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Purpose The purpose of this study is to investigate the link between downsizing cues and market performance prior to and after a major crisis. We use a recent exogenous shock – the COVID-19 pandemic – to test hypotheses on the nature of the relationship between downsizing cues and market performance within two distinct groups: pre and post-crisis. We purport that the sudden increase in uncertainty brought about by a major crisis widens information asymmetry between firms and their shareholders, and that top managers sending downsizing cues to the market with high levels of authenticity may be more likely to trigger positive market reactions. Design/methodology/approach The authors rely on computer-assisted text analysis (CATA) methodology, event-study methodology and a data set of 952 pre- and post-crisis earnings conference calls held by 476 S&P 500 firms to test the hypotheses in this study. Findings The authors find that downsizing cues have no effect on market performance in the pre-crisis group, but are negatively related to market performance in the post-crisis group. The authors also find that authenticity cues positively mitigate the relationship between downsizing cues and market performance relationship in the post-crisis group. Originality/value This empirical study extends our knowledge of the influence of a major crisis on the relationship between downsizing and market performance by leveraging the revelatory power of an exogenous environmental shock. The authors also explore the role played by managerial authenticity and find that the market is more inclined to accept post-crisis downsizing efforts when top managers are perceived as authentic.

Tubulin-binding vascular-disrupting agents (VDA) are currently in clinical trials for cancer therapy but the factors that influence tumor susceptibility to these agents are poorly understood. We evaluated the consequences of modifying tumor vascular morphology and function on vascular and therapeutic response to combretastatin-A4 3-O-phosphate (CA-4-P), which was chosen as a model VDA. Mouse fibrosarcoma cell lines that are capable of expressing all vascular endothelial growth factor (VEGF) isoforms (control) or only single isoforms of VEGF (VEGF120, VEGF164, or VEGF188) were developed under endogenous VEGF promoter control. Once tumors were established, VEGF isoform expression did not affect growth or blood flow rate. However, VEGF188 was uniquely associated with tumor vascular maturity, resistance to hemorrhage, and resistance to CA-4-P. Pericyte staining was much greater in VEGF188 and control tumors than in VEGF120 and VEGF164 tumors. Vascular volume was highest in VEGF120 and control tumors (CD31 staining) but total vascular length was highest in VEGF188 tumors, reflecting very narrow vessels forming complex vascular networks. I.v. administered 40 kDa FITC-dextran leaked slowly from the vasculature of VEGF188 tumors compared with VEGF120 tumors. Intravital microscopy measurements of vascular length and RBC velocity showed that CA-4-P produced significantly more vascular damage in VEGF120 and VEGF164 tumors than in VEGF188 and control tumors. Importantly, this translated into a similar differential in therapeutic response, as determined by tumor growth delay. Results imply differences in signaling pathways between VEGF isoforms and suggest that VEGF isoforms might be useful in vascular-disrupting cancer therapy to predict tumor susceptibility to VDAs. [Cancer Res 2008;68(7):2301–11]

Supplementary Figure 3 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Table 1 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figure 4 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figure 5 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figure 2 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figures, Table and Movie Legend from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Figure 1 from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

Supplementary Movie from Blood Vessel Maturation and Response to Vascular-Disrupting Therapy in Single Vascular Endothelial Growth Factor-A Isoform–Producing Tumors

PurposePast research has generally purported that market orientation (MO) leads to superior firm performance, despite emerging evidence suggesting that the highest levels of MO are not always rewarded. Drawing on resource-based view and MO literature, the authors posit that too much MO may be as detrimental as too little for firms seeking to achieve better performance, and that moderate MO capabilities may be the most beneficial. Furthermore, the authors propose and test for organizational confidence as a first potential moderator of the MO-performance inverted U-shaped link.Design/methodology/approachThe authors use Computer-Assisted-Text-Analysis (CATA) methodology assess constructs from annual reports matched with a 5-year longitudinal dataset of 2,245 firm-year observations drawn from the S&P 500.FindingsThe results not only support the presence of an inverted U-shaped link between MO and firm performance, but also identify organizational confidence as an important moderator of this newly uncovered curvilinear relationship.Practical implicationsWhen it comes to the effect of MO on firm performance, there can be indeed be “too much of a good thing,” and managers should be aware of the trade-offs that come attached with overcommitting to a MO strategy.Originality/valueThe authors contribute to extant research on the MO–performance link by moving beyond simple linear relationships and identifying an inverted U-shaped relationship between MO and firm performance. This newly found curvilinear relationship may explain and reconcile prior contradicting findings on the benefits of MO. Organizational confidence is also found to trigger a shape-flip of the MO–performance link, thereby suggesting a new boundary condition.

Triple-negative breast cancer (TNBC) remains the most lethal breast cancer subtype with poor response rates to the current chemotherapies and a lack of additional effective treatment options. We have identified deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) as a critical gatekeeper that protects tumour DNA from the genotoxic misincorporation of uracil during treatment with standard chemotherapeutic agents commonly used in the FEC regimen. dUTPase catalyses the hydrolytic dephosphorylation of deoxyuridine triphosphate (dUTP) to deoxyuridine monophosphate (dUMP), providing dUMP for thymidylate synthase as part of the thymidylate biosynthesis pathway and maintaining low intracellular dUTP concentrations. This is crucial as DNA polymerase cannot distinguish between dUTP and deoxythymidylate triphosphate (dTTP), leading to dUTP misincorporation into DNA. Targeting dUTPase and inducing uracil misincorporation during the repair of DNA damage induced by fluoropyrimidines or anthracyclines represents an effective strategy to induce cell lethality. dUTPase inhibition significantly sensitised TNBC cell lines to fluoropyrimidines and anthracyclines through imbalanced nucleotide pools and increased DNA damage leading to decreased proliferation and increased cell death. These results suggest that repair of treatment-mediated DNA damage requires dUTPase to prevent uracil misincorporation and that inhibition of dUTPase is a promising strategy to enhance the efficacy of TNBC chemotherapy.

PurposeThis paper aims to investigate whether cues of morality can mitigate stock sell-offs in the face of earnings uncertainty prior to earnings conference calls and draws on moral foundations theory to study the effect of universal moral cues (harm/care and fairness/reciprocity rhetoric) and primarily conservative moral cues (ingroup/loyalty, authority/respect and purity/sanctity rhetoric) on market performance.Design/methodology/approachThe study relies on a longitudinal data set of 1,920 firm-quarter observations corresponding to calls held by firms listed on the S&P 500 in 2015 and relies on computer-assisted-text-analysis and event-study methodology to test hypotheses.FindingsThe results suggest that cues of universal moral foundations have a mitigating effect on stock sell-offs and are able to create firm value; while cues primarily conservative moral foundations are not found to have an effect on market performance.Originality/valueThis investigation highlights why earnings conference calls may serve as a valuable tool for communicating a firm’s moral inclination and why universal morality may appeal to a wider range of shareholders than primarily conservative morality.

This article examines the phenomenon of dynamic capabilities in international new ventures (INVs) from emerging markets. While this research stream is gaining traction, the literature is fragmented as to how INVs from emerging markets develop dynamic capabilities to overcome resource constraints and legitimacy issues. The authors highlight the importance of a comprehensive international entrepreneurial culture (IEC) to better understand how these INVs develop dynamic capabilities and foster international performance. This study draws on organisational learning and the knowledge-based view (KBV) to examine the role of IEC in shaping dynamic capabilities and international performance under various levels of market turbulence. To conduct our analyses, this study uses a sample of INVs from India – a key emerging market. The results indicate that IEC shapes dynamic capabilities and both support superior international performance. The findings also confirm the utility of IEC towards dynamic capabilities and international performance when operating in turbulent markets.

At the start of the First World War, the estate of Cliveden was offered as a hospital to the Canadian Government by its owner William Astor. This article describes its history, Sir William Osler's involvement in the hospital, and the involvement of other doctors and some of their research. The rehabilitation programs to help the injured soldiers are described, including the physical, occupational, sporting and social activities undertaken in order to help them towards their return to civilian life. Political ambitions in Canada and friction between the owner of Cliveden, Nancy Astor, and the medical/military establishment led to turmoil which engulfed Osler and is known as the ‘Taplow Affair’. The hospital was dismantled after the war but became re-activated in the Second World War and is now a National Trust property.

Prosocial crowdfunding is a recent international business phenomenon which allows entrepreneurs from emerging nations to post microloan requests online for fundraising. While the crowdfunding topic has attracted much academic interest in recent years, little is known about the effect of cultural differences on crowdfunding dynamics. This study draws on the cultural entrepreneurship literature to assess whether a borrower’s cultural alignment with his or her own country increases or decreases funding speed. We investigate whether prosocial lenders reward borrower profiles that cue cultural distinctiveness through a Computer-Aided-Text-Analysis (CATA) of 127,597 profile loan descriptions and observations nested within 37 countries. It is found that cultural alignment on two dimensions—temporal awareness and commonality—is positively related to funding time, thus suggesting that a cultural misalignment is preferred by lenders. Our discussion highlights why nonconformity to local culture may be interpreted as legitimate distinctiveness in the prosocial crowdfunding context.

In recent years, earnings conference calls have become a popular disclosure tool through which top managers can provide more information to the market regarding the quarterly earnings of their firms. Although some research has indicated that the tone of earnings conference calls is crucial in mitigating investors’ negative reactions to earnings surprises, relatively little is still known about other rhetorical tactics that may be available for managers to create value during times of heightened earnings uncertainty. This article contends that warm-glow rhetoric may be another way to mitigate investors’ negative reactions to earnings surprises, as warm-glow theory suggests that individuals are willing to make suboptimal economic choices when they receive warm-glow payouts. Hypotheses drawing on warm-glow theory and the incremental useful information perspective are developed and tested using computer-assisted text analysis (CATA) and event study methodology on a longitudinal sample of 1920 calls, and it is suggested that warm-glow rhetoric positively moderates the relationship between earnings surprises and financial performance (as measured through cumulated abnormal returns). The findings illustrate how the warm-glow effect can be used as an unconventional, yet effective tactic with which managers can create market value. A discussion of the findings and their implications for theory and practice concludes the study.

The extant evidence evaluating consumers’ willingness to pay more for green products has been mixed. Existing investigations stem from an overemphasis on profiling consumers who are willing vs. unwilling to pay price premiums for green products using dispositional (socio-demographic and psychological) characteristics. However, little is known about what firm-initiated actions can be taken when consumers do not possess characteristics that favorably influence green purchase behaviors. This research demonstrates that customer participation improves consumers’ willingness to pay more even when consumers exhibit low sustainability-oriented motivation (environmental concern) and ability (eco-literacy). The findings are important for practitioners seeking practical ways to alleviate green purchase barriers.

Prosocial crowdfunding is a new business phenomenon which is transforming the microfinance sector, as more microloans are posted online for fundraising. Research suggests that prosocial lenders registered on crowdfunding platforms seek non-financial returns from their investments, such as the creation of value for the social good. This article adds moral ethics to the crowdfunding equation by drawing on Moral Foundations Theory (MFT). It is posited that cues of moral foundations embedded within borrower profile descriptions are likely to inform prosocial lenders about a borrower’s potential for social value creation, thus triggering lending decisions. A Computer-Assisted-Text-Analysis (CATA) of 130,964 funded microloan profile descriptions on a crowdfunding platform suggests that prosocial lenders fund borrowers who cue universal moral foundations ( Harm/Care and Fairness/Reciprocity) more quickly than those who cue primarily conservative moral foundations ( Ingroup/Loyalty, Authority/Respect and Purity/Sanctity).

Publicly traded firms release their earnings figures quarterly, and subsequently hold earnings conference calls where top managers can comment on firm strategy. Markets are particularly sensitive to earnings surprises, and conference calls are becoming an increasingly useful tool capable of mitigating shareholders’ negative reactions to surprises on earnings. This article argues that top managers who cue organizational-level positive psychological capital (PsyCap) are likely to mitigate investors’ reactions unanticipated changes in earnings. The developed hypotheses draw on arguments from the incremental useful information perspective, upper echelons theory, and the PsyCap literature. The analysis relies on a longitudinal data set composed of 1,920 observations including calls held for firms listed on the S&P 500 for all quarters of 2015. Computer-assisted text analysis is used to assess cues of organizational PsyCap included within each call, and event-study methodology is used to assess market performance. The findings suggest that organizational PsyCap mitigates stockholders’ negative reaction to earnings surprise, thereby indicating that psychological capital is well-perceived by investors and adds back market value for firms. A discussion of the findings and their implications for research and practice concludes the study.

Historical specimens, when available, can provide new insight into the distribution and evolution of pathogens that may not be discernible from more recent samples. We used ticks collected from hunter-killed white-tailed deer in New Jersey in 2002 to examine the prevalence and distribution of four pathogens transmitted by Ixodes scapularis, the blacklegged tick. Infection with Borrelia burgdorferi sensu stricto, Babesia microti, and Anaplasma phagocytophilum (the agents of Lyme disease, human babesiosis, and human granulocytic anaplasmosis, respectively) was highest in the Coastal Plain and lowest in the northwestern Skylands region. These patterns correspond well with the historically observed northward expansion of I. scapularis within New Jersey and the comparatively recent increase in human cases of these pathogens in the northern part of the state. Additionally, we provide evidence that Borrelia miyamotoi, a relatively new emerging pathogen and agent of relapsing fever, was widespread (though not common) throughout the state in 2002. Our findings highlight the need for enhanced awareness of tick-borne diseases other than Lyme and implementation of large-scale tick surveillance in endemic regions.

Entrepreneurs in emerging nations are increasingly seeking microloans on international crowdfunding platforms composed of prosocial lenders primarily seeking non-monetary returns. Drawing on signaling theory, we posit that economic signals (as illustrated by market orientation) and normative signals (as illustrated by psychological capital) embedded within borrower narratives will influence funding time. A Computer-Assisted-Text-Analysis (CATA) of 130,964 profiles across 49 countries suggests that borrower cues of customer orientation, competitor orientation, long-term focus, profitability focus, confidence, and optimism are positively associated funding time, while cues of coordination, hope, and resilience are negatively associated with funding time. Prosocial lenders seem less inclined to lend to borrowers that exhibit a desire for economic success or normative expectations for positive outcomes in the future, while they seem to lend more rapidly to those exhibiting current hardship or a concern for people. A discussion of these findings and their implications for poverty alleviation concludes the study.

Firm resources are important drivers of firm success, and both tangible and intangible resources have been suggested to have a positive linear effect on firm success when studied independently. In this study, we focus on a firm's entire resource portfolio composition, and posit that bundling dissimilar types of resources is a complex process that involves trade-offs. Drawing on complexity theory, we propose that firm success may be influenced by resource composition, as represented by relative intangibility—that is, a firm's share of intangible resources relative to the sum of both types of resources. Curvilinear hypotheses with environmental moderators are developed and tested using Computer-Assisted-Text-Analysis (CATA) methodology on a 5-year longitudinal sample of 2,245 S&P 500 firms. The results suggest that relative intangibility exhibits a U-shaped relationship with productivity, a key indicator of firm success. However, shape-flips are observed when environmental moderators are introduced, as the relationship becomes inverted U-shaped in less complex environments characterized by low instability and high munificence.

The primary purpose of this study was to examine the demographic characteristics of Boards of Directors in the hospitality industry, and how those characteristics can impact a firm's performance during a major crisis. More specifically, using the upper echelons perspective, this study examined the impact of finance-oriented directors, and directors who were outsiders, on a company's stock price during the great recession. Results using companies from the hospitality industry indicate that companies that had the highest percentage of finance-orientated directors tended to fall further and recover less quickly. Yet, in the aftermath of the crisis, companies that performed worse during the crisis tended to increase the percentage of finance-oriented directors. The authors of the study assert that extending the application of the blissful ignorance effect is a logical explanation for the behavior found in the results.

PurposeThe purpose of this paper is to investigate the effects of a firm’s entrepreneurial proclivity on market performance for large, publicly traded US firms. This study draws upon the five-dimensional view of corporate entrepreneurship (CE) and develops hypotheses aimed at understanding the effects of direct effect of CE cues of proactiveness, autonomy, innovativeness, competitive aggressiveness and risk-taking on stock performance during earnings conference calls.Design/methodology/approachThe entrepreneurial orientation of 339 firm post-earnings announcement conference calls is analyzed through a content analysis of transcripts, and the impact of CE cues on stock price is measured using event-study methodology.FindingsThe results suggest that the cueing the CE dimensions of innovativeness, risk-taking and especially autonomy have a positive effect on market performance during conference calls, while competitive aggressiveness has a negative effect. No effect was found for proactiveness.Research limitations/implicationsThe effect of entrepreneurial proclivity on firm value is not uniform. Not all dimensions of CE have a positive effect on market performance at a corporate level, and measuring each dimension of CE separately may be a valuable approach for future research.Practical implicationsFirms may create more value when they cue specific entrepreneurial attributes, and cueing competitive aggressiveness may not be desirable.Originality/valueThis study fills a gap in the literature by measuring the direct effect of CE cues on market performance through an innovative research design which relies on computer-aided text analysis.

Purpose – The purpose of this paper is to focus on investor reactions to unanticipated changes in income, and whether those reactions can be mitigated by managerial discussion. The authors investigate how top-management team certainty and optimism during post-earnings announcement conference calls can serve as corrective actions and add back firm value in times of unexpected changes in firm-specific risk. Design/methodology/approach – The research question is tested empirically in the context of large, publicly traded, US firms’ quarterly earnings announcements, and their subsequent post-earnings announcement conference calls. The authors use the advanced content analysis software DICTION to measure the levels of managerial certainty and optimism displayed during post-earnings announcement conference calls, and event-study methodology to measure investors’ reactions. Findings – Results indicate that earnings surprises are negatively associated with firm value, but that this relationship is mitigated positively by displays of managerial certainty and optimism during post-earnings announcement conference calls. Originality/value – This work uses an innovative research design to study top-management team rhetoric in post-earnings announcement conference calls, and how specific discussions mitigate investors’ negative reactions to increases in firm-specific risk. The study highlights the importance of top-management team certainty and optimism for value creation in times of change in firm-specific risk, and the importance of rhetoric as a tool for corrective action.

The balanced view of organizational ambidexterity contends that firms achieve superior performance when they successfully balance their exploitation and exploration activities. However, prior empirical research on the link between balanced ambidexterity and firm performance has yielded mixed results. Building on shortcomings identified in prior research, this study explores curvilinear relationships between relative exploration and firm performance for service and manufacturing firms, and considers environmental context as a potential moderator. Hypotheses are tested with Computer-Assisted-Text-Analysis (CATA) methodology on a 5-year longitudinal sample of 1420 service firms and 825 manufacturing firms listed on the S&P 500. Curvilinear relationships are uncovered, suggesting that balanced ambidexterity is associated with the highest level of performance for service firms, while the opposite is found for manufacturing firms. Additionally, balanced ambidexterity may not be beneficial for service firms operating in unstable environments. Lastly, the environmental munificence moderator was not found to be significant.

Purpose– This study is a replication of Wolff and Reed’s (2000) work. The purpose of this paper is to examine how the combination of resources brought to joint ventures influence parent-firm performance. This study is also interested in whether or not the exposure of immobile resources through the semi-transparent membrane of the joint venture can have negative effects on parent-firm performance.Design/methodology/approach– The sample consists of two-parent joint ventures formed by publicly traded US firms between 1997 and 2013. The event-study methodology is used to calculate each parent-firm’s abnormal returns. This work also uses content analysis to analyze parent-firms’ annual reports (10-K).Findings– While Wolff and Reed’s results on resource allocation within joint ventures were not statistically significant, this replication study provided strong support to the resource allocation hypothesis. It was found that intangible resource heterogeneity within a joint venture creates higher performance gains for parent-firms than tangible resource heterogeneity. This work also successfully replicated Wolff and Reed’s findings on the negative impact of immobile resources exposure on parent-firm performance. Wolff and Reed’s results on resource complementarity were, however, not successfully replicated.Originality/value– This replication study goes beyond simply showing that engaging in a joint venture strategy creates value for parent-firms. Through the use of a new content analysis method, this study was able to provide strong support for Wolff and Reed’s theory on the performance gains provided by resource heterogeneity in a joint venture setting, and to confirm the results on potential adverse performance effects of immobile resources exposure.

In all aspects of nursing appropriate care can only be delivered if patients' problems are appropriately identified. In palliative care assessment of need may be particularly difficult as patients experience such a wide range and complexity of problems. In this work Functional Health Patterns (FHP) were used to structure the assessment of a patient referred to as Maria. Once her needs were identified the data was verified and interpreted leading to nursing diagnoses. Case studies are a non-experimental approach in which a wealth of descriptive information is used to examine an issue in depth. In this paper a single case study design was used to apply FHP to identify the needs of Maria. In so doing the theoretical approach of FHP was applied in practice and was subjectively evaluated by an expert in the field of palliative care. The assessment outcomes are presented and may be of value to others wishing to review their patient assessment process.

The etiological agents that cause human babesiosis (Babesia microti) and Lyme disease (Borrelia burgdorferi) share a common tick vector (Ixodes scapularis Say) and rodent reservoir (Peromyscus leucopus), but because the geographical distribution of babesiosis is more restricted than Lyme disease, it was not considered a nationally notifiable disease until 2011. Although recent studies have shown dramatic increases in the number of cases of babesiosis and expansion of its range, little is known about infection and coinfection prevalence of these pathogens in the primary tick vector. Of the 478 I. scapularis nymphs collected within six Monmouth County, NJ, municipalities between 2004 and 2006, 4.0 and 10.0% were infected with B. microti and B. burgdorferi, respectively, while 2.9% were coinfected. Analysis of the 610 I. scapularis adults collected during the same period yielded an infection prevalence of 8.2% for B. microti and 45.2% for B. burgdorferi, while 6.2% were coinfected. The potential public health importance of these findings is discussed.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents.

The rate of blood flow through a tissue (F) is a critical parameter for assessing the functional efficiency of a blood vessel network following angiogenesis. This chapter aims to provide the principles behind the estimation of F, how F relates to other commonly used measures of tissue perfusion, and a practical approach for estimating F in laboratory animals, using small readily diffusible and metabolically inert radio-tracers. The methods described require relatively nonspecialized equipment. However, the analytical descriptions apply equally to complementary techniques involving more sophisticated noninvasive imaging.Two techniques are described for the quantitative estimation of F based on measuring the rate of tissue uptake following intravenous administration of radioactive iodo-antipyrine (or other suitable tracer). The Tissue Equilibration Technique is the classical approach and the Indicator Fractionation Technique, which is simpler to perform, is a practical alternative in many cases. The experimental procedures and analytical methods for both techniques are given, as well as guidelines for choosing the most appropriate method.

Study Type – Diagnosis (quality control) Level of Evidence 2b What's known on the subject? and What does the study add? Today, numerous assays for PSA detection are available from various manufacturers. However, these various assays do not detect PSA equally and several studies have demonstrated variability between them. In order to harmonise PSA results and reduce the discrepancies, reference materials are available for assay calibration. We have demonstrated significantly variability between 6 different assay methods currently in use in 9 hospitals despite assay calibration. Variability in PSA values was reduced with the standardisation of the assay method in 4 hospitals. Our results highlight the dilemma of PSA assay variability and stress the need for nationwide standardisation of PSA testing. OBJECTIVE • To determine whether standardization of total prostate-specific antigen (tPSA) assay methods reduces variability in tPSA measurements. PATIENTS AND METHODS • Blood samples from 84 patients attending a single urology department were distributed across nine hospitals selected throughout Ireland for the independent determination of tPSA under the same conditions. • The selected hospitals collectively used six different assay methods for tPSA detection: Beckman Hybritech WHO Calibrated (used as reference method), Tosoh AIA 1800, Roche E170 (used in three hospitals), Abbott AxSYM, Immulite 2500 2nd Generation (used in two hospitals) and Siemens ADVIA Centaur. • The method of tPSA detection was next standardized in a subset of four hospitals using the same assay method and the measurements were repeated. • The difference in mean tPSA in the cohort across the hospitals tested was determined and the Bland–Altman test was used to assess the agreement between each test. Analysis was performed over both the full (0.5–30 µg/L, N= 84) and a narrow (3–7 µg/L, n= 25) tPSA range. RESULTS • The range and the mean tPSA of the full cohort were inflated across the eight test hospitals, when compared with the reference hospital. • The poorest agreement between assay methods was associated with a bias of 2.2 ± 2.4 µg/L. The variability in tPSA measurements between assay methods was inconsistent across the range of tPSA values tested and increased with increasing mean tPSA. • Agreement in reported tPSA was excellent after standardization of tPSA assay methods (bias

Multimedia learning is widely used in life science education where the use of pictures and text can bring complex structures and processes to life. However the impact on academic performance and deeper understanding is not well documented. We therefore carried out a systematic review to evaluate the effectiveness of multimedia resources in tertiary level life science education. Comprehensive literature searches were conducted; studies were selected based on stringent pre-set criteria, and data were extracted for meta-analysis. In total, 17 studies were used in the meta-analyses with a total population of 2,290 students. The results show that, when used as a substitute for laboratory practicals, multimedia improved student learning gains assessed with an end-of-year examination, (mean difference 7.06, ±4.61). Although it did not improve short-term learning gains in this scenario, multimedia improved learning gains in 10 of the 16 sub-group comparisons made across all the studies. Overall, multimedia learning was more effective than many traditional educational methods although the numbers of studies included in the analysis were ultimately considered to be small due to many exclusions from the studies included in the analysis. Therefore, more good quality trials are required to evaluate a broader range of scenarios relevant to modern practices. Studies would benefit from being rigorous in design with good quality reporting of all aspects of methodology and study results. HEA Subject Centre for Bioscience

Markets are particularly sensitive to the quarterly earnings releases of publicly-traded firm, and tend to react negatively to earnings surprises, as they are indicative of increases in income stre...

New students face the challenge of making a smooth transition between school and university, and with regards to academic practice, there are often gaps between student expectations and university requirements. This study supports the use of the plagiarism detection service Turnitin to give students instant feedback on essays to help improve academic literacy. A student cohort ( n = 76) submitted draft essays to Turnitin and received instruction on how to interpret the 'originality report' themselves for feedback. The impact of this self-service approach was analysed by comparing the writing quality and incidence of plagiarism in draft and final essays, and comparing the results to a previous cohort ( n = 80) who had not used Turnitin formatively. Student and staff perceptions were explored by interview and questionnaire. Using Turnitin formatively was viewed positively by staff and students, and although the incidence of plagiarism did not reduce because of a worsening of referencing and citation skills, the approach encouraged students to develop their writing. To conclude, students were positive of their experience of using Turnitin. Further work is required to understand how to use the self-service approach more effectively to improve referencing and citation, and narrow the gap between student expectations and university standards. [ABSTRACT FROM AUTHOR]

Purpose: The therapeutic potential of combining the prototype tumor vascular-disrupting agent combretastatin A-4 3-O-phosphate (CA-4-P) with systemic nitric oxide synthase (NOS) inhibition was investigated preclinically. Experimental Design: Vascular response (uptake of 125I-labeled iodoantipyrine; laser Doppler flowmetry) and tumor response (histologic necrosis; cytotoxicity and growth delay) were determined. Results: Inducible NOS selective inhibitors had no effect on blood flow in the P22 rat sarcoma. In contrast, the non–isoform-specific NOS inhibitor Nω-nitro- l-arginine (l-NNA; 1 and 10 mg/kg i.v. or chronic 0.1 or 0.3 mg/mL in drinking water) decreased the P22 blood flow rate selectively down to 36% of control at 1 hour but did not induce tumor necrosis at 24 hours. CA-4-P, at clinically relevant doses, decreased the P22 blood flow rate down to 6% of control at 1 hour for 3 mg/kg but with no necrosis induction. However, l-NNA administration enhanced both CA-4-P–induced tumor vascular resistance at 1 hour (chronic l-NNA administration) and necrosis at 24 hours, with 45% or 80% necrosis for 3 and 10 mg/kg CA-4-P, respectively. Bolus l-NNA given 3 hours after CA-4-P was the most effective cytotoxic schedule in the CaNT mouse mammary carcinoma, implicating a particular enhancement by l-NNA of the downstream consequences of CA-4-P treatment. Repeated dosing of l-NNA with CA-4-P produced enhanced growth delay over either treatment alone in P22, CaNT, and spontaneous T138 mouse mammary tumors, which represented a true therapeutic enhancement. Conclusions: The combination of NOS inhibition with CA-4-P is a promising approach for targeting tumor vasculature, with relevance for similar vascular-disrupting agents in development.

Tubulin-binding vascular-disrupting agents (VDA) are currently in clinical trials for cancer therapy but the factors that influence tumor susceptibility to these agents are poorly understood. We evaluated the consequences of modifying tumor vascular morphology and function on vascular and therapeutic response to combretastatin-A4 3-O-phosphate (CA-4-P), which was chosen as a model VDA. Mouse fibrosarcoma cell lines that are capable of expressing all vascular endothelial growth factor (VEGF) isoforms (control) or only single isoforms of VEGF (VEGF120, VEGF164, or VEGF188) were developed under endogenous VEGF promoter control. Once tumors were established, VEGF isoform expression did not affect growth or blood flow rate. However, VEGF188 was uniquely associated with tumor vascular maturity, resistance to hemorrhage, and resistance to CA-4-P. Pericyte staining was much greater in VEGF188 and control tumors than in VEGF120 and VEGF164 tumors. Vascular volume was highest in VEGF120 and control tumors (CD31 staining) but total vascular length was highest in VEGF188 tumors, reflecting very narrow vessels forming complex vascular networks. I.v. administered 40 kDa FITC-dextran leaked slowly from the vasculature of VEGF188 tumors compared with VEGF120 tumors. Intravital microscopy measurements of vascular length and RBC velocity showed that CA-4-P produced significantly more vascular damage in VEGF120 and VEGF164 tumors than in VEGF188 and control tumors. Importantly, this translated into a similar differential in therapeutic response, as determined by tumor growth delay. Results imply differences in signaling pathways between VEGF isoforms and suggest that VEGF isoforms might be useful in vascular-disrupting cancer therapy to predict tumor susceptibility to VDAs. [Cancer Res 2008;68(7):2301–11]

The vascular effects of the endothelin B (ET(B)) receptor agonist IRL 1620 were investigated in the rat P22 carcinosarcoma and a range of normal tissues in BDIX rats. Tissue blood flow rate was calculated from measurements of tissue uptake of radiolabelled iodoantipyrine. A comparison of vascular effects in the P22 tumour and the HSN sarcoma growing in CBH/CBi rats was made using laser Doppler flowmetry, showing similar effects of IRL 1620, with red cell flux rapidly decreasing by 50-60% and then returning to control levels within approximately 30 min. This corresponded to similar levels but different spatial organisation of ET(B) binding sites in the two tumours, as measured by autoradiography. The decrease in tumour blood flow and an increase in vascular resistance suggest that the vascular component of ET(B) receptors in the P22 tumour is localised on contractile elements rather than on endothelial cells. ET(A) receptors were also identified. Vasoconstriction occurred uniformly throughout the P22 tumour mass, consistent with a measured homogeneous distribution of ET(B) receptors. IRL 1620 caused vasoconstriction in normal skeletal muscle, kidney and small intestine of the BDIX rat as well as in tumour, but did not affect blood flow in other tissues. These effects could be useful for limiting toxicity of certain chemotherapeutic agents. Fully functional ET(B) receptors are clearly expressed on tumour vasculature and IRL 1620 shows promise for short-term modification of tumour blood flow. Expression levels of ET(B) receptors on the tumour vasculature could be useful for predicting which tumours are likely to respond to IRL 1620.

Large numbers of different bacterial species are resident in the lumen of the distal gastrointestinal tract. The normal intestinal host–microbial interactions are not well understood, but the relationship is generally believed to be either mutually beneficial or beneficial to one without disadvantage to the other. Animal model and clinical studies suggest that IBD (inflammatory bowel disease) may develop in a susceptible individual when the normal host–bacterial relationship is dysregulated. In addition to rodent models, this article reviews studies that have investigated the cellular and molecular mechanisms of interactions between intestinal mucosal cells and the resident luminal bacteria in healthy individuals and patients with ulcerative colitis and Crohn's disease. Mechanisms by which the intestinal mucosa is able to avoid pro-inflammatory responses to commensal bacteria (and their products) but able to respond appropriately to luminal pathogens is currently an area of active investigation. Such studies are beginning to provide important clues regarding possible alterations in the mucosa that lead to the development of pro-inflammatory responses to resident bacteria in patients with IBD. Approaches to alter the intestinal microflora for therapeutic purposes and their potential mechanisms of action are also discussed.

Carbon monoxide (CO), one of the products of heme oxygenase (HO) catalyzed heme degradation, is a vasodilator. The aim of the present study was to clarify the role of HO in blood flow maintenance in tumors. Male BD9 rats bearing subcutaneous transplants of the P22 carcinosarcoma tumor were treated intraperitoneally (ip) with either tin-protoporphyrin IX (SnPP; 45 μmol/kg), a selective inhibitor of HO or copper-protoporphyrin IX (CuPP; 45 μmol/kg), used as a negative control. The extent of HO activity inhibition was measured using a spectrophotometric assay of bilirubin production and blood flow rates to the tumor and a range of normal tissues were assessed using the uptake of the radiolabelled tracer, iodo-antipyrine (125I-IAP). The animals were cannulated under fentanyl citrate/fluanisone (Hypnorm)/midazolam anesthesia. In the P22 tumor, SnPP, but not CuPP, caused a complete inhibition of HO activity 15 min post-treatment. Administration of SnPP 15 min before blood flow measurements reduced tumor blood flow by 17%, with no effects in any of the normal tissues studied. However, CuPP induced a greater reduction in tumor blood flow than SnPP (45% decrease). Furthermore, CuPP caused a reduction in blood flow to the skin and small intestine but a significant increase to skeletal muscle. The current findings conclusively establish only a minor role played by the HO/CO system in the maintenance of blood flow in this tumor system, despite relatively high levels of HO-1 protein and HO activity. The results also highlight the potential usefulness of CuPP as a tumor blood flow modifier.