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Article ; Online: The Impact of Tele-Education on Family Medicine Clerkship Students' Learning Outcomes.

Unger, Kendra / Bors, Kathleen / Xiang, Jun / Lapp, Madison / Oreskovich, Jason / Higinbotham, Ashley / Snyder, Telista / Hanks, Heather / Ashcraft, Amie M

Family medicine

2023 Volume 55, Issue 9, Page(s) 616–619

Abstract: Background and objectives: The COVID-19 pandemic necessitated rapid changes to medical education for student and patient protection. A dearth of published US studies examine resulting clinical education outcomes due to pandemic-induced curricula changes. ...

Abstract	Background and objectives: The COVID-19 pandemic necessitated rapid changes to medical education for student and patient protection. A dearth of published US studies examine resulting clinical education outcomes due to pandemic-induced curricula changes. We describe adaptations made to a family medicine clerkship to move it from traditional in-person delivery to virtual only, and then from virtual to hybrid; and compare educational outcomes of students across delivery types. Methods: We stratified 386 medical students in their third year completing their 8-week family medicine clerkship by type of content delivery, including in person, virtual only, and hybrid instruction. We examined the impact of these changes on three clerkship learning outcomes: the midblock assessment score, the National Board of Medical Examiners (NBME) exam score, and the final numeric score (FNS). Results: In our sample, 164 (42.5%) received content in person, 36 (9.3%) received virtual only, and 186 (48.2%) received hybrid content. Students receiving virtual only (M=76.4, SD=9.1) had significantly higher midblock assessment scores (F=8.06, df=2, P=.0004) than students receiving hybrid (M=71.7, SD=8.8) and in-person training (M=74.5, SD=7.2). No significant differences existed in students' NBME exam scores or FNSs across delivery types. Conclusions: Students receiving virtual-only or hybrid content performed at least as well on three clerkship-related educational outcomes as their pre-COVID peers participating in person. Further research is needed to understand how changes to medical education affected student learning and skill development.
MeSH term(s)	Humans ; Educational Measurement/methods ; Family Practice ; Pandemics ; Clinical Clerkship/methods ; Curriculum ; Students, Medical ; Clinical Competence
Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	639374-3
ISSN	1938-3800 ; 0742-3225
ISSN (online)	1938-3800
ISSN	0742-3225
DOI	10.22454/FamMed.2023.410835
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Zs.A 2327: Show issues

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Article ; Online: A novel dual ATM/DNA-PK inhibitor, XRD-0394, potently radiosensitizes and potentiates PARP and topoisomerase I inhibitors.

Gilmer, Tona M / Lai, Chun-Hsiang / Guo, Kexiao / Deland, Katherine / Ashcraft, Kathleen A / Stewart, Amy E / Wang, Yaode / Fu, Jianmin / Wood, Kris C / Kirsch, David G / Kastan, Michael B

Molecular cancer therapeutics

2024

Abstract: A majority of cancer patients receive radiation therapy as part of their treatment regimens whether using external beam therapy or locally-delivered radioisotopes. While often effective, some tumors are inadequately controlled with radiation and ... ...

Abstract	A majority of cancer patients receive radiation therapy as part of their treatment regimens whether using external beam therapy or locally-delivered radioisotopes. While often effective, some tumors are inadequately controlled with radiation and radiation therapy has significant short-term and long-term toxicities for cancer survivors. Insights into molecular mechanisms involved in cellular responses to DNA breaks introduced by radiation or other cancer therapies have been gained in recent years and approaches to manipulate these responses to enhance tumor cell killing or reduce normal tissue toxicity are of great interest. Here, we report the identification and initial characterization of XRD-0394, a potent and specific dual inhibitor of two DNA damage-response kinases, ATM and DNA-PKcs. This orally bioavailable molecule demonstrates significantly enhanced tumor cell kill in the setting of therapeutic ionizing irradiation in vitro and in vivo. XRD-0394 also potentiates the effectiveness of topoisomerase I inhibitors in vitro. Additionally, in cells lacking BRCA1/2 XRD-0394 shows single agent activity and synergy in combination with PARP inhibitors. A Phase Ia clinical trial (NCT05002140) with XRD-0394 in combination with RT has completed. These results provide a rationale for future clinical trials with XRD-0394 in combination with RT, PARP inhibitors and targeted delivery of topoisomerase I inhibitors.
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-23-0890
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Article ; Online: Implications of Increase in Vascular Permeability in Tumors by VEGF: A Commentary on the Pioneering Work of Harold Dvorak.

Dewhirst, Mark W / Ashcraft, Kathleen A

Cancer research

2016 Volume 76, Issue 11, Page(s) 3118–3120

Abstract: See related article by Senger et al., Cancer Res 1986;46:5629-32Visit the Cancer Research 75(th) Anniversary timeline. ...

Abstract	See related article by Senger et al., Cancer Res 1986;46:5629-32Visit the Cancer Research 75(th) Anniversary timeline.
MeSH term(s)	Animals ; Capillary Permeability ; Humans ; Neoplasms/blood supply ; Neoplasms/pathology ; Neovascularization, Pathologic/pathology ; Vascular Endothelial Growth Factor A/metabolism
Chemical Substances	Vascular Endothelial Growth Factor A
Language	English
Publishing date	2016--01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-16-1292
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Article ; Online: Exercise as Adjunct Therapy in Cancer.

Ashcraft, Kathleen A / Warner, Allison Betof / Jones, Lee W / Dewhirst, Mark W

Seminars in radiation oncology

2018 Volume 29, Issue 1, Page(s) 16–24

Abstract: Data from observational studies indicate that both physical activity as well as exercise (ie, structured physical activity) is associated with reductions in the risk of recurrence and cancer mortality after a diagnosis of certain forms of cancer. ... ...

Abstract	Data from observational studies indicate that both physical activity as well as exercise (ie, structured physical activity) is associated with reductions in the risk of recurrence and cancer mortality after a diagnosis of certain forms of cancer. Emerging evidence from preclinical studies indicates that physical activity/exercise paradigms regulate intratumoral vascular maturity and perfusion, hypoxia, and metabolism and augments the antitumor immune response. Such responses may, in turn, enhance response to standard anticancer treatments. For instance, exercise improves efficacy of chemotherapeutic agents, and there is rationale to believe that it will also improve radiotherapy response. This review overviews the current preclinical as well as clinical evidence supporting exercise modulation of therapeutic response and postulated biological mechanisms underpinning such effects. We also examine the implications for tumor response to radiation, chemotherapy, and immunotherapy.
MeSH term(s)	Antineoplastic Agents/therapeutic use ; Combined Modality Therapy ; Exercise Therapy/methods ; Humans ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/therapy ; Radiotherapy
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2018-12-20
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1146999-7
ISSN	1532-9461 ; 1053-4296
ISSN (online)	1532-9461
ISSN	1053-4296
DOI	10.1016/j.semradonc.2018.10.001
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Article ; Online: Impact of prostatic radiation therapy on bladder contractility and innervation.

Turner, Alexander C / Powers, Shelby A / Odom, Michael R / Pak, Elena S / Ashcraft, Kathleen A / Koontz, Bridget F / Hannan, Johanna L

Neurourology and urodynamics

2021 Volume 40, Issue 6, Page(s) 1470–1478

Abstract: Aims: To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats.: Methods: Male Sprague-Dawley rats (8 weeks) ... ...

Abstract	Aims: To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats. Methods: Male Sprague-Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2- and 10-weeks post-RT. Detrusor contractile responses to carbachol and electrical field stimulation (EFS) were measured. Bladders were stained with Masson's trichrome, and antibodies for nonspecific neuronal marker, cholinergic nerve marker choline acetyltransferase (ChAT), and alpha-smooth muscle actin. MPG gene expression was assessed by quantitative polymerase chain reaction for ubiquitin carboxy-terminal hydrolase L1 (Uchl1) and Chat. Results: At 2 weeks post-RT, bladder smooth muscle, detrusor cholinergic axon profiles, and MPG Chat gene expression were increased (p < .05), while carbachol and EFS-mediated contractions were decreased (p < .05). In contrast, at 10 weeks post-RT, nerve-mediated contractions were increased compared with control (p < .05), while bladder smooth muscle, detrusor cholinergic axon profiles, MPG Chat expression, and carbachol contractions had normalized. At both 2- and 10-weeks post-RT, there was no change in detrusor nonspecific axon profiles and MPG Uchl1 expression. Conclusion: In a rat model, RT of the prostate and MPG was associated with early changes in MPG Chat gene expression, and bladder cholinergic axon profiles and smooth muscle content which resolved over time. After RT recovery, bladder contractility decreased early and increased by 10 weeks. Long-term changes to the MPG and increased bladder cholinergic axons may contribute to RT-induced bladder dysfunction in prostate cancer survivors.
MeSH term(s)	Animals ; Carbachol/pharmacology ; Male ; Muscle Contraction ; Muscle, Smooth ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder
Chemical Substances	Carbachol (8Y164V895Y)
Language	English
Publishing date	2021-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	604904-7
ISSN	1520-6777 ; 0733-2467
ISSN (online)	1520-6777
ISSN	0733-2467
DOI	10.1002/nau.24705
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Zs.A 1828: Show issues

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Article ; Online: The future of biology in driving the field of hyperthermia.

Dewhirst, Mark W / Lee, Chen-Ting / Ashcraft, Kathleen A

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

2016 Volume 32, Issue 1, Page(s) 4–13

Abstract: In 2011 Hanahan and Weinberg updated their well-established paper 'The hallmarks of cancer'. The rationale for that review and its predecessor was to produce a conceptual framework for future research in cancer. The original Hallmarks included: cell ... ...

Abstract	In 2011 Hanahan and Weinberg updated their well-established paper 'The hallmarks of cancer'. The rationale for that review and its predecessor was to produce a conceptual framework for future research in cancer. The original Hallmarks included: cell signalling to enhance tumour cell proliferation, acquisition of ability to evade growth suppressors, developing mechanisms to resist cell death, enabling replicative immortality, initiating angiogenesis and activating processes to enable invasion and metastasis. In the more recent paper, Hanahan and Weinberg added important new features to this composite paradigm. The new features were: (1) altered metabolism, (2) evasion of immune destruction, (3) tumour promoting inflammation, and (4) the cellular microenvironment. These four new features are the main focus of this review. Hanahan and Weinberg did not specifically include the physiological microenvironment which is dominated by hypoxia and acidosis. In this review we will consider these features in addition to the cellular and metabolic components of the microenvironment. The purpose of this review is to present a vision of emerging fields of study in hyperthermia biology over the next decade and beyond. As such, we are focusing our attention on pre-clinical studies, primarily using mice. The application of hyperthermia in human patients has been thoroughly reviewed elsewhere.
MeSH term(s)	Animals ; Autoimmunity ; Humans ; Hyperthermia, Induced ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/pathology ; Neoplasms/therapy ; Neoplastic Stem Cells/radiation effects ; Neovascularization, Pathologic ; Oxidative Stress ; Tumor Microenvironment
Language	English
Publishing date	2016
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	632526-9
ISSN	1464-5157 ; 0265-6736
ISSN (online)	1464-5157
ISSN	0265-6736
DOI	10.3109/02656736.2015.1091093
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Zs.A 2051: Show issues

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Article ; Online: Can Exercise-Induced Modulation of the Tumor Physiologic Microenvironment Improve Antitumor Immunity?

Zhang, Xiaojie / Ashcraft, Kathleen A / Betof Warner, Allison / Nair, Smita K / Dewhirst, Mark W

Cancer research

2019 Volume 79, Issue 10, Page(s) 2447–2456

Abstract: The immune system plays an important role in controlling cancer growth. However, cancers evolve to evade immune detection. Immune tolerance and active immune suppression results in unchecked cancer growth and progression. A major contributor to immune ... ...

Abstract	The immune system plays an important role in controlling cancer growth. However, cancers evolve to evade immune detection. Immune tolerance and active immune suppression results in unchecked cancer growth and progression. A major contributor to immune tolerance is the tumor physiologic microenvironment, which includes hypoxia, hypoglucosis, lactosis, and reduced pH. Preclinical and human studies suggest that exercise elicits mobilization of leukocytes into circulation (also known as "exercise-induced leukocytosis"), especially cytotoxic T cells and natural killer cells. However, the tumor physiologic microenvironment presents a significant barrier for these cells to enter the tumor and, once there, properly function. We hypothesize that the effect of exercise on the immune system's ability to control cancer growth is linked to how exercise affects the tumor physiologic microenvironment. Normalization of the microenvironment by exercise may promote more efficient innate and adaptive immunity within the tumor. This review summarizes the current literature supporting this hypothesis.
MeSH term(s)	Adaptive Immunity ; Antibody Formation ; Exercise ; Glucose/metabolism ; Humans ; Immunity, Innate ; Lactic Acid/metabolism ; Neoplasms/immunology ; Neoplasms/metabolism ; Neoplasms/physiopathology ; Tumor Microenvironment
Chemical Substances	Lactic Acid (33X04XA5AT) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2019-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-18-2468
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Article ; Online: Risk of erectile dysfunction after modern radiotherapy for intact prostate cancer.

Hunt, Anastasia A / Choudhury, Kingshuk Roy / Nukala, Varun / Nolan, Michael W / Ahmad, Alina / Ashcraft, Kathleen A / Koontz, Bridget F

Prostate cancer and prostatic diseases

2020 Volume 24, Issue 1, Page(s) 128–134

Abstract: Background: Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate ... ...

Abstract	Background: Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate modern external beam radiotherapy and brachytherapy techniques to determine the incidence of radiotherapy (RT) induced ED. Methods: A systematic review of the literature published between January 2002 and December 2018 was performed to obtain patient reported rates of ED after definitive external beam radiotherapy, ultrafractionated stereotactic radiotherapy, and brachytherapy (BT) to the prostate in men who were potent prior to RT. Univariate and multivariate analyses of radiation dose, treatment strategy, and length of follow-up were analyzed to ascertain their relationship with RT-induced ED. Results: Of 890 articles reviewed, 24 met inclusion criteria, providing data from 2714 patients. Diminished erectile function status post RT was common and similar across all studies. The median increase in men reporting ED was 17%, 26%, 23%, and 23%, 3DCRT, IMRT, low dose rate BT, and SBRT, respectively, at 2-year median follow-up. Conclusion: ED is a common side effect of RT. Risk of post-RT ED is similar for both LDR brachytherapy and external beam RT with advanced prostate targeting and penile-bulb sparing techniques utilized in modern RT techniques.
MeSH term(s)	Brachytherapy/adverse effects ; Erectile Dysfunction/etiology ; Erectile Dysfunction/physiopathology ; Humans ; Male ; Penile Erection/radiation effects ; Prostatic Neoplasms/physiopathology ; Prostatic Neoplasms/radiotherapy ; Radiotherapy Dosage
Keywords	covid19
Language	English
Publishing date	2020-07-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	1419277-9
ISSN	1476-5608 ; 1365-7852
ISSN (online)	1476-5608
ISSN	1365-7852
DOI	10.1038/s41391-020-0247-x
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Zs.A 5277: Show issues

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Article ; Online: Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth.

Powers, Shelby A / Odom, Michael R / Pak, Elena S / Moomaw, Megan A / Ashcraft, Kathleen A / Koontz, Bridget F / Hannan, Johanna L

The journal of sexual medicine

2019 Volume 16, Issue 1, Page(s) 27–41

Abstract: Background: Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated.: Aim: ...

Abstract	Background: Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated. Aim: To determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model. Methods: Male rats underwent 0 Gy or 22 Gy single fraction of prostate-confined, conformal RT. At 2 weeks or 10 weeks post-RT (n = 10/group), cavernous nerve stimulation was performed and erections were assessed. Tissue bath experiments were performed to assess both penile artery and internal pudendal artery (IPA) function. MPGs were dissociated and neurons grown in culture for 72 hours. Immunofluorescence staining was done to quantify neuron survival (terminal deoxynucleotidyl transferase nick-end labeling), outgrowth (beta-tubulin III), type (nitric oxide synthase [nNOS] and tyrosine hydroxylase [TH]), and nerve injury markers (small GTPase Rac1 and ninjurin-1 [Ninj-1]). Whole MPG real-time quantitative polymerase chain reaction (qPCR) was performed to measure expression of genes related to nerve type, neuron injury, repair, and myelination, such as Ninj-1, Rac1, ATF3, GAP43, GFAP, SOX10, and KROX20. Outcomes: Intracavernosal pressure (ICP) to mean arterial pressure (MAP) ratio, smooth muscle contractility and relaxation, gene expression, neuritogenesis, and apoptosis. Results: Following RT, ICP/MAP was unchanged at 2 weeks or 10 weeks. Nerve-mediated penile contraction was increased at 2 weeks, whereas adrenergic contraction was reduced at 10 weeks. Penile relaxation and IPA vasoreactivity were unchanged. Neuronal apoptosis was more than doubled both early and late post-RT. RT caused a progressive decrease in neurite branching but an early increase and then late decrease in neurite lengthening. RT reduced the numbers of nNOS-positive neurons both early and late and also decreased MPG nitrergic gene expression. TH neurons and gene expression were unchanged at 2 weeks; however, both were decreased after 10 weeks. Although most markers of gene injury and repair were unaffected early post-RT, MPG expression of Ninj1 and GFAP increased. After 10 weeks, Ninj1 and GFAP remained elevated while markers of neuron injury (ATF3), outgrowth (GAP43 and Rac1), and myelin regulation (SOX10) were decreased. Clinical translation: RT-induced ED may result from damage to the ganglia controlling erections. Strengths & limitations: This study used a clinically relevant, prostate-confined model to examine neurovascular structures not accessible in human studies. Unfortunately, rats did not exhibit ED at this time point. Conclusion: This is the first study to demonstrate impaired health and regeneration potential of dissociated MPG neurons following RT. Neuronal injury was apparent early post-RT and persisted or increased over time but was insufficient to cause ED at the time points examined. Powers SA, Odom MR, Pak ES, et al. Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth. J Sex Med 2019;16:27-41.
MeSH term(s)	Animals ; Disease Models, Animal ; Erectile Dysfunction/etiology ; Ganglia/metabolism ; Hypogastric Plexus/metabolism ; Male ; Nitric Oxide Synthase/metabolism ; Nitric Oxide Synthase Type I/metabolism ; Penile Erection/radiation effects ; Penis/physiopathology ; Prostatic Neoplasms/radiotherapy ; Rats ; Rats, Sprague-Dawley ; Trauma, Nervous System/complications ; Tyrosine 3-Monooxygenase/metabolism
Chemical Substances	Nitric Oxide Synthase (EC 1.14.13.39) ; Nitric Oxide Synthase Type I (EC 1.14.13.39) ; Tyrosine 3-Monooxygenase (EC 1.14.16.2)
Language	English
Publishing date	2019-01-03
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2251959-2
ISSN	1743-6109 ; 1743-6095
ISSN (online)	1743-6109
ISSN	1743-6095
DOI	10.1016/j.jsxm.2018.11.010
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Article ; Online: Psychological stress exacerbates primary vaginal herpes simplex virus type 1 (HSV-1) infection by impairing both innate and adaptive immune responses.

Ashcraft, Kathleen A / Bonneau, Robert H

Brain, behavior, and immunity

2008 Volume 22, Issue 8, Page(s) 1231–1240

Abstract: Chronic psychological stress is generally immunosuppressive and contributes to an increase in herpes simplex virus (HSV) pathogenicity. We have previously shown that mice experiencing stress at the time of intranasal HSV infection have increased levels ... ...

Abstract	Chronic psychological stress is generally immunosuppressive and contributes to an increase in herpes simplex virus (HSV) pathogenicity. We have previously shown that mice experiencing stress at the time of intranasal HSV infection have increased levels of infectious virus in their nasal cavity, as compared to control mice that were not subjected to stress. We have extended our studies to determine the effects of stress at another clinically-relevant mucosal site by examining the immune response to and pathogenesis of vaginal HSV infection. Mice experiencing psychological stress during vaginal HSV infection exhibited an increase in both vaginal viral titers and the pathology associated with this HSV infection. We demonstrate that these observations result from the failure of both the innate and HSV-specific adaptive immune responses. At 2 days post-infection, NK cell numbers were significantly decreased in mice experiencing restraint stress. Studies examining the adaptive immune response revealed a decrease in the number of HSV-specific CD8(+) T cells in not only the vaginal tissue itself but also the draining iliac lymph nodes (ILN). Furthermore, the number of functional cells, in terms of both their degranulation and interferon-gamma production, in the ILN of stressed mice was decreased as compared to non-stressed mice. We conclude that psychological stress, through its suppression of both innate and adaptive immune responses, may be an important factor in the ability to control vaginal HSV infection.
MeSH term(s)	Administration, Intravaginal ; Animals ; Antigens, Surface/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Count ; Female ; Flow Cytometry ; Herpes Genitalis/immunology ; Herpesvirus 1, Human/immunology ; Herpesvirus 1, Human/pathogenicity ; Immunity, Mucosal/immunology ; Interferon-gamma/immunology ; Lymph Nodes/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; Restraint, Physical ; Stress, Psychological/immunology ; Time Factors ; Vagina/cytology ; Vagina/immunology
Chemical Substances	Antigens, Surface ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2008-06-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2008.06.008
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