bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of HER2/neuExpression Level on Response to the E75 Vaccine: From U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02
Authors: Benavides Linda C. , Gates Jeremy D. , Carmichael Mark G. , Patel Ritesh , Holmes Jarrod P. , Hueman Matthew T. , Mittendorf Elizabeth A. , Craig Dianna , Stojadinovic Alexander , Ponniah Sathibalan , Peoples George E.
Published: April 2009

Purpose: HER2/neu, a source of immunogenic peptides, is expressed in >75% of breast cancer patients. We have conducted clinical trials with the HER2/neu E75 peptide vaccine in breast cancer patients with varying levels of HER2/neu expression. Vaccine response based on HER2/neu expression level was analyzed.

Experimental Design: Patients were stratified by HER2/neu expression. Low expressors (n = 100) were defined as HER2/neu immunohistochemistry (IHC) 1+ to 2+ or fluorescence in situ hybridization < 2.0. Overexpressors (n = 51) were defined as IHC 3+ or fluorescence in situ hybridization ≥ 2.0. Additional analyses were done stratifying by IHC status (0-3+). Standard clinocopathlogic factors, immunologic response (in vivo delayed-type hypersensitivity reactions; ex vivo human leukocyte antigen A2:immunoglobulin G dimer assay), and clinical responses (recurrence; mortality) were assessed.

Results: Low-expressor (control, 44; vaccinated, 56) versus overexpressor patients (control, 22; vaccinated, 29) were assessed. Low expressors, overexpressors, and most IHC-status vaccinated groups responded immunologically. Vaccinated low-expressor patients had larger maximum immunologic responses compared with overexpressor patients (P = 0.04), and vaccinated IHC 1+ patients had increased long-term immune response (P = 0.08). More importantly, compared with controls, low-expressor patients had a mortality reduction (P = 0.08). The largest decrease in mortality was seen in IHC 1+ patients (P = 0.05). In addition, a subset of overexpressor patients (n = 7) received trastuzumab before vaccination, and this combination seems safe and immunologically beneficial.

Conclusions: Most patients with various levels of HER2/neu expression responded immunologically and seemed to benefit from vaccination. The low expressors, specifically IHC 1+ patients, had more robust immunologic responses and may derive the greatest clinical benefit from the E75 vaccine.
CREB in the Pathophysiology of Cancer: Implications for Targeting Transcription Factors for Cancer Therapy
Authors: Sakamoto Kathleen M. , Frank David A.
Published: April 2009

Transcription factors are key regulators of the pattern of gene expression in a cell and directly control central processes such as proliferation, survival, self-renewal, and invasion. Given this critical role, the function of transcription factors is normally regulated closely, often through transient phosphorylation. Although transcription factors are not often directly modified by mutations in cancer cells, they frequently become activated constitutively through mutations affecting “upstream” pathways. By continually driving the expression of key target genes, these oncogenic transcription factors play a central role in tumor pathogenesis. One such transcription factor is the cAMP-regulatory element-binding protein (CREB), which can be activated through phosphorylation by a number of kinases, including Akt, p90Rsk, protein kinase A, and calcium/calmodulin-dependent kinases and regulates genes whose deregulated expression promotes oncogenesis, including cyclins, Bcl-2 family members, and Egr-1. CREB is overexpressed and constitutively phosphorylated in a number of forms of human cancer, including acute myeloid leukemia (AML) and non–small cell lung cancer, and appears to play a direct role in disease pathogenesis and prognosis. Although transcription factors have not been a central focus of drug development, recent advances suggest that CREB and other such proteins may be worthwhile targets for cancer therapy.
β-Catenin Small Interfering RNA Successfully Suppressed Progression of Multiple Myeloma in a Mouse Model
Authors: Ashihara Eishi , Kawata Eri , Nakagawa Yoko , Shimazaski Chihiro , Kuroda Junya , Taniguchi Kyoko , Uchiyama Hitoji , Tanaka Ruriko , Yokota Asumi , Takeuchi Miki , Kamitsuji Yuri , Inaba Tohru , Taniwaki Masafumi , Kimura Shinya , Maekawa Taira
Published: April 2009

Purpose: β-catenin is the downstream effector of the Wnt signaling pathway, and it regulates cell proliferation. β-catenin overexpression correlates positively with prognosis in several types of malignancies. We herein assessed its effects on growth of multiple myeloma cells using a xenograft model.

Experimental Design: We first investigated the expression of β-catenin in multiple myeloma cell lines and multiple myeloma cells obtained from patients. Next, we investigated the growth inhibitory effects of β-catenin small interfering RNA on the growth of multiple myeloma cells in vivo. Six-week-old male BALB/c nu/nu mice were inoculated s.c. in the right flank with 5 × 106 RPMI8226 cells, followed by s.c. injections of β-catenin small interfering RNA, scramble small interfering RNA, or PBS/atelocollagen complex twice a week for a total of eight injections.

Results: Significantly higher levels of β-catenin expression were observed in multiple myeloma cell lines and in samples from patients with multiple myeloma than those found in mononuclear cells obtained from healthy volunteers. In in vivo experiments, no inhibitory effects were observed following treatment with scramble small interfering RNA or PBS/atelocollagen complexes, whereas treatment with β-catenin small interfering RNA/atelocollagen complex significantly inhibited growth of multiple myeloma tumors (P < 0.05).

Conclusions: β-catenin small interfering RNA treatment inhibited the growth of multiple myeloma tumors in a xenograft model. To our knowledge, this is the first report showing that the treatment with β-catenin small interfering RNA produces an inhibitory effects on growth of hematologic malignancies in vivo. Because treatment with β-catenin small interfering RNA inhibited growth of multiple myeloma cells, β-catenin is the attractive novel target for treating multiple myeloma.
Translating the Metastasis Paradigm from Scientific Theory to Clinical Oncology
Authors: Dong Fei , Budhu Anuradha S. , Wang Xin Wei
Published: April 2009

Cancer metastasis contributes to significant morbidity and mortality. Patients with metastatic cancer, often considered incurable, are provided with either supportive care or aggressive management without curative intent. Despite decades of research toward unraveling cancer progression mechanisms, the current body of knowledge has not translated into effective antimetastasis therapies, but recent findings challenge the classic notion that metastases develop during the late stages of carcinogenesis. Here, we evaluate the scientific evidence in the context of the multistage metastasis model. The resolution of current controversies has implications on both the prognostic value of molecular technology and the future of targeted therapies for the clinical benefit of metastasis patients.
p65 Activity and ZAP-70 Status Predict the Sensitivity of Chronic Lymphocytic Leukemia Cells to the Selective IκB Kinase Inhibitor BMS-345541
Authors: López-Guerra Mónica , Roué Gaël , Pérez-Galán Patricia , Alonso Roberto , Villamor Neus , Montserrat Emili , Campo Elias , Colomer Dolors
Published: April 2009

Purpose: Constitutive nuclear factor-κB (NF-κB) activation has been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL). Our purpose was to characterize the molecular mechanisms underlying for the selective IκB kinase inhibitor BMS-345541 in CLL cells together with the analysis of its combination with several antineoplasic drugs.

Experimental Design: Primary cells from 34 CLL patients were incubated with different doses of BMS-345541. NF-κB DNA-binding activity was analyzed by ELISA-based kits and the characterization of the apoptotic pathway was done by flow cytometry, immunoblotting, quantitative reverse transcription-PCR, and immunofluorescence techniques.

Results: BMS-345541 selectively induced apoptosis in CLL cells in the low micromolar range irrespective of p53 status. Noteworthy, the high ZAP-70 group was significantly more sensitive to BMS-345541 than the low ZAP-70 group, in correlation with high levels of p65 phosphorylation and DNA-binding activity. Following NF-κB inhibition, BMS-345541 led to induction of the mitochondrial apoptotic pathway and activation of both caspase-dependent and caspase-independent factors. Moreover, BMS-345541-induced apoptosis was accompanied by down-regulation of several antiapoptotic NF-κB-target genes, including both BCL2 family members and apoptotic endogenous inhibitors. In addition, we showed a strong synergism between BMS-345541 and conventional chemotherapeutics such as mitoxantrone and dexamethasone as well as with new promising drugs such as the BH3-mimetic GX15-070/Obatoclax or the anti-TRAIL-R1 monoclonal antibody mapatumumab.

Conclusions: These data confirm that NF-κB is a relevant target in CLL and indicate that inhibitors of IκB kinase, alone or in combination, represent a novel therapeutic strategy for the treatment of CLL patients, especially for the group with high ZAP-70.
Induction of Wilms' Tumor Protein (WT1)–Specific Antitumor Immunity Using a Truncated WT1-Expressing Adenovirus Vaccine
Authors: Osada Takuya , Woo Christopher Y. , McKinney Matthew , Yang Xiao Yi , Lei Gangjun , LaBreche Heather G. , Hartman Zachary C. , Niedzwiecki Donna , Chao Nelson , Amalfitano Andrea , Morse Michael A. , Lyerly H. Kim , Clay Timothy M.
Published: April 2009

Purpose: Wilms' tumor protein (WT1) is overexpressed in most leukemias and many solid tumors and is a promising target for tumor immunotherapy. WT1 peptide–based cancer vaccines have been reported but have limited application due to HLA restriction of the peptides. We sought to vaccinate using adenoviral (Ad) vectors encoding tumor-associated antigens such as WT1 that can stimulate tumor-associated antigen–specific immunity across a broad array of HLA types and multiple class I and class II epitopes.

Experimental Design: We developed a novel Ad vector encoding a truncated version of WT1 (Ad-tWT1) lacking the highly conserved COOH terminus zinc finger domains and tested its ability to stimulate WT1-specific immune responses and antitumor immunity in two murine models of WT1-expressing tumors.

Results: Despite encoding a transcription factor, we found that Ad-tWT1–transduced murine and human dendritic cells showed cytoplasmic expression of the truncated WT1 protein. In addition, vaccination of C57BL/6 mice with Ad-tWT1 generated WT1-specific cell-mediated and humoral immune responses and conferred protection against challenge with the leukemia cell line, mWT1-C1498. Moreover, in a tumor therapy model, Ad-tWT1 vaccination of TRAMP-C2 tumor-bearing mice significantly suppressed tumor growth.

Conclusions: This is the first report of a WT1-encoding Ad vector that is capable of inducing effective immunity against WT1-expressing malignancies. Based on these findings, Ad-tWT1 warrants investigation in human clinical trials to evaluate its applications as a vaccine for patients with WT1-expressing cancers.
Motility Induction in Breast Carcinoma by Mammary Epithelial Laminin 332 (Laminin 5)
Authors: Carpenter Philip M. , Dao Anh V. , Arain Zahida S. , Chang Michelle K. , Nguyen Hoa P. , Arain Shehla , Wang-Rodriguez Jessica , Kwon Soon-Young , Wilczynski Sharon P.
Published: April 2009

Host interactions with tumor cells contribute to tumor progression by several means. This study was done to determine whether mammary epithelium could interact with breast carcinoma by producing substances capable of inducing motility in the cancer cells. Conditioned medium of immortalized 184A1 mammary epithelium collected in serum-free conditions induced dose-dependent motility in the MCF-7 breast carcinoma cell line by both a semiquantitative scattering assay and a Boyden chamber assay. Purification of the motility factor revealed that it was laminin 332 (formerly laminin 5) by mass spectroscopy. A Western blot of the 184A1 conditioned medium using a polyclonal antibody confirmed the presence of laminin 332 in the conditioned medium. Blockage of the motility with antibodies to the laminin 332 and its receptor components, α3 and β1 integrins, provided further evidence that tumor cell motility was caused by the laminin 332 in the conditioned medium. Invasion of MCF-7, BT-20, and MDA-MB-435S was induced by purified laminin 332 and 184A1 conditioned medium and blocked by an anti-α3 integrin antibody. Staining of carcinoma in situ from breast cancer specimens revealed that laminin 332 in the myoepithelium adjacent to the preinvasive cells provided a source of laminin 332 that could potentially encourage the earliest steps of stromal invasion. In metaplastic breast carcinomas, the presence of laminin 332-producing cells coexpressing α3 integrin and the greater metastatic potential of tumors with higher laminin 332 levels suggest that laminin 332 expression is associated with aggressive features in these human breast cancers.(Mol Cancer Res 2009;7(4):462–75)
Exposure to Supplemental Oxygen Downregulates Antioxidant Enzymes and Increases Pulmonary Arterial Contractility in Premature Lambs
Authors: Patel Anupama , Lakshminrusimha Satyan , Ryan Rita M. , Swartz Daniel D. , Wang Huamei , Wynn Karen A. , Kumar Vasanth H.
Published: April 2009

Background: The optimal oxygen concentration for the resuscitation of premature infants remains controversial. Objectives: We studied the effects of 21 versus 100% oxygen at initial resuscitation and also the effects of 24-hour exposure to 100% oxygen on arterial blood gases, oxidant lung injury, activities of lung antioxidant enzymes (AOEs) and isolated pulmonary artery (PA) contractility in preterm newborn lambs. Methods: Preterm lambs at 128 days’ gestation (term = 145 days) were delivered and ventilated with 21 (RAR; n = 5) or 100% oxygen (OXR; n = 5) for the first 30 min of life. Subsequently, FiO2 was adjusted to maintain an arterial PO2 (PaO2) between 45 and 70 mm Hg for 24 h. A third group of lambs was mechanically ventilated with 100% oxygen for 24 h (OX24; n = 5). Results: Oxidized glutathione levels in whole blood correlated highly with PaO2. Reduced to oxidized glutathione ratio was significantly different between the groups, the ratio increasing with decreasing oxygen exposure. The OX24 group had significantly higher activities of lipid hydroperoxide and myeloperoxidase and significantly lower activities of superoxide dismutase, catalase and glutathione peroxidase in the lung at 24 h. Activities of AOEs correlated inversely with alveolar PO2. PA contractility to norepinephrine and KCl was greater with increasing oxygen exposure. Pretreatment with superoxide dismutase and catalase significantly reduced PA contractility in the OXR and OX24 groups, but not in the RAR group. Conclusions: We conclude that ventilated premature lambs are unable to appropriately increase AOE activity in response to hyperoxia and that increasing exposure to oxygen aggravates systemic oxidant stress, oxidant lung injury and pulmonary arterial contractility in these lambs.
Area at Risk and Viability after Myocardial Ischemia and Reperfusion Can Be Determined by Contrast-Enhanced Cardiac Magnetic Resonance Imaging
Authors: Vosseler M. , Abegunewardene N. , Hoffmann N. , Petersen S.E. , Becker D. , Cleppien D. , Kunz P. , Kreitner K.-F. , Lauterbach M. , Bierbach B. , Düber C. , Gori T. , Münzel T. , Schreiber L.M. , Horstick G.
Published: April 2009

Background/Aims: Clinical differentiation between infarcted and viable myocardium in the ischemic area at risk is controversial. We investigated the potential of contrast-enhanced cardiac magnetic resonance imaging (ceCMRI) in determining the area at risk 24 h after ischemia. Methods: Myocardial ischemia was induced by percutaneous coronary intervention of the left anterior descending coronary artery in pigs. Coronary occlusion time was 30 min in group A, which caused little myocardial infarction and 45 min in group B, which led to irreversible damage. 24 h after reperfusion ceCMRI was performed at 2 and 15 min after administration of gadolinium-diethylenetriamine pentaacetic acid. The area at risk was determined by intravenous injection of Evans blue and myocardial viability by triphenyltetrazolium-chloride staining. Results: The signal-intense areas at 2 and 15 min after contrast administration matched the area at risk in groups A and B. Nonviable myocardium in group A was overestimated (14–15%) while good agreement was present in group B. Conclusion: The area at risk of reperfused ischemic myocardium can be determined by ceCMRI 24 h after coronary recanalization. This type of information might have relevant clinical implications in the treatment and stratification of patients with acute coronary syndrome in particular after surgical interventions.
Stability of Different Subtypes of Mild Cognitive Impairment among the Elderly over a 2- to 3-Year Follow-Up Period
Authors: Loewenstein David A. , Acevedo Amarilis , Small Brent J. , Agron Joscelyn , Crocco Elizabeth , Duara Ranjan
Published: April 2009

Background/Aims: To investigate the longitudinal stability and progression of different subtypes of mild cognitive impairment (MCI) in older adults. Methods: We classified 217 individuals with no cognitive impairment (NCI), amnestic MCI (aMCI) based on a single test (aMCI-1) or multiple tests (aMCI-2+), nonamnestic MCI (naMCI) based on a single test (naMCI-1) or multiple tests (naMCI-2+), or amnestic + nonamnestic MCI (a+naMCI), using their baseline neuropsychological test scores, and performed annual follow-up evaluations for up to 3 years. Results: None of the subjects with aMCI-2+ reverted to normal during follow-up, with 50% of these subjects remaining stable and 50% worsening over time. Similarly, less than 20% of subjects with aMCI-2+ and a+naMCI reverted to NCI during the follow-up period, whereas 50% of aMCI-1 and 37% with naMCI-1 reverted to NCI during this same period. Conclusion: Reversion to NCI occurs much more frequently when the diagnosis of MCI is based on the results of a single neuropsychological test than when it is based on the results of more memory tests. In epidemiological studies and clinical trials the diagnosis of MCI will likely be more stable if impairment on more than one test is required for amnestic and/or nonamnestic domains.
Increased Mortality for Neurological and Mental Diseases following Early Bilateral Oophorectomy
Authors: Rivera Cathleen M. , Grossardt Brandon R. , Rhodes Deborah J. , Rocca Walter A.
Published: April 2009

Background: The effects of oophorectomy on brain aging remain uncertain. Methods: We conducted a cohort study with long-term follow-up of women in Olmsted County, Minn., USA, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied underlying and contributory causes of death in 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women. Results: Mortality for neurological or mental diseases was increased in women who underwent bilateral oophorectomy before age 45 years compared with referent women (hazard ratio = 5.24; 95% confidence interval = 2.02–13.6; p < 0.001). Within this age stratum, mortality was similar in women who were or were not treated with estrogen from the time of oophorectomy through age 45 years, and in women who had bilateral oophorectomy for prophylaxis or for treatment of a benign ovarian condition. Mortality was also increased in women who underwent unilateral oophorectomy before age 45 years without concurrent hysterectomy. Conclusions: Bilateral oophorectomy performed before age 45 years is associated with increased mortality for neurological or mental diseases.
Factor Analysis of Motor and Nonmotor Signs in Essential Tremor: Are These Signs All Part of the Same Underlying Pathogenic Process?
Authors: Louis Elan D.
Published: April 2009

Essential tremor (ET) has traditionally been viewed as monosymptomatic. However, there is an emerging appreciation of an expanded number of motor manifestations as well as a new awareness of nonmotor manifestations. The current goal, through factor analyses, was to determine how these diverse signs relate to one another and shed light on their pathogenic bases. One hundred and thirty-eight ET patients had detailed neurological examinations. In these analyses, three separate factors emerged, explaining 58.7% of the variance. Factor I was comprised of the hallmark feature of ET, action tremor. It also included intention tremor, which is generally viewed as a sign of cerebellar dysfunction, and tremor duration. Factor II was comprised of cognitive test scores and age, and factor III, of rest tremor. Cognitive test scores did not fall into the same domain as motor features or tremor duration. These results suggest that: (1) the process that underlies cognitive dysfunction in ET is distinct from that which is responsible for action and intention tremors and their progression over time, and (2) cognitive dysfunction in ET is not likely due to cerebellar degeneration. Age loaded with cognitive test scores, further raising the possibility that age-related processes (e.g. Alzheimer-type changes) could underlie cognitive changes in ET.
Respiratory Monitoring by Inductive Plethysmography in Unrestrained Subjects Using Position Sensor-Adjusted Calibration
Authors: Brüllmann Gregor , Fritsch Karsten , Thurnheer Robert , Bloch Konrad E.
Published: April 2009

Background: Portable respiratory inductive plethysmography (RIP) is promising for noninvasive monitoring of breathing patterns in unrestrained subjects. However, its use has been hampered by requiring recalibration after changes in body position. Objectives: To facilitate RIP application in unrestrained subjects, we developed a technique for adjustment of RIP calibration using position sensor feedback. Methods: Five healthy subjects and 12 patients with lung disease were monitored by portable RIP with sensors incorporated within a body garment. Unrestrained individuals were studied during 40–60 min while supine, sitting and upright/walking. Position was changed repeatedly every 5–10 min. Initial qualitative diagnostic calibration followed by volume scaling in absolute units during 20 breaths in different positions by flow meter provided position-specific volume-motion coefficients for RIP. These were applied during subsequent monitoring in corresponding positions according to feedback from 4 accelerometers placed at the chest and thigh. Accuracy of RIP was evaluated by face mask pneumotachography. Results: Position sensor feedback allowed accurate adjustment of RIP calibration during repeated position changes in subjects and patients as reflected in a minor mean difference (bias) in breath-by-breath tidal volumes estimated by RIP and flow meter of 0.02 liters (not significant) and limits of agreement (±2 SD) of ±19% (2,917 comparisons). An average of 10 breaths improved precision of RIP (limits of agreement ±14%). Conclusions: RIP calibration incorporating position sensor feedback greatly enhances the application of RIP as a valuable, unobtrusive tool to investigate respiratory physiology and ventilatory limitation in unrestrained healthy subjects and patients with lung disease during everyday activities including position changes.
Role of Reinforcement Geometry on the Steady State Creep Behavior of a Rotating Composite Disc
Authors: Gupta V.K. , Singh S.B. , Ray S.
Published: April 2009

A mathematical model has been developed to predict steady state creep response of a rotating disc made of SiC (particle/whisker) reinforced 6061Al matrix composite. The model is used to investigate the effect of SiC morphology on the creep behavior of composite disc. The steady state creep behavior has been described by Sherby’s creep law. The creep stresses and creep rates are significantly affected by the morphology of SiC. The steady state creep rates in whisker reinforced disc are observed to be significantly lower than those observed in particle reinforced disc.
Additional Effects of Urea and Hexamethylenetetramine on Preparation and Acidic Properties of Aluminum Polyphosphates
Authors: Onoda Hiroaki , Kohno Masakazu , Kojima Kazuo , Takenaka Atsushi
Published: April 2009

Aluminum polyphosphate was prepared from aluminum nitrate solution and sodium polyphosphate solution with cation exchange resin in the molar ratio of Al/P = 1/3. Urea and hexamethylenetetramine were added in this preparation process. The thermal behavior of the obtained phosphates was analyzed by differential thermal analyses, X‐ray diffraction, and Fourier transform infrared spectroscopy. Furthermore, these materials and their thermal products were estimated by specific surface area, pore size distribution, particle size distribution, acid strength, amount of acidic sites, and adsorption of trimethylamine.
Assessing Progress in Analysis Interminable
Authors: Josephs Lawrence , Anderson Eric , Bernard Amy , Fatzer Kristine , Streich Jodi
Published: April 2009

A case study is provided of a schizoid patient in her mid-sixties who in a lengthy analysis had made significant clinical improvement. The treating analyst's impression of clinical improvement was independently verified through systematic analysis of transcripts of audiotapes of thirty-six sessions over a four-year period of treatment. The patient showed significant improvement on measures of character pathology, object relations, mentalization, and superego anxiety. The results suggest that some patients with entrenched character pathology who seem to be in analysis interminable may still make clinically significant improvement. It is suggested that the scientific status of psychoanalysis would be greatly enhanced if the anecdotal evidence generated in private practice were supported by independent verification. The current study illustrates one methodology, “case study plus,” for providing independent verification while retaining the richness of the traditional case study.
Rethinking Desire: The Objet Petit A in Lacanian Theory
Authors: Kirshner Lewis A.
Published: April 2009

The concept of the objet petit a is central to Lacan's theory of desire, which arguably represents his major contribution to psychoanalysis. It is an expression of the lack inherent in human beings, whose incompleteness and early helplessness produce a quest for fulfillment beyond the satisfaction of biological needs. The objet petit a is a fantasy that functions as the cause of desire; as such, it determines whether desire will be expressed within the limits of the pleasure principle or “beyond,” in pursuit of an unlimited jouissance, an impossible and even deadly enjoyment. Parallels between the objet petit a and Winnicott's transitional object are explored and its functions illustrated through analysis of Pedro Almodovar's film Talk to Her. A clinical case is presented in which the question of desire seemed crucial.
Cordelia, Lear, and Forgiveness
Authors: Schafer Roy
Published: April 2009

Painful human interactions are often followed by urges to forgive, be forgiving, or seek forgiveness. The insight analysands develop into their transferences highlights their finding gratification in constantly reenacting painful interactions. Their new understanding can make forgiveness seem irrelevant; waiving the question of forgiveness might then seem the wiser course to follow. Also thrown into question is whether total forgiveness of self and others can ever be achieved. Shakespeare's The Tragedy of King Lear raises these questions. There we encounter, first, the painful interaction of Cordelia and Lear and, finally, Cordelia's response, “No cause, no cause,” to a dying Lear's begging her forgiveness for having initially treated her cruelly. Cordelia's response seems to be waiving the question of guilt and forgiveness, but could it be whole-hearted? In a search for answers, a reading of Cordelia's and Lear's lines is interwoven with interpretations of unconscious conflict that might be considered were one to encounter clinically a “Cordelia” abused by an aging and failing father at a turning point in her womanly development. Unconsciously, it is concluded, unforgivingness persists alongside the loving, insightful waiving of forgiveness made possible by higher-level ego functioning. Methodological reflections on reading and interpretation are included.
Parental Status and Punitiveness
Authors: Welch Kelly
Published: April 2009

Previously identified predictors of public punitiveness include attitudinal, experiential, background, and demographic characteristics. Given the influence of parenthood on certain attitudes and beliefs, it may also affect how strongly individuals endorse harsh punishment for criminals. Few studies have explored how parenthood influences general policy preferences or support for criminal justice measures specifically, and findings have been mixed. The author estimated linear ordinary least squares regression equations, using national random telephone survey data, to test for direct effects of parenthood on measures of punitive attitudes toward juveniles and adults and overall. Two- and three-way interactions with gender and concern about crime were also estimated, and although the additive effects of parenthood on punitiveness were significant only for attitudes toward adult offenders, gender and concern about crime moderated its effects on punitive policy support, with fathers and parents for whom crime was less salient being more punitive. These findings suggest that research testing only linear influences may overlook more complex relationships.
Manipulating Public Opinion About Trying Juveniles as Adults: An Experimental Study
Authors: Steinberg Laurence , Piquero Alex R.
Published: April 2009

Public attitudes about juvenile crime play a significant role in fashioning juvenile justice policy; variations in the wording of public opinion surveys can produce very different responses and can result in inaccurate and unreliable assessments of public sentiment. Surveys that ask about policy alternatives in vague terms are especially problematic. The authors conducted an experiment in which a large sample of respondents were presented with a crime scenario in which the offender’s age and prior record, the type of crime, and the inclusiveness of the policy in question were varied. Respondents were asked about the extent to which they support trying juveniles in adult court. Responses varied significantly as a function of the offender’s age, criminal record, and offense but not as a function of inclusiveness. For legislators using public opinion polls to guide their decisions, blanket statements describing the results of vaguely worded surveys items can be misleading and can lead to poorly informed policy making.
Does Gender Moderate the Predictive Utility of the Level of Service Inventory—Revised (LSI-R) for Serious Violent Offenders?
Authors: Manchak Sarah M. , Skeem Jennifer L. , Douglas Kevin S. , Siranosian Maro
Published: April 2009

A prison inmate's risk of recidivism is central to decisions about whether to release her to serve a portion of her sentence on parole. Although several tools have been developed to improve accuracy in estimating the risk of future reoffense, few have been validated with the ever-growing population of female offenders. This study compared the utility of the Level of Service Inventory—Revised (LSI-R) in predicting recidivism for 70 female and 1,035 male offenders who had been convicted of serious violent offenses. The LSI-R predicted 1-year general recidivism quite well for women. Although gender did not moderate the utility of the LSI-R in predicting recidivism, risk factors that best predicted recidivism differed for men and women. Implications for risk assessment and parole decision making with female inmates are discussed.
Life in the Fast Lane
Authors: Tranter Paul J. , Lowes Mark
Published: April 2009

The article explores links between sport and health, focusing on a range of health outcomes of staging motorsport megaevents in significant public spaces in Australian cities. The article argues that an oversimplification of the links between sport and health produces a cultural filter that diverts attention from the negative health outcomes of sport. A major contribution of this study is the consideration of economic health and environmental health as well as public health. The interactions between these types of health are considered in a more holistic assessment of links between sport and health. The article concludes that the symbolic location of motorsport events in Australian cities both reflects and reinforces societal values that have important implications for health, both now and into the future.
Total miniaturized cardiopulmonary bypass: the next step in minimally invasive aortic valve replacement
Authors: Dimarakis I , Stefanou D , Yarham G , Mulholland J , Anderson J
Published: April 2009

Minimally invasive aortic valve replacement has been established in many centres over the last decade. Although numerous modifications have been described to date, these solely involve variations of the utilized operative incision. Total miniaturized cardiopulmonary bypass (tMCPB) offers the theoretical potential of reducing even further the overall procedural “invasiveness”. We describe our initial experience of an application of MCPB for aortic valve replacement through a minimal incision.
High-dose selective serotonin reuptake inhibitors in OCD: a systematic retrospective case notes survey
Authors: Pampaloni I. , Sivakumaran T. , Hawley CJ , Al Allaq A. , Farrow J. , Nelson S. , Fineberg NA
Published: April 2009

This article presents a systematic, retrospective case-note survey of a specialist obsessive-compulsive disorder (OCD) outpatient service. We explore the frequency of ‘high-dose’ selective serotonin reuptake inhibitor (SSRI) prescribing and describe clinical outcomes in a naturalistic clinical setting. Patients receiving high doses were compared with ‘control’ cases at the following three time-points: referral, initiation of high-dose SSRI and last clinical assessment.Twenty-six (13.5%) out of 192 patients received high-dose treatment for 3—364 weeks (mean 81.5 weeks; SD = ±95.1). At referral, high-dose patients were significantly more likely than controls to be male, and to have received Cognitive Behavioural Therapy (CBT), although illness severity and complexity did not differ. At initiation of dose escalation, however, high-dose patients were significantly more symptomatic than controls (Yale-Brown Obsessive Compulsive Scale score [Y-BOCS 25.4 vs. 17.7]). At the last assessment, patients on high-dose treatment showed significant within-group improvements (Y-BOCS 25.35 vs. 20.95), although endpoint scores for the high-dose group remained significantly higher than control patients treated for a matched period (Y-BOCS 21.0 vs. 15.5), suggesting enduring treatment-resistance. Frequency of adverse effects did not significantly differ between the two groups. Our results suggest that high-dose SSRI was associated with clinical improvement and well-tolerated in a particularly refractory OCD sample.
Individual Differences in Early Numeracy
Authors: Kroesbergen E.H. , Van Luit J.E.H. , Van Lieshout E.C.D.M. , Van Loosbroek E. , Van de Rijt B.A.M.
Published: April 2009

In this study, the question was raised how basic cognitive processes are related to math abilities and how it can be best determined which children are at risk for developing those disabilities. The role of four distinct basic processes in the development of early mathematics was investigated: executive functions, fluid intelligence, subitizing, and language. The counting skills of 115 five- and six-year-old children were also assessed. The results showed that both executive functions and number sense were important factors in children's development of counting skills. Both executive functions and subitizing explained a significant part of variance in children's counting skills. IQ scores could not add further explanation to the variance in early math. The implications of this study are that it seems promising to use the concept of executive functions for the early identification of children at risk for math learning difficulties.
Teacher Time Use in Special Education
Authors: Vannest Kimberly J. , Hagan-Burke Shanna
Published: April 2009

How special education teachers spend their time is largely unknown. Yet conceptually, “time” is one of the most tangible and salient variables of the effective instruction literature, Carroll's model of school learning and many economic models of performance measures. This currently unknown use of teacher time has clear and important implications for special education research and practice that include teacher quality, the professional roles of educator's, accountability and student achievement. 36 special education teachers representing 4 variations of instructional arrangements recorded 2200 hours of data in the spring of 2006. Special educators reported their time use via a web-based monitoring system while continuous and interval direct observation data were simultaneously collected. Data provide a snapshot view of teacher time use and reflect the percentages of a school day spent in academic instruction, non-academic instruction, instructional support, consultation/collaboration, assessment, planning/preparation, discipline, supervision, paperwork, and other responsibilities throughout the year.
Circadian Clock Genes of Goldfish, Carassius auratus: cDNA Cloning and Rhythmic Expression of Period and Cryptochrome Transcripts in Retina, Liver, and Gut
Authors: Velarde E. , Haque R. , Iuvone P.M. , Azpeleta C. , Alonso-Gómez A.L. , Delgado M.J.
Published: April 2009

Clock genes are known to be the molecular core of biological clocks of vertebrates. They are expressed not only in those tissues considered central pacemakers, but also in peripheral tissues. In the present study, partial cDNAs for 6 of the principal clock genes ( Period 1-3 and Cryptochrome 1-3) were cloned from a teleost fish, the goldfish ( Carassius auratus ). These genes showed high homology (approximately 90%) with the respective cDNAs of zebrafish ( Danio rerio), the only other teleost from which clock genes have been cloned. The daily expression pattern of each gene in retina, gut, and liver of goldfish was investigated using quantitative RT-PCR and cosinor analysis. All clock genes analyzed in the retina showed circadian rhythmicity; however, only Per 2-3 and Cry 2-3 were rhythmic in goldfish liver and gut. The amplitude and phase of the expression in liver and gut were different from those found in goldfish retina. Such differences suggest that other cues, such as feeding time, may contribute to the entrainment of oscillators in goldfish liver and gut. Our results support the use of goldfish as a teleost model to investigate the location and functioning of the circadian oscillators.
The Progression of Circadian Phase during Light Exposure in Animals and Humans
Authors: Beersma Domien G.M. , Comas Marian , Hut Roelof A. , Gordijn Marijke C.M. , Rueger Melanie , Daan Serge
Published: April 2009

Studies in humans and mice revealed that circadian phase shifting effects of light are larger at the beginning of a light exposure interval than during subsequent exposure. Little is known about the dynamics of this response reduction phenomenon. Here the authors propose a method to obtain information on the progression of phase during light exposure. Phase response curves to intervals of light exposure over a wide range in duration are available for flesh flies, mice, and humans. By comparing the phase shifts induced by pulses of various durations but starting at the same circadian phase, the progression of phase during a long interval (hours) of light exposure is reconstructed for each of these 3 species. For flies, the phase progression curves show that light pulses—if long enough— eventually make the pacemaker stabilize around InT18 (near subjective dusk), as is typical for strong resetting. The progression of phase toward the final value never shows advances larger than 7 h, while delays can be as large as 18 h. By applying the phase progression curve method presented in this study, differences between advances and delays in type-0 phase response curves can be distinguished clearly. In flesh flies ( Sarcophaga) this bifurcation between delays and advance occurs when light exposure starts at InT0 (subjective midnight). The present study confirms earlier findings in mice showing that the beginning of the light pulse generates stronger phase shifts than subsequent hours of light. Response reduction is complete within 1 h of exposure. It is argued that the variation is not so much due to light adaptation processes, but rather to response saturation. In contrast to light adaptation, response saturation is fundamental to proper functioning of the circadian pacemaker during natural entrainment. For understanding entrainment of the pacemaker to natural light, phase progression curves in which naturalistic light profiles are applied could be an important tool.
Differential Testicular Gene Expression in Seasonal Fertility
Authors: Maywood Elizabeth S. , Chahad-Ehlers Samira , Garabette Martine L. , Pritchard Claire , Underhill Phillip , Greenfield Andrew , Ebling Francis J. P. , Akhtar Ruth A. , Kyriacou Charalambos P. , Hastings Michael H. , Reddy Akhilesh B.
Published: April 2009

Spermatogenesis is an essential precursor for successful sexual reproduction. Recently, there has been an expansion in the knowledge of the genes associated with particular stages of normal, physiological testicular development and pubertal activation. What has been lacking, however, is an understanding of those genes that are involved in specifically regulating sperm production, rather than in maturation and elaboration of the testis as an organ. By using the reversible (seasonal) fertility of the Syrian hamster as a model system, the authors sought to discover genes that are specifically involved in turning off sperm production and not involved in tissue specification and/or maturation. Using gene expression microarrays and in situ hybridization in hamsters and genetically infertile mice, the authors have identified a variety of known and novel factors involved in reversible, transcriptional, translational, and posttranslational control of testicular function, as well those involved in cell division and macromolecular metabolism. The novel genes uncovered could be potential targets for therapies against fertility disorders.
Theories About the Role of Theory in Nonprofit and Philanthropic Studies
Authors: Donmoyer Robert
Published: April 2009

As the nonprofit and philanthropic studies field achieves increased acceptance within colleges and universities, academics within the field must confront a conundrum: Most academics are inclined to develop academic programs that resemble the theory-oriented academic programs in which they were educated; most students who enroll in nonprofit programs, however, are current or future practitioners who are not preparing for—and are unlikely to pursue—academic careers in which theory development is a primary goal. The focus, here, is on two emerging perspectives on the role that theoretical knowledge should play in the nonprofit/philanthropic studies field and the implications of these perspectives for academic program development. One perspective is relatively traditional. The other requires a more radical rethinking of the form and function of theoretical knowledge in applied fields like nonprofit/philanthropic studies and a different approach to university preparation programs than the theory-dissemination approach found in traditional academic programs.
Bimbo or boffin? Women in science: an analysis of media representations and how female scientists negotiate cultural contradictions
Authors: Chimba Mwenya , Kitzinger Jenny
Published: April 2009

This paper examines the gendered representations of scientists in the UK media. Our analysis reveals the asymmetrical ways in which men and women working in science, engineering and technology are portrayed, in particular through the emphasis on women’s appearance and a focus on their exceptional status. It also highlights the way female scientists may be used to “sex up” the discipline in the context of increasing concern about the (un)popularity of science. This media analysis is contextualized by drawing on data from 86 scientists examining how women themselves experience press and television coverage and address the cultural contradictions surrounding their role. The research highlights the challenges facing women working in these fields and the dilemmas for those seeking to develop a “human” face for science and promote a positive image for women.
Disclosing a Cancer Diagnosis to Friends and Family: A Gendered Analysis of Young Men's and Women's Experiences
Authors: Hilton Shona , Emslie Carol , Hunt Kate , Chapple Alison , Ziebland Sue
Published: April 2009

Little is known about how young adults disclose their cancer diagnosis to family and friends, and whether there are similarities or differences between men and women. This article compares young adults' experiences of disclosing a cancer diagnosis, drawing on narrative interviews with 37 respondents aged 18 to 34 years. Most respondents were open about their diagnosis, and there were striking similarities in the difficulties that men and women described and in their desire to protect relatives. However, men made up most of the minority of respondents who were more secretive about their diagnosis. Men also made more explicit connections between their gendered identity and disclosure; worries about being perceived differently by peers resulted in some men hiding their diagnosis and others using humor to pre-empt sympathy. These findings are discussed in the context of gender stereotypes of “expressive” women and “stoical” men.
Heterogeneity in Antisocial Trajectories in Youth of Adult Sexual Aggressors of Women
Authors: Cale Jesse , Lussier Patrick , Proulx Jean
Published: April 2009

Recent explanatory models of sexual aggression of women have emphasized the role of an antisocial tendency in explaining sexual aggression. If those models agree about the importance of an antisocial propensity, they disagree about the presence of a single or multiple pathways leading to sexual aggression. Currently, no empirical studies have examined within-individual changes of antisocial behavior in youth of sexual aggressors of women and whether those changes are related to the unfolding of the sexual and nonsexual criminal activity in adulthood. This study examines the presence of antisocial trajectories in childhood and adolescence using a sample of 209 convicted adult sexual aggressors of women. A dynamic classification procedure using cluster analyses yields five distinct antisocial trajectories, which are then compared using analysis of covariance on various parameters of criminal activity in adulthood. The results highlight the heterogeneity of antisocial development in youth of adult sexual aggressors of women. Patterns of initiation, persistence, and escalation in youth are related to the general, violent, and sexual offending in adulthood.