bluuebunny/crossref_metadata_2025 huggingface dataset:
Why the Cosmological Constant Is Small and Positive
Authors: Steinhardt Paul J. , Turok Neil
Published: May 2006

Within conventional big bang cosmology, it has proven to be very difficult to understand why today's cosmological constant is so small. In this paper, we show that a cyclic model of the universe can naturally incorporate a dynamical mechanism that automatically relaxes the value of the cosmological constant, including contributions to the vacuum density at all energy scales. Because the relaxation time grows exponentially as the vacuum density decreases, nearly every volume of space spends an overwhelming majority of the time at the stage when the cosmological constant is small and positive, as observed today.
Parkinson's disease and primate research: past, present, and future
Authors: Pereira E A C , Aziz T Z
Published: May 2006

Scientific research involving non-human primates has contributed towards many advances in medicine and surgery. This review discusses its role in the progress made towards our understanding of Parkinson's disease and its treatment. Established medical treatments like dopamine agonists continue to need primate models to assess their efficacy, safety, and mechanism of action. The recently developed treatment of deep brain stimulation of the subthalamic nucleus required validation in primates before entering the clinic. Controversies surrounding future treatments such as gene therapy show the need for properly evaluated preclinical research using appropriate animal models before progression to clinical trials. Research on primates has played—and continues to play—a crucial part in deepening our understanding of Parkinson's disease, improving current therapies, and developing new treatments that are both safe and effective. In animal research, the “three Rs” of humane technique—reduction, refinement, and replacement—should be adhered to.
A wandering fish bone
Authors: Patel V M , Barai R S , Thomas P R
Published: May 2006

A unique case is described of an ingested fish bone migrating into the common hepatic duct, without perforation. Most foreign bodies are known to pass through the gastrointestinal tract uneventfully. Sharper objects such as fish bones have been known to cause perforation. This is more common, in countries where fish consumption is considerably higher, such as, south east Asia. However, even in these regions there have been no reports of such a proximal migration.
THE LHC MACHINE AND EXPERIMENTS
Authors: ROLANDI GIGI
Published: May 2006

This paper is a very short report on the status of the Large Hadron Collider(LHC) and its four experiments at the end of August 2005.
HAS THE QUARK-GLUON PLASMA BEEN SEEN?
Authors: STACHEL JOHANNA
Published: May 2006

Data from the first three years of running at RHIC are reviewed and put into context with data obtained previously at the AGS and SPS and with the physics question of creation of a quark-gluon plasma in high energy heavy ion collisions. Also some very recent and still preliminary data from run are included.
NEUTRINO PHYSICS AT SHORT BASELINE
Authors: ZIMMERMAN ERIC D.
Published: May 2006

Neutrino oscillation searches at short baseline (defined as ≲ 1 km) have investigated oscillations with Δm2 ≳ 0.1 eV 2. One positive signal, from the LSND collaboration, exists and is being tested by the MiniBooNE experiment. Neutrino cross-section measurements are being made, which will be important for reducing systematic errors in present and future oscillation measurements.
NEUTRINO OSCILLATIONS AND MASSES
Authors: GOSWAMI SRUBABATI
Published: May 2006

The present status of neutrino oscillation parameters are summarised. The sensitivity of the future planned and proposed experiments are discussed.
PARTICLE DETECTOR R&D
Authors: DANILOV MICHAEL V.
Published: May 2006

Recent results on the particle detector R&D for new accelerators are reviewed. Different approaches for the muon systems, hadronic and electromagnetic calorimeters, particle identification devices, and central trackers are discussed. Main emphasis is made on the detectors for the International Linear Collider and Super B-factory. A detailed description of a novel photodetector, a so called Silicon Photomultiplier, and its applications in scintillator detectors is presented.
Luminal glucose sensing in the rat intestine has characteristics of a sodium-glucose cotransporter
Authors: Freeman S. L. , Bohan D. , Darcel N. , Raybould H. E.
Published: May 2006

The presence of glucose in the intestinal lumen elicits a number of changes in gastrointestinal function, including inhibition of gastric emptying and food intake and stimulation of pancreatic and intestinal secretion. The present study tested the hypothesis that Na+-glucose cotransporter (SGLT)-3, a member of the SGLT family of transport proteins, is involved in detection of luminal glucose in the intestine. Gastric emptying, measured in awake rats, was significantly inhibited by perfusion of the intestine with glucose (60 and 90 mg); this effect was mimicked by α-methyl glucose (nonmetabolizable substrate of SGLT-1 and -3) but not 2-deoxy-d-glucose (substrate for GLUT-2) or isoosmotic mannitol. Gastric motility and intestinal fluid secretion, measured in anesthetised rats, were significantly inhibited and stimulated, respectively, by duodenal glucose but not galactose, which has a much lower affinity for SGLT-3 than glucose. Duodenal glucose but not galactose stimulated the release of 5-HT into mesenteric lymph and stimulated the discharge of duodenal vagal afferent fibers. mRNA for SGLT-3 was identified in the duodenal mucosa. Together these data suggest that detection of glucose in the intestine may involve SGLT-3, possibly expressed by enterochromaffin cells in the intestinal mucosa, and release of 5-HT.
Oxygen consumption and metabolite concentrations during transitions between different work intensities in heart
Authors: Korzeniewski Bernard
Published: May 2006

Steady-state metabolite (ADP, ATP, Pi, PCr, and NADH) concentrations usually differ little between different workloads with significantly different oxygen consumption rates in the heart. However, during transitions between steady states, metabolite concentrations may in some cases change transiently, exhibiting a significant overshoot or undershoot, whereas in other cases they approach near-exponentially new steady-state values. Oxygen consumption rate usually reaches the new steady-state value very quickly (within a few seconds). The present in silico studies, performed using a previously developed computer model of oxidative phosphorylation in the heart, demonstrate that such a behavior of the oxidative phosphorylation system can be reproduced only under the assumption that ATP usage, substrate dehydrogenation, and (particular steps of) oxidative phosphorylation are directly activated to a similar extend by some cytosolic factor/mechanism during transition from low work to high work (the so-called parallel-activation mechanism). Computer simulations show that some differences observed between different experimental systems can be explained by a slightly different balance of the activation of particular components of the system and/or by a delay in time of the activation/inactivation of substrate dehydrogenation and oxidative phosphorylation during low-to-high and high-to-low work transitions. Thus the presented theoretical approach offers a general idea that is able to unify, at least semiquantitatively, different experimental data available in the literature.
Changes in activation sequence of embryonic chick atria correlate with developing myocardial architecture
Authors: Sedmera David , Wessels Andy , Trusk Thomas C. , Thompson Robert P. , Hewett Kenneth W. , Gourdie Robert G.
Published: May 2006

To characterize developmental changes in impulse propagation within atrial musculature, we performed high-speed optical mapping of activation sequence of the developing chick atria using voltage-sensitive dye. The activation maps were correlated with detailed morphological studies using scanning electron microscopy, histology, and whole mount confocal imaging with three-dimensional reconstruction. A preferential pathway appeared during development within the roof of the atria, transmitting the impulse rapidly from the right-sided sinoatrial node to the left atrium. The morphological substrate of this pathway, the bundle of Bachman, apparent from stage 29 onward, was a prominent ridge of pectinate muscles continuous with the terminal crest. Further acceleration of impulse propagation was noted along the ridges formed by the developing pectinate muscles, ramifying from the terminal crest toward the atrioventricular groove. In contrast, when the impulse reached the interatrial septum, slowing was often observed, suggesting that the septum acts as a barrier or sink for electrical current. We conclude that these inhomogeneities in atrial impulse propagation are consistent with existence of a specialized network of fast-conducting tissues. The purpose of these preferential pathways appears to be to assure synchronous atrial activation and contraction rather than rapid impulse conduction between the sinoatrial and atrioventricular nodes.
Long-Term Outcome after Vitrectomy for Diabetic Macular Edema
Authors: Kralinger Martina T. , Pedri Markus , Kralinger Franz , Troger Josef , Kieselbach Gerhard F.
Published: May 2006

Background: To determine the benefit of vitrectomy on eyes with diabetic macular edema. Methods: A retrospective institutional case series was used including 66 patients (69 eyes) who had undergone pars plana vitrectomy for diabetic macular edema between 1992 and 2000. Prior to surgery, the patients had been treated with laser coagulation as recommended by the Early Treatment Diabetic Retinopathy Study. In the case of persistent macular edema, vitrectomy with removal of the posterior hyaloid in all cases and the inner limiting mem brane in 51 (74%) of all cases was performed. Results: The mean preoperative best-corrected visual acuity improved from 20/320 to 20/80 at the time of best postoperative best-corrected visual acuity (p < 0.0001). The mean increase in Snellen lines was 2.7 ± 7.9. In 90% of eyes, the macular edema improved. A persistence of the edema was observed in 10%. All eyes had at least 12 months of follow-up with a mean of 55 months and a maximum of 120 months. Conclusions: Our findings confirm that vitrectomy might represent a therapeutic alternative in the case of persisting diabetic macular edema after laser photocoagulation.
Ocular Findings in Japanese Children with Nephrotic Syndrome Receiving Prolonged Corticosteroid Therapy
Authors: Hayasaka Yoriko , Hayasaka Seiji , Matsukura Hiroyoshi
Published: May 2006

Objective: To examine ocular findings in Japanese children with nephrotic syndrome who receive prolonged corticosteroid treatment. Methods: Information was retrospectively obtained from each patient’s record. Results: A total of 45 children (30 boys and 15 girls) were enrolled. Twenty-one patients (46.7%) had epiblepharon with inverted eyelashes. The incidence of epiblepharon was associated with overweight and obesity. Fifteen patients (33.3%) developed posterior subcapsular cataract in both eyes. Of the 15 patients, 4 had visual acuity less than 0.4 and underwent cataract extraction in both eyes. Nine patients (20%) developed intraocular pressure higher than 22 mm Hg during corticosteroid treatment. The total dose and duration of corticosteroid treatment were associated with cataract formation but were unassociated with elevated intraocular pressure. One boy had elevated intraocular pressure after cessation of corticosteroid therapy and underwent trabeculectomy. One patient had repeated hordeolum in the left eyelid. Three patients had bilateral bacterial conjunctivitis. Conclusion: Children with nephrotic syndrome who receive corticosteroid treatment may have epiblepharon, cataract, ocular hypertension, hordeolum and bacterial conjunctivitis.
Dietary Polyunsaturated Fatty Acids in Gestation Alter Fetal Cortical Phospholipids, Fatty Acids and Phosphatidylserine Synthesis
Authors: Tam Odilia , Innis Sheila M.
Published: May 2006

Docosahexaenoic acid (DHA; 22:6 n–3) is high in brain phosphatidylserine (PS) and phosphatidylethanolamine (PE), but low in phosphatidylcholine (PC). PS is synthesized from PE or PC by exchange of ethanolamine or choline for serine. PS can be decarboxylated to PE, and PC is synthesized from PE by phosphatidylethanolamine N-methyltransferase (PEMT). We characterized the perinatal changes in rat brain cortex phospholipids and metabolism and determined if maternal dietary n–3 fatty acid intake alters newborn brain cortex phospholipids, serine base exchange, PS decarboxylase or PEMT activities. PE became increasingly predominant, with an increase in the cortex PC/PE ratio from 2:1 at gestation day 19 to 1:1 at postnatal day 20. DHA increased and n–6 docosapentaenoic acid (DPA; 22:5 n–6) decreased in all phospholipids during development. [3H]serine incorporation into PS was higher in the fetal than neonatal brain cortex. Newborn rats of dams fed an n–3 fatty acid-deficient diet with 0.02% energy alpha-linolenic acid (ALA; 18:3 n–3) had approximately 50% lower DHA and higher DPA in cortex PE, PS and PC than newborns of rats fed a control diet with 1.5% energy ALA. [3H]serine incorporation into PS was significantly lower in the brain cortex of n–3 fatty acid-deficient than control newborns. n–3 Fatty acid deficiency had no effect on newborn brain PEMT or serine decarboxylase activities. These studies show that maternal dietary n–3 fatty acid deprivation impairs fetal brain DHA accretion and PS metabolism; altered PS metabolism may change release of lipid mediators and neurotransmitter precursors important in brain function.
Natural Scalp Hair Regression in Preclinical Stages of Male Androgenetic Alopecia and Its Reversal by Finasteride
Authors: van Neste D.
Published: May 2006

Using contrast-enhanced phototrichogram (CE-PTG) at monthly intervals during 48 months, we measured the duration of the hair cycle, i.e. anagen, catagen and telogen at the exclusion of exogen. Exogen, a recently identified phase of the hair cycle, is characterized by weakening of anchorage of the club hair to the surrounding epithelium. The processing of the club hair terminates at the time of exogen hair release, i.e. hair shedding. We combined a noninvasive exogen sampling before each CE-PTG so that the area contained only anagen, catagen and telogen hair or empty follicular openings. During the first 24 months of this study, natural regression of hair cycling in early i.e. preclinical stages of androgenetic alopecia (AGA) in androgen sensitive areas was documented. Shortening of the hair cycle of thicker hair characterized progression of AGA. During the next 24 months, finasteride (1 mg/day) was introduced into the system. Shortening of the hair cycle was reversed by finasteride in androgen sensitive sites as long as the affected follicle was able to produce a thick hair fiber at the time of treatment initiation. Compared to the baseline period, responding follicles did not produce thicker hair. On average, they initiated active growth more rapidly by reducing the duration of the lag phase by 40%. The duration of the anagen phase of thick hair showed an average 23% increase. In this particular experiment, the already miniaturized follicles producing thinner hair (<40 µm thickness) at the time of finasteride introduction regressed further on treatment. Our results seem to indicate that reversal of ‘hair loss’ by finasteride probably means that the terminal type follicles that are functionally deficient – a stage of reversible hypotrophy – will be reactivated by two non-mutually exclusive mechanisms: faster regrowth followed by extension of the duration of anagen. In our study, there was no clear evidence in favour of reversal of miniaturized hair into terminal hair. This new interpretation indicates that miniaturized hair follicles may be an important diagnostic marker of AGA in males but also that it might be less contributive to the therapeutic response to finasteride. Our results highlight that precise measurement of terminal type hair follicle functionalities opens up avenues for the selection of ‘drug-responsive organs’ in the human scalp in vivo and these may possibly serve to predict ‘quality of response to treatment’.
On the Relationship between Speech- and Nonspeech-Evoked Auditory Brainstem Responses
Authors: Song J.H. , Banai K. , Russo N.M. , Kraus N.
Published: May 2006

Auditory brainstem response (ABR) reflects activation of the neural generators along the ascending auditory pathway when a sound is heard. In this study, we explored the relationship between brainstem encoding of click and speech signals in normal-learning children and in those with language-based learning problems. To that end, ABR was recorded from both types of stimuli. We found that the normal pattern of correlation between click- and speech-evoked ABRs was disrupted when speech-evoked ABRs were delayed. Thus, delayed responses to speech were not indicative of clinically abnormal responses to clicks. We conclude that these two responses reflect largely separate neural processes and that only processes involved in encoding complex signals such as speech are impaired in children with learning problems.
Comparing Beta-Blocking Effects of Bisoprolol, Carvedilol and Nebivolol
Authors: Stoschitzky Kurt , Stoschitzky Gergana , Brussee Helmut , Bonell Claudia , Dobnig Harald
Published: May 2006

Objective: Bisoprolol, carvedilol and nebivolol have been shown to be effective in the treatment of heart failure. However, the beta-blocking effects of these drugs have never been compared directly. Methods: Therefore, we performed a randomized, double-blind, placebo-controlled, cross-over trial in 16 healthy males. Subjects received 10 mg bisoprolol, 50 mg carvedilol, 10 mg nebivolol and placebo on the first morning followed by 5 mg bisoprolol once daily, 25 mg carvedilol twice daily, 5 mg nebivolol once daily and placebo for 1 week. Heart rate and blood pressure were measured at rest and exercise 3 and 24 h following intake of the first dose, and immediately before and 3 hours following intake of the last dose of each drug. In addition, effects of the drugs on nocturnal melatonin release were determined, and quality of life (QOL) was evaluated. Results: Heart rate at exercise was decreased at 3 h following intake of the first single dose of each drug by bisoprolol (–24%), carvedilol (–17%) and nebivolol (–15%), and at 24 h following intake of the respective last dose of each drug following 1 week of chronic administration by bisoprolol (–14%), carvedilol (12 h; –15%) and nebivolol (–13%) (p < 0.05 in all cases). Thus, trough-to-peak-ratios at long-term were as follows: Bisoprolol, 58%; carvedilol (12 h), 85%; nebivolol, 91%. Nocturnal melatonin release was decreased by bisoprolol (–44%, p < 0.05) whereas nebivolol and carvedilol had no effect. QOL with carvedilol was slightly but significantly lower than with the other drugs, whereas bisoprolol and nebivolol did not alter QOL. Conclusions: These data show that peak beta-blocking effects of bisoprolol appear stronger than those of nebivolol and carvedilol. On the other hand, nebivolol exerts the highest trough-to-peak-ratio. However, beta-blocking effects of all the three drugs are similar at trough. Only bisoprolol but neither nebivolol nor carvedilol decreased nocturnal melatonin release, a feature which might cause sleep disturbances. Finally, only carvedilol slightly decreased QOL, whereas nebivolol and bisoprolol did not affect QOL. We conclude that different beta-blockers may exert clinically relevant different effects.
Increased Neurofibrillary Tangles in the Brains of Older Pedestrians Killed in Traffic Accidents
Authors: Gorrie C.A. , Rodriguez M. , Sachdev P. , Duflou J. , Waite P.M.E.
Published: May 2006

Background/Aims: Older people are over-represented in pedestrian fatalities, and it has been suggested that the presence of cognitive impairment or dementia in these individuals may contribute to their accidents. Using neuropathological methods, we aimed to compare the prevalence of dementia pathology in fatally injured older pedestrians with similarly aged ambulatory subjects who died from other causes. Methods: The brains of 52 pedestrians (65–93 years) and 52 controls (65–92 years) were assessed for neurofibrillary tangles (NFT), neuritic plaques, Lewy bodies and vascular lesions using established neuropathological criteria. Results: The examination for Alzheimer’s disease (AD) pathology showed that 43% of the pedestrians had NFT scores of III–VI using Braak and Braak staging, compared with 23% of the controls (p < 0.05, Fisher’s exact test), indicating incipient, possible or probable AD. There were no differences in the prevalence of pathology for vascular dementia or dementia with Lewy bodies. Conclusion: These results suggest that cognitive decline associated with AD, even in the earliest stages of the disease, may be a factor in fatal traffic accidents for older pedestrians. Special measures for pedestrian safety are necessary in areas with high densities of older citizens and especially for those diagnosed as having a mild cognitive impairment or AD.
Targeting the Epidermal Growth Factor Receptor in Colorectal Cancer: Advances and Controversies
Authors: Italiano Antoine
Published: May 2006

Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. Even with the significant improvement in traditional chemotherapy, there remain limitations with this treatment. One of the most promising new targets in the treatment of CRC is the epithelial growth factor receptor (EGFR). Agents that inhibit the EGFR have demonstrated clinical activity as single agents and in combination with chemotherapy and the most promising of these agents is cetuximab, which blocks the binding of EGF and transforming growth factor-α (TGF-α) to EGFR. Thus, the finding that monoclonal antibodies against EGFR caused a response in patients, and reversed resistance to chemotherapy, was exciting news. However, expression of EGFR did not correlate with clinical benefit. Clearly, the search for markers of response to treatment against EGFR must go on.
Deep Neck Infections: A Constant Challenge
Authors: Boscolo-Rizzo Paolo , Marchiori Carlo , Montolli Francesca , Vaglia Alberto , Da Mosto Maria Cristina
Published: May 2006

Background: Although the advent of antibiotics and improved dental care decreased the incidence and mortality, deep neck infections (DNIs) are not uncommon and present a challenging problem due to the complex anatomy and potentially lethal complications that may arise. Objectives: This study reviews our experience with DNIs and tries to identify the predisposing factors of life-threatening complications. Methods: A retrospective review was conducted of patients who were diagnosed as having DNIs in the Department of Otolaryngology and in the Department of Infectious Diseases at Treviso Regional Hospital from 1995 to 2003. Associations between life-threatening complications and other factors were determined by χ2 test, Fisher’s exact test and Student’s t test as appropriate. Results: One hundred sixty-seven charts were recorded; 95 (56.9%) were men, and 72 (43.1%) were women, with a mean age of 49.6 ± 20.4 years (range: 2–96). There were 39 patients (23.4%) who had associated systemic diseases, with 53.8% (21/39) of those having diabetes mellitus. The lateral pharyngeal and submandibular spaces were the most commonly involved spaces. Upper airway infections and odontogenic infections were the two most common causes of DNIs (47.5 and 27.9% of the known causes, respectively). The pathogenesis remained unknown in 45 patients (26.9%). Coagulase-negative staphylococcus (36.9%) and Streptococcusviridans (28.8%) were the most common organisms, identified through cultures. Of the abscess group (77 patients), 42 patients (54.5%) underwent surgical drainage under general anesthesia. Thirty-one patients (18.6%) developed life-threatening complications: airway obstruction (n = 18), descending mediastinitis (n = 6), jugular vein thrombosis (n = 4), and pneumonia (n = 3). Compared with other patients, the unique features of patients with life-threatening complications were as follows: older age (p = 0.04), a higher white blood cell count (p = 0.01), abscess formation (p = 0.02), associated systemic disease (p < 0.001), diabetes mellitus (p < 0.001), anterior visceral space involvement (p < 0.001), and multiple-space involvement (p < 0.001). Conclusions: DNIs continue to occur and these are associated with significant morbidity and mortality even in this era of antibiotics. Furthermore, the widespread and inappropriate use of antibiotics may change the clinical presentation and course of these infections, making them more elusive and less predictable also in complicated cases. The clinical assessment of patients who are older, with abscess formation, underlying systemic diseases, diabetes mellitus, visceral anterior space or multiple-space involvement requires careful consideration of potential complications.
Progression to Dementia in Clinical Subtypes of Mild Cognitive Impairment
Authors: Alexopoulos P. , Grimmer T. , Perneczky R. , Domes G. , Kurz A.
Published: May 2006

Objective: To examine the outcome among patients diagnosed with different types of mild cognitive impairment (MCI). Patients: A follow-up examination (average follow-up period: 3.49 ± 2.2 years) was performed in 81 cognitively impaired, non-demented patients aged >55 years at baseline. Results: 8 of 32 patients with amnestic MCI (25%), 22 of 41 patients with multiple-domain MCI (54%), and 3 of 8 patients with single non-memory MCI (37.5%) progressed to dementia. The clinical type of MCI is significantly associated with the likelihood of conversion to dementia. Discussion: When the clinical syndrome of MCI evolves on a neurodegenerative basis, the multiple-domain type of MCI has a less favorable prognosis than the amnestic type and may represent a more advanced prodromal stage of dementia.
Impact of Behavioural Problems on Spousal Caregivers: A Comparison between Alzheimer’s Disease and Frontotemporal Dementia
Authors: de Vugt Marjolein E. , Riedijk Samantha R. , Aalten Pauline , Tibben Aad , van Swieten John C. , Verhey Frans R.J.
Published: May 2006

Background: Behavioural changes are a key factor in distinguishing frontotemporal dementia (FTD) from Alzheimer’s disease (AD), however, little is known about the impact of these changes on caregivers. The aim of this study was to compare caregivers’ distress related to behavioural symptoms of AD and FTD. Methods: 47 spouse caregivers of consecutively referred patients with AD and 27 spouse caregivers of patients with FTD participated in this study. Behavioural disturbances in the patient and caregivers’ emotional reactions were measured with the Neuropsychiatric Inventory. Results: Patients with FTD had significantly higher levels of agitation, apathy, disinhibition and aberrant motor behaviour than did patients with AD. High distress scores were found for disinhibition, depression and apathy in caregivers of FTD patients whereas caregivers of AD patients reported patient apathy, depression and anxiety as being severely distressing. Higher mean distress scores were found for disinhibition in the FTD group. Furthermore, caregivers of FTD patients reported higher levels of general burden, and felt less competent than AD caregivers. Conclusions: Caregivers of FTD patients were overall more distressed by the behaviour of their partners than were the caregivers of AD patients.Findings from this study underscore the importance of differentiating between diagnostic groups and specific behavioural domains when focusing on caregiver reactions to problem behaviour.
Influence of Nanoencapsulation on Human Skin Transport of Flufenamic Acid
Authors: Luengo J. , Weiss B. , Schneider M. , Ehlers A. , Stracke F. , König K. , Kostka K.-H. , Lehr C.-M. , Schaefer U.F.
Published: May 2006

The effect of the inclusion of flufenamic acid in poly(lactide-co-glycolide) nanoparticles on the transport of flufenamic acid into excised human skin was investigated. Penetration and permeation data were acquired using two different in vitro test systems: the Saarbrücken penetration model, where the skin acts as its own receptor medium, and the Franz diffusion cell, where the receptor medium is a buffer solution. For the stratum corneum, no differences were found between nanoencapsulated and free drug. Drug accumulation in the deeper skin layers and drug transport across human epidermis were slightly delayed for the nanoencapsulated drug compared to the free drug after shorter incubation times (<12 h). In contrast, after longer incubation times (>12 h), the nanoencapsulated drug showed a statistically significantly enhanced transport and accumulation (p < 0.05). Additionally, nanoencapsulated flufenamic acid was visualized by multiphoton fluorescence microscopy. Particles were found homogeneously distributed on the skin surface and within the dermatoglyphs, but no nanoparticles were detected within or between the corneocytes.
Follicular Penetration: Development of a Method to Block the Follicles Selectively against the Penetration of Topically Applied Substances
Authors: Teichmann Alexa , Otberg Nina , Jacobi Ute , Sterry Wolfram , Lademann Jürgen
Published: May 2006

Investigations into the penetration pathways of topically applied substances through the skin play an important role in dermatological science. Recently, the hair follicles have increasingly been recognized as an important pathway for percutaneous penetration, although the role of the follicles has still not been clarified in detail. Therefore, the aim of the present study was to develop an in vivo method for the analysis of the follicular rate of penetration processes. In order to reach this goal, the follicles were excluded from the penetration process of topically applied substances. Different study designs were evaluated, and we were able to show that the application of nail varnish to each follicular orifice represents an effective method of blocking the follicles selectively against the penetration of topically applied substances. In dermatological science, there is new information on the physiology of skin penetration processes, thus allowing examination of the follicular rate of penetration and improvement of the pharmacokinetics of topically applied substances.
Corticotropin-Releasing Hormone Receptor Expression on Normal and Tumorous Human Adrenocortical Cells
Authors: Willenberg Holger S. , Haase Matthias , Papewalis Claudia , Schott Matthias , Scherbaum Werner A. , Bornstein Stefan R.
Published: May 2006

Corticotropin-releasing hormone (CRH) is not only the principal regulator of the central hypothalamic-pituitary-adrenal (HPA) axis but also exerts direct actions on peripheral tissues. We analyzed the expression of CRH receptors in microdissected preparations of normal human adrenal glands and in adrenocortical and adrenomedullary tumors, employing immunohistochemistry, quantitative RT-PCR of microdissected adrenal tissues, and in situ hybridization. The effect of CRH on adrenal steroidogenesis was tested in adrenal cells. Immunoreactive CRH1R was found primarily within the zona reticularis. In addition, we found a higher expression of CRH type-1 and 2 receptors mRNAs in preparations of adrenal cortices as compared to pheochromocytomas, a 6-fold increase in preparations of clinically unapparent adrenocortical adenomas, and a 10- to 60-fold increase in cortisol-producing adrenal adenomas. Stimulation of the adrenal tumor cell line NCI-H295R with CRH elicited a 1.4-fold increase in DHEA secretion. This result could be reproduced in a culture of primary human adrenocortical cells. We conclude that adrenocortical cells exhibit a higher expression of functional CRH receptors than chromaffin cells and that CRH acts on adrenal DHEA production. The data support the assertion of a direct action of CRH on human adrenocortical cells in addition to an intra-adrenal CRH receptor/adrenocorticotropin system. Enhanced CRH1R expression may be involved in adrenocortical tumorigenesis.
Genomic Alterations in Ectopic and Eutopic Endometria of Women with Endometriosis
Authors: Wu Yan , Strawn Estil , Basir Zainab , Wang Yuedong , Halverson Gloria , Jailwala Parthav , Guo Sun-Wei
Published: May 2006

Background/Aims: Ectopic and eutopic endometria of women with endometriosis have been shown to contain genomic alterations. In this study, we sought to identify genomic alterations in both ectopic and eutopic endometria of 5 women with endometriosis and to examine whether the two tissues share any genomic alterations. We also attempted to classify tissue samples based on the alteration profiles. Methods: Laser capture microdissection was used to harvest epithelial cells. High-resolution comparative genomic hybridization microarrays were used to identify genomic alterations in eutopic and ectopic endometria from 5 women with endometriosis. The results were validated by real-time RT-PCR and loss of heterozygosity analysis. Results: All 5 patients had genomic alterations in their eutopic and ectopic endometria. The ectopic and eutopic endometria shared a sizable portion of genomic alterations. Cluster analysis of the genomic alteration profile correctly and consistently classified tissue samples from the 5 patients into two groups: peritoneal implants and ovarian cysts. Conclusions: The correct classification of tissue samples into two groups suggests that these two subtypes of endometriosis may have distinct genomic alteration profiles and are thus distinct entities, as previously proposed. The shared alterations are likely the ones that harbor genes responsible for an increased propensity of endometrial debris to implant to the ectopic sites and for early events that lead to the establishment of lesions. Alternatively, these shared alterations may harbor genes that are dysregulated in both eutopic and ectopic endometria. The identified genomic alterations should help to zero in genes involved in the pathogenesis of endometriosis in future studies.
Hematoma Growth and Outcome in Treated Neurocritical Care Patients With Intracerebral Hemorrhage Related to Oral Anticoagulant Therapy
Authors: Huttner Hagen B. , Schellinger Peter D. , Hartmann Marius , Köhrmann Martin , Juettler Eric , Wikner Johannes , Mueller Stephan , Meyding-Lamade Uta , Strobl Ralf , Mansmann Ulrich , Schwab Stefan , Steiner Thorsten
Published: May 2006

Background and Purpose—

Intracerebral hemorrhage (ICH) is the most serious and potentially fatal complication of oral anticoagulant therapy (OAT). Still, there are no universally accepted treatment regimens for patients with OAT-ICH, and randomized controlled trials do not exist. The aim of the present study was to compare the acute treatment strategies of OAT-associated ICH using vitamin K (VAK), fresh frozen plasma (FFP), and prothrombin complex concentrates (PCCs) with regard to hematoma growth and outcome.

Methods—

In this retrospective study, a total of 55 treated patients were analyzed. Three groups were compared by reviewing the clinical, laboratory, and neuroradiological parameters: (1) patients who received PCCs alone or in combination with FFP or VAK (n=31), (2) patients treated with FFP alone or in combination with VAK (n=18), and (3) patients who received VAK as a monotherapy (n=6). The end points of early hematoma growth and outcome after 12 months were analyzed including multivariate analysis.

Results—

Hematoma growth within 24 hours occurred in 27% of patients. Incidence and extent of hematoma growth were significantly lower in patients receiving PCCs (19%/44%) compared with FFP (33%/54%) and VAK (50%/59%). However, this effect was no longer seen between PCC- and FFP-treated patients if international normalized ratio (INR) was completely reversed within 2 hours after admission. The overall outcome was poor (modified Rankin scale 4 to 6 in 77%). Predictors for hematoma growth were an increased INR after 2 hours, whereas administration of PCCs was significantly protective in multivariate analyses. Predictors for a poor outcome were age, baseline hematoma volume, and occurrence of hematoma growth.

Conclusions—

Overall, PCC was associated with a reduced incidence and extent of hematoma growth compared with FFP and VAK. This effect seems to be related to a more rapid INR reversal. Randomized controlled trials are needed to identify the most effective acute treatment regimen for lasting INR reversal because increased levels of INR were predisposing for hematoma enlargement.
Association of Phosphodiesterase 4D Polymorphisms With Ischemic Stroke in a US Population Stratified by Hypertension Status
Authors: Brophy Victoria H. , Ro Sunhee K. , Rhees Brian K. , Lui Li-Yung , Lee Jocelyn M. , Umblas Nanette , Bentley L. Gordon , Li Jia , Cheng Suzanne , Browner Warren S. , Erlich Henry A.
Published: May 2006

Background and Purpose—

Phosphodiesterase 4D (PDE4D) underlies the STRK1 linkage peak for stroke on chromosome 5q12 identified in Iceland. We tested association of 13 single-nucleotide polymorphisms (SNPs) and 1 microsatellite in a nested case-control sample of elderly white women (>65 years of age) from the Study of Osteoporotic Fractures (SOF) in the United States.

Methods—

The genotypes of 248 women who experienced an incident ischemic stroke during an average of 5.4 years of follow-up were compared with 560 controls.

Results—

Marginal associations with stroke (
P
<0.10) were found for 3 polymorphisms. Stratification of the population by hypertension markedly strengthened the association. SNPs 9 (hazard ratio [HR], 0.48; 95% CI, 0.26 to 0.91), 42 (HR, 1.73; 95% CI, 1.10 to 2.70), 219 (HR, 1.73; 95% CI, 1.13 to 2.64), and 220 (HR, 1.56; 95% CI, 1.05 to 2.32) showed significant association with stroke (
P
<0.05) under a dominant model in subjects without hypertension at baseline, and SNP 175 was significantly associated with stroke under an additive model (HR, 0.76; 95% CI, 0.59 to 0.98) in subjects with hypertension. Furthermore, the microsatellite AC008818-1 showed association with stroke only in the nonhypertensive subjects. Based on results in Iceland, specific haplotypes were tested in SOF, and stratification by hypertension also affected these association results.

Conclusion—

These data are consistent with an association of the PDE4D gene with stroke in a non-Icelandic sample and suggest an effect of hypertension status.
Lipoprotein(a) and Incident Ischemic Stroke
Authors: Ohira Tetsuya , Schreiner Pamela J. , Morrisett Joel D. , Chambless Lloyd E. , Rosamond Wayne D. , Folsom Aaron R.
Published: May 2006

Background and Purpose—

Numerous case-control and cross-sectional studies have reported higher median lipoprotein(a) [Lp(a)] levels among stroke patients than controls, but existing prospective studies have not consistently shown an association. We sought to examine the relationship between plasma Lp(a) levels and the incidence of ischemic stroke among blacks and whites.

Methods—

Between 1987 and 1989, 14 221 men and women (3647 blacks and 10 574 whites) aged 45 to 64 years and free of clinical cardiovascular disease, took part in the first examination of the Atherosclerosis Risk in Communities (ARIC) study cohort. Lp(a) and other risk factors for cardiovascular disease were measured at baseline.

Results—

During the 13.5-year follow-up, 496 ischemic strokes occurred. Participants with Lp(a) ≥300 μg/mL had a 79% higher age, sex, and race-adjusted rate ratio (RR) of ischemic stroke than did those with Lp(a) levels <100 μg/mL. Compared with Lp(a) <100 μg/mL, the multivariate adjusted RRs for Lp(a) ≥300 μg/mL were 1.84 (95% CI, 1.05 to 3.07) in black women, 1.72 (95% CI, 0.86 to 3.48) in black men, 2.42 (95% CI, 1.30 to 4.53) in white women, and 1.18 (95% CI, 0.47 to 2.90) in white men. There was no significant increment in the RRs for 100 to 199 μg/mL and 200 to 299 μg/mL groups.

Conclusions—

A high Lp(a) concentration is associated with a higher incidence of ischemic stroke in blacks and white women, but not in white men.
Effective Thermal Conductivity of Continuous Matrix-spherical Dispersed Phase Composite with Single-point Interfacial Thermal Contact: Free Molecular Gas Conduction in the Gap
Authors: Thomas J. R. , Hasselman D. P. H.
Published: May 2006

Analytical solutions are presented for the lower bound of the effective thermal conductivity of a continuous matrix composite for the limiting case of fully debonded spherical inclusions in single-point contact with the matrix, with heat conduction across the interfacial gap occurring by gaseous heat transfer in the free-molecular regime. Imposed temperature gradients parallel and perpendicular to the diameter through the point-of-contact are considered. The composite thermal conductivity in addition to the generally accepted variables identified in the literature at any given pressure is found to be a function of the accommodation coefficients of the surfaces of the interfacial gap, but independent of the width of the gap. When the accommodation coefficient of one of the surfaces approaches zero, the composite thermal conductivity approaches Maxwell's value for a matrix with spherical pores, regardless of the value of the contact conductance. Instantaneous closure of the gap results in a discontinuous increase in the composite thermal conductivity to the value predicted by Maxwell for perfect interfacial thermal contact or the one predicted by Hasselman and Johnson for finite values of the interfacial thermal conductance. Numerical results are presented for a sodaborosilicate glass with spherical nickel inclusions. The composite thermal conductivity for imposed temperature gradients parallel or perpendicular to the diameter through the point of contact is found to differ significantly depending on the values for the interfacial thermal contact conductance and accommodation coefficients.
Relationship between Water Absorption and Dielectric Behavior of Glass Fiber Reinforced Unsaturated Polyester Resin
Authors: Fraga A. N. , Frullloni E. , de la Osa O. , Kenny J. M. , Vázquez A.
Published: May 2006

Water uptake at 25°C is measured for unsaturated polyester matrix and glass fiber composites as a function of time. Dielectric measurement in the frequency range of 1 MHz-1 GHz has been performed on the specimens during the water absorption process. The dielectric constant decreases as the frequency increases for matrix and composites. The dielectric constant of unsaturated polyester is lower than their composites based on glass fibers. A Fickian diffusion model is applied for water absorption studies, and the effective diffusion coefficient is calculated for each sample. An empirical model describing the increase in dielectric constant with water absorption is proposed.
Piezoelectric Control of Edge Debonding in Beams Strengthened with Composite Materials: Part II - Failure Criteria and Optimization
Authors: Rabinovitch Oded
Published: May 2006

The prevention of the edge debonding failure in RC beams strengthened with externally bonded composite materials by means of optimized piezoelectric control is investigated. The study uses the mathematical model derived and verified in Part I of this paper to assess the structural response of the strengthened beam to the electrical and mechanical loads. The electrical actuation is optimized using two objective functions corresponding to two approaches for the prediction of the debonding failure. The first approach is based on evaluation of the stresses at the critical region near the edge of the bonded strip. The second approach adopts the fracture mechanics concept of the energy release rate, which is evaluated through the generalized J-integral. The formulation of the objective functions and the constraints associated with the restricted operational range of the piezoelectric actuators is presented. A procedure for the construction of the linear or quadratic response and objective functions through a relatively small number of evaluations of the structural model is presented and discussed. A numerical optimization study that focuses on the ability of different combinations of piezoelectric actuators to control, prevent, or delay the edge debonding failure is presented. The main contribution of this study is in providing a systematic approach to optimize the piezoelectric control under different debonding failure criteria and in demonstrating the feasibility of using the piezoelectric system in the full-scale civil engineering structure.
Dielectric Characteristics of E-glass-Polyester Composite Containing Conductive Carbon Black Powder
Authors: Chin Woo Seok , Lee Dai Gil
Published: May 2006

The electromagnetic (EM) absorption or shielding characteristics of a material is an important issue not only for military purposes but also for commercial use such as in radar, electric and telecommunication devices. Nowadays studies on investigating the radar absorbing structures (RAS) using fiber reinforced polymeric (FRP) composites are becoming a popular research field. Since carbon black is widely used for EM absorption applications, in this study, the dielectric properties of the E-glass-polyester composite containing conductive carbon black are measured with the free space method in the X-band frequency range. In order to describe the dielectric behavior of the anisotropic FRP composite containing carbon black, the quantitative analysis of the measured permittivity is performed with respect to the content of carbon black, and the two-dimensional tensor transformation equation for estimating its dielectric properties is modified. Finally, the modified tensor transformation equation for the FRP composite with lossy ingredient is suggested and experimentally verified.
Lessons from Teachers
Authors: Delpit Lisa
Published: May 2006

This article argues that with changes in attitudes and actions in classrooms, teachers can alter what happens in urban schools and transform the lives of students. Ten precepts are offered to assist them in that role: teach more, not less, content to poor, urban children; ensure all children gain access to conventions/strategies essential to success in American society; whatever methodology/instructional program used, demand critical thinking; provide the emotional ego strength to challenge racist societal views of the competence and worthiness of children and their families; recognize and build on children’s strengths; use familiar metaphors, analogies, and experiences from the children’s world to connect what children already know to school knowledge; create a sense of family and caring in the service of academic achievement; monitor/assess children’s needs and address them with a wealth of diverse strategies; honor and respect children’s home culture; and foster a sense of children’s connection to community.
Civil-Military Relations in Post-Sandinista Nicaragua
Authors: Ruhl J. Mark
Published: May 2006

When Nicaragua's Sandinista Revolution ended in 1990 with the electoral victory of an opposition coalition, the Sandinista Popular Army remained under the control of its revolutionary officers. This study examines the subsequent evolution of civil-military relations in postrevolutionary Nicaragua under the governments of Violeta Chamorro (1990-1997) and Arnoldo Alemdn (1997-2002). It then assesses the level of civilian control achieved by combining for the first time Alfred Stepan's widely used military prerogatives indicators with an alternative measurement system recently designed by his ciitic Samuel Fitch. This analysis reveals that the Nicaraguan military has become a nonpartisan force exercising little influence in civilian politics, but it still enjoys wide de facto institutional autonomy and a margin of political independence. The Nicaraguan case falls between the “conditional subordination” and “democratic control” categories in Fitch's civil-military relations typology. Although Latin American armed forces are invariably blamed for most of the difficulties of democractizing civil-military relations in the region, this article concludes by arguing that Nicaragua's civilian political class not its military' leaders-is most responsible for the failure to complete the process of subordinating the armed forces to democratic authority.