bluuebunny/crossref_metadata_2025 huggingface dataset:
Establishing Final Infarct Volume
Authors: Gaudinski Martin R. , Henning Erica C. , Miracle Aaron , Luby Marie , Warach Steven , Latour Lawrence L.
Published: July 2008

Background and Purpose—

Lesion volume measured on MRI has been used as an objective surrogate marker for outcome in clinical trials. However, lesion volumes vary over time because of edema and tissue loss. This study aims to determine if lesion volumes measured at 30 and 90 days after ictus significantly differ.

Methods—

We performed a retrospective study of 18 patients who had acute (<24 hours) DWI and follow-up fluid-attenuated inversion recovery imaging at 5, 30, and 90 days. Two expert readers segmented lesions and the mean volumes of both reads were used in all statistical analyses.

Results—

Patient age was 65.8 (SD, 13.7) years and median NIHSS at baseline was 11.5. Inter-rater variability for lesion volume measurements was 3.7 (5.8) mL. Acute DWI volume was 19.3 (17.3) mL. Fluid-attenuated inversion recovery volumes for 5, 30, and 90 days were 34.3 (23.5), 18.6 (14.0), and 15.9 (13.8) mL, respectively. These volumes differed significantly (
P
<0.001). Linear regression revealed a strong correlation (
r
=0.96;
P
<0.001) between lesion volumes at 30 and 90 days with a slope that did not vary significantly from 1.0 (
P
=0.448).

Conclusions—

Lesions continue to evolve between 5 and 90 days, but by 30 days lesion volume approaches final infarct volume. While clinical response is the most meaningful outcome measure, our findings suggest that lesion volumes measured at 30 days may provide a sufficient approximation for final infarct volume for use in early phase clinical trials.
Management of Stroke in Infants and Children
Authors: Roach E. Steve , Golomb Meredith R. , Adams Robert , Biller Jose , Daniels Stephen , deVeber Gabrielle , Ferriero Donna , Jones Blaise V. , Kirkham Fenella J. , Scott R. Michael , Smith Edward R.
Published: July 2008

Purpose—

The purpose of this statement is to review the literature on childhood stroke and to provide recommendations for optimal diagnosis and treatment. This statement is intended for physicians who are responsible for diagnosing and treating infants, children, and adolescents with cerebrovascular disease.

Methods—

The Writing Group members were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee. The panel included members with several different areas of expertise. Each of the panel’s recommendations was weighted by applying the American Heart Association Stroke Council’s Levels of Evidence grading algorithm. After being reviewed by panel members, the manuscript was reviewed by 4 expert peer reviewers and by members of the Stroke Council Leadership Committee and was approved by the American Heart Association Science Advisory and Coordinating Committee. We anticipate that this statement will need to be updated in 4 years.

Results—

Evidence-based recommendations are provided for the prevention of ischemic stroke caused by sickle cell disease, moyamoya disease, cervicocephalic arterial dissection, and cardiogenic embolism. Recommendations on the evaluation and management of hemorrhagic stroke also are provided. Protocols for dosing of heparin and warfarin in children are suggested. Also included are recommendations on the evaluation and management of perinatal stroke and cerebral sinovenous thrombosis in children.
Dural Arteriovenous Shunts
Authors: Geibprasert Sasikhan , Pereira Vitor , Krings Timo , Jiarakongmun Pakorn , Toulgoat Frederique , Pongpech Sirintara , Lasjaunias Pierre
Published: July 2008

Background and Purpose—

The craniospinal epidural spaces can be categorized into 3 different compartments related to their specific drainage role of the bone and central nervous system, the ventral epidural, dorsal epidural, and lateral epidural groups. We propose this new classification system for dural arteriovenous shunts and compare demographic, angiographic, and clinical characteristics of dural arteriovenous shunts that develop in these 3 different locations.

Methods—

Three hundred consecutive cases (159 females, 141 males; mean age: 47 years; range, 0 to 87 years) were reviewed for patient demographics, clinical presentation, multiplicity, presence of cortical and spinal venous reflux, and outflow restrictions and classified into the 3 mentioned groups.

Results—

The ventral epidural group (n=150) showed a female predominance, more benign clinical presentations, lower rate of cortical and spinal venous reflux, and no cortical and spinal venous reflux without restriction of the venous outflow. The dorsal epidural group (n=67) had a lower mean age and a higher rate of multiplicity. The lateral epidural group (n=63) presented later in life with a male predominance, more aggressive clinical presentations, and cortical and spinal venous reflux without evidence of venous outflow restriction. All differences were statistically significant (
P
<0.001).

Conclusion—

Dural arteriovenous shunts predictably drain either in pial veins or craniofugally depending on the compartment involved by the dural arteriovenous shunt. Associated conditions (outflow restrictions, high-flow shunts) may change that draining pattern. The significant differences between the groups of the new classification support the hypothesis of biological and/or developmental differences in each epidural region and suggest that dural arteriovenous shunts are a heterogeneous group of diseases.
Curable Cause of Paraplegia
Authors: Aghakhani Nozar , Parker Fabrice , David Philippe , Lasjaunias Pierre , Tadie Marc
Published: July 2008

Background and Purpose—

The rarity of spinal dural arteriovenous fistulae makes physicians often overlook this potential diagnosis in patients with progressive gait disturbance and paraparesis. Consequently, patients with spinal dural arteriovenous fistulae can gradually become completely paraplegic if the final diagnosis is delayed considerably. The objective of the current study is to demonstrate that, particularly in patients with paraplegia, surgical treatment of fistula is necessary and often has a favorable outcome.

Methods—

Of 42 patients with spinal dural arteriovenous fistulae treated in our institution (surgery or endovascular treatment), 6 were paraplegic preoperatively (Grade IV on the McCormick scale and Grade V on the Aminoff scale, Grade 5 of modified Rankin Scale with motor ASIA between 0 and 10 for both lower limbs). Their clinical history revealed that paraplegia appeared progressively within a period of <3 months. All patients were clinically evaluated at 6 weeks, 6 months, and then annually during an average follow-up of 3 years. Patients received at least one spinal angiography and MRI test during the follow-up period.

Results—

Total exclusion of the fistula was performed surgically in all cases and was confirmed by spinal angiography. No surgical complications were recorded. All patients improved postoperatively. Three patients showed almost normal walking (Grade I on the McCormick scale, I on the Aminoff scale, Grade 1 of modified Rankin Scale) and 3 were able to walk with a cane (Grade II on McCormick, Grade III on Aminoff scale, Grade 2 of modified Rankin Scale). MRI tests were normal in all patients.

Conclusions—

Our results indicate that treatment of fistula is a necessary intervention, even in patients with complete paraplegia.
Ipsilateral Motor-Related Hyperactivity in Patients With Cerebral Occlusive Vascular Disease
Authors: Oshino Satoru , Kato Amami , Hirata Masayuki , Kishima Haruhiko , Saitoh Youichi , Fujinaka Toshiyuki , Yoshimine Toshiki
Published: July 2008

Background and Purpose—

Cerebral occlusive vascular disease is an established risk factor for ischemic stroke; however, little is known about its effects on brain function in patients without stroke. To detect possible functional alterations, we used magnetoencephalography and evaluated cerebral cortical activity during hand motor tasks in a group of such patients.

Method—

Event-related desynchronization (ERD) during hand-grasping and self-paced finger-tapping tasks was examined in 38 right-hand-dominant patients with occlusive disease of the internal carotid or middle cerebral artery caused by diverse pathologies (atherosclerosis, 28; others, 10) and in 8 control subjects. All patients had no apparent motor impairments. The spatial distribution and the intensity (
t
value) of ERD in the beta band were analyzed with synthetic aperture magnetometry. According to the laterality index calculated from the ratios of peak
t
values on ipsilateral vs contralateral (with respect to the hand movement) hemispheres, the distribution of ERD was classified into 3 patterns: contralateral, bilateral, and ipsilateral.

Results—

Abnormal ipsilateral dominant distribution of beta ERD was observed significantly more often during contralesional hand grasping in patients with atherosclerotic vascular lesion. It was accompanied by significantly higher
t
values on the ipsilateral hemisphere, without a decrease in those on the contralateral side. The age, the rating scores of periventricular hyperintensity, and ventricular size were all significantly higher in patients who showed the ipsilateral-dominant pattern.

Conclusion—

Abnormal ipsilateral hyperactivity may indicate the presence of subclinical functional alterations related to atherosclerotic occlusive vascular disease.
Sleep Duration and Risk of Ischemic Stroke in Postmenopausal Women
Authors: Chen Jiu-Chiuan , Brunner Robert L. , Ren Hong , Wassertheil-Smoller Sylvia , Larson Joseph C. , Levine Douglas W. , Allison Matthew , Naughton Michelle J. , Stefanick Marcia L.
Published: July 2008

Background and Purpose—

Many studies have shown a U-shape association between sleep duration and mortality, but epidemiological evidence linking cardiovascular diseases with habitual sleep patterns is limited and mixed.

Methods—

We conducted a prospective study on 93 175 older women (aged 50 to 79 years) in the Women’s Health Initiative Observational study cohort to examine the risk of ischemic stroke in relation to self-reported sleep duration. Cox models were used to investigate the putative associations, adjusting for multiple sociodemographic and lifestyle factors, depression, snoring, sleepiness symptoms, and other cardiovascular disease-related clinical characteristics.

Results—

At baseline, 8.3% of subjects had reported their sleep duration as ≤5 hours per night and 4.6% reported long duration of sleep (≥9 hours/night). After an average of 7.5 years of follow-up, 1166 cases of ischemic stroke had occurred. Multivariable-adjusted relative risk (RR) and 95% CI for ischemic stroke (using a sleep time of 7 hours/night as the reference) were 1.14 (0.97, 1.33), 1.24 (1.04, 1.47), and 1.70 (1.32, 2.21) for women reporting ≤6, 8, and ≥9 hours of sleep. A modestly stronger association with sleep duration ≤6 hours per night (RR, 1.22; 1.03, 1.44) was noted among women without prevalent cardiovascular disease at baseline. Our analyses also reveal that the adverse effect of long sleep is likely independent of the increased risk for ischemic stroke associated with frequent snoring and sleepiness (RR, 1.31; 1.00, 1.72).

Conclusions—

Habitual sleep patterns are important neurobehavioral determinants of risk for ischemic stroke in postmenopausal women. The underlying neurobiology and mechanistic mediators for the putative adverse effect of long sleep (≥9 hours/night) need further elucidation.
Comparison of Advanced Radar Polarimetric Techniques for Operational Attenuation Correction at C Band
Authors: Vulpiani Gianfranco , Tabary Pierre , Parent du Chatelet Jacques , Marzano Frank S.
Published: July 2008

Rain path attenuation correction is a challenging task for quantitative use of weather radar measurements at frequencies higher than S band. The proportionality relationship between specific attenuation αhh (specific differential attenuation αdp) and specific differential phase Kdp is the basis for simple path-integrated attenuation correction using differential phase Φdp. However, the coefficients of proportionality are known to be dependent upon temperature, on the one hand, and shape and raindrop size distribution, on the other hand. To solve this problem, a Bayesian classification scheme is proposed to empirically find the prevailing rain regime and adapt the Φdp-based method. The proposed approach herein is compared with other polarimetric techniques currently available in the literature. Several episodes observed in the Paris, France, area by the C-band dual-polarized weather radar operating in Trappes (France) are analyzed and results are discussed.
Three-Way Error Analysis between AATSR, AMSR-E, and In Situ Sea Surface Temperature Observations
Authors: O’Carroll Anne G. , Eyre John R. , Saunders Roger W.
Published: July 2008

Using collocations of three different observation types of sea surface temperatures (SSTs) gives enough information to enable the standard deviation of error on each observation type to be derived. SSTs derived from the Advanced Along-Track Scanning Radiometer (AATSR) and Advanced Microwave Scanning Radiometer for Earth Observing System (EOS; AMSR-E) instruments are used, along with SST observations from buoys. Various assumptions are made within the error theory, including that the errors are not correlated, which should be the case for three independent data sources. An attempt is made to show that this assumption is valid and that the covariances between the different observations because of representativity error are negligible. Overall, the spatially averaged nighttime AATSR dual-view three-channel bulk SST observations for 2003 are shown to have a very small standard deviation of error of 0.16 K, whereas the buoy SSTs have an error of 0.23 K and the AMSR-E SST observations have an error of 0.42 K.
Explorations of Atmosphere–Ocean–Ice Climates on an Aquaplanet and Their Meridional Energy Transports
Authors: Enderton Daniel , Marshall John
Published: July 2008

The degree to which total meridional heat transport is sensitive to the details of its atmospheric and oceanic components is explored. A coupled atmosphere, ocean, and sea ice model of an aquaplanet is employed to simulate very different climates—some with polar ice caps, some without—even though they are driven by the same incoming solar flux. Differences arise due to varying geometrical constraints on ocean circulation influencing its ability to transport heat meridionally. Without complex land configurations, the results prove easier to diagnose and compare to theory and simple models and, hence, provide a useful test bed for ideas about heat transport and its partition within the climate system. In particular, the results are discussed in the context of a 1978 study by Stone, who argued that for a planet with Earth’s astronomical parameters and rotation rate, the total meridional heat transport would be independent of the detailed dynamical processes responsible for that transport and depend primarily on the distribution of incoming solar radiation and the mean planetary albedo. The authors find that in warm climates in which there is no ice, Stone’s result is a useful guide. In cold climates with significant polar ice caps, however, meridional gradients in albedo significantly affect the absorption of solar radiation and need to be included in any detailed calculation or discussion of total heat transport. Since the meridional extent of polar ice caps is sensitive to details of atmospheric and oceanic circulation, these cannot be ignored. Finally, what has been learned is applied to a study of the total heat transport estimated from the Earth Radiation Budget Experiment (ERBE) data.
Error Growth in a Whole Atmosphere Climate Model
Authors: Liu H-L. , Sassi F. , Garcia R. R.
Published: July 2008

It has been well established that the atmosphere is chaotic by nature and thus has a finite limit of predictability. The chaotic divergence of initial conditions and the predictability are explored here in the context of the whole atmosphere (from the ground to the thermosphere) using the NCAR Whole Atmosphere Community Climate Model (WACCM). From ensemble WACCM simulations, it is found that the early growth of differences in initial conditions is associated with gravity waves and it becomes apparent first in the upper atmosphere and progresses downward. The differences later become more profound on increasingly larger scales, and the growth rates of the differences change in various atmospheric regions and with seasons—corresponding closely with the strength of planetary waves. For example, in December–February the growth rates are largest in the northern and southern mesosphere and lower thermosphere and in the northern stratosphere, while smallest in the southern stratosphere. The growth rates, on the other hand, are not sensitive to the altitude where the small differences are introduced in the initial conditions or the physical nature of the differences. Furthermore, the growth rates in the middle and upper atmosphere are significantly reduced if the lower atmosphere is regularly reinitialized, and the reduction depends on the frequency and the altitude range of the reinitialization.
Two Dynamical Core Formulation Flaws Exposed by a Baroclinic Instability Test Case
Authors: Williamson David L. , Olson Jerry G. , Jablonowski Christiane
Published: July 2008

Two flaws in the semi-Lagrangian algorithm originally implemented as an optional dynamical core in the NCAR Community Atmosphere Model (CAM3.1) are exposed by steady-state and baroclinic instability test cases. Remedies are demonstrated and have been incorporated in the dynamical core. One consequence of the first flaw is an erroneous damping of the speed of a zonally uniform zonal wind undergoing advection by a zonally uniform zonal flow field. It results from projecting the transported vector wind expressed in unit vectors at the arrival point to the surface of the sphere and is eliminated by rotating the vector to be parallel to the surface. The second flaw is the formulation of an a posteriori energy fixer that, although small, systematically affects the temperature field and leads to an incorrect evolution of the growing baroclinic wave. That fixer restores the total energy at each time step by changing the provisional forecast temperature proportionally to the magnitude of the temperature change at that time step. Two other fixers are introduced that do not exhibit the flaw. One changes the provisional temperature everywhere by an additive constant, and the other changes it proportionally by a multiplicative constant.
Micro-Mechanics of Failure (MMF) for Continuous Fiber Reinforced Composites
Authors: Sung Kyu Ha  , Kyo Kook Jin  , Yuanchen Huang
Published: July 2008

The micromechanics of failure was developed to predict the failure of continuous fiber reinforced composites. A micromechanical approach using unit cells of square and hexagonal arrays was employed to compute the micro stresses of constituents and at the fiber—matrix interface, which were used to determine the failure initiation of a unidirectional ply. The constituent properties include two tensile and compressive strengths of fiber and matrix, plus normal and shear strengths at the interface. The matrix and interfacial dominated strength properties are determined by matching the micro stresses at the constituent levels with the observed transverse tensile and compressive strengths on the macro ply level. The longitudinal shear failure is then expected to be a result of damage progression after initial failure. Based on the current MMF, in the graphite/epoxy considered in this study both transverse tensile and compressive failure are expected to occur via matrix failure. However, in the glass/epoxy the transverse tensile and compressive failures are respectively caused by matrix failure and interfacial tensile failure. These predictions are compared with predictions from other widely used failure criteria as well as experimental data. Lastly, we predicted the failure of laminates. Instead of using a unidirectional ply-based failure theory, starting with the fiber, matrix, and their interface will lead to a much simpler, more generic theory.
Practical Therapeutic Drug Management in HIV‐Infected Patients: Use of Population Pharmacokinetic Models Supplemented by Individualized Bayesian Dose Optimization
Authors: Neely Michael , Jelliffe Roger
Published: July 2008

Individualized, model‐based, target‐oriented optimal concentration‐controlled dosing of HIV medications can be beneficial to patients for whom there are limited dosing guidelines, such as children, adolescents, or patients with altered physiologic function. Barriers to this approach include lack of training, expertise, and access to appropriate software to assist the clinician. The authors present 4 illustrative clinical cases of HIV‐infected patients whose therapy was optimized using population pharmacokinetic models (here generated from published studies) and supplemented by individualized Bayesian adaptive control of dosage regimens as implemented in the MM‐USCPACK software. These 4 cases illustrate how clinicians can maximize therapeutic success in (1) patients with reduced drug clearance, (2) young adolescents transitioning to adult physiology, (3) patients with dose‐dependent toxicity, and (4) adolescents with limited therapeutic options.
Risk of cerebrovascular events in elderly users of antipsychotics
Authors: Kleijer BC , van Marum RJ , Egberts ACG , Jansen PAF , Knol W. , Heerdink ER
Published: July 2008

It has been shown that elderly patients with dementia treated with atypical and conventional antipsychotics have a twofold increased risk of cerebrovascular adverse events (CVAEs). To investigate the temporal relationship between exposure to antipsychotics and the risk of CVAE, a case-control analysis nested within a cohort of 26,157 community-dwelling patients (mean age 76 ± 9.7) with at least one antipsychotic prescription was conducted. Data were used from Dutch community pharmacies and hospital discharge records. Five hundred and eighteen cases of hospital admission for CVAE were identified. For each case, four randomly selected controls matched by sex and age were sampled from the cohort. To evaluate the temporal relationship between antipsychotic use and the occurrence of CVAE, two measures were used: the first being a current, recent or past user, and the second for the current users, the duration of use up to the index date. In addition, the cumulative exposure was assessed. Current and recent exposure to antipsychotics were associated with an increased risk of CVAE compared with non-users (odds ratio [OR] 1.7, CI 1.4—2.2). A strong temporal relationship was found; the OR for a history of use less than a week is 9.9 (5.7—17.2). The risk decreases in time and is comparable to non-users after 3 months of use (OR 1.0, CI 0.7—1.3). Cumulative exposure was not associated with an increase in risk. The risk of CVAE in elderly patients associated with antipsychotics is elevated especially during the first weeks of treatment. This risk decreases over time and is back on base level after 3 months of treatment. Chronic use is not associated with CVAE.
The effects of opioid receptor blockade on experimental panic provocation with CO 2
Authors: Esquivel G. , Fernández-Torre O. , Schruers KRJ , Wijnhoven LLW , Griez EJL
Published: July 2008

Several reports have linked, among other aspects, the role of an opioid system in respiratory physiology with underlying mechanisms of panic attacks. The involvement of the opioid system in experimental panic is to be further probed. This study aimed to determine whether opioid blockade would increase panic-related symptomatology on provocation with 35% CO2 inhaled by healthy volunteers. Participants in a double-blind, randomised crossover design orally received either 50 mg of naltrexone or placebo. Most subjects undertook a double inhalation of 35% CO2 one hour after pre-medication, and a separate group did so after five hours. The reactivity to CO2 and the symptoms elicited by naltrexone alone were measured. Among other findings, naltrexone pre-medication alone elicited significant increments in panic-related symptoms. Responses to CO2 were not significantly different between conditions in either group. These preliminary findings suggest that exposure to opioid blockade alone can potentially elicit symptoms that resemble panic, however, without modifying the response to experimental panic provocation with 35% CO2.
Advance Directive Decision Making Among Independent Community-Dwelling Older Adults
Authors: Sessanna Loralee , Jezewski Mary Ann
Published: July 2008

The purpose of this systematic review of health science literature was to examine the current state of science regarding advance directive decision making (ADDM) among independent community-dwelling older adults. Seventeen studies fitting study inclusion criteria established for the purpose of this systematic review were examined. Findings revealed that ADDM has predominantly been explored among widowed, divorced, or never married female Caucasian independent community-dwelling older adults aged 65 years and older possessing a high school level of education. Numerous older adult/health care provider barriers to advance directive discussion and completion were found to exist. There is a lack of research regarding ADDM among independent community-dwelling male older adults, older adults from various ethnic and cultural backgrounds, and older adults receiving lower levels of education. Study replication and the implementation of new studies are needed to strengthen the existing body of older adult, advance directive, evidence-based research.
Inclusion of Diverse Older Populations in Volunteering
Authors: Tang Fengyan , Morrow-Howell Nancy , Hong Songiee
Published: July 2008

As older adults volunteer in greater numbers, concerns are being expressed about the exclusion of older adults who have historically been marginalized from volunteering. This study identifies the importance of institutional facilitation of older adults in volunteer programs, especially for those of lower socioeconomic status. A questionnaire assessing the importance of institutional facilitation in volunteering was completed by 374 volunteers aged 60 years and older from a national sample. Institutional facilitation was measured by multidimensional items capturing role flexibility, compensation, recognition, and accommodation. Flexibility—especially, choice of activities and ability to set own schedule— was perceived as most important to volunteers. Low-income and non-White volunteers gave more importance to institutional facilitators of engagement. This study suggests that voluntary organizations can facilitate the inclusion of older adults from diverse backgrounds through increasing flexibility, compensation, and recognition.
Likely Errors When Linking Supplementary Homicide Report Records for Large U.S. Cities
Authors: Loftin Colin , McDowall David , Xie Min
Published: July 2008

When linking records from the Supplementary Homicide Report (SHR) with information from other sources, such as data from the U.S. Census Bureau, errors are likely to occur because police service areas in some cities do not match the political definitions of the cities. Also, errors may occur because different places have the same or similar names. This article illustrates the problem with six cities (Jacksonville, Honolulu, Indianapolis, Baton Rouge, Las Vegas, and Nashville) and explains how discrepancies can be identified and corrected.
The lateral mobility of cell adhesion molecules is highly restricted at septate junctions in Drosophila
Authors: Laval Monique , Bel Christophe , Faivre-Sarrailh Catherine
Published: July 2008

Background

A complex of three cell adhesion molecules (CAMs) Neurexin IV(Nrx IV), Contactin (Cont) and Neuroglian (Nrg) is implicated in the formation of septate junctions between epithelial cells in Drosophila. These CAMs are interdependent for their localization at septate junctions and e.g. null mutation of nrx IV or cont induces the mislocalization of Nrg to the baso-lateral membrane. These mutations also result in ultrastructural alteration of the strands of septate junctions and breakdown of the paracellular barrier. Varicose (Vari) and Coracle (Cora), that both interact with the cytoplasmic tail of Nrx IV, are scaffolding molecules required for the formation of septate junctions.

Results

We conducted photobleaching experiments on whole living Drosophila embryos to analyze the membrane mobility of CAMs at septate junctions between epithelial cells. We show that GFP-tagged Nrg and Nrx IV molecules exhibit very stable association with septate junctions in wild-type embryos. Nrg-GFP is mislocalized to the baso-lateral membrane in nrx IV or cont null mutant embryos, and displays increased mobile fraction. Similarly, Nrx IV-GFP becomes distributed to the baso-lateral membrane in null mutants of vari and cora, and its mobile fraction is strongly increased. The loss of Vari, a MAGUK protein that interacts with the cytoplasmic tail of Nrx IV, has a stronger effect than the null mutation of nrx IV on the lateral mobility of Nrg-GFP.

Conclusion

The strands of septate junctions display a stable behavior in vivo that may be correlated with their role of paracellular barrier. The membrane mobility of CAMs is strongly limited when they take part to the multimolecular complex forming septate junctions. This restricted lateral diffusion of CAMs depends on both adhesive interactions and clustering by scaffolding molecules. The lateral mobility of CAMs is strongly increased in embryos presenting alteration of septate junctions. The stronger effect of vari by comparison with nrx IV null mutation supports the hypothesis that this scaffolding molecule may cross-link different types of CAMs and play a crucial role in stabilizing the strands of septate junctions.
Childhood TB epidemiology and treatment outcomes in Thailand: a TB active surveillance network, 2004 to 2006
Authors: Lolekha Rangsima , Anuwatnonthakate Amornrat , Nateniyom Sriprapa , Sumnapun Surin , Yamada Norio , Wattanaamornkiat Wanpen , Sattayawuthipong Wanchai , Charusuntonsri Pricha , Sanguanwongse Natpatou , Wells Charles D , Varma Jay K
Published: July 2008

Background

Of the 9.2 million new TB cases occurring each year, about 10% are in children. Because childhood TB is usually non-infectious and non-fatal, national programs do not prioritize childhood TB diagnosis and treatment. We reviewed data from a demonstration project to learn more about the epidemiology of childhood TB in Thailand.

Methods

In four Thai provinces and one national hospital, we contacted healthcare facilities monthly to record data about persons diagnosed with TB, assist with patient care, provide HIV counseling and testing, and obtain sputum for culture and susceptibility testing. We analyzed clinical and treatment outcome data for patients age < 15 years old registered in 2005 and 2006.

Results

Only 279 (2%) of 14,487 total cases occurred in children. The median age of children was 8 years (range: 4 months, 14 years). Of 197 children with pulmonary TB, 63 (32%) were bacteriologically-confirmed: 56 (28%) were smear-positive and 7 (4%) were smear-negative, but culture-positive. One was diagnosed with multi-drug resistant TB. HIV infection was documented in 75 (27%). Thirteen (17%) of 75 HIV-infected children died during TB treatment compared with 4 (2%) of 204 not known to be HIV-infected (p < 0.01).

Conclusion

Childhood TB is infrequently diagnosed in Thailand. Understanding whether this is due to absence of disease or diagnostic effort requires further research. HIV contributes substantially to the childhood TB burden in Thailand and is associated with high mortality.
AFP, PIVKAII, GP3, SCCA-1 and follisatin as surveillance biomarkers for hepatocellular cancer in non-alcoholic and alcoholic fatty liver disease
Authors: Beale Gary , Chattopadhyay Dipankar , Gray Joe , Stewart Stephen , Hudson Mark , Day Christopher , Trerotoli Paolo , Giannelli Gianluigi , Manas Derek , Reeves Helen
Published: July 2008

Background

The incidence and mortality of hepatocellular cancer (HCC) complicating alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD) is rising in western societies. Despite knowing the at risk populations for HCC development, the lack of sensitive and specific means of surveillance hampers disease detection at curable stages. The most widely used serum HCC marker is alpha-fetoprotein (AFP), while PIVKA-II, glypican-3 (GP3) and Squamous Cell Carcinoma Antigen -1 (SCCA-1) have been proposed as new biomarkers. Assessment of these HCC biomarkers has largely been performed in patients with viral hepatitis. We conducted a cross sectional study assessing the value of these serum proteins, as well a novel candidate biomarker -follistatin – in patients with HCC arising on a background of ALD or NAFLD.

Methods

Pre-treatment serum samples from 50 patients with HCC arising on a background of ALD (n = 31) or NAFLD (n = 19) were assessed by specific ELISA assay for PIVKAII, Glypican-3, SCCA-1 and Follistatin. Results were compared and contrasted with a control patient group with biopsy proven steatohepatitis-related cirrhosis (n = 41). The diagnostic accuracy of each of the candidate biomarkers was evaluated using receiver operating characteristic (ROC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). Performance was compared to that of the established biomarker, AFP.

Results

Serum levels of all proteins were assessed by specific ELISA assays. GP3, SCCA-1 and follistatin had no HCC surveillance benefit in these patients. AFP and PIVKAII were superior to the other markers, particularly in combination.

Conclusion

We conclude that while novel means of surveillance are urgently required, the combination of AFP and PIVKAII for HCC is an improvement on AFP alone in ALD/NAFLD patients. Furthermore, our data in this homogenous subset of patients- particularly that confirming no role for SCCA-1 – suggests that the choice of optimal biomarkers for HCC surveillance may be determined by the aetiology of underlying chronic liver disease.
The Sertindole Safety Survey: A retrospective analysis under a named patient use programme in Europe
Authors: Lançon Christophe , Toumi Mondher , Sapin Christophe , Hansen Karina
Published: July 2008

Background

After sertindole's suspension, health authorities established a specific named-patient use (NPU) programme in order to supply sertindole to patients who did not respond to or did not tolerate alternative treatments. This programme provided the possibility of prospectively following an exhaustive cohort of patients treated with sertindole after its suspension. A survey was performed to assess sertindole's modalities of prescription, assess and document any serious adverse events (SAEs), and assess the mortality rate within the NPU cohort.

Methods

The study comprised a survey of sertindole-treated patients in eleven European countries. All patients treated with sertindole within the NPU programme were eligible for the study.

Results

1,432 patients were included in the study. The reason for sertindole prescription was lack of efficacy (approximately 50%) or adverse events (approximately 20%) of other antipsychotic treatments. The mean sertindole dose was 13.4 mg daily. Lack of efficacy and adverse events were reported as reasons for sertindole discontinuation.

A total of 97 SAEs were recorded, including ten fatal outcomes, which occurred during the study period or within thirty days after sertindole discontinuation. The all-cause mortality rate was 0.51 per 100 Person-Years of Exposure (95% Poisson confidence interval: 0.23–0.97). QTc prolongation was reported in 15 patients (1.05% of total patients), being a rate of 0.85 per 100 Person-Years of Exposure [95% CI: 0.48–1.41].

Conclusion

Although prescribing and supplying sertindole were subject to administrative constraints, a significant number of patients were treated with sertindole, thus supporting the need for sertindole in specific cases.

Trial registration number

Not applicable.
Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells
Authors: Vacharaksa Anjalee , Asrani Anil C , Gebhard Kristin H , Fasching Claudine E , Giacaman Rodrigo A , Janoff Edward N , Ross Karen F , Herzberg Mark C
Published: July 2008

Background

Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner.

Results

To study the fate of HIV-1, immortalized oral keratinocytes (OKF6/TERT-2; TERT-2 cells) were characterized for the fate of HIV-specific RNA and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1gag RNA was detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2 cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Δenv-EGFP. AZT inhibited EGFP expression in a dose-dependent manner, suggesting that viral replication can be supported if receptors are bypassed. Within 3 h post inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not detectable up to 72 h post inoculation, suggesting that HIV replication may abort and that infection is non-productive. Within 48 h post inoculation, however, virus harbored by CD4 negative TERT-2 cells trans infected co-cultured peripheral blood mononuclear cells (PBMCs) or MOLT4 cells (CD4+ CCR5+) by direct cell-to-cell transfer or by releasing low levels of infectious virions. Primary tonsil epithelial cells also trans infected HIV-1 to permissive cells in a donor-specific manner.

Conclusion

Oral keratinocytes appear, therefore, to support stable non-replicative integration, while harboring and transmitting infectious X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.
FISH mapping of Philadelphia negative BCR/ABL1 positive CML
Authors: Virgili Anna , Brazma Diana , Reid Alistair G , Howard-Reeves Julie , Valgañón Mikel , Chanalaris Anastasios , De Melo Valeria AS , Marin David , Apperley Jane F , Grace Colin , Nacheva Ellie P
Published: July 2008

Background

Chronic myeloid leukaemia (CML) is a haematopoietic stem cell disorder, almost always characterized by the presence of the Philadelphia chromosome (Ph), usually due to t(9;22)(q34;q11) or its variants. The Ph results in the formation of the BCR/ABL1 fusion gene, which is a constitutively activated tyrosine kinase. Around 1% of CML patients appear to have a Ph negative karyotype but carry a cryptic BCR/ABL1 fusion that can be located by fluorescence in situ hybridisation (FISH) at chromosome 22q11, 9q34 or a third chromosome. Here we present FISH mapping data of BCR and ABL1 flanking regions and associated chromosomal rearrangements in 9 Ph negative BCR/ABL1 positive CML patients plus the cell line CML-T1.

Results

BCR/ABL1 was located at 9q34 in 3 patients, 22q11 in 5 patients and CML-T1 and 22p11 in 1 patient. In 3 of 6 cases with the fusion at 22q11 a distal breakpoint cluster was found within a 280 Kb region containing the RAPGEF1 gene, while in another patient and the CML-T1 the distal breakpoint fell within a single BAC clone containing the 3' RXRA gene. Two cases had a duplication of the masked Ph while genomic deletions of the flanking regions were identified in 3 cases. Even more complex rearrangements were found in 3 further cases.

Conclusion

BCR/ABL1 formation resulted from a direct insertion (one step mechanism) in 6 patients and CML-T1, while in 3 patients the fusion gene originated from a sequence of rearrangements (multiple steps). The presence of different rearrangements of both 9q34 and 22q11 regions highlights the genetic heterogeneity of this subgroup of CML. Future studies should be performed to confirm the presence of true breakpoint hot spots and assess their implications in Ph negative BCR/ABL1 positive CML.
Paraganglioma-like dermal melanocytic tumor: a case report
Authors: Sarma Deba P , Teruya Bryan , Wang Bo
Published: July 2008

Paraganglioma-like dermal melanocytic tumor is a rare subtype of benign dermal melanocytic tumors. Its histopathologic features resemble those of paraganglioma, but the immunostaining characteristics are those of melanocytic lesions.

We report a case of a 60-year-old male with a paraganglioma-like dermal melanocytic tumor of his left cheek and briefly review the English literature.
Regulator of G Protein Signaling-4 Controls Fatty Acid and Glucose Homeostasis
Authors: Iankova Irena , Chavey Carine , Clapé Cyrielle , Colomer Claude , Guérineau Nathalie C. , Grillet Nicolas , Brunet Jean-François , Annicotte Jean-Sébastien , Fajas Lluis
Published: July 2008

Circulating free fatty acids are a reflection of the balance between lipogenesis and lipolysis that takes place mainly in adipose tissue. We found that mice deficient for regulator of G protein signaling (RGS)-4 have increased circulating catecholamines, and increased free fatty acids. Consequently, RGS4−/− mice have increased concentration of circulating free fatty acids; abnormally accumulate fatty acids in liver, resulting in liver steatosis; and show a higher degree of glucose intolerance and decreased insulin secretion in pancreas. We show in this study that RGS4 controls adipose tissue lipolysis through regulation of the secretion of catecholamines by adrenal glands. RGS4 controls the balance between adipose tissue lipolysis and lipogenesis, secondary to its role in the regulation of catecholamine secretion by adrenal glands. RGS4 therefore could be a good target for the treatment of metabolic diseases.
Origin and shaping of the laterality organ in zebrafish
Authors: Oteíza Pablo , Köppen Mathias , Concha Miguel L. , Heisenberg Carl-Philipp
Published: July 2008

Handedness of the vertebrate body plan critically depends on transient embryonic structures/organs that generate cilia-dependent leftward fluid flow within constrained extracellular environments. Although the function of ciliated organs in laterality determination has been extensively studied, how they are formed during embryogenesis is still poorly understood. Here we show that Kupffer's vesicle (KV), the zebrafish organ of laterality, arises from a surface epithelium previously thought to adopt exclusively extra-embryonic fates. Live multi-photon confocal imaging reveals that surface epithelial cells undergo Nodal/TGFβ signalling-dependent ingression at the dorsal germ ring margin prior to gastrulation, to give rise to dorsal forerunner cells (DFCs), the precursors of KV. DFCs then migrate attached to the overlying surface epithelium and rearrange into rosette-like epithelial structures at the end of gastrulation. During early somitogenesis, these epithelial rosettes coalesce into a single rosette that differentiates into the KV with a ciliated lumen at its apical centre. Our results provide novel insights into the morphogenetic transformations that shape the laterality organ in zebrafish and suggest a conserved progenitor role of the surface epithelium during laterality organ formation in vertebrates.
The History and Development of the Human Genetics Society of Australasia
Authors: Sutherland Grant R.
Published: July 2008

The Human Genetics Society of Australasia is a vibrant professional society with more than 900 members that promotes and regulates the practice of human and medical genetics in Australia and New Zealand. The growth of human genetics was stimulated by the development of diagnostic clinical cytogenetics laboratories in the early to mid 1960s. This coincided with the recognition by medical specialists, mainly pediatricians, that genetic disorders, especially inborn errors of metabolism and birth defects, were of clinical interest and potentially challenging areas for their skills. The organization of professionals in human genetics was slow to evolve. There was an early Western Australian Human Genetics Society, and the cytogenetics community had begun to meet annually from about 1966 but was coordinated by a mailing list rather than as a formal organization. In 1976, as part of the celebrations of the Centenary Year of the Adelaide Children's Hospital, a clinical genetics meeting involving several high profile international speakers and most of the senior medical geneticists in Australia and New Zealand along with the annual meeting of the loose-knit cytogeneticists group agreed that a small working group be charged with setting up a Human Genetics Society. The society was formally incorporated in South Australia in 1977.
Facing Death: Buddhist and Western Hospice Approaches
Authors: Baugher John Eric
Published: July 2008

This article draws on ethnographic data to examine how moral person‐hood, emotions, and social relationships are constructed quite differently within two organizations with the similar goal of holistically caring for the dying. The analysis shows how the moral rhetoric and related practices at a mainstream hospice encourage volunteers to esteem a static conception of the self‐as‐character, whereas the Buddhist approach requires volunteers to engage in a process of transcending a self that is continually being worked on. The analysis points to paradoxes in the hospice conceptions of a “good death” and offers critical reflection on the assumption that Western and Buddhist approaches to hospice care are largely equivalent. Organizational, structural, and phenomenological strands of symbolic interactionist thought are drawn on to interpret these findings.
Grappling with the Medicated Self: The Case of ADHD College Students
Authors: Loe Meika , Cuttino Leigh
Published: July 2008

Drawing on interview data, this article is a case study of the “medicated self.” Specifically, we analyze how ADHD‐diagnosed college students construct how they are shaped by the behavioral effects of medicine. Students may perceive that pharmaceutical enhancement is necessary in the context of a competitive academic ethic. In this context something akin to Lareau's concept of concerted cultivation thrives as students practice what we call concerted medicalization in an attempt to literally embody the academic ideal. However, while medicine may enable students to manage academic performance and take control of “disordered bodies,” many remain uneasy about the extent to which they feel controlled by a drug. In the context of medical ambivalence, ADHD students engage in reflexive identity management and strategic pharmaceutical use to achieve some semblance of self‐control and self‐preservation during their college years. As their college education comes to a close, many prepare to return to what they construct as their “authentic,” nonmedicated selves as they enter the work world.