Challenges and opportunities faced by nurse scientists in integrating data and technology in research to promote health equity.

Advances in technologies including omics, apps, imaging, sensors, and big data are increasingly being integrated into research by nurse scientists, but the impact on improving health equity is still unclear. In this article, nursing research faculty from one institution discuss challenges and opportunities experienced when integrating various technologies into their research aimed at promoting health equity. Using exemplars from faculty experiences, a three-pronged approach to keeping patients and communities and the goal of health equity central in research while incorporating advancing technologies is described. This approach includes establishing long-term engagement with populations underrepresented in research, adopting strategies to increase diversity in study participant recruitment, and training and collaboration among a diverse workforce of educators, clinicians, and researchers. Training nurse scientists in integrating data and technology for advancing the science on health equity will shift the culture of how we understand, collaborate, and grow with the communities in which we train and practice as nurse scientists.

Factors Associated With Hospital Readmissions Among U.S. Dialysis Facilities.

INTRODUCTION: The Centers for Medicare and Medicaid uses the standardized readmission ratio (SRR) to evaluate 30-day readmissions among dialysis providers in the U.S. Readmissions among dialysis recipients remains 37%. This study investigates associations among dialysis facilities and patient characteristics with facility's performance on the SRR. METHODS: Descriptive, longitudinal, approach using multivariate regression analysis on data retrieved from the Dialysis Facility Report to evaluate the associations between facility-level (staffing, profit status, chain membership, clinic size, care, length of care, vascular access type, glomerular filtration rate (GFR), creatinine, hemoglobin, use of erythropoietin-stimulating agent, albumin, and primary dialysis modality) with the SRR. RESULTS: Factors associated with a high SRR included nurse ratios, facility average GFR, and Northeast geographic location. Factors associated with a low SRR included patient care technician ratio, length of predialysis nephrology care, initiation of dialysis with an arteriovenous fistula, average hemoglobin, and Western geographic location. CONCLUSIONS: This study defines the influence predialysis nephrology care has on dialysis facilities SRRs. Access to care, adequate preparation for dialysis, and transitional support affect facilities' performance; however, without an appropriate staffing model, dialysis facilities may continue to struggle to reduce readmissions.

Polish adaptation and validation of the Perceived Implicit Rationing of Nursing Care (PIRNCA) questionnaire: a cross-sectional validation study.

OBJECTIVES: To develop a Polish adaptation of the Perceived Implicit Rationing of Nursing Care (PIRNCA)questionnaire. DESIGN: Cross-sectional validation study. SETTINGS: Nurses working in surgical and cancer wards in Poland. PARTICIPANTS: A sample of 513 professionally active nurses was enrolled in the study. INTERVENTION: To complete a Polish translation of the full original PIRNCA questionnaire. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was translation and adaptation of the full original PIRNCA tool and its validation to the Polish conditions. The secondary outcome was determination of relationships between sociodemographic variables, nurses' assessment of patient care quality and their overall job satisfaction on the one hand, and PIRNCA scores on the other. RESULTS: The respondents' mean score was 1.27 points (SD=0.68) on a scale from 0 to 3. Cronbach's alpha for the entire instrument was 0.957. All items of the questionnaire were found to have a positive item-total correlation. The developed linear regression model showed that nurses' assessment of patient care quality and their overall job satisfaction were independent predictors of PIRNCA scores (p<0.05). 94.15% of nurses reported rationing at least one of the 31 care activities. CONCLUSIONS: The present findings indicate a high level of reliability and validity of the translated PIRNCA questionnaire, fully comparable to that of the original. The questionnaire can be used for the assessment of PIRNCA in Polish hospitals.

Virological assessment of hospitalized patients with COVID-2019.

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.

Systems, economics, and neoliberal politics: Theories to understand missed nursing care.

The phenomenon of missed nursing care is endemic across all sectors. Nurse leaders have drawn attention to the implications of missed care for patient outcomes, with calls to develop clear political, methodological, and theoretical approaches. As part of this call, we describe three structural theories that inform frameworks of missed care: systems theory, economic theory, and neoliberal politics. The final section provides commentary on the strengths and limitations of these three theories, in the light of structuration theory and calls to balance this research agenda by reinstating nurse agency and examining the interactions between nurses as agents and the health systems as structures. The paper argues that a better understanding of variations in structure-agency interaction across the healthcare system might lead to more effective interventions at strategic leverage points.

Factor analysis, validity of the perceived implicit rationing of nursing care instrument and prevalence and patterns of unfinished nursing care in Slovakia.

AIM: The aim of the study was to adapt and validate the perceived implicit rationing of nursing care instrument in the Slovak nurse work environment and to evaluate the prevalence of unfinished nursing care in acute care hospitals. BACKGROUND: The measurement of unfinished nursing care could be assumed as a proxy indicator of nurse staffing adequacy or higher risk of adverse events. METHODS: A cross-sectional survey design was used. The sample of 1,429 registered nurses from 21 hospitals in Slovakia was recruited. Exploratory factor analysis, confirmatory factor analysis and internal reliability were performed. RESULTS: The instrument is essentially rather an inventory than scale per se. Concurrent validity of the Slovak version was supported by the significant associations between unfinished nursing care and clinically relevant variables. CONCLUSIONS: The prevalence of unfinished nursing care based the percentage of positive responses was higher than prevalence based on composite mean scores. Findings from the study raise questions about a unidimensional structure of nursing tasks reflected in most commonly used survey instruments of unfinished nursing care internationally. IMPLICATIONS FOR NURSING MANAGEMENT: The periodical measurement of unfinished nursing care based on the percentage of positive responses should be assumed as a key strategy to increase patient safety and quality of nursing care.

Monthly variation of unfinished nursing care at the US Army Burn Center.

OBJECTIVE: To describe the monthly variation in the prevalence and patterns of unfinished nursing care and to determine the relationships between the system of nursing care and unfinished nursing care at the US Army Burn Center. METHODS: This was a repeated measures, descriptive study. For one week per month for six months, all nurses providing direct patient care on two inpatient burn units (intensive care and progressive care) were asked to complete an anonymous paper survey, which contained the Perceived Implicit Rationing of Nursing Care instrument, to estimate the prevalence of unfinished nursing care on their unit. Unit administrative data also were collected from the unit nursing leaders each month. Descriptive statistics and multilevel modeling were used in the analysis. RESULTS: Most (80.5%) eligible nurses participated at least once; 46.6% participated three or more times. A high proportion (85.7-100%) of nurses left at least one element of care unfinished; the mean number of activities left unfinished over each 7 shift period per nurse was 16.2. Only nursing care hours provided by float staff significantly predicted nurse estimates of unfinished nursing care, ß=.008, SE=.001, p<.05. CONCLUSIONS: The prevalence of unfinished nursing care at the US Army Burn Center was high and generally consistent with other studies of unfinished nursing care in non-burn settings. The inability to meet the demand for nursing care, as evidenced by the presence of unfinished nursing care, may be the result of a limited surge capacity. Implications for research, policy, and practice were discussed.

OLT1177, a ß-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation.

Activation of the NLRP3 inflammasome induces maturation of IL-1ß and IL-18, both validated targets for treating acute and chronic inflammatory diseases. Here, we demonstrate that OLT1177, an orally active ß-sulfonyl nitrile molecule, inhibits activation of the NLRP3 inflammasome. In vitro, nanomolar concentrations of OLT1177 reduced IL-1ß and IL-18 release following canonical and noncanonical NLRP3 inflammasome activation. The molecule showed no effect on the NLRC4 and AIM2 inflammasomes, suggesting specificity for NLRP3. In LPS-stimulated human blood-derived macrophages, OLT1177 decreased IL-1ß levels by 60% and IL-18 by 70% at concentrations 100-fold lower in vitro than plasma concentrations safely reached in humans. OLT1177 also reduced IL-1ß release and caspase-1 activity in freshly obtained human blood neutrophils. In monocytes isolated from patients with cryopyrin-associated periodic syndrome (CAPS), OLT1177 inhibited LPS-induced IL-1ß release by 84% and 36%. Immunoprecipitation and FRET analysis demonstrated that OLT1177 prevented NLRP3-ASC, as well as NLRP3-caspase-1 interaction, thus inhibiting NLRP3 inflammasome oligomerization. In a cell-free assay, OLT1177 reduced ATPase activity of recombinant NLRP3, suggesting direct targeting of NLRP3. Mechanistically, OLT1177 did not affect potassium efflux, gene expression, or synthesis of the IL-1ß precursor. Steady-state levels of phosphorylated NF-κB and IkB kinase were significantly lowered in spleen cells from OLT1177-treated mice. We observed reduced IL-1ß content in tissue homogenates, limited oxidative stress, and increased muscle oxidative metabolism in OLT1177-treated mice challenged with LPS. Healthy humans receiving 1,000 mg of OLT1177 daily for 8 d exhibited neither adverse effects nor biochemical or hematological changes.

Protocol: systematic review of the association between socio-economic status and survival in adult head and neck cancer.

BACKGROUND: Head and neck cancer incidence is increasing worldwide. Despite overall improvements in survival, numerous studies suggest worse survival in more disadvantaged populations; however, this literature has not been systematically reviewed. The aim of this review is to investigate whether lower compared to higher socioeconomic status (SES) influences survival in head and neck squamous cell cancer (HNSCC) and explore possible explanations for any relationship found. METHOD: A systematic strategy will be used to identify articles, appraise their quality and extract data. Online databases including MEDLINE, Web of Knowledge, ESBCO Host and Scopus will be used to locate observational studies of adults with a primary diagnosis of head and neck cancer in EU15+ countries (15 members of the EU, Australia, Canada, Norway, USA and New Zealand) where the outcomes report associations between SES and survival. This will be augmented by searching for grey literature and through reference lists. Data will be extracted using a standardised form. Study quality will be assessed using the Newcastle Ottawa scale and where possible meta-analysis of the pooled data will be conducted. DISCUSSION: This review will quantify the association between SES and survival outcomes for adult head and neck cancer patients in developed countries. The results will help identify gaps in the literature and therefore direct further novel research in the field. Ultimately, this will inform public policy and strategies to reduce the inequalities in HNSCC survival. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016037019 .

Resource scarcity drives lethal aggression among prehistoric hunter-gatherers in central California.

The origin of human violence and warfare is controversial, and some scholars contend that intergroup conflict was rare until the emergence of sedentary foraging and complex sociopolitical organization, whereas others assert that violence was common and of considerable antiquity among small-scale societies. Here we consider two alternative explanations for the evolution of human violence: (i) individuals resort to violence when benefits outweigh potential costs, which is likely in resource poor environments, or (ii) participation in violence increases when there is coercion from leaders in complex societies leading to group level benefits. To test these hypotheses, we evaluate the relative importance of resource scarcity vs. sociopolitical complexity by evaluating spatial variation in three macro datasets from central California: (i) an extensive bioarchaeological record dating from 1,530 to 230 cal BP recording rates of blunt and sharp force skeletal trauma on thousands of burials, (ii) quantitative scores of sociopolitical complexity recorded ethnographically, and (iii) mean net primary productivity (NPP) from a remotely sensed global dataset. Results reveal that sharp force trauma, the most common form of violence in the record, is better predicted by resource scarcity than relative sociopolitical complexity. Blunt force cranial trauma shows no correlation with NPP or political complexity and may reflect a different form of close contact violence. This study provides no support for the position that violence originated with the development of more complex hunter-gatherer adaptations in the fairly recent past. Instead, findings show that individuals are prone to violence in times and places of resource scarcity.

Unfinished nursing care: An important performance measure for nursing care systems.

Performance measurement is a core administrative function and an essential component of organizational quality programs. The prevalence of performance measurement initiatives increased significantly after the release of the Institute of Medicine series on quality. Nursing performance measures are limited in their scope, resulting in an underrepresentation of process measures. Development of performance indicators that reflect how effectively organizational units actually transform nursing resources into nursing services should be a high priority. Unfinished nursing care is a nursing process performance measure that reflects the complexity of the nursing care environment and can be useful in comparing process performance across systems and organizations. Unfinished nursing care is congruent with many of the National Quality Forum requirements for endorsement and warrants further refinement as an important nurse-sensitive performance measure.

Texas Nurse Staffing Trends Before and After Mandated Nurse Staffing Committees.

This article describes the evolution of mandated nurse staffing committees in Texas from 2002 to 2009 and presents a study that analyzed nurse staffing trends in Texas using a secondary analysis of hospital staffing data (N = 313 hospitals) from 2000 to 2012 obtained from the American Hospital Association Annual Survey. Nurse staffing patterns based on three staffing variables for registered nurses (RNs), licensed vocational nurses (LVNs), and total licensed nurses were identified: full-time equivalents per 1,000 adjusted patient days, productive hours per adjusted patient day, and RN skill mix. Similar to national trends between 2000 and 2012, most Texas hospitals experienced an increase in RN and total nurse staffing, decrease in LVN staffing, and an increase in RN skill mix. The magnitude of total nurse staffing changes in Texas (5% increase) was smaller than national trends (13.6% increase). Texas's small, rural, government hospitals and those with the highest preregulation staffing levels experienced the least change in staffing between 2000 and 2012: median change of 0 to .13 full-time equivalents per 1,000 adjusted patient days and median change in productive hours per patient day of 0 to .23. The varying effects of staffing committees in different organizational contexts should be considered in future staffing legislative proposals and other policy initiatives.

A Descriptive Analysis of Implicit Rationing of Nursing Care: Frequency and Patterns in Texas.

The frequency and patterns of implicit rationing of nursing care in the United States are not known. The purpose of this study was to examine the phenomenon of implicit rationing among nurses in Texas. Implicit rationing was measured using a 31-item survey instrument adapted from the parent instrument originating in Switzerland. Some degree of rationing on at least one of the nursing care activities was reported by almost all of the respondents and most rationed multiple activities. Rationing preference patterns favor completion of activities directed to meet immediate physiological needs over other activities. If the relationships documented in other countries between implicit rationing and adverse patient outcomes are also present in the United States, then implicit rationing may serve as an important quality indicator.

Unfinished nursing care, missed care, and implicitly rationed care: State of the science review.

OBJECTIVES: The purposes of this review of unfinished care were to: (1) compare conceptual definitions and frameworks associated with unfinished care and related synonyms (i.e. missed care, implicitly rationed care; and care left undone); (2) compare and contrast approaches to instrumentation; (3) describe prevalence and patterns; (4) identify antecedents and outcomes; and (5) describe mitigating interventions. METHODS: A literature search in CINAHL and MEDLINE identified 1828 articles; 54 met inclusion criteria. Search terms included: implicit ration*, miss* care, ration* care, task* undone, and unfinish*care. Analysis was performed in three phases: initial screening and sorting, comprehensive review for data extraction (first author), and confirmatory review to validate groupings, major themes, and interpretations (second author). RESULTS: Reviewed literature included 42 quantitative reports; 7 qualitative reports; 1 mixed method report; and 4 scientific reviews. With one exception, quantitative studies involved observational cross-sectional survey designs. A total of 22 primary samples were identified; 5 involved systematic sampling. The response rate was >60% in over half of the samples. Unfinished care was measured with 14 self-report instruments. Most nursing personnel (55-98%) reported leaving at least 1 task undone. Estimates increased with survey length, recall period, scope of response referent, and scope of resource scarcity considered. Patterns of unfinished care were consistent with the subordination of teaching and emotional support activities to those related to physiologic needs and organizational audits. Predictors of unfinished care included perceived team interactions, adequacy of resources, safety climate, and nurse staffing. Unfinished care is a predictor of: decreased nurse-reported care quality, decreased patient satisfaction; increased adverse events; increased turnover; decreased job and occupational satisfaction; and increased intent to leave. DISCUSSION & CONCLUSIONS: Unfinished care is a significant problem in acute care hospitals internationally. Prioritization strategies of nurses leave patients vulnerable to unmet educational, emotional, and psychological needs. Key limitations of the science include the threat of common method/source bias, a lack of transparency regarding the use of combined samples and secondary analysis, inconsistency in the reporting format for unfinished care prevalence, and a paucity of intervention studies.

Validation of the Perceived Implicit Rationing of Nursing Care (PIRNCA) instrument.

BACKGROUND: An inverse relationship between implicit rationing and quality patient outcomes has been demonstrated in European hospitals, but this relationship has not been explored in the United States. OBJECTIVE: To evaluate the psychometric properties of a new measure of implicit rationing, the Perceived Implicit Rationing of Nursing Care (PIRNCA). METHOD: A cross-sectional survey design with a stratified random sample of 226 medical surgical nurses was used to evaluate the PIRNCA. The internal structure was evaluated using exploratory factor analysis. Pearson correlations were used to assess the associations between implicit rationing and three related constructs: work environment, overall job satisfaction, and quality of care. RESULTS: A single-factor solution explaining 55% of the total variance and excellent reliability, Cronbach's alpha = 0.97, was supported for the PIRNCA. Moderate inverse relationships with related constructs provided evidence of concurrent validity: work environment (-0.44), overall job satisfaction (-0.48), and quality of care (-0.56). The majority of nurses (97%) reported rationing at least one of the 30 care activities listed; however, mean scores reflected a low frequency ("rarely") of rationing overall. CONCLUSION: The phenomenon of implicit rationing is experienced by nurses in U.S. hospitals, and the PIRNCA instrument is a valid and reliable measure of this phenomenon.

Economic theory and nursing administration research--is this a good combination?

TOPIC: Economic theory is used to describe and explain decision making in the context of scarce resources. PURPOSE: This paper presents two applications of economic theory to the delivery of nursing services in acute care hospitals and evaluates its usefulness in guiding nursing administration research. SOURCES OF INFORMATION: The description of economic theory and the proposed applications for nursing are based on current nursing, healthcare, and economic literature. Evaluation of the potential usefulness of economic theory in guiding nursing administration research is based on the criteria of significance and testability as described by Fawcett and Downs. CONCLUSIONS: While economic theory can be very useful in explaining how decisions about nursing time allocation and nursing care production are made, it will not address the issue of how they should be made. Normative theories and ethical frameworks also must be incorporated in the decision-making process around these issues. Economic theory and nursing administration are a good fit when balanced with the values and goals of nursing.

Pharmacoeconomics of low-molecular-weight heparins: limitations of studies comparing them to unfractionated heparin.

Unfractionated heparin (UFH) entered medical usage in the 1930s and was the mainstay of acute anticoagulation until the 1980s, when low-molecular-weight heparins (LMWHs) became available. At this time, the acquisition cost of LMWHs, being greater than that of UFH, was a significant barrier to their use even though there was evidence that this was offset by savings in monitoring and other areas. Evidence of the superiority of LMWHs over UFH in many clinical settings has been accumulating and, along with economic analyses that have demonstrated overall cost savings when LMWH is compared to UFH, has resulted in rapidly expanding sales of LMWH, whereas sales of UFH, are in decline. In addition to being more effective than UFH, LMWHs may cause less bleeding, are less likely to cause heparin-induced thrombocytopenia (HIT) and exhibit less inter-patient variability. In addition to the savings from reduced monitoring, the greater acquisition costs for LMWHs are also offset by reduced costs of treating adverse effects and unprevented venous thromboembolism. LMWHs are usually administered once daily via the subcutaneous route, and this often allows treatment to be undertaken in the community rather than in hospitals, thereby saving considerable sums on inpatient costs. Pharmacoeconomic analyses are limited by a variety of factors including geographical and temporal variability in cost inputs, cost shifting, cost inputs that are omitted and payer perspective. Some of these limitations, including the economic impact of HIT and the savings in hospital costs, will be discussed. The effect of changes in acquisition costs since their introduction and the potential impact of medicolegal costs, will also be explored. Settings where evidence of benefit of LMWH over UFH is lacking will also be discussed.

Assessment of inter- and intrapatient variability in C15O2 positron emission tomography measurements of blood flow in patients with intra-abdominal cancers.

PURPOSE: The aim of the study was to evaluate the inter- and intrapatient variability of positron emission tomography (PET) measurements of perfusion in advanced solid cancers. EXPERIMENTAL DESIGN: Thirty-seven patients with predominantly intra-abdominal tumors underwent PET imaging using inhaled C15O2. Repeat data were obtained by scanning five patients twice, 1 week apart, with no intervening therapy. Regional flow and the volume of distribution (V(d)) were measured from dynamic images by use of a one-compartment model. Inter- and intrapatient variability were measured as the coefficient of variability (CV). Data were also obtained for regions of interest in normal liver, spleen, and kidney. RESULTS: The mean (+/-SD) regional flow in the tumors was 0.46 +/- 0.19 ml(blood)/min/ml(tissue), and the mean V(d) was 0.74 +/- 0.15 ml(blood)/ml(tissue). Variability in tumor flow was greater between (n = 37; CV = 41%) than within (n = 5; CV = 11%) patients. Variability in tumor V(d) was greater between (CV = 21%) than within (CV = 6%) patients. There was a good correlation between the repeat tumor data for both regional flow (rho = 0.82; P = 0.023) and V(d) (rho = 0.89; P = 0.007). Normal tissue variability was also greater between than within patients. In all cases, no statistically significant differences were seen between repeat measurements in the same patient. CONCLUSIONS: Dynamic C15O2 PET measurements of regional flow are reproducible in patients with predominantly intra-abdominal malignancies and may be useful for the pharmacodynamic evaluation of novel antivascular and antiangiogenic cancer therapeutic agents.

Assessment of pharmacodynamic vascular response in a phase I trial of combretastatin A4 phosphate.

PURPOSE: Clinical evaluation of novel agents that target tumor blood vessels requires pharmacodynamic end points that measure vascular damage. Positron emission tomography (PET) was used to measure the effects of the vascular targeting agent combretastatin A4 phosphate (CA4P) on tumor and normal tissue perfusion and blood volume. PATIENTS AND METHODS: Patients with advanced solid tumors were enrolled onto part of a phase I, accelerated-titration, dose-escalation study. The effects of 5 to 114 mg/m2 CA4P on tumor, spleen, and kidney were investigated. Tissue perfusion was measured using oxygen-15 (15O)-labeled water and blood volume was measured using 15O-labeled carbon monoxide (C15O). Scans were performed immediately before, and 30 minutes and 24 hours after the first infusion of each dose level of CA4P. All statistical tests were two sided. RESULTS: PET data were obtained for 13 patients with intrapatient dose escalation. Significant dose-dependent reductions were seen in tumor perfusion 30 minutes after CA4P administration (mean change, -49% at >or= 52 mg/m2; P =.0010). Significant reductions were also seen in tumor blood volume (mean change, -15% at >or= 52 mg/m2; P =.0070). Although by 24 hours there was tumor vascular recovery, for doses >or= 52 mg/m2 the reduction in perfusion remained significant (P =.013). Thirty minutes after CA4P administration borderline significant changes were seen in spleen perfusion (mean change, -35%; P =.018), spleen blood volume (mean change, -18%; P =.022), kidney perfusion (mean change, -6%; P =.026), and kidney blood volume (mean change, -6%; P =.014). No significant changes were seen at 24 hours in spleen or kidney. CONCLUSION: CA4P produces rapid changes in the vasculature of human tumors that can be assessed using PET measurements of tumor perfusion.