bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitigating application-level denial of service attacks on Web servers
Authors: Srivatsa Mudhakar , Iyengar Arun , Yin Jian , Liu Ling
Published: July 2008

Recently, we have seen increasing numbers of denial of service (DoS) attacks against online services and Web applications either for extortion reasons or for impairing and even disabling the competition. These DoS attacks have increasingly targeted the application level. Application-level DoS attacks emulate the same request syntax and network-level traffic characteristics as those of legitimate clients, thereby making the attacks much harder to detect and counter. Moreover, such attacks often target bottleneck resources such as disk bandwidth, database bandwidth, and CPU resources. In this article, we propose handling DoS attacks by using a twofold mechanism. First, we perform admission control to limit the number of concurrent clients served by the online service. Admission control is based on port hiding that renders the online service invisible to unauthorized clients by hiding the port number on which the service accepts incoming requests. Second, we perform congestion control on admitted clients to allocate more resources to good clients. Congestion control is achieved by adaptively setting a client's priority level in response to the client's requests in a way that can incorporate application-level semantics. We present a detailed evaluation of the proposed solution using two sample applications: Apache HTTPD and the TPCW benchmark (running on Apache Tomcat and IBM DB2). Our experiments show that the proposed solution incurs low performance overhead and is resilient to DoS attacks.
Common weakness enumeration (CWE) status update
Authors: Martin Robert A. , Barnum Sean
Published: July 2008

This paper is a status update on the Common Weakness Enumeration (CWE) initiative [1], one of the efforts focused on improving the utility and effectiveness of code-based security assessment technology. As hoped, the CWE initiative has helped to dramatically accelerate the use of tool-based assurance arguments in reviewing software systems for security issues and invigorated the investigation of code implementation, design, and architecture issues with automation.
Failed Forensics: How Forensic Science Lost Its Way and How It Might Yet Find It
Authors: Saks Michael J. , Faigman David L.
Published: July 2008

A group of nonscience forensic sciences has developed over the past century. These are fields within the broader forensic sciences that have little or no basis in actual science. They are not applications of established basic sciences, they have not systematically tested their own hypotheses, and they make unsupported assumptions and exaggerated claims. This review explains the nature and origins of those nonscience forensic fields, which include the forensic individualization sciences and certain other areas, such as fire and arson investigation. We explore the role of the courts in maintaining the underdeveloped state of these fields and consider suggestions for improving this state of affairs (addressing the potential role that could be played by these fields themselves, by the courts, and by normal sciences).
Antitumor activity of histone deacetylase inhibitors in non-small cell lung cancer cells: development of a molecular predictive model
Authors: Miyanaga Akihiko , Gemma Akihiko , Noro Rintaro , Kataoka Kiyoko , Matsuda Kuniko , Nara Michiya , Okano Tetsuya , Seike Masahiro , Yoshimura Akinobu , Kawakami Akiko , Uesaka Haruka , Nakae Hiroki , Kudoh Shoji
Published: July 2008

To ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the antitumor effects of trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. TSA and vorinostat both displayed strong antitumor activities in 50% of NSCLC cell lines, suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001). To identify a molecular model of sensitivity to HDAC inhibitor treatment in NSCLC, we conducted a gene expression profiling study using cDNA arrays on the same set of cell lines and related the cytotoxic activity of TSA to corresponding gene expression pattern using a modified National Cancer Institute program. In addition, pathway analysis was done with Pathway Architect software. We used nine genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine algorithm model by which sensitive cell lines were distinguished from resistant cell lines. The prediction performance of the support vector machine model was validated by an additional nine cell lines, resulting in a prediction value of 100% with respect to determining response to TSA and vorinostat. Our results suggested that (a) HDAC inhibitors may be promising anticancer drugs to NSCLC and (b) the nine-gene classifier is useful in predicting drug sensitivity to HDAC inhibitors and may contribute to achieving individualized therapy for NSCLC patients. [Mol Cancer Ther 2008;7(7):1923–30]
Antitumor activity and pharmacokinetic properties of PF-00299804, a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor
Authors: Gonzales Andrea J. , Hook Kenneth E. , Althaus Irene W. , Ellis Paul A. , Trachet Erin , Delaney Amy M. , Harvey Patricia J. , Ellis Teresa A. , Amato Danielle M. , Nelson James M. , Fry David W. , Zhu Tong , Loi Cho-Ming , Fakhoury Stephen A. , Schlosser Kevin M. , Sexton Karen E. , Winters R. Thomas , Reed Jessica E. , Bridges Alex J. , Lettiere Daniel J. , Baker Deborah A. , Yang Jianxin , Lee Helen T. , Tecle Haile , Vincent Patrick W.
Published: July 2008

Signaling through the erbB receptor family of tyrosine kinases contributes to the proliferation, differentiation, migration, and survival of a variety of cell types. Abnormalities in members of this receptor family have been shown to play a role in oncogenesis, thus making them attractive targets for anticancer treatments. PF-00299804 is a second-generation irreversible pan-erbB receptor tyrosine kinase inhibitor currently in phase I clinical trials. PF-00299804 is believed to irreversibly inhibit erbB tyrosine kinase activity through binding at the ATP site and covalent modification of nucleophilic cysteine residues in the catalytic domains of erbB family members. Oral administration of PF-00299804 causes significant antitumor activity, including marked tumor regressions in a variety of human tumor xenograft models that express and/or overexpress erbB family members or contain the double mutation (L858R/T790M) in erbB1 (EGFR) associated with resistance to gefitinib and erlotinib. Furthermore, PF-00299804 shows exceptional distribution to human tumor xenografts and excellent pharmacokinetic properties across species. [Mol Cancer Ther 2008;7(7):1880–9]
Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity
Authors: Maira Sauveur-Michel , Stauffer Frédéric , Brueggen Josef , Furet Pascal , Schnell Christian , Fritsch Christine , Brachmann Saskia , Chène Patrick , De Pover Alain , Schoemaker Kevin , Fabbro Doriano , Gabriel Daniela , Simonen Marjo , Murphy Leon , Finan Peter , Sellers William , García-Echeverría Carlos
Published: July 2008

The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin inhibitor (mTOR) pathway is often constitutively activated in human tumor cells, providing unique opportunities for anticancer therapeutic intervention. NVP-BEZ235 is an imidazo[4,5-c]quinoline derivative that inhibits PI3K and mTOR kinase activity by binding to the ATP-binding cleft of these enzymes. In cellular settings using human tumor cell lines, this molecule is able to effectively and specifically block the dysfunctional activation of the PI3K pathway, inducing G1 arrest. The cellular activity of NVP-BEZ235 translates well in in vivo models of human cancer. Thus, the compound was well tolerated, displayed disease stasis when administered orally, and enhanced the efficacy of other anticancer agents when used in in vivo combination studies. Ex vivo pharmacokinetic/pharmacodynamic analyses of tumor tissues showed a time-dependent correlation between compound concentration and PI3K/Akt pathway inhibition. Collectively, the preclinical data show that NVP-BEZ235 is a potent dual PI3K/mTOR modulator with favorable pharmaceutical properties. NVP-BEZ235 is currently in phase I clinical trials. [Mol Cancer Ther 2008;7(7):1–13 [Mol Cancer Ther 2008;7(7):1851–13]
RANK ligand inhibition plus docetaxel improves survival and reduces tumor burden in a murine model of prostate cancer bone metastasis
Authors: Miller Robert E. , Roudier Martine , Jones Jon , Armstrong Allison , Canon Jude , Dougall William C.
Published: July 2008

Tumor cells induce excessive osteoclastogenesis, mediating pathologic bone resorption and subsequent release of growth factors and calcium from bone matrix, resulting in a “vicious cycle” of bone breakdown and tumor proliferation. RANK ligand (RANKL) is an essential mediator of osteoclast formation, function, and survival. In metastatic prostate cancer models, RANKL inhibition directly prevents osteolysis via blockade of osteoclastogenesis and indirectly reduces progression of skeletal tumor burden by reducing local growth factor and calcium concentrations. Docetaxel, a well-established chemotherapy for metastatic hormone-refractory prostate cancer, arrests the cell cycle and induces apoptosis of tumor cells. Suppression of osteoclastogenesis through RANKL inhibition may enhance the effects of docetaxel on skeletal tumors. We evaluated the combination of the RANKL inhibitor osteoprotegerin-Fc (OPG-Fc) with docetaxel in a murine model of prostate cancer bone metastasis. Tumor progression, tumor area, and tumor proliferation and apoptosis were assessed. OPG-Fc alone reduced bone resorption (P < 0.001 versus PBS), inhibited progression of established osteolytic lesions, and reduced tumor area (P < 0.0001 versus PBS). Docetaxel alone reduced tumor burden (P < 0.0001 versus PBS) and delayed the development of osteolytic lesions. OPG-Fc in combination with docetaxel suppressed skeletal tumor burden (P = 0.0005) and increased median survival time by 16.7% (P = 0.0385) compared with docetaxel alone. RANKL inhibition may enhance docetaxel effects by increasing tumor cell apoptosis as evident by increased active caspase-3. These studies show that inhibition of RANKL provides an additive benefit to docetaxel treatment in a murine model of prostate cancer bone metastasis and supports clinical evaluation of this treatment option in patients. [Mol Cancer Ther 2008;7(7):2160–9]
Thrombin Peptide (TP508) Promotes Adipose Tissue-Derived Stem Cell Proliferation via PI3 Kinase/Akt Pathway
Authors: Freyberg Susanne , Song Yao-Hua , Muehlberg Fabian , Alt Eckhard
Published: July 2008

A synthetic peptide representing the receptor-binding domain of human thrombin (TP508) promotes angiogenesis and accelerates wound healing in animal models. However, the mechanisms underlying the therapeutic effects of TP508 have not been clearly defined. In this study, we set out to determine whether TP508 could stimulate stem cell proliferation. Adipose tissue-derived stem cells (ASCs) were incubated with TP508 (5 μg/ml) and cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation. Our data showed that TP508 treatment significantly stimulated BrdU incorporation in ASCs (p < 0.01). The increased BrdU incorporation induced by TP508 was abolished by the PI3 kinase (PI3K) inhibitor LY294002 at 50 μM. Western blot analysis of ASCs revealed increased phosphorylation of Akt in response to TP508 when compared to unstimulated controls. These results indicate that TP508 exerts proliferative effects on ASCs via the PI3K/Akt pathway.
Subcutaneous Sarcoidosis Masquerading as Cellulitis
Authors: Papadavid Evangelia , Dalamaga Marianna , Stavrianeas Nikolaos , Papiris Spiridon A.
Published: July 2008

Sarcoidosis is a multisystem disease encountered by general physicians as well as medical specialists. Subcutaneous sarcoidosis is not an uncommon clinical presentation of sarcoidosis and is challenging for physicians because it can mimic cellulitis or several chronic infections. Our patient presented with a swollen forearm and hand which were initially treated as acute cellulitis with antibiotics by general physicians but without any improvement. A skin biopsy showed granulomatous panniculitis but confirmation of the diagnosis of systemic sarcoidosis was based on the characteristic chest roentgenogram, the high CD4/CD8 ratio of T lymphocytes in bronchoalveolar lavage, and the typical ‘panda’ and ‘lambda’ signs on the 67Ga scan. Such cases with atypical clinical presentation cause some difficulty in reaching the diagnosis but a skin biopsy as well as typical imaging and laboratory signs are usually important to establish the diagnosis of sarcoidosis, when invasive procedures cannot be performed to get confirmation from a second target organ.
Serous Cystic Tumors of the Pancreas: When to Observe and When to Operate
Authors: Zanini Nicola , Fantini Lorenzo , Casadei Riccardo , Pezzilli Raffaele , Santini Donatella , Calculli Lucia , Minni Francesco
Published: July 2008

Background: Pancreatic serous cystic tumors are considered to have a benign biological and clinical course with only few malignant cases. Methods: We retrospectively analyzed data from 26 patients affected by serous cystic tumors consecutively observed in our Pancreas Unit. We explored the different clinical pictures in operated and nonoperated patients. Results: Eighteen of the 26 patients were female (69%), median age at diagnosis was 61.5 years and 20 patients (77%) underwent surgery. The median diameter of the tumors was greater in patients who underwent surgery than in those who did not (5.5 versus 2.3 cm, p < 0.001). Major pancreatic resections were carried out in 15 of the 20 operated patients (75%). Postoperative morbidity and mortality were 20 and 5%, respectively. During follow-up, there was no observed development of malignancy or any significant increase in the diameter of the lesion among nontreated patients. Conclusions: In asymptomatic patients with a clear imaging diagnosis of serous cystic tumor a wait and see management should be recommended, with a careful follow-up. Surgery should be suggested in symptomatic patients or when the preoperative diagnosis is doubtful.
Endoscopic Retrograde Cholangiography of a Hepaticojejunostomy Using Double Balloon Enteroscopy
Authors: Zuber-Jerger I. , Klebl F. , Schoelmerich J.
Published: July 2008

Examination of a biliodigestive anastomosis presents a diagnostic and therapeutic challenge. Visualization of biliodigestive anastomosis and endoscopic retrograde cholangiography with intervention is possible with a double balloon enteroscope.
Development of Crohn’s Disease in a Patient with Multiple Sclerosis Treated with Copaxone
Authors: Charach Gideon , Grosskopf Itamar , Weintraub Moshe
Published: July 2008

Background: Copaxone (glatiramer acetate) is a synthetic copolymer mimicking a portion of myelin basic protein, one of several putative autoantigens in multiple sclerosis (MS). Copaxone suppresses the production of tumor necrosis factor (TNF)-α, a key mediator of inflammation in MS as well as in other pathologies, such as colitis of interstitial bowel disease (IBD). Copaxone is a drug approved for the treatment of MS, and one that is very well tolerated with a high safety profile and relatively few side effects. Crohn’s disease has not been associated with its administration. Methods: We describe a patient with MS in remission who had not exhibited any signs of IBD in the past. She had been on Copaxone 20 mg/day treatment for 2 years when she first exhibited gastrointestinal symptoms. Results: Our patient developed Crohn’s disease while on Copaxone treatment as a consequence of long-term immunosuppression. Conclusions: Clinicians should be aware that Crohn’s disease is a potential novel adverse drug effect of Copaxone.
Fetal Cerebrovascular Circulation: A Review of Prenatal Ultrasound Assessment
Authors: Degani S.
Published: July 2008

Antenatal intrauterine cerebrovascular events were found to play an important role in the pathogenesis of perinatal brain damage. Changes in placental vascular resistance, cardiac contractibility, vessel compliance, and blood viscosity alter the normal dynamics of fetal cerebral circulation. The circulatory mechanisms described in animal fetuses also operate in the human fetus. The isthmus of the aorta represents a watershed area reflecting the redistribution of blood during increased peripheral resistance and hypoxia. The fetal cerebrovascular system acts locally within the skull and interacts with the other components of fetal circulation to compensate by redistribution of blood in case of shortage in resources. The introduction of various sonographic techniques and the collection of data from the arterial and venous cerebral circulation have improved our understanding of the regulatory mechanisms involved in fetal cerebral hemodynamic events. Anatomical and physiological considerations of cerebral vasculature in health and disease are relevant in the research of variations in fetal brain blood perfusion. Changes in flow characteristics in fetal cerebral vasculature can be used for clinical decisions. However, caution is advised before applying research data into practice. The clinical utility is well established in situations of fetal compromise such as growth restriction and anemia.
Randomized, Controlled Trial of Coronary Artery Bypass Surgery Versus Percutaneous Coronary Intervention in Patients With Multivessel Coronary Artery Disease
Authors: Booth Jean , Clayton Tim , Pepper John , Nugara Fiona , Flather Marcus , Sigwart Ulrich , Stables Rodney H.
Published: July 2008

Background—

The Stent or Surgery Trial is a randomized, controlled trial comparing percutaneous coronary intervention with coronary artery bypass grafting (CABG) for patients with multivessel disease. Initial results at a median follow-up of 2 years showed a survival advantage for patients randomized to CABG. This article reports survival outcome at a median follow-up of 6 years.

Methods and Results—

A total of 988 (n=488 percutaneous coronary intervention, n=500 CABG) patients were randomized at 53 centers during the period from 1996 to 1999. Investigators established survival status from hospital or community medical records or national databases or by direct contact with patients and their relatives. All-cause mortality was compared with hazard ratios and confidence intervals calculated from Cox proportional hazards models. Prespecified subgroup analyses for diabetes mellitus, angina grade, and angiographic severity of coronary disease at baseline were performed with tests for interaction. At a median follow-up of 6 years, 53 patients (10.9%) died in the percutaneous coronary intervention group compared with 34 (6.8%) in the CABG group (hazard ratio 1.66, 95% confidence interval 1.08 to 2.55,
P
=0.022). Little evidence was found that the treatment effect on mortality differed between subgroups according to baseline angina grade (interaction test
P
=0.52), the severity of coronary disease (
P
=0.92), or diabetic status (
P
=0.15).

Conclusions—

At a median follow-up of 6 years, a continuing survival advantage was observed for patients managed with CABG, which is not consistent with results from other stent-versus-CABG studies.
Mast Cells Play a Critical Role in the Pathogenesis of Viral Myocarditis
Authors: Higuchi Hirokazu , Hara Masatake , Yamamoto Kanjo , Miyamoto Tadashi , Kinoshita Makoto , Yamada Tasuku , Uchiyama Koji , Matsumori Akira
Published: July 2008

Background—

Mast cells are powerful producers of multiple cytokines and chemical mediators playing a pivotal role in the pathogenesis of various cardiovascular diseases. We examined the role of mast cells in murine models of heart failure due to viral myocarditis, using 2 strains of mast cell–deficient mice.

Methods and Results—

Two strains of mast cell–deficient mice, WBB6F1-Kit
W
/Kit
W-v
(W/W
V
) and WCB6F1-Kitl
Sl
/Kitl
Sl-d
(Sl/Sl
d
), were inoculated with 10 plaque-forming units of the encephalomyocarditis virus intraperitoneally. On day 14 after inoculation, survival of W/W
V
mice was significantly higher than that of their control littermates (77% versus 31%;
P
=0.03; n=13). On histological examination on day 7, myocardial necrosis and cellular infiltration were significantly less pronounced in W/W
V
and Sl/Sl
d
mice than in their control littermates (area of infiltration, 7.6±3.5% versus 29.3±15.6%;
P
=0.002; area of necrosis, 7.6±3.5% versus 30.0±17.2%;
P
=0.003; n=10). Histological examination showed more severe changes in mast cell–reconstituted than in –nonreconstituted W/W
V
and Sl/Sl
d
mice. The gene expressions of mast cell proteases were upregulated in the acute phase of viral myocarditis and rose further in the subacute phase of heart failure. Their activation coincided with the development of myocardial necrosis and fibrosis and correlated with the upregulation of gene expression of matrix metalloproteinase-9. The histamine H1-receptor antagonist bepotastine improved encephalomyocarditis viral myocarditis.

Conclusions—

These observations suggest that mast cells participate in the acute inflammatory reaction and the onset of ventricular remodeling associated with acute viral myocarditis and that the inhibition of their function may be therapeutic in this disease.
Aerobic Interval Training Versus Continuous Moderate Exercise as a Treatment for the Metabolic Syndrome
Authors: Tjønna Arnt Erik , Lee Sang Jun , Rognmo Øivind , Stølen Tomas O. , Bye Anja , Haram Per Magnus , Loennechen Jan Pål , Al-Share Qusai Y. , Skogvoll Eirik , Slørdahl Stig A. , Kemi Ole J. , Najjar Sonia M. , Wisløff Ulrik
Published: July 2008

Background—

Individuals with the metabolic syndrome are 3 times more likely to die of heart disease than healthy counterparts. Exercise training reduces several of the symptoms of the syndrome, but the exercise intensity that yields the maximal beneficial adaptations is in dispute. We compared moderate and high exercise intensity with regard to variables associated with cardiovascular function and prognosis in patients with the metabolic syndrome.

Methods and Results—

Thirty-two metabolic syndrome patients (age, 52.3±3.7 years; maximal oxygen uptake [V̇
o
2
max], 34 mL · kg
−1
· min
−1
) were randomized to equal volumes of either moderate continuous moderate exercise (CME; 70% of highest measured heart rate [Hfmax]) or aerobic interval training (AIT; 90% of Hfmax) 3 times a week for 16 weeks or to a control group. V̇
o
2
max increased more after AIT than CME (35% versus 16%;
P
<0.01) and was associated with removal of more risk factors that constitute the metabolic syndrome (number of factors: AIT, 5.9 before versus 4.0 after;
P
<0.01; CME, 5.7 before versus 5.0 after; group difference,
P
<0.05). AIT was superior to CME in enhancing endothelial function (9% versus 5%;
P
<0.001), insulin signaling in fat and skeletal muscle, skeletal muscle biogenesis, and excitation-contraction coupling and in reducing blood glucose and lipogenesis in adipose tissue. The 2 exercise programs were equally effective at lowering mean arterial blood pressure and reducing body weight (−2.3 and −3.6 kg in AIT and CME, respectively) and fat.

Conclusions—

Exercise intensity was an important factor for improving aerobic capacity and reversing the risk factors of the metabolic syndrome. These findings may have important implications for exercise training in rehabilitation programs and future studies.
Deletion of Transient Receptor Potential Vanilloid Type 1 Receptors Exaggerates Renal Damage in Deoxycorticosterone Acetate-Salt Hypertension
Authors: Wang Youping , Babánková Dagmar , Huang Jie , Swain Greg M. , Wang Donna H.
Published: July 2008

To determine whether the transient receptor potential vanilloid type 1 (TRPV1) channel provides protection against hypertension-induced renal damage, hypertension was induced by uninephrectomy and by giving deoxycorticosterone acetate (DOCA)-salt in wild-type (WT) and TRPV1-null mutant (TRPV1
−/−
) mice. Mean arterial pressure, as determined by radiotelemetry, increased significantly and reached the peak 7 days after DOCA-salt treatment in both WT and TRPV1
−/−
mice. There was no difference in mean arterial pressure between the 2 strains at the baseline or at the peak that lasted for 4 treatment weeks. DOCA-salt treatment in both WT and TRPV1
−/−
mice led to increased urinary excretion of albumin and 8-isoprostane, glomerulosclerosis, renal cortical tubulointerstitial injury, tubulointerstitial fibrosis, increased number of tubular proliferating cell nuclear antigen–positive cells, and renal monocyte/macrophage infiltration, all of which were much more severe in DOCA-salt–treated TRPV1
−/−
compared with DOCA-salt-treated WT mice. Renal TRPV1 protein expression, but not the renal anandamide content, was elevated in DOCA-salt–treated WT compared with vehicle-treated WT mice. Renal anandamide levels were markedly elevated in DOCA-salt–treated TRPV1
−/−
but not in vehicle-treated TRPV1
−/−
mice. Thus, our data show that ablation of the TRPV1 gene exacerbates renal damage induced by DOCA-salt hypertension, indicating that TRPV1 may constitute a protective mechanism against end-organ damage induced by hypertension.
Impaired Purinergic Neurotransmission to Mesenteric Arteries in Deoxycorticosterone Acetate-Salt Hypertensive Rats
Authors: Demel Stacie L. , Galligan James J.
Published: July 2008

Sympathetic nerves release norepinephrine and ATP onto mesenteric arteries. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, there is increased arterial sympathetic neurotransmission attributable, in part, to impaired prejunctional regulation of norepinephrine release. Prejunctional regulation purinergic transmission in hypertension is less well understood. We hypothesized that α2-adrenergic receptor dysfunction alters purinergic neurotransmission to arteries in DOCA-salt hypertensive rats. Mesenteric artery preparations were maintained in vitro, and intracellular electrophysiological methods were used to record excitatory junction potentials (EJPs) from smooth muscle cells. EJP amplitude was reduced in smooth muscle cells from DOCA-salt (4±1 mV) compared with control arteries (9±1 mV;P<0.05). When using short trains of stimulation (0.5 Hz; 5 pulses), the α2adrenergic receptor antagonist yohimbine (1 μmol/L) potentiated EJPs in control more than in DOCA-salt arteries (180±35% versus 86±7%;P<0.05). Norepinephrine (0.1 to 3.0 μmol/L), the α2adrenergic receptor agonist UK 14304 (0.001 to 0.100 μmol/L), the A1adenosine receptor agonist cyclopentyladensosine (0.3 to 100.0 μmol/L), and the N-type calcium channel blocker ω-conotoxin GVIA (0.0003 to 0.1000 μmol/L) decreased EJP amplitude equally well in control and DOCA-salt arteries. Trains of stimuli (10 Hz) depleted ATP stores more completely, and the latency to EJP recovery was longer in DOCA-salt compared with control arteries. These data indicate that there is reduced purinergic input to mesenteric arteries of DOCA-salt rats because of decreased ATP bioavailability in sympathetic nerves. These data highlight the potential importance of impaired purinergic regulation of arterial tone as a target for drug treatment of hypertension.
Cerebral Hemodynamics During Treatment With Sodium Nitroprusside Versus Labetalol in Malignant Hypertension
Authors: Immink Rogier V. , van den Born Bert-Jan H. , van Montfrans Gert A. , Kim Yu-Sok , Hollmann Markus W. , van Lieshout Johannes J.
Published: July 2008

In patients with malignant hypertension, immediate blood pressure reduction is indicated to prevent further organ damage. Because cerebral autoregulatory capacity is impaired in these patients, a pharmacologically induced decline of blood pressure reduces cerebral blood flow with the danger of cerebral hypoperfusion. We compared the reduction in transcranial Doppler–determined middle cerebral artery blood velocity during blood pressure lowering with sodium nitroprusside with that of labetalol. Therefore, in 15 patients, fulfilling World Health Organization criteria for malignant hypertension, beat-to-beat mean arterial pressure, systemic vascular resistance (Modelflow), mean middle cerebral artery blood velocity, and cerebrovascular resistance index (mean blood pressure:mean middle cerebral artery blood flow velocity ratio), were monitored during treatment with sodium nitroprusside (n=8) or labetalol (n=7). The reduction in mean arterial blood pressure with sodium nitroprusside (−28±3%; mean±SEM) and labetalol (−28±4%) was comparable. With labetalol, both systemic and cerebral vascular resistance decreased proportionally (−13±10% and −17±5%), whereas with sodium nitroprusside, the decline in systemic vascular resistance was larger than that in cerebral vascular resistance (−53±4% and −7±4%). The rate of reduction in middle cerebral artery blood velocity was smaller with labetalol than with sodium nitroprusside (0.45±0.05% versus 0.78±0.04% cm · s
−1
· %mm Hg
−1
;
P
<0.05). In conclusion, sodium nitroprusside reduced systemic vascular resistance rather than cerebral vascular resistance with a larger rate of reduction in middle cerebral artery blood velocity, suggesting a preferential blood flow to the low resistance systemic vascular bed rather than the cerebral vascular bed.
Relationship of Dietary Linoleic Acid to Blood Pressure
Authors: Miura Katsuyuki , Stamler Jeremiah , Nakagawa Hideaki , Elliott Paul , Ueshima Hirotsugu , Chan Queenie , Brown Ian J. , Tzoulaki Ioanna , Saitoh Shigeyuki , Dyer Alan R. , Daviglus Martha L. , Kesteloot Hugo , Okayama Akira , Curb J. David , Rodriguez Beatriz L. , Elmer Patricia J. , Steffen Lyn M. , Robertson Claire , Zhao Liancheng
Published: July 2008

Findings from observational and interventional studies on the relationship of dietary linoleic acid, the main dietary polyunsaturated fatty acid, with blood pressure have been inconsistent. The International Study of Macro-Micronutrients and Blood Pressure is an international cross-sectional epidemiological study of 4680 men and women ages 40 to 59 years from 17 population samples in China, Japan, United Kingdom, and United States. We report associations of linoleic acid intake of individuals with their blood pressure. Nutrient intake data were based on 4 in-depth multipass 24-hour dietary recalls per person and 2 timed 24-hour urine collections per person. Systolic and diastolic blood pressures were measured 8 times at 4 visits. With several models to control for possible confounders (dietary or other), linear regression analyses showed a nonsignificant inverse relationship of linoleic acid intake (percent kilocalories) to systolic and diastolic blood pressure for all of the participants. When analyzed for 2238 “nonintervened” individuals (not on a special diet, not consuming nutritional supplements, no diagnosed cardiovascular disease or diabetes, and not taking medication for high blood pressure, cardiovascular disease, or diabetes), the relationship was stronger. With adjustment for 14 variables, estimated systolic/diastolic blood pressure differences with 2-SD higher linoleic acid intake (3.77% kcal) were −1.42/−0.91 mm Hg (
P
<0.05 for both) for nonintervened participants. For total polyunsaturated fatty acid intake, blood pressure differences were −1.42/−0.98 mm Hg (
P
<0.05 for both) with 2 SD higher intake (4.04% kcal). Dietary linoleic acid intake may contribute to prevention and control of adverse blood pressure levels in general populations.
The Change to Engagement in Britain's Cold War Policy: The Origins of the Thatcher-Gorbachev Relationship
Authors: Brown Archie
Published: July 2008

Using previously unseen British Cabinet Office and Foreign Office papers obtained through the UK Freedom of Information Act, this article shows how a change in Britain's stance in the Cold War was initiated in 1983. As a result of this process, the British government of Prime Minister Margaret Thatcher decided to move to greater engagement with the Soviet Union and Eastern Europe. Distrusting the Foreign Office as an institution, Thatcher asked for papers from eight outside academic specialists, on whose analyses she placed considerable weight. The desire for East-West dialogue was strongly favored by Foreign Office ministers and officials, whose advice, paradoxically, was more readily accepted by Thatcher when similar policy recommendations (though with some differences in analysis) were made by the academics. The invitation to Mikhail Gorbachev to visit Britain in 1984, prior to his becoming leader of the Soviet Union, had its origins in a Chequers seminar involving both academics and officials on 8–9 September 1983. This was the beginning of an important, and surprising, political relationship that transformed Britain's militantly anti-socialist prime minister into the strongest supporter—certainly among conservative politicians worldwide—of the new leader of the Soviet Communist Party.
Subunit Size, Work System Interdependence, and Employee Absenteeism
Authors: Bridges Edwin M. , Hallinan Maureen T.
Published: July 2008

This study is concerned with the effects of subunit size and work system interdependence on short-term absenteeism among elementary teachers. The results of the path analyses show that these two structural characteristics have a direct effect on teacher absenteeism. Moreover, these effects persist after total size of the organization and various personal characteristics are taken into account.
Charismatic Authority in the Rational Organization
Authors: Scott Lowell K.
Published: July 2008

A rationale for the antithesis of Weber's theory of the routinization of charisma is presented. The hypothesis that charismatic authority is a function of the superintendent's tenure in office was tested using a ran dom sample of Kentucky school superintendents, stratified by tenure in office. Superintendents' charismatic authority was evaluated by their administrative staffs using the Charismatic Authority Scale. Superin tendents in the high tenure group were perceived as possessing greater charismatic authority than superintendents in the low and medium tenure groups. District size and superintendent's age were not significantly related to charismatic authority.
`Becoming Planning Minded': The Theory and Practice of Relief 1940—1945
Authors: Shephard Ben
Published: July 2008

In the wake of the Iraq War, it has become axiomatic that the aftermath of a war should be planned for. This article disentangles the different strands woven into Allied planning for 'postwar relief' in the early 1940s. The rhetorical planners – great and good people such as Leonard Woolf and veterans of relief work – feared that the humanitarian aftermath of the second world war would be even worse than that of the first. The political planners had to reconcile many conflicting forces: the need to keep allied governments in exile happy, the British blockade, the interests of the Russians, and the concerns of the United States Congress. The new instrument they produced, the United Nations Relief and Rehabilitation Administration, struggled to establish itself under the weak leadership of Governor Herbert Lehman. In practice, therefore, military planning mattered most. Allied armies discovered, in Italy in 1943-44, the necessity in modern warfare of feeding, fumigating and rehousing civilians and, in the process, developed expertise in new medical technologies such as DDT, nutrition, and penicillin, which prevented the expected epidemics. But the reluctance of the military to 'do welfare' or to engage in rehabilitation also became apparent. The main achievement of the long planning process was in creating the dominant mental construct of postwar relief, that of the 'displaced person', on which the hierarchy of assessment of refugees' needs was based, and new institutional mechanisms of doubtful effectiveness. Planning, some contemporaries concluded, did not in itself guarantee success.
`For the Love of Christ': Strategies of International Catholic Relief and the Allied Occupation of Germany, 1945—1948
Authors: Weindling Paul
Published: July 2008

The end of the second world war saw the Allied occupation authorities faced by substantial problems of malnutrition, refugees and crime. The military and Allied occupation authorities lacked the resources to resolve these problems, and had to rely on a range of external assistance organizations to cope with malnutrition and the refugee problem. Assistance came from a complicated array of organizations, including international agencies associated with the new United Nations, bilateral assistance from neutral countries, and religious and welfare organizations. While the Allies would have been happier working with organizations that they could exert leverage on, for example, the Red Cross, such was the enormity of the problems that they had to admit a broad range of relief organizations. This article will consider the politics of assistance, as organizations steered a course between the Allied authorities, local Germans and Displaced Persons. In the case of the Roman Catholic Church, the Americans recognized that to maintain the legitimacy of the occupation, it was politic to keep the Vatican and Catholic organizations sympathetically. On the other hand, the Church saw that it could gain support by supporting German dissent and complaints about the inadequacy of provision. I will consider the tense political relations surrounding relief through a number of such case studies.
Latina Province, 1944—1950
Authors: Snowden Frank
Published: July 2008

The province of Latina in Italy provides an exceptional case in the history of postwar problems involving refugees, evacuees, and displaced persons. Famous until the 1930s as a largely uninhabited malarial swamp, the province was drained, reclaimed, and settled by Mussolini's regime. This was a massive and complex intervention that had propaganda, public health, and eugenic purposes as the swamps of the Pontine Marshes were transformed into a showcase of the new society the fascists intended to construct. Mussolini's foreign policy objectives, however, were incompatible with the goal of public health, and by 1944 the new province became a battlefield between the Allies and the retreating German army. The result was extreme environmental devastation and the unleashing of a major epidemic of malaria that intensified the sufferings of the recently settled civilian population that found itself homeless, hungry, and seriously ill as the war ended. This article examines the strategies employed by the United Nations Relief and Rehabilitation Administration (UNRRA), the Rockefeller Foundation, and the returning Italian authorities to deal with this complex emergency. Part of the interest of Latina province in this period is that it became the site for the earliest use of DDT to control a major epidemic of malaria, and an important precedent for the worldwide eradication effort of the World Health Organization. It is useful, therefore, to examine the grounds for the success of the antimalarial effort in Latina, which was in fact multifaceted. In addition, the paper addresses the political purposes that motivated the UNRRA relief effort as the Allies sought to prevent the threat of social unrest and revolution as well as to combat hunger, unemployment, homelessness and disease.
Representation of the Online Tourism Domain in Search Engines
Authors: Zheng Xiang  , Wöber Karl , Fesenmaier Daniel R.
Published: July 2008

With the growing importance of the Internet for travel planning, understanding the online domain of tourism is vital in order to identify the challenges and potential solutions for effectively marketing travel destinations. This study focuses attention on understanding the representation of the tourism domain on the Internet. Analyses of search results from a major search engine were conducted in order to assess: 1) the visibility of destination-related information; 2) the visibility of various industry sectors within destinations; and 3) the power structure of websites that represent a specific destination. The results show that although there is a huge amount of information indexed, travelers can only access a tiny fraction of the domain. Also, there are a relatively small number of websites dominating the search results. This study provides a number of important insights into the challenges facing the tourism industry with respect to representing a destination online.
Estimating the Economic Impact of an Increase in Inbound Tourism on the German Economy Using TSA Results
Authors: Ahlert Gerd
Published: July 2008

This article shows which additional analysis options are available within the framework of model-based macroeconomic analyses using structural information provided by tourism satellite accounts (TSAs). Based on their modular, product-specific documentation of results, TSAs provide optimal linkages to input–output models. In addition to the use of the simple input–output approaches, dynamically formulated macroeconomic structural models should be considered. After a brief characterization of the main demands placed on a macroeconomic model, the dynamic macroeconomic forecasting and simulation model for the German economy, Interindustry Forecasting Germany (INFORGE), is presented. Against the background of Germany being able to increase its market share in international tourism over the next several years, the corresponding scenario is elaborated in more specific terms using TSA results. After an explanation of the assumed scenario relating to the future development of inbound tourism, some simulation results using the INFORGE model to estimate the overall effects on income and employment are presented.
Television, Tourism, and Rural Life
Authors: Mordue Tom
Published: July 2008

This article analyzes the relationship among dramaturgy, tourism, and rurality. Through an ethnographic study of Goathland in North Yorkshire—the filming location for the U.K. television drama series Heartbeat—the rural is shown to be a cultural performance that invokes certain lifestyle preferences that are both reliant and counterpoised to urban society. However, when urban viewers exchange the virtuality of television viewing for the corporeality of visiting the rural scenes that have become a familiar part of their cultural landscapes, the consequences are much more profound, nuanced, and complex than the demarcation of positive or negative impacts reified in certain managerialist discourses. Moreover, the article shows how the public and private spaces of the rural are being fundamentally transformed by the types of global consumption and mobility that “film-induced tourism” represents.
Differing management of people with advanced cancer and delirium by four sub-specialties
Authors: Agar M , Currow DC , Plummer J , Chye R , Draper B
Published: July 2008

Introduction: Delirium in advanced cancer is prevalent, with limited prospective data to guide management. The aim was to survey current practice of specialists using two contrasting cases of delirium in cancer. Methods: A questionnaire was designed to identify investigations and treatment used, in relation to two cases. Results: Overall response rate ( n = 270) was 30%. Place of care: Only 35% of medical oncologists would consider care at home for a patient with reversible delirium compared with 66% of other specialists. Investigations: 85% specialists would order basic bloods, however, medical oncologists were more likely to use oxygen saturation and head computed tomography, psychogeriatricians more likely to order thyroid function and palliative medicine specialists less likely to order chest X-ray and urine culture. Greater than 40% of specialists would do no investigations for terminal delirium. Treatment: Medical oncologists use more pre-emptive therapies and more likely to use a benzodiazepine as agent of choice, and Palliative medicine specialists used significantly more neuroleptics to treat hypoactive symptoms of delirium. Discussion: The survey emphasise significant areas of variability in the management of delirium in advanced cancer. Furthermore, evidence to guide management in ways that draw on the strengths and knowledge of each specialty is urgently needed.
Inappropriateness of using opioids for end-stage palliative sedation: a Dutch study
Authors: Reuzel RPB , Hasselaar GJ , Vissers KCP , van der Wilt GJ , Groenewoud JMM , Crul BJP
Published: July 2008

To be able to distinguish end-stage palliative sedation from euthanasia without having to refer to intentions that are difficult to verify, physicians must be able to manage palliative sedation appropriately (i.e., see that death is not hastened as a result of disproportionate medication). In the present study, we assessed whether or not this requirement is met in the Netherlands. We sent a retrospective questionnaire to 1464 medical specialists, general practitioners, and nursing home physicians in the Netherlands. Furthermore, we held two sets of 20 and 22 semi-structured in-depth interviews with general practitioners, internists, lung specialists, and nursing home physicians. Although most guidelines discourage the administration of opioids alone for purposes of palliative sedation, opioids alone were administered for 22% of all the patients reported upon. Those physicians who were more experienced, general practitioners, and physicians who had consulted a palliative care expert administered only opioids significantly less often than the other physicians. The interviewees reported difficulties in assessing the appropriateness of medication, feeling uncertain about the pharmacokinetics of drugs used in moribund patients. Given that no more than 2% of the respondents perceived palliative sedation to be used as a form of euthanasia and that the use of opioids alone was not associated with shorter survival rates, the inappropriate use of opioids can only be attributed to a lack of knowledge or skill and/or a tradition of alleviating refractory dyspnoea with the use of opioids and not as an intentional means of hastening death.
Developing a Citywide Youth Violence Prevention Plan
Authors: Payne Brian K. , Button Deeanna M.
Published: July 2008

Researchers suggest that violence prevention requires community-wide efforts and partnerships that demonstrate commitment to youth development. Missing from this research, however, are studies considering how these partnerships are formed and how members of various groups involved in these partnerships perceive youth violence prevention. This study sought to fill this void. A series of seven focus group interviews were conducted with 85 stakeholders involved in developing a youth violence prevention plan in one community. Results suggest that the stakeholders were optimistic about developing violence prevention strategies and forging partnerships between various groups. Participants pointed to specific themes that provide a framework for understanding youth violence prevention planning efforts. Implications are provided.
A Response to Guerrien and Benicourt
Authors: Case Karl E.
Published: July 2008

This response is a defense of neoclassical economics. Neoclassical economics contains more than the perfectly competitive model: much of it concerns the problems of market failure including public goods, externalities, imperfect structure, and asymmetric information. The article acknowledges that economic models are abstract, but argues that abstraction can be useful, and that full-blown utility theory is not required to gain insights from the concepts. Neoclassical economics helps us understand how the world works.