bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Vitamin E, Pentoxifylline and Aprotinin on Light-Induced Retinal Injury
Authors: Yılmaz Turgut , Aydemir Orhan , Özercan İbrahim H. , Üstündağ Bilal
Published: April 2007

Purpose: A considerable amount of clinical and experimental evidence exists suggesting the involvement of reactive oxygen species (ROS) in the etiology of light-induced retinal injury. The aim of this study was to investigate the protective role of vitamin E, pentoxifylline (PTX) and aprotinin against light-induced retinal injury in guinea pigs. Methods: Thirty adult male guinea pigs were divided into 5 groups of 6 animals each. The first group was used as control. The guinea pigs were kept in cyclic light for 2 weeks before the experiments. The animals were maintained in 12-hour light-dark cycles, before and after exposure to intense white fluorescent light, for as long as 12 h and then returned to cyclic light. Groups 3–5 received intraperitoneal injections of vitamin E, PTX and aprotinin, respectively. One eye of each animal was selected for histopathological evaluation and the other for biochemical assay. Retinal malondialdehyde (MDA) levels and the thickness of the outer nuclear layers were measured. Results: The compounds had the following relationships: vitamin E more than PTX more than aprotinin in preventing light-induced retinal damage. All 3 gave significant protection against the formation of MDA. Retinas of all 3 treatment groups had been protected from light-induced injury. Conclusion: The intraperitoneal vitamin E, PTX and aprotinin supplementations may strengthen the antioxidant defense system because of decreased ROS, and these agents may play a role in treating light-induced retinal injury.
Primary Ocular Natural Killer/T-Cell Lymphomas: Clinicopathologic Features and Diagnosis
Authors: Yang Yuli , Luo Qingli , He Weiming , Tang Li
Published: April 2007

Purpose: Primary ocular natural killer/T-cell lymphoma (NKTL) is rare. This study aims to characterize the clinical manifestations, diagnosis and treatment methods of primary ocular NKTL. Methods: Clinical data of seven patients with ocular NKTL from 1982 to 2004 were collected. A morphologic, immunohistochemical and molecular analysis was undertaken. Results: Clinical manifestations and computed tomography of the patients were typical. LCA CD56 CD3Ε Ki-67 granzyme B (GrB) and T-cell intracellular antigen-1(TIA-1) were mostly positive. Clonal T-cell-receptor gene rearrangements of five patients showed negative findings, and the detection of Epstein-Barr virus showed positive. All patients died 5 months to 28 months after presentation. Conclusion: Ocular NKTL is a highly aggressive clinical course with poor prognosis. The diagnosis relies on clinicopathologic findings.
Nerve Fibre Layer Analysis with GDx with a Variable Corneal Compensator in Patients with Multiple Sclerosis
Authors: Della Mea Giovanni , Bacchetti Sonia , Zeppieri Marco , Brusini Paolo , Cutuli Daniela , Gigli Gian Luigi
Published: April 2007

Purpose: To evaluate the ability of GDx with variable corneal compensator (VCC) compared to visual-evoked potentials (VEPs) and standard automated perimetry (SAP) in the detection of early optic nerve damage in patients with multiple sclerosis (MS). Methods: 46 eyes of 23 MS patients were included. Ten of them had a history of acute retrobulbar optic neuritis. A control group of 20 normal subjects was also included. All subjects underwent a complete ophthalmological examination and testing with SAP, GDx VCC and VEPs. Results: 19 eyes (41.3%) were abnormal with GDx VCC compared to 38 eyes (82.6%) with SAP and 31 (64.4%) with VEPs. In the optic neuritis group, 9 eyes (69.2%) had optic nerve pallor; SAP was abnormal in 8 of these eyes (61.5%) while VEPs and GDx VCC were abnormal in 6 eyes (46.1%). 2/20 eyes (10.0%) in the control group gave a false-positive abnormal result with SAP. GDx VCC and VEP were normal for all the eyes in the control group. Conclusions: GDx VCC is less able to detect early defects in MS patients compared to the currently used standard techniques of SAP and VEPs.
The Influence of Low to Moderate Myopia on Retinal Nerve Fiber Layer as Assessed by Scanning Laser Polarimetry with Variable Corneal Compensator
Authors: Vetrugno Michele , Trabucco Tiziana , Sisto Dario , Troysi Valeria , Sborgia Giancarlo
Published: April 2007

Purpose: To evaluate the influence of different degrees of myopia on retinal nerve fiber layer (RNFL) as measured by scanning laser polarimetry (SLP) with variable corneal compensator (VCC) in healthy eyes. Methods: One hundred and seventy-four healthy age-matched subjects with low to high myopic and emmetropic eyes underwent RNFL measurement by means of GDxVCC. The GDx parameters included in the analysis were: Temporal-superior-nasal-inferior thickness (TSNIT) average, Superior average, Inferior average, TSNIT standard deviation, Inter-eye symmetry, NFI, Symmetry, Superior ratio, Inferior ratio, Superior/nasal, Maximum modulation, Superior maximum, Inferior maximum, Ellipse modulation, Normalized superior area, Normalized inferior area, Ellipse standard deviation, Ellipse average. The mean value of each SLP parameter of myopic eyes was compared with the mean value of the same parameter of emmetropic eyes. Results: Mean myopia was 3.9 ± 1.5 dpt (range: –2 to –8.25 dpt). TNSIT average was higher in myopic group (p = 0.0111), together with Superior average (p = 0.0244), Symmetry (p < 0.0001) and Ellipse average (p = 0.0111). Two ratio parameters, Superior ratio and Inferior ratio, were higher in emmetropic eyes (p = 0.0179 in both cases). In both the myopic and the emmetropic group, all the SLP assessments of the RNFL fell within the normal range, according to the GDx database. Conclusions: Low to high myopia is not related to clinically relevant variations of SLP parameters, as assessed with GDx-VCC.
A Case of Lacrimal Gland Dirofilariasis
Authors: Juri Jelena , Kuzman Tomislav , Stiglmayer Neda , Tojagić Miljenka
Published: April 2007

A patient with a diagnosis of chronic and idiopathic unilateral dacryoadenitis was submitted to our clinic for diagnostic reasons from a regional hospital. Within a period of 1 year, this was the second onset of a swelling in the region of the lacrimal gland which – unlike the first time – showed resistance to antibiotic treatment. The patient’s general and ophthalmic condition was good, and his only complaint was of cosmetic nature because of the disfiguring swelling in the lateral part of the left upper eyelid. Basic laboratory findings showed no abnormalities and radiographic imaging showed enlargement of the left lacrimal gland without bony destruction. Guided by epidemiological data for noninfectious dacryoadenitis we decided to perform excisional biopsy of the left lacrimal gland. To our surprise, the pathologist verified the presence of a worm of the genus Dirofilaria, which is, to the best of our knowledge, the second reported case of lacrimal gland dirofilariasis in the literature and the second reported case of such a disease in Croatia.
The Use of the Orbital Septum in Inferior Palpebral Reconstruction: The Pocket Technique
Authors: Marabotti Andrea , Cariello Anna , La Mattina Gian Carmelo , Romani Andrea , Giannecchini Iacopo , Carena Simonetta , Bedei Andrea
Published: April 2007

Background: Surgery involving massive inferior palpebral demolition often imposes the use of free flaps for the reconstruction of the anterior and posterior lamellae. Purpose: We describe a surgical technique which provides for the use of a homologous pedunculated elastic flap on which we wrap the free flap as in a pocket, in order to guarantee that the free flap itself takes root better. Methods: A study of 10 patients admitted to our hospitals for massive inferior palpebral demolition surgery between March 2002 and November 2004 was undertaken, and clinical records (age, sex, involved site of lesions, surgery technique) were accurately noted: in all patients we performed the ‘pocket technique’. Results: The pocket technique has encouraged optimal attachment of the implanted free tissue, in absence of necrotic phenomena or tissue extrusion. Conclusions: Reconstructive surgery of the inferior eyelid avails itself of consolidated techniques. In case of extreme tissue reduction, the variation we wish to suggest is simple to understand and easy to perform, significantly reducing inflammatory reaction and/or post-surgical rejection, allowing excellent aesthetic results.
Metacognition and Reflexivity in Patients with Schizophrenia
Authors: Kircher Tilo T.J. , Koch Kathrin , Stottmeister Frank , Durst Volker
Published: April 2007

Background: Many patients with schizophrenia demonstrate a lack of insight into their disorder and often do not complain about their cognitive impairments. This might be due to generally reduced metacognitive abilities. Sampling and Methods: Twenty-seven patients with a DSM IV diagnosis of schizophrenia and 19 healthy control subjects performed 2 separate tasks tapping into metacognitive functions. In the first experiment the participants encoded words. In the following recognition part they judged their level of subjective confidence in the correctness of their answer. In the second experiment reaction time was measured, whilst judgments were made about personality trait adjectives describing the subjects themselves or other familiar people. Results: Although the recognition rate in the first experiment was equal between the groups, the patients showed a significantly reduced ability to correctly judge their memory performance. There was no correlation between metamemory and psychopathology nor insight measures. The patients further needed significantly more time to characterize themselves compared to the healthy participants. The response rates for self-characterization correlated with the ability to recognize symptoms as part of a disorder but did not correlate with psychopathology. Conclusions: Metacognitive faculties seem to be, at least in part, a separable cognitive entity. Patients with schizophrenia demonstrate impaired metacognitive capacities, independent of current symptoms or memory performance.
Perspectives on Triggering Communism's Collapse
Authors: Kemp-Welch Tony , Korbonski Andrzej , Szporer Michael
Published: April 2007

Marjorie Castle's volume in the Harvard Cold War Studies Book Series, Triggering Communism's Collapse: Perceptions and Power in Poland's Transition, discusses events in the late 1980s that induced the leaders of the Polish Communist party to open negotiations with senior opposition figures, including the head of the still-banned Solidarity trade union. Preliminary talks in 1988 led to agreement on the holding of Round Table talks, which formally began on 6 February 1989 and ended two months later, on 5 April 1989, with arrangements to hold partly free parliamentary elections in early June. Contrary to the expectations of both the regime and the opposition, those elections resulted in an overwhelming victory for Solidarity, starting a chain of events that led to the formation of the first non-Communist government in a Soviet-bloc country since 1948. Three distinguished experts on Poland comment on Castle's analysis of Poland's transition and offer their own assessments of the importance and legacy of the Round Table talks.
The Tito-Stalin Split: A Reassessment in Light of New Evidence
Authors: Perović Jeronim
Published: April 2007

This article reassesses the Tito-Stalin split of 1948 based on findings from former East-bloc archives. In particular, it shows that the version propagated in the official Yugoslav historiography, suggesting that the break with Moscow arose because of Yugoslavia's distinct path toward socialism, is incorrect. Instead, Josip Broz Tito's unwillingness to give up on his territorial and political ambitions in the Balkans, especially Albania, despite Moscow's objections is the main factor that ultimately sparked the conflict in 1948. Yugoslavia fell afoul of Moscow's policy of enforced Sovietization of the socialist camp, though not because of a long-term Soviet plan or because of particular animosity toward the Yugoslav leadership. Rather, Tito's independent foreign policy provided a welcome pretext to clamp down on Yugoslavia and thereby tighten Soviet control over the other East European states.
A Most Special Relationship: The Origins of Anglo-American Nuclear Strike Planning
Authors: Young Ken
Published: April 2007

This article examines a hitherto unexplored aspect of the Anglo-American “special relationship,” the development of arrangements to coordinate U.S. and British forces in a joint nuclear strike against the Soviet Union. During the early Cold War, British political leaders and military officers struggled for a closer relationship with the U.S. Air Force in the hope of gaining greater insight into U.S. war plans, predicated as they were on nuclear strikes launched from bases in England. U.S. willingness to supply nuclear (and later thermo-nuclear) bombs for delivery by British bombers prompted bilateral talks from 1956 about their deployment in a joint air offensive. This prospective partnership raised difficult issues for the UK Air Staff, which was committed to the maintenance of an independent nuclear deterrent and countervalue rather than counterforce targeting. Nevertheless, the advantages of joint strike planning were such that by 1962 Bomber Command's planning had become fully integrated with that of Strategic Air Command.
Molecular, Biologic, and Pharmacokinetic Properties of Monoclonal Antibodies: Impact of These Parameters on Early Clinical Development
Authors: Mascelli Mary Ann , Zhou Honghui , Sweet Raymond , Getsy Jay , Davis Hugh M. , Graham Martin , Abernethy Darrell
Published: April 2007

Currently, 14 intact, unconjugated, monoclonal antibodies (Mabs) are approved for therapeutic use in the United States, and more than 100 Mabs are presently undergoing clinical development or regulatory review. Mabs are large molecular weight glycoproteins that embody structural, biochemical, and pharmacologic properties distinct from other biologics or chemically synthesized compounds. Early therapeutic Mabs were murine proteins, and clinical testing of these agents revealed serious immune‐mediated toxicities. The side effect profile of murine Mab therapeutic agents restricted the clinical development of these agents to indications with high morbidity and/or mortality (ie, oncology, graft vs host rejection). Advances in genetic engineering and protein expression technologies resulted in the development of Mabs composed either predominately (ie, mouse/human chimeric, “humanized”) or completely (ie, “fully human” Mabs) of the human amino acid sequence. The production of chimeric, humanized, and fully human Mabs significantly reduced the immune‐mediated toxicities and expanded the utility for these agents in numerous therapeutic areas, particularly in chronic disorders requiring either long‐term administration (ie, rheumatoid arthritis) or treatment upon the flare up of disease (Crohn's disease, psoriasis). This review provides an overview of the molecular, biochemical, and pharmacokinetic properties and clinical development history of Mabs and details how these factors currently affect the scope and design of early clinical development strategies for these drug candidates. Emphasis is placed on the criteria for selecting appropriate subject populations for phase I testing of Mabs.
Smart Textiles: A New Drug Delivery System for Symptomatic Treatment of a Common Cold
Authors: Wienforth F. , Landrock A. , Schindler C. , Siegert J. , Kirch W.
Published: April 2007

Smart textiles provide the possibility of being coated with cineole, menthol, and camphor. Due to over‐the‐counter availability, ethereal oils are frequently used to treat a common cold. The existing pharmaceutical forms entail the risk of oral ingestion by children, which can cause severe intoxications. This risk could be limited by a smart textile application. Prior to applicability tests in children, the principal traceability of smart textile–applied ethereal oils at their site of action in the alveoli has to be demonstrated. Therefore, a crossover trial (ointment vs smart textiles) with 6 healthy volunteers was carried out as a proof‐of‐concept study. As a result, the principle proof is given that smart textile–applied ethereal oils are available at their site of action. Because of the volatility of the active ingredients, a close‐fitting textile form has to be developed for further clinical development of smart textiles to achieve higher concentrations in the alveoli. Slower liberation properties and a more convenient skin sensation in comparison to available pharmaceutical forms may provide advantages for the applicability in both children and adults.
Nuclear Receptors and the Regulation of Drug‐Metabolizing Enzymes and Drug Transporters: Implications for Interindividual Variability in Response to Drugs
Authors: Urquhart Bradley L. , Tirona Rommel G. , Kim Richard B.
Published: April 2007

Erratic or unpredictable response to drugs remains a challenge of modern drug therapy. An important determinant of such interindividual differences in drug response is variability in the expression of drug‐metabolizing enzymes and/or transporters at sites of absorption and/or tissue distribution. Variable drug‐metabolizing enzyme and transporter expression can result in unpredictable exposure and tissue distribution of drugs and may manifest as adverse effects or therapeutic failure. In the past decade, important new insights have been made relating to the regulatory mechanisms governing the expression of drug‐metabolizing enzymes and transporters by ligand‐activated nuclear receptors. Specifically, there is compelling evidence to demonstrate that PXR, CAR, FXR, LXR, VDR, HNF4α, and AhR form a battery of nuclear receptors that regulate the expression of many important drug‐metabolizing enzyme and transporters. In this review, the authors focus on clinically important drug‐metabolizing enzymes such as CYP3A4, CYP2B6, CYP2C9, CYP2C19, UGT1A1, SULT2A1, and glutathione S‐transferases and their regulation by nuclear receptors. They also review the nuclear receptor–mediated regulation of drug transporters such as MDR1, MRP2, MRP4, BSEP, BCRP, NTCP, OATP1B3, and OATP1A2. Finally, they outline how the drug development process has been affected by the current understanding of the involvement of nuclear receptors in the regulation of drug disposition genes.
Laying It on Thin: Analogical Cue Frequency in the Manipulation of Choice
Authors: McGlone Matthew S. , Bortfeld Heather , Kobrynowicz Diane
Published: April 2007

Persuasive analogies consist of linguistic cues that invite audiences to represent a problem in terms of an analog and to make choices compatible with this manipulated representation. The authors explore how the frequency of linguistic cues moderates analogical bias in choice behavior. Participants read versions of a managerial decision scenario differing in the number of sports (e.g., game plan) or family (e.g., parent company) idioms used to describe situational attributes and then chose between analogically consistent and inconsistent response options. Analogies consisting of an intermediate number of cues elicited higher rates of analogically consistent responding than those of higher and lower cue frequency. When explaining their responses, participants referred to the sports or family analogies most often to rationalize rejecting the analogically consistent response option after reading high cue frequency versions. These findings indicate that there are lower and upper boundaries to a persuasive analogy's optimal cue frequency.
Determination of a Safe Range of Knee Flexion Angles for Fixation of the Grafts in Double-Bundle Anterior Cruciate Ligament Reconstruction
Authors: Vercillo Fabio , Woo Savio L-Y. , Noorani Sabrina Y. , Dede Özgür
Published: April 2007

Background

For anterior cruciate ligament reconstruction with a double-bundle procedure, one of the major concerns is to not predispose either one of the grafts to risk of failure by overloading.

Hypothesis

Knee flexion angles between 15° and 45° for anteromedial graft fixation and 15° for posterolateral graft fixation are safe for both grafts in double-bundle anterior cruciate ligament reconstruction.

Study Design

Controlled laboratory study.

Methods

Nine human cadaveric knees were tested. The double-bundle anterior cruciate ligament reconstruction was conducted with both grafts fixed at 15° of knee flexion (fixation protocol 15/15) and again with the anteromedial and posterolateral grafts fixed at 45° and 15° of knee flexion (fixation protocol 45/15). For both fixation protocols, the knee kinematics and the in situ forces of the reconstructed anterior cruciate ligament and its individual grafts were measured and collected under an anterior tibial load of 134 N and combined rotatory loads of 10 N·m of valgus and 5 N·m of internal tibial torque. The data from both fixation protocols were compared with those of an intact knee.

Results

In response to the 2 external loading conditions, both fixation protocols (15/15 and 45/15) could restore the knee kinematics to within 2 mm of the intact knee (although statistically significant differences were found between fixation protocol 15/15 and the intact knee) and the overall in situ forces in the grafts similar to the intact anterior cruciate ligament. In response to the 134-N anterior tibial load, the in situ forces in the anteromedial graft for both fixation protocols did not exceed those of the intact anteromedial bundle. But at 30° and 45° of knee flexion, the in situ forces for fixation protocol 15/15 were 20.7% and 22.1% lower, respectively, when compared with the intact anteromedial bundle. Under combined rotatory loads, the anteromedial graft for fixation protocol 15/15 had in situ forces that were 45% lower than the intact anteromedial bundle at 30° of knee flexion. The in situ force in the posterolateral graft for both fixation protocols did not exceed those of the intact posterolateral bundle, nor were they significantly different from the intact posterolateral bundle at any of the flexion angles tested.

Conclusion

Both fixation protocols restored knee kinematics without predisposing either graft to failure. Therefore, knee flexion angles between 15° and 45° for graft fixation were found to be safe for the anteromedial graft, while 15° of knee flexion was safe for the posterolateral graft.

Clinical Relevance

A range of knee flexion angles that is safe for the fixation of both grafts in double-bundle anterior cruciate ligament reconstruction was determined.
Patellofemoral Contact Pressures and Lateral Patellar Translation after Medial Patellofemoral Ligament Reconstruction
Authors: Beck Paul , Brown Nicholas A. T. , Greis Patrick E. , Burks Robert T.
Published: April 2007

Background

Overtensioning of medial patellofemoral ligament reconstructions may lead to adverse surgical outcomes.

Hypothesis

Increasing tension on a medial patellofemoral ligament graft will increase patellofemoral contact forces and decrease lateral patellar translation.

Study Design

Controlled laboratory study.

Methods

Patellofemoral contact pressures were measured in 8 fresh-frozen cadaveric knees before and after transection of the medial patellofemoral ligament and after a standardized reconstruction surgery. Contact pressures were measured at 3 knee angles (30°, 60°, and 90°) and under 3 levels of tension applied to the graft (2, 10, and 40 N). For each condition, patellar translation was measured at 30° of knee flexion as a 22-N lateral force was applied.

Results

Graft tension of 2 N restored normal translation, but 10 N and 40 N significantly restricted motion (5.2 mm and 1.9 mm, respectively). Compared with the intact knee, medial patellofemoral contact pressures significantly increased (P < .05) when 40 N of tension was applied to the reconstruction. Medial contact pressures were restored to normal with 2 N of graft tension. Lateral patellar translation was significantly greater (P < .05) after the medial patellofemoral ligament was cut (16.3 mm) compared with intact (7.7 mm).

Conclusion

Low (2-N) tension applied to a medial patellofemoral ligament reconstruction stabilized the patella and did not increase medial patellofemoral contact pressures. Higher loads (10 N and 40 N) progressively restricted lateral patellar translation and inappropriately redistributed patellofemoral contact pressures.

Clinical Relevance

Overtensioning can be avoided by applying low loads to medial patellofemoral ligament reconstructions, which reestablished normal translation and patellofemoral contact pressures.
Concomitant Meniscal Allograft Transplantation and Autologous Chondrocyte Implantation
Authors: Farr Jack , Rawal Ashish , Marberry Kevin M.
Published: April 2007

Background

Although recent studies have shown intermediate-term success of both meniscal allograft transplantation (MAT) and autologous chondrocyte implantation (ACI) performed separately, there have been no peer-reviewed studies focused prospectively on the combined procedure. By potentially reestablishing a compartment contact area closer to normal, MAT may allow a more optimal environment for ACI by reducing stress (stress = force/unit area). On the other hand, the literature suggests that MAT alone in the presence of extensive chondrosis performs poorly. Restoring the articular cartilage may allow the MAT to perform more similarly to series with nearly normal articular cartilage.

Hypothesis

Performed concomitantly, ACI and MAT will result in significant improvements in knee function as measured by functional scoring scales and visual analog pain scales.

Study Design

Case series; Level of evidence, 4.

Methods

Preoperative and postoperative comparisons of Browne modified Cincinnati functional levels, Lysholm, visual analog rest and maximum pain, and satisfaction scores were recorded. Thirty-six total procedures were performed between 1999 and 2004.

Results

Of the 36 patients entering the series, 29 had >2-year evaluation and scores. Four patients were recorded as failures before the 2-year follow-up and required revision surgery. Three patients were lost to follow-up. A total of 21 medial and 8 lateral MAT/femoral condyle ACIs were performed. Sixteen of 29 patients had concomitant procedures performed, including tibial tuberosity osteotomy, anterior cruciate ligament reconstruction, and high tibial osteotomy. Patients demonstrated statistically significant improvement in the standardized outcome surveys, visual analog pain, and satisfaction scores. The Browne Cincinnati (Patient and Clinician, respectively) showed an improvement from 3.9 (standard deviation [SD], 1.5) and 4.0 (SD, 1.4) preoperatively to 6.3 (SD, 1.9) postoperatively for both. The Lysholm also showed an improvement from 57.7 (SD, 16.2) preoperatively to 77.7 (SD, 19.3) postoperatively. There were no significant differences noted in any of the subgroups (medial vs lateral, isolated vs concomitant, or unipolar vs bipolar).

Conclusion

At a minimum of 2-year follow-up, MAT in combination with ACI demonstrates improvement in both symptoms and knee function. However, the improvements are less than literature-reported outcomes of either procedure performed in isolation.
A Quantitative Model of Sleep-Wake Dynamics Based on the Physiology of the Brainstem Ascending Arousal System
Authors: Phillips A.J.K. , Robinson P.A.
Published: April 2007

A quantitative, physiology-based model of the ascending arousal system is developed, using continuum neuronal population modeling, which involves averaging properties such as firing rates across neurons in each population. The model includes the ventrolateral preoptic area (VLPO), where circadian and homeostatic drives enter the system, the monoaminergic and cholinergic nuclei of the ascending arousal system, and their interconnections. The human sleep-wake cycle is governed by the activities of these nuclei, which modulate the behavioral state of the brain via diffuse neuromodulatory projections. The model parameters are not free since they correspond to physiological observables. Approximate parameter bounds are obtained by requiring consistency with physiological and behavioral measures, and the model replicates the human sleep-wake cycle, with physiologically reasonable voltages and firing rates. Mutual inhibition between the wake-promoting monoaminergic group and sleep-promoting VLPO causes ``flip-flop'' behavior, with most time spent in 2 stable steady states corresponding to wake and sleep, with transitions between them on a timescale of a few minutes. The model predicts hysteresis in the sleep-wake cycle, with a region of bistability of the wake and sleep states. Reducing the monoaminergic-VLPO mutual inhibition results in a smaller hysteresis loop. This makes the model more prone to wake-sleep transitions in both directions and makes the states less distinguishable, as in narcolepsy. The model behavior is robust across the constrained parameter ranges, but with sufficient flexibility to describe a wide range of observed phenomena.
Daily Light Exposure in Morning-Type and Evening-Type Individuals
Authors: Goulet Geneviève , Mongrain Valérie , Desrosiers Catherine , Paquet Jean , Dumont Marie
Published: April 2007

Morning-type individuals (M-types) have earlier sleep schedules than do evening types (E-types) and therefore differ in their exposure to the external light-dark cycle. M-types and E-types usually differ in their endogenous circadian phase as well, but whether this is the cause or the consequence of the difference in light exposure remains controversial. In this study, ambulatory monitoring was used to measure 24-h light exposure in M-type and E-type subjects for 7 consecutive days. The circadian phase of each subject was then estimated in the laboratory using the dim-light melatonin onset in saliva (DLMO) and the core body temperature minimum (Tmin). On average, M-types had earlier sleep schedules and earlier circadian phases than E-types. They also showed more minutes of daily bright light exposure (> 1000 lux) than E-types. As expected, the 24-h patterns of light exposure analyzed in relation to clock time indicated that M-types were exposed to more light in the morning than E-types and that the reverse was true in the late evening. However, there was no significant difference when the light profiles were analyzed in relation to circadian phase, suggesting that, on average, the circadian pacemaker of both M-types and E-types was similarly entrained to the light-dark cycle they usually experience. Some M-types and E-types had different sleep schedules but similar circadian phases. These subjects also had identical light profiles in relation to their circadian phase. By contrast, M-types and E-types with very early or very late circadian phases showed large differences in their profiles of light exposure in relation to their circadian phase. This observation suggests that in these individuals, early or late circadian phases are related to relatively short and long circadian periods and that a phase-delaying profile of light exposure in M-types and a phase-advancing profile in E-types are necessary to ensure a stable entrainment to the 24-h day.
Separate Sets of Cerebral Clock Neurons Are Responsible for Light and Temperature Entrainment of Drosophila Circadian Locomotor Rhythms
Authors: Miyasako Yoko , Umezaki Yujiro , Tomioka Kenji
Published: April 2007

The fruit fly Drosophila melanogaster shows a bimodal circadian locomotor rhythm with peaks at lights-on and before lights-off, which are regulated by multiple clocks in the brain. Even under light-dark cycles, the timing of the evening peak is highly dependent on temperature, starting earlier under lower ambient temperature but terminating almost at the same time. In the present study, using behavioral and immunohistochemical assays, the authors show that separate groups of clock neurons, either light-entrainable or temperature-entrainable, form a functional system driving the locomotor rhythm. When subjected to a light cycle combined with a temperature cycle advanced by 6 h relative to the light cycle, the dorsally located neurons (DNs) and lateral posterior neurons (LPNs) shifted their phase of TIMELESS expression, but the laterally located protocerebral neurons (LNs) basically maintained their original phase. Thus, the LNs seem to be preferentially light-entrainable and the DNs and LPNs to be primarily temperature-entrainable. In pdf01 mutant flies that lack the neuropeptide PDF in the ventral groups of LNs, the onset of the evening peak was greatly advanced even under synchronized light and temperature cycles and was shifted even more than in wild-type flies in response to a 6-h phase shift of the temperature cycle, suggesting that ventral LNs have a strong impact on the phase of the other cells. It seems likely that the 2 sets of clock cells with different entrainability to light and temperature, and the coupling between them, enable Drosophila to keep a proper phase relationship of circadian activity with respect to the daily light and temperature cycles.
Nursing, Healthcare, and Culture: A View for the Year 2050 From Colombia
Authors: Fawcett Jacqueline , Moreno María Elisa
Published: April 2007

This column presents a dialogue with Colombian nurse scholar María Elisa Moreno, who shares her vision and understanding of her country's vision of nursing, healthcare, and quality of life in the year 2050.
A Research Synthesis Overview
Authors: Bowman Katherine G.
Published: April 2007

The volume of research literature is enormous, so keeping up with the latest studies is difficult. Systematic reviews are a form of research that pools the results of multiple studies. Quantitative reviews statistically pool results, and qualitative reviews narratively pool results. Reviews are becoming common, but some nurses may be unaware of what a systematic review is and how to conduct one. The aim of this overview is to acquaint nurses with qualitative systematic reviews (research syntheses) by providing information about where to begin a synthesis, the stages of the synthesis process, and how to write a manuscript to report synthesis results.
II. Emotional Labour in the Beauty Salon
Authors: Toerien Merran , Kitzinger Celia
Published: April 2007

Research on emotional labour in the workplace — including beauty salons — has relied on workers' reports of emotional labour; few researchers have examined workers' moment-by-moment workday experience to explicate the practices of emotional labour in action. Using conversation analysis (CA) of a single interaction between a client and a beauty therapist, we show how task-directed talk, and even aspects of the physical work itself, may be designed to perform a dual function: to complete, satisfactorily, the procedure for which the client is paying, and to perform some of those actions that researchers have dubbed `emotional labour'. In our data, the therapist gives precedence to performing the emotional labour over the immediate accomplishment of the institutionally defined goal (hair removal), thereby providing concrete, recorded evidence for the claim that emotional labour is a job requirement for beauty therapy.
Solar UV Forecasts
Authors: Dixon Helen G. , Hill David J. , Karoly David J. , Jolley Damien J. , Aden Said M.
Published: April 2007

This study examined the effectiveness of solar UV forecasts and supporting communications in assisting adults to protect themselves from excessive weekend sun exposure. The study was conducted in Australia, where 557 adult participants with workplace e-mail and Internet access were randomly allocated to one of three weather forecast conditions: standard forecast (no UV), standard forecast + UV, standard forecast + UV + sun-protection messages. From late spring through summer and early autumn, they were e-mailed weekend weather forecasts late in the working week. Each Monday they were e-mailed a prompt to complete a Web-based questionnaire to report sun-related behavior and any sunburn experienced during the previous weekend. There were no significant differences between weather forecast conditions in reported hat use, sunscreen use, sun avoidance, or sunburn. Results indicate that provision of solar-UV forecasts in weather forecasts did not promote markedly enhanced personal sun-protection practices among the adults surveyed.
Contact, Perspective Taking, and Anxiety as Predictors of Stereotype Endorsement, Explicit Attitudes, and Implicit Attitudes
Authors: Aberson Christopher L. , Haag Sarah C.
Published: April 2007

We proposed a model of intergroup contact wherein contact promotes understanding of outgroup perspectives, perspective taking relates to reduced intergroup anxiety that in turn is associated with lessened stereotyping and more positive intergroup attitudes. Additionally, we examined if implicit attitudes followed this model or were directly impacted by contact. White undergraduates ( n = 153) completed measures of contact, perspective taking, intergroup anxiety, stereotype endorsement, and implicit and explicit intergroup attitudes. Our model fitted the data well but explained explicit attitudes and stereotyping better than implicit attitudes. Supporting an environmental association interpretation, contact was the only significant predictor of implicit attitudes. Findings support a dual-process model wherein implicit and explicit attitudes represent separate constructs and support the value of contact in improving intergroup attitudes.
Politically-oriented tourism in Jerusalem
Authors: Brin Eldad
Published: April 2007

Politics plays an important role for a growing number of visitors, Israeli and otherwise, who have been coming to Jerusalem over the past few years. `Politically-oriented tourism' in the city includes private or organized excursions to sites related to the Israeli—Palestinian Conflict. While most politically-oriented tourists come to Jerusalem to show their support for either of the two main belligerent ethnic groups residing in the city, others are more politically `neutral' and are just curious to learn more of the conflict and how it manifests itself in the high-profile Jerusalem setting. In the city, both Israeli and Palestinian official bodies and private tour operators exploit tourism as an opportunity to propagate partisan political agendas. More often than not, `political' tourist interest in Jerusalem differs from that in other politically unstable locales in the high degree of involvement felt by many towards this city of great religious and spiritual importance.
Prospects for progress in penal reform
Authors: Faulkner David
Published: April 2007

The article considers the situation which the Government's reforms of sentencing and penal treatment had reached by the autumn of 2006, and the issues which are likely to arise as the changes take effect. It examines the underlying attitudes to the purpose and nature of punishment, and of criminal justice more generally; the implications for sentencing and the relationship between sentencers and those responsible for giving effect to the sentences imposed; and the prospects for the reforms' success. It reviews the questions that arise from the evidence for `what works', the `science' of risk assessment and the Government's plans for `contestability' and the related issues of accountability and legitimacy. It concludes with some suggestions for themes that might be further developed and new themes that might be introduced.
Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry
Authors: Murphy Anthony T. , Witcher Derrick R. , Luan Peng , Wroblewski Victor J.
Published: April 2007

The hepatic peptide hormone hepcidin is considered the central regulator of iron metabolism. Characterizing the circulating levels of this peptide is critical to understanding its role in the development of clinically relevant syndromes, such as anemia of inflammation/chronic disease, and may provide insight into potential clinical interventions. While quantitative methods have been published for the determination of urinary hepcidin and serum prohepcidin, no definitive methods have been published for the determination of hepcidin in serum. In this report, we describe a quantitative method for the determination of both human and mouse hepcidin in serum and plasma. The method employs protein precipitation and solid-phase extraction followed by liquid chromatographic separation and tandem mass spectrometry detection. The method has a quantitative range of 0.25 ng/mL to 500 ng/mL serum for mouse hepcidin and 1 ng/mL to 500 ng/mL serum for human hepcidin. The method uses small sample volumes (50 μL for mice and 100 μL for humans) and 96-well formats for rapid sample processing. The method was used to establish baseline serum and plasma concentrations of hepcidin in normal C57Bl/6 mice and healthy human volunteers.
Functional analysis of fibrin γ-chain cross-linking by activated factor XIII: determination of a cross-linking pattern that maximizes clot stiffness
Authors: Standeven Kristina F. , Carter Angela M. , Grant Peter J. , Weisel John W. , Chernysh Irina , Masova Leona , Lord Susan T. , Ariëns Robert A. S.
Published: April 2007

Activated coagulation factor XIII (FXIIIa) cross-links the γ-chains of fibrin early in clot formation. Cross-linking of the α-chains occurs more slowly, leading to high molecular weight multimer formations that can also contain γ-chains. To study the contribution of FXIIIa-induced γ-chain cross-linking on fibrin structure and function, we created 2 recombinant fibrinogens (γQ398N/Q399N/K406R and γK406R) that modify the γ-chain cross-linking process. In γK406R, γ-dimer cross-links were absent, but FXIIIa produced a cross-linking pattern similar to that observed in tissue transglutaminase cross-linked fibrin(ogen) with mainly α-γ cross-links. In Q398N/Q399N/K406R, cross-links with any γ-chain involvement were completely absent, and only α-chain cross-linking occurred. Upon cross-linking, recombinant normal fibrin yielded a 3.5-fold increase in stiffness, compared with a 2.5-fold increase by α-chain cross-linking alone (γQ398N/Q399N/K406R). γK406R fibrin showed a 1.5-fold increase in stiffness after cross-linking. No major differences in clot morphology, polymerization, and lysis rates were observed, although fiber diameter was slightly lower in cross-linked normal fibrin relative to the variants. Our results show that γ-chain cross-linking contributes significantly to clot stiffness, in particular through γ-dimer formation; α-γ hybrid cross-links had the smallest impact on clot stiffness.
SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection
Authors: Petrovas Constantinos , Price David A. , Mattapallil Joseph , Ambrozak David R. , Geldmacher Christof , Cecchinato Valentina , Vaccari Monica , Tryniszewska Elzbieta , Gostick Emma , Roederer Mario , Douek Daniel C. , Morgan Sara H. , Davis Simon J. , Franchini Genoveffa , Koup Richard A.
Published: April 2007

Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell exhaustion. Here, we examined the expression of PD-1 on simian immunodeficiency virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of cytokine production, proliferation, and survival of these cells. The majority of SIV-specific CD8+ T cells expressed a PD-1high phenotype, independent of their differentiation status, in all tissues tested. PD-1 expression gradually declined on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational escape, indicating that antigen-specific TCR stimulation is the primary determinant of PD-1 expression. SIV-specific PD-1highCD8+ T cells produced IFN-γ, TNF-α, and IL-2 under cognate peptide stimulation. While CD8+ T cells that proliferated in response to antigen had a PD-1high phenotype, it was determined that there was a reduced proliferative capacity of PD-1high compared with PD-1low SIV-specific CD8+ T cells. PD-1high SIV-specific CD8+ T cells were highly susceptible to cell death leading to loss of such cells after in vitro stimulation. Thus, PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death. Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8+ T-cell responses in SIV infection.
Toward a Molecular Classification of Melanoma
Authors: Fecher Leslie A. , Cummings Staci D. , Keefe Megan J. , Alani Rhoda M.
Published: April 2007

The incidence of melanoma is increasing at one of the highest rates of any form of cancer in the United States, with the current lifetime risk being one in 68. At present, there are limited systemic therapies to treat advanced stages of melanoma, and the key to improved survival remains early detection. Recent discoveries have allowed for a clearer picture of the molecular events leading to melanoma development and progression. Since identifying prevalent activating mutations of the BRAF kinase in melanomas, there has been a flood of additional molecular studies to further clarify the role of this pathway and others in melanomagenesis. In particular, recent genetic studies have demonstrated specific genotype-phenotype correlations that provide the first major insights into the molecular subclassification of melanoma and the heterogeneous nature of this malignancy. In this article, we review the most up-to-date molecular discoveries in melanoma biology and provide a framework for understanding their significance in melanoma development and progression. We also provide details on the development of novel therapies based on these recent molecular discoveries and insight into current and planned clinical trials. It is expected that these latest studies in melanoma will help define the critical molecular events involved in disease onset and progression and allow us to move rapidly toward a true molecular classification. We eagerly anticipate rationally designed melanoma therapies based on such a classification scheme and the associated improvements in patient outcomes.
Femoral Head Osteonecrosis in Pediatric and Young Adult Patients With Leukemia or Lymphoma
Authors: Karimova Evguenia J. , Rai Shesh N. , Howard Scott C. , Neel Michael , Britton Lunetha , Pui Ching-Hon , Kaste Sue C.
Published: April 2007

Purpose

Osteonecrosis of the capital femoral epiphysis is a significant late toxicity of treatment for childhood leukemia and lymphoma. We determined clinical and imaging risk factors predicting clinical joint outcomes of femoral head osteonecrosis in pediatric patients with leukemia or lymphoma.

Patients and Methods

We reviewed retrospectively medical records and magnetic resonance imaging scans of 80 patients with osteonecrosis of the capital femoral epiphysis. Logistic regression was used to examine relationships between risk factors and outcomes of joint surface collapse and arthroplasty. We used Kaplan-Meier survival curves to display the time to joint surface collapse and arthroplasty based on selected predictors.

Results

Median time between primary diagnosis and diagnosis of osteonecrosis of the hip was 1.7 years (range, 0.1 to 17.5 years). Twenty-three patients (29%) underwent arthroplasty in 36 hips at a mean of 1.3 years (range, 0.5 to 8.6 years) after diagnosis of osteonecrosis. Median age at time of first arthroplasty was 20.1 years (range, 15.1 to 35.4 years). Joint outcome of osteonecrosis was predicted solely by lesion size at diagnosis of osteonecrosis. The worst prognosis was associated with lesions occupying more than 30% of the femoral head volume; 80% of hips with these lesions collapsed within 2 years of diagnosis and 50% required arthroplasty.

Conclusion

Lesion size of osteonecrosis is the best predictor of clinical joint outcome of hip osteonecrosis in survivors of pediatric hematologic malignancy. Lesions occupying more than 30% of the femoral head have high likelihood of joint deterioration necessitating arthroplasty at a young age.