bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventilatory sensitivity to carbon dioxide before and after episodic hypoxia in women treated with testosterone
Authors: Ahuja Deepti , Mateika Jason H. , Diamond Michael P. , Safwan Badr M.
Published: February 2007

We hypothesized that the ventilatory threshold and sensitivity to carbon dioxide in the presence of hypoxia and hyperoxia during wakefulness would be increased following testosterone administration in premenopausal women. Additionally, we hypothesized that the sensitivity to carbon dioxide increases following episodic hypoxia and that this increase is enhanced after testosterone administration. Eleven women completed four modified carbon dioxide rebreathing trials before and after episodic hypoxia. Two rebreathing trials before and after episodic hypoxia were completed with oxygen levels sustained at 150 Torr, the remaining trials were repeated while oxygen was maintained at 50 Torr. The protocol was completed following 8–10 days of treatment with testosterone or placebo skin patches. Resting minute ventilation was greater following treatment with testosterone compared with placebo (testosterone 11.38 ± 0.43 vs. placebo 10.07 ± 0.36 l/min; P < 0.01). This increase was accompanied by an increase in the ventilatory sensitivity to carbon dioxide in the presence of sustained hyperoxia (VSco2hyperoxia) compared with placebo (3.6 ± 0.5 vs. 2.9 ± 0.3; P < 0.03). No change in the ventilatory sensitivity to carbon dioxide in the presence of sustained hypoxia (VSco2 hypoxia) following treatment with testosterone was observed. However, the VSco2 hypoxia was increased after episodic hypoxia. This increase was similar following treatment with placebo or testosterone patches. We conclude that treatment with testosterone leads to increases in the VSco2hyperoxia, indicative of increased central chemoreflex responsiveness. We also conclude that exposure to episodic hypoxia enhances the VSco2 hypoxia, but that this enhancement is unaffected by treatment with testosterone.
Does local heating-induced nitric oxide production attenuate vasoconstrictor responsiveness to lower body negative pressure in human skin?
Authors: Low David A. , Shibasaki Manabu , Davis Scott L. , Keller David M. , Crandall Craig G.
Published: February 2007

We tested the hypothesis that local heating-induced nitric oxide (NO) production attenuates cutaneous vasoconstrictor responsiveness. Eleven subjects (6 men, 5 women) had four microdialysis membranes placed in forearm skin. Two membranes were perfused with 10 mM of NG-nitro-l-arginine (l-NAME) and two with Ringer solution (control), and all sites were locally heated to 34°C. Subjects then underwent 5 min of 60-mmHg lower body negative pressure (LBNP). Two sites (a control and an l-NAME site) were then heated to 39°C, while the other two sites were heated to 42°C. At the l-NAME sites, skin blood flow was elevated using 0.75–2 mg/ml of adenosine in the perfusate solution (Adn + l-NAME) to a similar level relative to control sites. Subjects then underwent another 5 min of 60-mmHg LBNP. At 34°C, cutaneous vascular conductance (CVC) decreased (Δ) similarly at both control and l-NAME sites during LBNP (Δ7.9 ± 3.0 and Δ3.4 ± 0.8% maximum, respectively; P > 0.05). The reduction in CVC to LBNP was also similar between control and Adn + l-NAME sites at 39°C (control Δ11.4 ± 2.5 vs. Adn + l-NAME Δ7.9 ± 2.0% maximum; P > 0.05) and 42°C (control Δ1.9 ± 2.7 vs. Adn + l-NAME Δ 4.2 ± 2.7% maximum; P > 0.05). However, the decrease in CVC at 42°C, regardless of site, was smaller than at 39°C ( P < 0.05). These results do not support the hypothesis that local heating-induced NO production attenuates cutaneous vasoconstrictor responsiveness during high levels of LBNP. However, elevated local temperature, per se, attenuates cutaneous vasoconstrictor responsiveness to LBNP, presumably through non-nitric oxide mechanisms.
Effects of Perceptual Learning on Local Stereopsis and Neuronal Responses of V1 and V2 in Prism-Reared Monkeys
Authors: Nakatsuka C. , Zhang B. , Watanabe I. , Zheng J. , Bi H. , Ganz L. , Smith E. L. , Harwerth R. S. , Chino Y. M.
Published: February 2007

Visual performance improves with practice (perceptual learning). In this study, we sought to determine whether or not adult monkeys reared with early abnormal visual experience improve their stereoacuity by extensive psychophysical training and testing, and if so, whether alterations of neuronal responses in the primary visual cortex (V1) and/or visual area 2 (V2) are involved in such improvement. Strabismus was optically simulated in five macaque monkeys using a prism-rearing procedure between 4 and 14 wk of age. Around 2 yr of age, three of the prism-reared monkeys (“trained” monkeys) were tested for their spatial contrast sensitivity and stereoacuity. Two other prism-reared monkeys received no training or testing (“untrained” monkeys). Microelectrode experiments were conducted around 4 yr of age. All three prism-reared trained monkeys showed improvement in stereoacuity by a factor of 7 or better. However, final stereothresholds were still ∼10–20 times worse than those in normal monkeys. In V1, disparity sensitivity was drastically reduced in both the trained and untrained prism-reared monkeys and behavioral training had no obvious effect. In V2, the disparity sensitivity in the trained monkeys was better by a factor of ∼2.0 compared with that in the untrained monkeys. These data suggest that the observed improvement in stereoacuity of the trained prism-reared monkeys may have resulted from better retention of disparity sensitivity in V2 and/or from “learning” by upstream neurons to more efficiently attend to residual local disparity information in V1 and V2.
Mechanoafferent Neuron With An Inexcitable Somatic Region: Consequences for the Regulation of Spike Propagation and Afferent Transmission
Authors: Evans Colin G. , Ludwar Bjoern Ch. , Cropper Elizabeth C.
Published: February 2007

In the Aplysia mechanoafferent B21, afferent transmission is in part regulated via the control of active spike propagation. When B21 is peripherally activated at its resting membrane potential, spikes fail to propagate to an output process, and afferent transmission does not occur. In this report, we show that the propagation failure is in part a result of the fact that the somatic region of B21 is relatively inexcitable. We isolate this region and demonstrate that net currents evoked by depolarizing pulses are outward. Furthermore, we show that all-or-none spikes are not triggered when current is injected. Previous reports have, however shown that spiking is triggered when current is somatically injected and cells are intact. We demonstrate that spikes evoked under these circumstances do not originate in the soma. Instead they originate in an adjacent part of the neuron that is excitable (the medial process). In summary, we show that the mechanoafferent B21 consists of excitable input and output processes separated by a relatively inexcitable somatic region. A potential advantage of this arrangement is that somatic depolarization can be used to modify spike propagation from the input to the output processes without altering the encoding of peripherally generated activity.
In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1
Authors: Lansing Timothy J. , McConnell Randy T. , Duckett Derek R. , Spehar Glenn M. , Knick Victoria B. , Hassler Daniel F. , Noro Nobuhiro , Furuta Masaaki , Emmitte Kyle A. , Gilmer Tona M. , Mook Robert A. , Cheung Mui
Published: February 2007

Polo-like kinase 1 (PLK1) plays key roles in the regulation of mitotic progression, including mitotic entry, spindle formation, chromosome segregation, and cytokinesis. PLK1 expression and activity are strongly linked to proliferating cells. Many studies have shown that PLK1 expression is elevated in a variety of tumors, and high expression often correlates with poor prognosis. Using a variety of methods, including small-molecule inhibition of PLK1 function and/or activity, apoptosis in cancer cell lines, cell cycle arrest in normal cell lines, and antitumor activity in vivo have been observed. In the present study, we have examined the in vitro biological activity of a novel and selective thiophene benzimidazole ATP-competitive inhibitor of PLK1 and PLK3 (5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-{[2-(trifluoromethyl)-benzyl]oxy}thiophene-2-carboxamide, called compound 1). Compound 1 has low nanomolar activity against the PLK1 and PLK3 enzymes and potently inhibits the proliferation of a wide variety of tumor cell lines. In the lung adenocarcinoma cell line NCI-H460, compound 1 induces a transient G2-M arrest, mitotic spindle defects, and a multinucleate phenotype resulting in apoptosis, whereas normal human diploid fibroblasts arrest in G2-M and show little apoptosis. We also describe a cellular mechanistic assay that was developed to identify potent intracellular inhibitors of PLK1. In addition to its potential as a therapeutic agent for treating cancer, compound 1 is also a useful tool molecule for further investigation of the biological functions of PLK1 and PLK3. [Mol Cancer Ther 2007;6(2):450–9]
High Frequency of a Retinoid X Receptor γ Gene Variant in Familial Combined Hyperlipidemia That Associates With Atherogenic Dyslipidemia
Authors: Nohara Atsushi , Kawashiri Masa-aki , Claudel Thierry , Mizuno Mihoko , Tsuchida Masayuki , Takata Mutsuko , Katsuda Shoji , Miwa Kenji , Inazu Akihiro , Kuipers Folkert , Kobayashi Junji , Koizumi Junji , Yamagishi Masakazu , Mabuchi Hiroshi
Published: February 2007

Objective—The genetic background of familial combined hyperlipidemia (FCHL) has not been fully clarified. Because several nuclear receptors play pivotal roles in lipid metabolism, we tested the hypothesis that genetic variants of nuclear receptors contribute to FCHL.

Methods and Results—We screened all the coding regions of the PPARα, PPARγ2, PPARδ, FXR, LXRα, and RXRγ genes in 180 hyperlipidemic patients including 60 FCHL probands. Clinical characteristics of the identified variants were evaluated in other 175 patients suspected of coronary disease. We identified PPARα Asp140Asn and Gly395Glu, PPARγ2 Pro12Ala, RXRγ Gly14Ser, and FXR −1g−>t variants. Only RXRγ Ser14 was more frequent in FCHL (15%,P<0.05) than in other primary hyperlipidemia (4%) and in controls (5%). Among patients suspected of coronary disease, we identified 9 RXRγ Ser14 carriers, who showed increased triglycerides (1.62±0.82 versus 1.91±0.42 [mean±SD] mmol/L,P<0.05), decreased HDL-cholesterol (1.32±0.41 versus 1.04±0.26,P<0.05), and decreased post-heparin plasma lipoprotein lipase protein levels (222±85 versus 149±38 ng/mL,P<0.01). In vitro, RXRγ Ser14 showed significantly stronger repression of the lipoprotein lipase promoter than RXRγ Gly14.

Conclusion—These findings suggest that RXRγ contributes to the genetic background of FCHL.
Phospholipid Transfer Protein Augments Apoptosis in THP-1–Derived Macrophages Induced by Lipolyzed Hypertriglyceridemic Plasma
Authors: Wehinger Andreas , Tancevski Ivan , Schgoer Wilfried , Eller Philipp , Hochegger Kathrin , Morak Maria , Hermetter Albin , Ritsch Andreas , Patsch Josef R. , Foeger Bernhard
Published: February 2007

Objective—

Lipolysis of triglyceride-rich lipoproteins (TGRLPs) generates phospholipid-rich surface remnants and induces cytotoxic effects in adjacent vascular cells. We hypothesized that by integrating surface remnants into HDL, phospholipid transfer protein (PLTP) alleviates cytotoxicity.

Methods and Results—

To test this hypothesis and gain insight into cytotoxicity during the postprandial phase in vivo, we injected normo-TG and hyper-TG human volunteers after a standardized fat meal (postprandial sample) with heparin, thereby stimulating lipolysis (postprandial heparinized sample). Incubation of (primary) human macrophages and primary human endothelial cells with postprandial heparinized hyper-TG plasma induced pronounced cytotoxic effects that were dose dependent on the TG content of the sample. No such effects were seen with normo-TG and postprandial hyper-TG plasma. In vitro lipolysis of VLDL and chylomicrons indicated that both lipoprotein fractions can cause cytotoxicity. Interestingly, in experiments with THP-1–derived macrophages stably transfected with PLTP, PLTP substantially augmented both net phospholipid uptake and apoptotic cell death due to postprandial heparinized hyper-TG plasma. We observed that activation of caspase-3/7, poly-ADP-ribose polymerase, and enhanced bioactivity of acid sphingomyelinase may all contribute to this augmented apoptosis.

Conclusions—

Our data show that lipolysis of TGRLPs and their remodelling by PLTP interact to disturb cellular phospholipid flux and intracellular signaling processes, ultimately leading to apoptosis in human macrophages and endothelial cells.
Role of Naturally Occurring CD4
+
CD25
+
Regulatory T Cells in Experimental Atherosclerosis
Authors: Mor Adi , Planer David , Luboshits Galia , Afek Arnon , Metzger Shula , Chajek-Shaul Tova , Keren Gad , George Jacob
Published: February 2007

Objective—

Naturally occurring CD4
+
CD25
+
regulatory T cells (Tregs) exert suppressive effects on effector CD4 cells and downregulate experimental autoimmune disorders. We investigated the importance and potential role of Tregs in murine atherogenesis.

Methods and Results—

Tregs were investigated comparatively between aged and young apolipoprotein E–knockout (ApoE-KO) mice and age-matched C57BL/6 littermates. The effect of oxidized LDL (oxLDL) was tested on the functional suppressive properties of Tregs from ApoE-KO and C57BL/6 mice. Tregs, CD4
+
CD25
−
cells, and saline were infused into ApoE-KO mice to study their effects on atherogenesis. Treg numbers were reduced in atherosclerotic compared with nonatherosclerotic ApoE-KO mice. The functional suppressive properties of Tregs from ApoE-KO mice were compromised in comparison with those from their C57BL/6 littermates. Thus, oxLDL attenuated the suppressive properties of Tregs from C57BL/6 mice and more so in ApoE-KO mice. Transfer of Tregs from age-matched ApoE-KO mice resulted in significant attenuation of atherosclerosis compared with that after delivery of CD4
+
CD25
+/−
T cells or phosphate-buffered saline.

Conclusions—

CD4
+
CD25
+
Tregs may play a protective role in the progression of atherosclerosis and could be considered a therapeutic tool if results from human studies can solidify observations in murine models.
Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia
Authors: Umemura Kimiko , Kato Ichiro , Hirashima Yutaka , Ishii Yoko , Inoue Takao , Aoki Junken , Kono Nozomu , Oya Takeshi , Hayashi Nakamasa , Hamada Hideo , Endo Shunro , Oda Masaya , Arai Hiroyuki , Kinouchi Hiroyuki , Hiraga Koichi
Published: February 2007

Background and Purpose—

Platelet-activating factor (PAF) and oxidized unsaturated free fatty acids have been postulated to aggravate neuronal damage in the postischemic brain. Type II PAF-acetylhydrolase (PAF-AH II) not only terminates signals by PAF by its PAF-hydrolyzing activity but also protects cells against oxidative stress. We examined whether PAF-AH II can rescue cerebral neurons against ischemic insults.

Methods—

Transgenic mice overexpressing human PAF-AH II in neurons were generated and enzyme expressions were examined biochemically and histochemically. The mice were subjected to 60 minutes of transient middle cerebral artery occlusion followed by reperfusion for 24 hours. The infarction and apoptosis were estimated by TTC staining and fluorescence TUNEL staining, respectively.

Results—

Overexpression of PAF-AH II was found in brains of transgenic mice by Western blot and enzymatic activity analyses. In immunohistochemistry, human PAF-AH II expression was found throughout the central nervous system, especially in neurons of neocortex, hippocampus, and basal ganglia. The neurological deficit scores, cerebral edema index, and relative infarction volume were all significantly (
P
<0.05) lower in transgenic mice (1.30±0.72, 1.12±0.04, and 14.0±7.7%, respectively) than in wild-type mice (2.56±0.93, 1.23±0.12, and 31.9±9.7%, respectively). Percentages of apoptotic cells were also significantly (
P
<0.001) lower in transgenic mice (cortex, 5.2±3.3%; hippocampus, 3.4±7.0%) than in wild-type mice (cortex, 41.1±16.9%; hippocampus, 58.9±15.3%).

Conclusions—

These results indicate that PAF-AH II exerts strong neuroprotective effects against ischemic injury and suggest a possibility for clinical use of this enzyme in cerebral ischemia.
Feature Geometry from the Perspective of Polish, Russian, and Ukrainian
Authors: Rubach Jerzy
Published: February 2007

This article looks at two current models of feature geometry, the Halle-Sagey model as modified by Halle (2005) and the Clements-Hume model, from the perspective of palatalization and related processes in Polish, Russian, and Ukrainian. The Halle-Sagey model predicts that palatalization should be analyzed by assuming derivational levels and is thus at odds with the tenet of strict parallelism in Optimality Theory. In contrast, the Clements-Hume model appears to be able to achieve the same goal without recourse to derivational stages because it is based on the assumption that, in the ways relevant for palatalization, vowels and consonants are characterized by the same features. However, analysis of palatalization and related processes shows that this assumption is incorrect. The consequence is that derivational stages cannot be avoided and that the tenet of strict parallelism must be rejected.
Three-Dimensional Ageostrophic Motion in Mesoscale Vortex Dipoles
Authors: Pallàs-Sanz Enric , Viúdez Álvaro
Published: February 2007

The three-dimensional motion of mesoscale baroclinic dipoles is simulated using a nonhydrostatic Boussinesq numerical model. The initial conditions are two ellipsoidal vortices of positive and negative potential vorticity anomalies. The flow is moderately ageostrophic with a maximum absolute Rossby number equal to 0.71. The trajectory of the dipole is related to the maximum potential vorticity anomaly and size of the vortices. Three cases are considered depending on the curvature of the dipole trajectory: negative, close to zero, and positive. The ageostrophic flow strongly depends on the distance between the ellipsoidal vortices d0. For small d0 the vortices move steadily as a compact dipole, and the vertical velocity w has an octupolar three-dimensional pattern. The horizontal ageostrophic velocity is due to the advective acceleration of the flow, particularly the centripetal acceleration. The speed acceleration is only relatively important at the rear and front parts of the dipole axis, where the flow curvature is small but where the flow confluence and diffluence are, respectively, large. The geostrophy is maximal at the dipole center, on the dipole axis, where both curvature and speed acceleration are minimal. As d0 increases, the dipole self-propagating velocity and the extreme values of |w| decrease, and vortex oscillations highly distort the octupolar pattern of w. In all cases, as is typical of balanced mesoscale geophysical flows, the vertical velocity is related to the advection of vertical vorticity by the horizontal shear velocity uhz · ∇hζ.
Watermass Properties of the Antarctic Slope Front: A Simple Model*
Authors: Ou Hsien-Wang
Published: February 2007

In the Antarctic, dense shelf water is formed in coastal polynyas and is differentiated from the fresher surface water by the wind-induced ice motion that displaces offshore the ice melt from production zones. Where the shelf water discharges into the deep ocean, the Antarctic Slope Front (ASF) is V shaped, separating the shelf and surface waters (referred to as “frontal” waters) from the Circumpolar Deep Water (CDW). To elucidate basic constraints on frontal properties, a minimal model of homogeneous water masses forced by offshore wind and freshwater input in a perpetual winter is considered. With the surface water stirred by—and hence aligned with—the ice cover, there is little leakage of ice or meltwater from the frontal system, so ice production and melt merely redistribute heat and salt between frontal waters. As such, the heat loss to the atmosphere needs to be supplied by entraining CDW, which then necessitates the shelf water discharge on account of the mass balance. Because of the freshwater input, the discharged shelf water may not be saltier than the CDW, which thus may descend the slope to form bottom water only because of its coldness. With both frontal waters cooled to the freezing point, dominant balances are formulated to determine their salinity and exchange rate with the ambient CDW. Although extremely crude, the model derivations are favorably compared with observations, which thus may provide physically based parameterizations for the bottom-water formation that can be incorporated into global models.
Ecological Unequal Exchange: Consumption, Equity, and Unsustainable Structural Relationships within the Global Economy
Authors: Rice James
Published: February 2007

We discuss and elaborate upon the theory of cross-national ecological unequal exchange. Drawing upon world-systems theoretical propositions, ecological unequal exchange refers to the increasingly disproportionate utilization of ecological systems and externalization of negative environmental costs by core industrialized countries and, consequentially, declining utilization opportunities and imposition of exogenous environmental burdens within the periphery. We provide a descriptive overview of theoretical and empirical efforts to date examining this issue. Ecological unequal exchange provides a framework for conceptualizing how the socioeconomic metabolism or material throughput of core countries may negatively impact more marginalized countries in the global economy. It focuses attention upon the global uneven fl ow of energy, natural resources, and waste products of industrial activity. Further, the recognition of the distributional processes of ecological unequal exchange is relevant to considerations of both the socioeconomic and environmental imperatives underlying the pursuit of sustainable development, as it contributes to underdevelopment within the periphery of the world-system. We conclude by highlighting the interconnections between uneven natural resource fl ows, global environmental change, and the challenge of broad-based sustainable development.
Artificially generated dendritic cells misdirect antiviral immune responses
Authors: Noone Cariosa , Manahan Ellen , Newman Robert , Johnson Patricia
Published: February 2007

Dendritic cells (DCs) are critical to the outcome of many viral infections. Questions still remain as to the relevance of artificially generated DCs in models of in vivo immune responses. We compared different DC generation pathways, in terms of phenotypic expression, cytokine production, apoptosis, and T cell proliferation, following viral infection. Direct viral infection of monocytes or monocytes cultured with supernatants from virally infected lung epithelial cells (A549 DCs) induce distinct DC subsets compared with viral infection of artificially generated IL-4 DCs and IFN-DCs. These virally infected DC subsets stimulated different cytokine secretion profiles and displayed contrasting sensitivities to viral-induced apoptosis. It is most interesting that we observed marked differences in the proliferation of purified CD3+ T cells from the virally infected DC subsets. In conclusion, artificially generated DCs skew immune responses to viral infections, and direct viral infection of monocytes and DCs, generated from monocytes cultured with supernatants from infected epithelial cells, appears to be a more relevant pathway of producing DCs, which mimic those generated in vivo.
Cancer risk among parents and siblings of patients with
schizophrenia
Authors: Levav Itzhak , Lipshitz Irena , Novikov Ilya , Pugachova Inna , Kohn Robert , Barchana Micha , Ponizovsky A. , Werner Haim
Published: February 2007

Background

A reduced risk of cancer has been noted among people with schizophrenia.
Given that genetic causes have been proposed as an explanation of this
finding, one would expect that the risk of cancer among first-degree
relatives would be equally reduced.

Aims

To investigate the risk of cancer among the biological parents and full
siblings of people receiving in-patient care for schizophrenia.

Method

Linkage analysis was conducted between national population, psychiatric
and cancer databases. Standardised incidence ratios for all cancer sites
were calculated by comparing the incident rates among first-degree
relatives with national incidence rates.

Results

A reduced cancer risk was found across all groups examined. Among
parents, whose numbers were adequately large, the findings reached
statistical significance. For index cases and siblings – a markedly
younger population – only a trend was elicited.

Conclusions

The genetic hypothesis – namely, the presence of a gene with the dual
effect of reducing the cancer risk and disrupting neurodevelopment – is a
plausible explanation for these findings.
Therapeutic use of soap operas in autistic-spectrum disorders
Authors: Breen Lynda
Published: February 2007

‘Soap opera’ is a popular television genre that ‘invites the audience to … identify with characters' (Livingstone, 1990). Storylines tend to be shaped by national and local culture, although they may feature a disproportionate number of unstable relationships and tragedies (Liebes & Livingstone, 1998). Narratives evolve continually, allowing scriptwriters to incite viewer debate on myriad topical social issues, including mental illness (Reveley, 1997).
Protecting patients in psychiatric care: the St Andrew's Human Rights Project
Authors: Sugarman Philip , Dickens Geoff
Published: February 2007

Aims and Method

The Human Rights Act was incorporated into UK law in 2000, but little is known about how it is implemented in psychiatric care. We explored the understanding of multidisciplinary teams of the restriction and protection of patients' human rights using an open-response questionnaire. Content analysis was employed to summarise written, narrative data about the human rights of 102 patients in secure psychiatric care.

Results

Our clinical teams considered human rights to be protected through risk assessment and management, ongoing monitoring, local policy and existing UK mental health legislation. Understanding of the proper and proportionate restriction of ‘qualified’ rights (such as article 5 liberty) and the positive enablement and promotion of human rights (such as article 8 family and private life) appeared to be limited.

Clinical Implications

A cultural shift in focus is required in mental health services to understand and ensure positive promotion of human rights. Clinicians should directly address the human rights of their patients and articulate the rationale for proportionate restrictions of qualified rights. Clinical policy, training and audit should explicitly embody the protection of human rights.
A Randomized Comparison Trial of Case‐based Learning versus Human Patient Simulation in Medical Student Education
Authors: Schwartz Lawrence R. , Fernandez Rosemarie , Kouyoumjian Sarkis R. , Jones Kerin A. , Compton Scott
Published: February 2007

Objectives

Human patient simulation (HPS), utilizing computerized, physiologically responding mannequins, has become the latest innovation in medical education. However, no substantive outcome data exist validating the advantage of HPS. The objective of this study was to evaluate the efficacy of simulation training as compared with case‐based learning (CBL) among fourth‐year medical students as measured by observable behavioral actions.

Methods

A chest pain curriculum was presented during a one‐month mandatory emergency medicine clerkship in 2005. Each month, students were randomized to participate in either the CBL‐based or the HPS‐based module. All students participated in the same end‐of‐clerkship chest pain objective structured clinical examination that measured 43 behaviors. Three subscales were computed: history taking, acute coronary syndrome evaluation and management, and cardiac arrest management. Mean total and subscale scores were compared across groups using a multivariate analysis of variance, with significance assessed from Hotelling's T2 statistic.

Results

Students were randomly assigned to CBL (n= 52) or HPS (n= 50) groups. The groups were well balanced after random assignment, with no differences in mean age (26.7 years; range, 22–44 years), gender (male, 52.0%), or emergency medicine preference for specialty training (28.4%). Self‐ratings of learning styles were similar overall: 54.9% were visual learners, 7.8% auditory learners, and 37.3% kinetic learners. Results of the multivariate analysis of variance indicated no significant effect (Hotelling's T2 [3,98] = 0.053; p = 0.164) of education modality (CBL or HPS) on any subscale or total score difference in performance.

Conclusions

HPS training offers no advantage to CBL as measured by medical student performance on a chest pain objective structured clinical examination.
Fasting Inhibits the Growth and Reproductive Axes via Distinct Y2 and Y4 Receptor-Mediated Pathways
Authors: Lin Shu , Lin En-Ju D. , Boey Dana , Lee Nicola J. , Slack Katy , During Matthew J. , Sainsbury Amanda , Herzog Herbert
Published: February 2007

Neuropeptide Y, a neuropeptide abundantly expressed in the brain, has been implicated in the regulation of the hypothalamo-pituitary-somatotropic axis and the hypothalamo-pituitary-gonadotropic axis. Elevated hypothalamic neuropeptide Y expression, such as that occurs during fasting, is known to inhibit both of these axes. However, it is not known which Y receptor(s) mediate these effects. Here we demonstrate, using Y receptor knockout mice, that Y2 and Y4 receptors are separately involved in the regulation of these axes. Fasting-induced inhibition of hypothalamic GHRH mRNA expression and reduction of circulating IGF-I levels were observed in wild-type and Y4−/− mice but not Y2−/− or Y2−/−Y4−/− mice. In contrast, fasting-induced reduction of GnRH expression in the medial preoptic area and testis testosterone content were abolished in the absence of Y4 receptors. Colocalization of Y2 receptors and GHRH in the arcuate nucleus (Arc) suggests that GHRH mRNA expression in this region might be directly regulated by Y2 receptors. Indeed, hypothalamic-specific deletion of Y2 receptors in conditional knockout mice prevented the fasting-induced reduction in Arc GHRH mRNA expression. On the other hand, fasting-induced decrease in GnRH mRNA expression in the medial preoptic area is more likely indirectly influenced by Y4 receptors because no Y4 receptors could be detected on GnRH neurons in this region. Together these data show that fasting inhibits the somatotropic axis via direct action on Y2 receptors in the Arc and indirectly inhibits the gonadotropic axis via Y4 receptors.
cAMP production by adenylyl cyclase G induces prespore differentiation inDictyosteliumslugs
Authors: Alvarez-Curto Elisa , Saran Shweta , Meima Marcel , Zobel Jenny , Scott Claire , Schaap Pauline
Published: February 2007

Encystation and sporulation are crucial developmental transitions for solitary and social amoebae, respectively. Whereas little is known of encystation, sporulation requires both extra- and intracellular cAMP. After aggregation of social amoebae, extracellular cAMP binding to surface receptors and intracellular cAMP binding to cAMP-dependent protein kinase (PKA) act together to induce prespore differentiation. Later, a second episode of PKA activation triggers spore maturation. Adenylyl cyclase B (ACB) produces cAMP for maturation, but the cAMP source for prespore induction is unknown. We show that adenylyl cyclase G (ACG) protein is upregulated in prespore tissue after aggregation. acg null mutants show reduced prespore differentiation,which becomes very severe when ACB is also deleted. ACB is normally expressed in prestalk cells, but is upregulated in the prespore region of acgnull structures. These data show that ACG induces prespore differentiation in wild-type cells, with ACB capable of partially taking over this function in its absence.
The role ofArabidopsis SCARgenes in ARP2-ARP3-dependent cell morphogenesis
Authors: Uhrig Joachim F. , Mutondo Moola , Zimmermann Ilona , Deeks Michael J. , Machesky Laura M. , Thomas Philipp , Uhrig Silke , Rambke Claudia , Hussey Patrick J. , Hülskamp Martin
Published: February 2007

The actin-nucleating ARP2-ARP3 complex controls cell shape in plants in many different cell types. Its activity is controlled by a multimeric complex containing BRK1 (also known as HSPC300), NAP1, SRA1, ABI and SCAR/WAVE. In this study, we focus on the function of the five putative SCAR homologues in Arabidopsis and we provide biochemical evidence that AtSCAR2 can activate the ARP2-ARP3 complex in vitro. Among the single mutants, mutations in only AtSCAR2 result in a subtle or weak phenotype similar to ARP2, ARP3 and other `distorted' mutants. Double-mutant analysis revealed a redundancy with AtSCAR4. Systematic application of the yeast two-hybrid system and Bimolecular Fluorescence Complementation (BiFC)revealed a complex protein-interaction network between the ARP2-ARP3 complex and its genetically defined regulators. In addition to protein interactions known in other systems, we identified several new interactions, suggesting that SPIKE1 may be an integral component of the SCAR/WAVE complex and that SCAR proteins in plants might act as direct effectors of ROP GTPases.
Cyclic gas-exchange in the Chilean red cricket: inter-individual variation and thermal dependence
Authors: Nespolo Roberto F. , Artacho Paulina , Castañeda Luis E.
Published: February 2007

One of the most puzzling features of respiration in insects is cyclic gas exchange (CGE, the extreme form of discontinuous gas exchange-cycles, DGC), a periodic respiratory pattern that appeared independently several times in the evolution of arthropods. Although it is a striking feature of insects and some non-insect species, to date there is no clear knowledge of how widespread it is, or its adaptive significance. Here we show for the first time that a cricket (Cratomelus armatus) from the Stenopelmatidae family exhibits CGE. C. armatus shows a conspicuous, convective O-phase, with significantly repeatable ventilatory period and O-phase duration (intraclass correlation coefficients of 0.51 and 0.74, respectively). Also, C. armatus exhibits high variation in the CGE patterns, ranging from continuous to highly periodic records, sometimes including the classic F-phase. No record went to zero and we found significant (inverse) effects of ambient temperature on O-phase duration but not on the ventilatory period. Average V̇CO2 and O-phase amplitude (i.e. mean V̇CO2 of the peaks) increased with temperature whereas the amplitude of the interburst did not change significantly with ambient temperature. C. armatus is a species that lives below ground in humid forests, so our results support the chthonic-hygric hypothesis (i.e. facilitation of gas exchange under hypoxic and hypercapnic conditions, minimizing evaporative water loss), although this assertion needs to be confirmed statistically by a strong inference approach.
Interspecific scaling of the morphology and posture of the limbs during the locomotion of cats (Felidae)
Authors: Day Lisa M. , Jayne Bruce C.
Published: February 2007

For phylogenetically diverse mammals, ranging from small rodents to large ungulates, the generalization that limb erectness increases with increased size is supported by some size-dependent scaling relationships of appendicular skeletal anatomy as well as a limited number of direct observations of limb posture during locomotion. If size alone is the causal basis for different limb posture, then the erectness of limbs should increase significantly with increased size within a phylogenetically narrow lineage, but such data are sparse. Thus, to better establish the correlation between size and posture of mammalian limbs, we quantified the scaling relationships between mass and limb dimensions and kinematics during walking of nine species within the felid(cat) clade, which has qualitatively similar limb design. We studied the domestic cat, serval, ocelot, lynx, leopard, cheetah, cougar, lion and tiger,which had masses ranging from <4 kg to nearly 200 kg. Apart from variation associated with overall size, the lengths of the appendicular skeletal structures of most of the felid species were morphologically very similar in multivariate space. The kinematics of the limbs were also relatively uniform,and size had little predictive value for limb posture among felid species. Only three out of a total of 24 angular variables at footfall and midstance changed significantly (0.02<P<0.05) with increased mass. Thus,in contrast to previous broadly comparative studies of mammals, larger species of felids did not have more upright limbs than smaller species.
Belt-pulley mechanical loss for a metal belt continuously variable transmission
Authors: Ryu Wansik , Kim Hyunsoo
Published: February 2007

In this paper, the belt-pulley mechanical loss for a metal belt continuously variable transmission is investigated. A bond-graph model for the belt-pulley mechanical loss is developed from the viewpoint of the power flow by assuming that all power losses are attributed to the torque loss. The coefficients of the power loss model are obtained from the experiments. It is found from the simulations and experiments that the steady state belt-pulley loss depends on the line pressure, the input torque, and the rotational speed while the transient loss depends on the rotational speed, the shift speed, and the inertial torque.
Are Technology Improvements Contractionary?
Authors: Basu Susanto , Fernald John G , Kimball Miles S
Published: February 2007

Yes. We construct a measure of aggregate technology change, controlling for aggregation effects, varying utilization of capital and labor, nonconstant returns, and imperfect competition. On impact, when technology improves, input use and nonresidential investment fall sharply. Output changes little. With a lag of several years, inputs and investment return to normal and output rises strongly. The standard one-sector real-business-cycle model is not consistent with this evidence. The evidence is consistent, however, with simple sticky-price models, which predict the results we find: when technology improves, inputs and investment generally fall in the short run, and output itself may also fall.
Accounting for the Growth of MNC-Based Trade Using a Structural Model of U.S. MNCs
Authors: Feinberg Susan E , Keane Michael P
Published: February 2007

In recent decades, U.S. foreign trade grew much faster than GDP, but there is no consensus why. Notably lacking is an understanding of the role of multinational corporations (MNCs), which mediate over half of world trade. We use Bureau of Economic Analysis data on U.S. MNCs to study the rapid growth of MNC-based trade from 1983 to 1996. Using a model of U.S. MNCs and Canadian affiliates, we decompose this growth by source. Tariff reductions can largely explain increases in arms-length MNC-based trade. But intra-firm trade growth is attributed mostly to “technical change.” We present additional evidence suggesting just-in-time production facilitated intra-firm trade. (JEL F13, F14, F23)
Crises and Prices: Information Aggregation, Multiplicity, and Volatility
Authors: Angeletos George-Marios , Werning Iván
Published: February 2007

Crises are volatile times when endogenous sources of information are closely monitored. We study the role of information in crises by introducing a financial market in a coordination game with imperfect information. The asset price aggregates dispersed private information acting as a public noisy signal. In contrast to the case with exogenous information, our main result is that uniqueness may not obtain as a perturbation from perfect information: multiplicity is ensured with small noise. In addition, we show that: (a) multiplicity may emerge in the financial price itself; (b) less noise may contribute toward nonfundamental volatility even when the equilibrium is unique; and (c) similar results obtain for a model where individuals observe one another's actions, highlighting the importance of endogenous information more generally.
Declining Volatility in the U.S. Automobile Industry
Authors: Ramey Valerie A , Vine Daniel J
Published: February 2007

Dramatic changes in the volatility of output occurred in the U.S. auto industry in the early 1980s. Namely, output volatility declined, the covariance of inventory investment and sales grew more negative, and adjustments to production schedules, which in earlier decades stemmed primarily from plants hiring and laying off workers, were more often accomplished with changes in average hours per worker after the mid-1980s. Using a linear quadratic inventory model with intensive and extensive labor adjustments, we show how all of these changes could have stemmed from one underlying factor—a decline in the persistence of motor vehicle sales.
Illegal Migration from Mexico to the United States
Authors: Hanson Gordon H
Published: February 2007

In this paper, I selectively review recent literature on illegal migration from Mexico to the United States. I begin by discussing methods for estimating stocks and flows of illegal migrants. While there is uncertainty about the size of the unauthorized population, new data sources make it possible to examine the composition of legal and illegal populations and the time-series covariates of illegal labor flows. I then consider the supply of and demand for illegal migrants. Wage differentials between the United States and Mexico are hardly a new phenomenon, yet illegal migration from Mexico did not reach high levels until recently. An increase in the relative size of Mexico's working-age population, greater volatility in U.S.–Mexico relative wages, and changes in U.S. immigration policies are all candidate explanations for increasing labor flows from Mexico. Finally, I consider policies that regulate the cross-border flow of illegal migrants. While U.S. laws mandate that authorities prevent illegal entry and punish firms that hire unauthorized immigrants, these laws are imperfectly enforced. Lax enforcement may reflect political pressure by employers and other interests that favor open borders.
The Real Effects of European Monetary Union
Authors: Lane Philip R
Published: February 2007

We explore the impact of European monetary union on the economies of the member countries. Inflation differentials across the euro area have been persistent, such that cumulative real exchange rate movements across the euro area have been quite substantial. The adoption of the euro has indeed contributed to greater economic integration; however, economic linkages with the rest of the world have also been growing strongly, such that the relative importance of trade within the European monetary union has not dramatically increased. In terms of future risks, a severe economic downturn or financial crisis in a member country will be the proving ground for the future political viability of the euro.
A comparison of writing exercises to motivate young women to practise breast self‐examinations
Authors: Smith Susan L. , Kloss Jacqueline D. , Kniele Kathryn , Anderson Shakesha S.
Published: February 2007

Objectives. This study investigated the novel use of written emotional disclosure procedures for motivating health behavior change, specifically engagement in breast self examination (BSE) among college‐aged women. Writing instructions were tailored to a precontemplative stage of change in accordance with the transtheoretical model proposed by Prochaska and DiClemente (1983) to test the hypothesis that stagematched writing strategy would facilitate greater contemplation than a stage‐mismatched writing strategy and a control condition.

Design and methods. Precontemplative women (N = 55) were randomly assigned to one of three groups: (a) a stage‐matched consciousness‐raising writing exercise; (b) a stage‐mismatched BSE action‐oriented exercise; or (c) a control condition, and measured on contemplation, preparation, and action, as well as performance of BSEs.

Results. Analyses indicated that both the consciousness‐raising writing exercise and the BSE action‐oriented exercise increased participants' level of contemplation when compared to the control condition. Women assigned to the BSE action‐oriented exercise endorsed more statements indicative of an action stage of change and exhibited a trend for greater performance of BSE compared to the other two conditions.

Conclusion. The application of writing exercises and the relevance of stage‐matching is discussed in the context of the stage of change model.
Control of regio- and stereoselectivity in electrophilic addition reactions of allenes
Authors: Ma Shengming
Published: February 2007

The halohydroxylation reaction of 1,2-allenyl sulfoxides exhibitsE-selectivity while those of analogous sulfides and selenides showZ-selectivity. Rationales for the stereoselectivities are proposed. The reaction of 2,3-allenols with X+affords 3-halo-2,5-dihydrofurans or 3-halo-3-enals depending on the nature of the alcohols.
Biomimetic synthesis via polyepoxide cyclizations
Authors: McDonald Frank E. , Tong Rongbiao , Valentine Jason C. , Bravo Fernando
Published: February 2007

The biomimetic synthesis of trans,syn,trans-fused polycyclic ether natural products involving a cascade of stereospecific and regioselective oxacyclizations of polyepoxide substrates is described as applied to the synthesis of polyoxepane and polypyran structures. In addition, an extension of biomimetic polyene cyclizations to terpenoid natural products is outlined.
HPLC-Electrospray Tandem Mass Spectrometry for Rapid Determination of Dihydropyrimidine Dehydrogenase Activity
Authors: van Kuilenburg André BP , van Lenthe Henk , Zoetekouw Lida , Kulik Willem
Published: February 2007

Background: Patients with a partial dihydropyrimidine dehydrogenase (DPD) deficiency have an increased risk of developing severe 5-fluorouracil–associated toxicity. We developed a rapid and specific method to measure the DPD activity in peripheral blood mononuclear cells using HPLC tandem-mass spectrometry (HPLC-MS/MS).

Methods: The activity of DPD was measured with thymine as the substrate, followed by reversed-phase HPLC combined with electrospray ionization MS/MS and detection of the product dihydrothymine with multiple-reaction monitoring. Stable-isotope labeled dihydrothymine was used as the internal standard.

Results: Dihydrothymine was measured within an analytical run of 10 min, with a lower limit of quantification of 54 μg/L (0.4 μmol/L). The intraassay and interassay variations of the DPD activity assay were both <7%. A linear correlation (R2 = 0.980; P <0.001) was observed between the HPLC-MS/MS data and those obtained with a reference method using radiolabeled thymine. There were no systematic differences between the 2 methods, and both methods yielded similar results.

Conclusion: The analysis of the DPD activity with HPLC-MS/MS is rapid, accurate, and sufficiently sensitive to be used as a screening method for patients with a DPD deficiency.