS bloodstream isolates is rapid and may improve patient care as well as reduce unnecessary antibiotic use.

Costs of nosocomial Clostridium difficile-associated diarrhoea.

Nosocomial Clostridium difficile-associated disease (CDAD) is a common infection in hospitals. A matched case-control study was carried out to determine hospital-wide excess costs due to CDAD. Cases were assessed by prospective hospital-wide surveillance in a tertiary care university hospital in 2006. Nosocomial cases of CDAD (>72h after admission) were matched to control patients without CDAD in a ratio 1:3 using the same diagnosis-related group in the same year, for a hospital stay at least as long as the time of risk of the CDAD cases before infection and a Charlson comorbidity index +/-1. Data on overall costs per case were provided by the finance department. Matching was possible for 45 nosocomial CDAD cases. The difference in the length of stay showed that CDAD cases stayed significantly longer (median 7 days; P=0.006) than their matched controls. The average cost per CDAD patient was euro 33,840. The difference in the cost per patient showed that the cost for CDAD patients was significantly more than for their matched controls (median euro 7,147; 95% confidence interval: 4,067-9,276). Nosocomial CDAD is associated with high costs for healthcare systems. Clinicians should be aware of the financial impact of this disease and the application of appropriate infection control measures is recommended to reduce spread.

Strong quasi-experimental designs for research on the effectiveness of rehabilitation.

Medical rehabilitation needs better understanding of the effectiveness of its treatments and of patient characteristics most responsive to alternative intervention strategies. The goal of this paper is to improve understanding of research design in medical rehabilitation. More specifically, it describes two potentially rigorous but infrequently used "quasi-experimental" research designs--the regression-discontinuity design and the multiple interrupted time-series design. These are contrasted with the strongest research design--the randomized experiment--and to weaker designs, such as the nonequivalent group designs. Pre-experimental research, including qualitative, descriptive, and predictive studies, should not be confused with experimental research designs. More frequent use of randomized experimental and strong quasi-experimental designs can provide knowledge that will augment the effectiveness of rehabilitation practice.

Effective services for homeless substance abusers.

A heterogeneous and representative sample of 323 homeless individuals in the metropolitan-Denver area with alcohol or other substance abuse problems received a comprehensive array of substance-abuse treatment services. Following treatment, these individuals showed dramatic improvement on average in their (a) levels of alcohol and drug use, (b) housing status, (c) physical and mental health, (d) employment, and (e) quality of life. Those who received more service improved more than those who received less service. These improvements are attributable, at least partly, to the treatment rather than to alternative hypotheses such as spontaneous remission. However, the rate of improvement generally slowed during the six-month follow-up period. A random half of the clients received intensive case management in addition to the other services. Case management marginally increased clients' contacts with addictions counselors, but had little effect on the level of other services received or on the tailoring of services to client needs. As a result, case management also had little, if any, effect on outcomes.

The Criteria for Convergent and Discriminant Validity in a Multitrait-Multimethod Matrix.

Two basic structures have been proposed for the data in a multitrait-multimethod matrix; additive and multiplicative. The well-known criteria for assessing convergent and discriminant validity proposed by Campbell and Fiske (1959) are shown, in general, to be inadequate for either structure. Model-specific criteria for assessing convergent and discriminant validity hold greater promise than the Campbell and Fiske criteria.

Taking account of time lags in causal models.

Although it takes time for a cause to exert an effect, causal models often fail to allow adequately for time lags. In particular, causal models that contain cross-sectional relations (i.e., relations between values of 2 variables at the same time) are unsatisfactory because they omit the values of variables at prior times, they omit effects that variables can have on themselves, and they fail to specify the length of the causal interval that is being studied. These omissions can produce severe biases in estimates of the size of causal effects. Longitudinal models also can fail to take account of time lags properly, and this too can lead to severely biased estimates. The discussion illustrates the biases that can occur in both cross-sectional and longitudinal models, introduces the latent longitudinal approach to causal modeling, and shows how latent longitudinal models can be used to reduce bias by taking account of time lags even when data are available for only 1 point in time.

Contingent associations and the double-function, verbal-discrimination task.

Three experiments examined the role of contingent associations in learning double-function, verbal-discrimination lists. Some 15-pair lists of category instances were constructed in such a way that the learning of three contingent associations based on category names would mediate correct performance for all 15 pairs. The first experiment gave no evidence that the three contingencies aided learning. The second experiment showed that subjects could be taught the three contingent associations in isolation and that they could then apply them successfully to the double-function list. To make the contingencies more apparent to the subjects, the category names were used during feedback in the third experiment. The learning was not facilitated by such feedback. It was concluded that the learning observed for the usual double-function list does not involve contingent associations.