bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis and validation of Challenging Minisatellite Payload (CHAMP) radio occultation data
Authors: Gorbunov M. E. , Kornblueh L.
Published: September 2003

We performed statistical comparisons of data from Challenging Minisatellite Payload (CHAMP) with European Centre for Medium‐Range Weather Forecasting (ECMWF) analyses. Our data processing technique includes: (1) radio holographic (radio optics) and canonical transform analysis of wave fields, (2) visualization of the local spatial spectra of wave fields for interactive data quality control, (3) ionospheric correction and noise reduction based on statistical optimization, (4) Abel inversion, and (5) comparison of CHAMP and ECMWF data based on forward modeling and inversion of artificial radio occultation data. In the tropics and midlatitudes at heights below 10 km, the CHAMP‐ECMWF differences are significantly greater than the GPS Meteorology (GPS/MET)‐ECMWF differences. Because big systematic negative differences between observed and simulated refraction angles are also observed in this region, we can explain that by poor quality of the CHAMP data in multipath regions due to signal tracking errors. Elsewhere, systematic CHAMP‐ECMWF differences do not exceed 1 K in the tropics and polar latitudes, and 0.5 K in midlatitudes, and deviations of CHAMP data from ECMWF analyses are smaller than those of GPS/MET data. This can be explained by enhancement in the latest ECMWF analyses.
Use of tritium and helium to define groundwater flow conditions in Everglades National Park
Authors: Price René M. , Top Zafer , Happell James D. , Swart Peter K.
Published: September 2003

The concentrations of tritium (3H) and helium isotopes (3He and 4He) were used as tracers of groundwater flow in the surficial aquifer system (SAS) beneath Everglades National Park (ENP), south Florida. From ages determined by 3H/3He dating techniques, groundwater within the upper 28 m originated within the last 30 years. Below 28 m, waters originated prior to 30 years before present with evidence of mixing at the interface. Interannual variation of the 3H/3He ages within the upper 28 m was significant throughout the 3 year investigation, corresponding with varying hydrologic conditions. In the region of Taylor Slough Bridge, younger groundwater was consistently detected below older groundwater in the Biscayne Aquifer, suggesting preferential flow to the lower part of the aquifer. An increase in 4He with depth in the SAS indicated that radiogenic 4He produced in the underlying Hawthorn Group migrates into the SAS by diffusion. Higher Δ4He values in brackish groundwaters compared to fresh waters from similar depths suggested a possible enhanced vertical transport of 4He in the seawater mixing zone. Groundwater salinity measurements indicated the presence of a wide (6–28 km) seawater mixing zone. Comparison of groundwater levels with surface water levels in this zone indicated the potential for brackish groundwater discharge to the overlying Everglades surface water.
Effects of local dispersion and sampling volume on the evolution of concentration fluctuations in aquifers
Authors: Andričević Roko
Published: September 2003

The evolution of concentration variance σc2 for conservative solutes in aquifers is presented by accounting for advection heterogeneity, local dispersion, and sampling volume. The concentration variance distribution is obtained by scaling the zero local dispersion form of σc2. The scaling function results from the local dispersion and it is derived in a closed integral form such that it satisfies the measure of total concentration variance, obtained from the Eulerian mass balance using spatially integrated concentration moments. The use of spatially integrated concentration moments avoids the need to apply closing hypothesis on joint moments between velocity and concentration field. This study finds that sampling volume and local dispersion act as a smoothing mechanism on the concentration fluctuations. Contrary to the sampling volume, the smoothing due to the local dispersion is a slow occurring process compared to the advection and increases with transport time. At early stage of transport, the source size, its orientation with respect to the mean flow, and size of the sampling volume are key factors in determining the magnitude of concentration variance. The local dispersion becomes a dominant factor at the later stage and its influence on collected samples is significantly reduced by the presence of sampling volume. The local dispersion dimensionless number is introduced as an indicator for local dispersion importance in modeling the evolution of concentration fluctuations in the subsurface (in the absence of sampling volume). The presented model for concentration variance compares favorably with field data and numerical simulations.
Role of smoking and HbA1c level in periodontitis among insulin‐dependent diabetic patients
Authors: Syrjälä Anna‐Maija H. , Ylöstalo Pekka , Niskanen Mirka C. , Knuuttila Matti L. E.
Published: September 2003

Objectives:  The aim was to analyse the role of smoking and HbA1c level in attachment loss (AL) and probing depths (PDs) among insulin‐dependent diabetic patients.

Material and Methods:  The study subjects were selected from a group of 149 insulin‐dependent diabetic patients and included 64 patients (39 men and 25 women) aged 30 years or older. Data were obtained from patient records and by clinical examination. The outcome variables were the number of sites with AL and PDs of 5–9 mm. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated using Poisson regression models. RR was adjusted for the number of teeth, dental calculus and age.

Results:  RR for AL among the smokers was 4.15 (95% CI: 2.30–7.63) and that for PD among the smokers was 7.96 (95% CI: 4.91–13.19). HbA1c was not related to AL or PD. Among smokers with HbA1c>8.5, RR for AL was 12.34 (95% CI: 4.14–39.35), but RR was not elevated for PD.

Conclusions:  It can be concluded that the poor metabolic control together with smoking is extremely detrimental for AL.
Clinical course of chronic periodontitis
Authors: Schätzle Marc , Löe Harald , Bürgin Walter , Ånerud Åge , Boysen Hans , Lang Niklaus P.
Published: September 2003

Objectives:  The purpose of this study was to determine the influence of long‐standing gingival inflammation on periodontal attachment loss. On the basis of repeated examinations, the present report describes the influence of gingival inflammation on the initiation of periodontitis from 16 to 59 years of age.

Material and Methods:  The data originated from a 26‐year longitudinal study of Norwegian males, who practiced daily oral home care and received state‐of‐the‐art dental care. The initial examination included 565 individuals. Subsequent examinations took place in 1971, 1973, 1975, 1981, 1988 and 1995. Thus, the study covers the age range of 16–59 years. All tooth sites were divided into four categories according to their history of gingival inflammation over the entire observation period: sites always scoring GI=0, GI=1 and GI=2 sites (GI=gingival index). Sites disclosing various GI scores at different observation periods were not considered.

Results:  The mean cumulative attachment loss for non‐inflamed (GI=0) sites in individuals approaching 60 years of age was 1.94 mm. Sites always scoring GI=1 yielded 2.42 mm, and sites that always scored GI=2 exhibited 3.31 mm of periodontal attachment loss. At interproximal sites of all three groups where gingival trauma was assumed to be minimal or non‐existent, only very few sites expressed attachment loss due to gingival recession (2–4%). At interproximal sites always scoring GI=0, 20% loss of attachment was in the form of pocket formation by 59 years of age. The GI=1 and the GI=2 cohorts exhibited attachment loss with pocket formation in 28% and 54%, respectively.

Conclusion:  This study has shown that, as men approach 60 years of age, gingival sites that throughout the 26 years of observation bled on probing had approximately 70% more attachment loss than sites that were consistently non‐inflamed (GI=0). Before 40 years of age, there was a slight increase in periodontal attachment loss due to pocket formation, but after this, the frequency increased significantly. Loss of attachment due to gingival recession was very small in all three groups.The fact that sites with non‐inflamed gingiva also exhibited some loss of attachment and pocket formation may be explained by fluctuation in the variations of tissue status during long observation intervals combined with the presence of subclinical inflammation.
Effect of various chlorhexidine regimens on salivary bacteria and de novo plaque formation
Authors: Sekino Satoshi , Ramberg Per , Uzel Naciye Guzin , Socransky Sigmund , Lindhe Jan
Published: September 2003

Aim: The aim of the present experiment was to study the effect of different chlorhexidine regimens on the number of bacteria in saliva, and on de novo plaque formation.

Material and Methods: Ten subjects with gingivitis, but no signs of destructive periodontitis, were recruited. Following a screening examination, the volunteers were given oral hygiene instruction, meticulous scaling and professional mechanical tooth cleaning (PTC). The PTC was repeated once every 3 days during a 2‐week period to establish healthy gingival conditions. The study was designed as a double‐blind cross‐over clinical trial including three phases. Each experimental phase comprised one preparatory period of 7 days and one plaque accumulation period (no oral hygiene measures) of 4 days. During all preparatory periods, the volunteers (i) performed mechanical tooth cleaning using a toothbrush and dentifrice and (ii) were, in addition, given two sessions of PTC. The final PTC was delivered after bacterial sampling had been made on Day 0. Preparatory period A: the participants continued the self‐performed plaque control regimen that employed only mechanical means. Preparatory period B: the participants were in addition instructed to rinse and gargle, twice daily, with a 0.2% chlorhexidine mouthrinse. Preparatory period C: in addition to the above, the participants were instructed to brush the dorsum of the tongue for 60 s, twice daily, with a 1.0% chlorhexidine gel. Following each plaque accumulation period, there was a 10‐day washout interval. The presence and amount of dental plaque (QHI) was scored after 1, 2 and 4 days of no oral hygiene. Samples of saliva were obtained on Day 0 and after 1 and 2 days. The samples were placed on Brucella agar plates and incubated (anaerobically) for 5 days. The total number of colony‐forming units was determined and used to estimate the density of bacteria in saliva.

Results: In period A, the mean QHI increased from 1.0 (Day 1) to 1.4 (Day 2) and 2.1 (Day 4). The corresponding scores for periods B and C were 0.5, 0.8, 1.6 and 0.3, 0.8, 1.2, respectively. At all re‐examination intervals more plaque formed during period A than during periods B and C. Further, during period C, less plaque formed than that during period B. Saliva samples from Day 0 in period A contained a larger number of TVC than the baseline samples in periods B and C. There was no significant difference in TVC among the groups on Day 2.

Conclusion: The daily use of chlorhexidine as an adjunct to mechanical tooth cleaning markedly reduced the number of microorganisms that could be detected in saliva. The number of salivary bacteria may have influenced the amount of plaque that formed during an early phase of no oral hygiene.
Trauma, Dissociation, and Posttraumatic Stress Disorder in Female Borderline Patients With and Without Substance Abuse Problems
Authors: Van Den Bosch Louisa M. C. , Verheul Roel , Langeland Willie , Van Den Brink Wim
Published: September 2003

Objective: To examine the associations of childhood traumatic experiences and childhood neglect with dissociative experiences and posttraumatic stress disorder (PTSD) in a population of female borderline personality disorder (BPD) patients with and without substance abuse.

Method: The sample included 64 female patients with BPD. Childhood traumatic experiences and childhood neglect were measured using the Structured Trauma Interview, dissociative experiences with the Dissociative Experiences Scale, and PTSD with the Structured Clinical Interview for DSM-IV.

Results: In general, dissociation scores were higher among those with a history of childhood trauma and neglect, in particular among those who reported both sexual and physical abuse before age 16, more than one perpetrator and severe maternal dysfunction. The prevalence of PTSD was clearly associated with the severity of childhood sexual abuse (CSA) in terms of the occurrence of penetration during CSA, intrafamilial CSA, a duration of CSA longer than 1 year and more than one perpetrator. Comorbid substance abuse problems modified the observed associations such that the associations mentioned above were also present or even more pronounced among those without substance abuse, whereas no associations were found in those with substance abuse.

Conclusions: The results suggest a moderately strong association between childhood trauma and neglect with dissociation and PTSD. However, trauma-dissociation and trauma-PTSD links were only observed among BPD patients without addictive problems. The findings are largely consistent with the literature. Potential explanations for the lack of a trauma-dissociation and trauma-PTSD link in the addicted subgroup are discussed.
Which Anxiety Disorders May Differentiate Attention Deficit Hyperactivity Disorder, Combined Type with Dysthymic Disorder from Attention Deficit Hyperactivity Disorder, Combined Type Alone?
Authors: Vance Alasdair , Harris Katrina , Boots Marilyn , Talbot Jessica , Karamitsios Mary
Published: September 2003

Objective: Attention deficit hyperactivity disorder, combined type (ADHD-CT), dysthymic disorder, and anxiety disorders frequently co-occur in primary school age children, although there have been no published data describing their association. We investigated the association of anxiety, defined from a parent or child perspective, with primary school-age children with ADHD-CT with and without dysthymic disorder.

Method: One hundred and forty-six medication naïve children with ADHD-CT were studied. Two groups with and without dysthymic disorder were formed to compare parent and child reports of anxiety, using categorical and continuous measures of anxiety, using logistic regression.

Results: Separation anxiety disorder and social phobia were associated with primary school-age children with ADHD-CT and dysthymic disorder, compared to children with ADHD-CT without dysthymic disorder.

Conclusions: The recognition of dysthymic disorder and anxiety disorders and their management in primary school-age children with ADHD-CT is generally poorly understood. The identification and elucidation of composite anxiety and depressive phenomena that may be systematically investigated through longitudinal studies of epidemiologically derived samples is needed in this particular group of children.
A Population-Based Study of Help-Seeking for Self-Harm in Young Adults
Authors: Nada-Raja Shyamala , Morrison Dianne , Skegg Keren
Published: September 2003

Objective: To examine help-seeking for self-harm in a population-based sample of young adults.

Method: Nine hundred and sixty-five participants aged 26 years were interviewed about help-seeking and barriers to help-seeking for a range of self-harmful behaviours. Self-harm included the traditional methods of suicide (ICD-9 self-harm) and other self-harmful behaviours such as self-battery and self-biting.

Results: Just over half of the 25 in the ICD-self-harm group (based on ICD-9 self-harm criteria) and one-fifth of the 119 in the other self-harmful behaviour group had sought professional help. Counsellors, psychologists, and general practitioners were the commonest sources of help. Most participants rated help received from health services favourably, however, emergency services were rated less favourably than other health services. Among 77 self-harm participants who did not seek help, just over one-third reported attitudinal barriers.

Conclusions: To encourage help-seeking by young adults who self-harm, especially young men who are at high risk for self-harm and suicide, it may be necessary to identify ways to reduce attitudinal barriers.
Clinical and Parenting Skills Outcomes Following Joint Mother–Baby Psychiatric Admission
Authors: Salmon Margaret , Abel Kathryn , Cordingley Lis , Friedman Trevor , Appleby Louis
Published: September 2003

Objective: To examine maternal clinical and parenting outcomes as a function of diagnosis following joint mother–baby admission; to identify the associations of poor outcome.

Method: Demographic and clinical information was collected on 1081 joint mother–baby admissions, including 224 women with schizophrenia, 155 with bipolar disorder and 409 with non-psychotic depression. Information was based on clinical judgements of senior staff in participating units using the Marcé checklist. Predictors of poor maternal clinical outcome, practical problems in baby care, poor emotional responsiveness to infant and perceived risk of harm to baby were identified by logistic regression.

Results: Good clinical outcome was reported in 848 (78%) cases. On each parenting outcome, good outcome was reported in at least 80%. The predictors of poor outcome were similar for all four outcomes. These were a diagnosis of schizophrenia, behavioural disturbance, low social class and either psychiatric illness in the woman's partner or a poor relationship with the partner. Of those with poor outcome on all four variables, 66% suffered with schizophrenia. Women with schizophrenia showed more behavioural disturbance, were more likely to experience hallucinations and delusions, and were more likely to be of low social class. They were also less likely to have a partner and more likely to have a partner with a psychiatric illness.

Conclusions: Clinical and parenting outcomes, as reported by clinical staff, are usually good following joint mother–baby admission. Women with schizophrenia may need particular measures to improve their parenting. A marital approach to treatment, directed at the woman's relationship with her partner or the latter's own mental health may improve outcome.
An audit of antiretroviral treatment use in HIV‐infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use
Authors: Sabin CA , Lampe FC , Chaloner C , Madge SJ , Lipman MCI , Youle M , Phillips AN , Johnson MA
Published: September 2003

Objective

To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines.

Methods

All patients under follow‐up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow‐up, were used to identify which patients should be receiving HAART according to the guidelines.

Results

One thousand two hundred and sixty‐four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/µL and over 80% had previously had a viral load above 4 log10 HIV‐1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty‐five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it.

Conclusion

Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.
Determinants of adherence to highly active antiretroviral therapy (HAART) in Chinese HIV/AIDS patients
Authors: Fong OW , Ho CF , Fung LY , Lee FK , Tse WH , Yuen CY , Sin KP , Wong KH
Published: September 2003

Objective

Drug adherence is crucial to the success of highly active antiretroviral therapy (HAART) in the treatment of HIV disease. Adherence to HAART and its determinants may, however, differ across HIV/AIDS populations.

Methods

We retrospectively studied drug adherence by self‐report in HIV‐1 infected Chinese patients who have been on HAART for at least 1 year as at the end of year 2000. HAART is defined as three or more antiretrovirals with at least one protease inhibitor or non‐nucleoside analogue reverse transcriptase inhibitor.

Results

The last drug adherence level assessed by self‐report in 161 Chinese patients were: grade A (100%) – 130, 80.7%; grade B (95–99%) – 25, 15.5%; grade C (90–94%) – three, 1.9% and grade D (< 90%) – three, 1.9%. Patients with full adherence were more likely to have undetectable (< 500 copies/mL) plasma virus level (adjusted OR, 4.22; 95% CI, 1.75–12.33). Patients' demographics, HIV disease status and antiretroviral regimen did not affect adherence. Partial drug adherence was, however, independently associated with the psychosocial factors of missing clinic appointments (adjusted OR, 3.13; 95% CI, 1.23–8.33), forgetfulness (adjusted OR, 4.55; 95% CI, 1.64–12.5) and a busy work life (adjusted OR, 6.67; 95% CI, 1.75–25).

Conclusion

There were similarities and differences in determinants affecting HAART adherence in Chinese compared with other patients. Psychosocial factors rather than HIV disease or treatment were more important factors in our Chinese patients. The relevance of patient populations and care setting for adherence to HAART shall be further studied.
Prevalence and Correlates of Recognized Depression in U.S. Nursing Homes
Authors: Jones Richard N. , Marcantonio Edward R. , Rabinowitz Terry
Published: September 2003

Objectives: To provide descriptive epidemiological information on identified depression in nursing home residents.

Design: Survey of the 1996 Medical Expenditure Panel Survey—Nursing Home Component (MEPS‐NHC).

Setting: Nine hundred fifty‐one nursing facilities.

Participants: Three thousand seven hundred ten noncomatose residents.

Measurements: Demographic characteristics and health care and functional data were collected using key informant interview and medical‐record review. Depression diagnoses were derived from Minimum Data Set (MDS) diagnoses and are nonspecific with regard to formal diagnostic criteria.

Results: The prevalence of identified depression was 20.3 cases per 100 residents (95% confidence interval=18.9–21.7). Younger age, female sex, marital status other than never married, white non‐Hispanic ethnicity, better cognitive functioning, heart disease, Parkinson's disease, and length of stay between 1 and 2 years were significantly and independently associated with a greater prevalence of identified depression.

Conclusion: The prevalence of identified depression in the MEPS‐NHC is lower than that previously estimated using formal diagnostic assessment techniques for threshold and subthreshold depressive states combined. Therefore, MDS‐identified depression may underestimate the burden of depression. Underrecognition may be particularly acute in black or African‐American residents, the oldest old, and the cognitively impaired. Further research on the relationship of MDS‐identified depression and depression identified through structured diagnostic interviews in broadly representative samples of nursing home residents is needed to expand the availability of descriptive epidemiological data, to help clarify the results of research making use of MDS data, and to suggest methods for optimizing clinical and administrative data systems.
The Effect of Evercare on Hospital Use
Authors: Kane Robert L. , Keckhafer Gail , Flood Shannon , Bershadsky Boris , Siadaty Mir Said
Published: September 2003

Objectives: To examine the use of hospital and related medical care services of a novel managed care program using nurse practitioners (NPs) and directed specifically at long‐stay nursing home residents.

Design: Quasi‐experimental posttest design with two control groups to minimize selection bias.

Setting: Nursing homes.

Participants: Evercare enrollees in five sites were compared with two sets of controls: nursing home residents in the same nursing homes who did not enroll in Evercare (control‐in) and residents of nursing homes that did not participate in Evercare (control‐out).

Measurements: Utilization data from Medicare and United Healthcare (the parent corporation for Evercare) were obtained for slightly more than 2 years. Patterns of use were assessed by calculating the monthly use rate for each group and aggregating to form annual rates. Usages addressed included hospital admissions and days, emergency room visits, therapy services, mental health services, and podiatry. Adjustments were made to correct for age, race, and sex. Because the groups differed in terms of the rate of cognitive impairment, the analysis was stratified on this variable.

Results: The incidence of hospitalizations was twice as high in control residents as in Evercare residents (4.63 and 4.67 per 100 enrollees per month vs 2.43 in the 15 months after census, P<.001). This difference corresponded to Evercare's use of intensive service days. The same pattern held for preventable hospitalizations (0.80 and 0.86 vs 0.28, P<.001). The pattern held when residents were stratified by cognitive status. On average, using a NP is estimated to save about $103,000 a year in hospital costs per NP.

Conclusion: The use of active primary care provided by NPs may have prevented the occurrence of some hospitalizable events, but its major effect was allowing cases to be managed more cost‐effectively.
The Mini‐Cog as a Screen for Dementia: Validation in a Population‐Based Sample
Authors: Borson Soo , Scanlan James M. , Chen Peijun , Ganguli Mary
Published: September 2003

Objectives: To test the Mini‐Cog, a brief cognitive screening test, in an epidemiological study of dementia in older Americans.

Design: A population‐based post hoc examination of the sensitivity and specificity of the Mini‐Cog for detecting dementia in an existing data set.

Setting: The Monongahela Valley in Western Pennsylvania.

Participants: A random sample of 1,119 older adults enrolled in the Monongahela Valley Independent Elders Survey (MoVIES).

Measurements: The effectiveness of the Mini‐Cog in detecting independently diagnosed dementia was compared with that of the Mini‐Mental State Examination (MMSE) and a standardized neuropsychological battery.

Results: The Mini‐Cog, scored by an algorithm as “possibly impaired” or “probably normal,” and the MMSE, at a cutpoint of 25, had similar sensitivity (76% vs 79%) and specificity (89% vs 88%) for dementia, comparable with that achieved using a conventional neuropsychological battery (75% sensitivity, 90% specificity).

Conclusion: When applied post hoc to an existing population, the Mini‐Cog was as effective in detecting dementia as longer screening and assessment instruments. Its brevity is a distinct advantage when the goal is to improve identification of older adults in a population who may be cognitively impaired. Prior evidence of good performance in a multiethnic community‐based sample further supports its validity in the ethnolinguistically diverse populations of the United States in which widely used cognitive screens often fail.
Early Virologic Response to Treatment With Peginterferon Alfa–2B Plus Ribavirin in Patients With Chronic Hepatitis C
Authors: Davis Gary L. , Wong John B. , McHutchison John G. , Manns Michael P. , Harvey Joann , Albrecht Janice
Published: September 2003

Interferon–based regimens for the treatment of chronic hepatitis C have become increasingly effective and are able to eradicate virus in more than one half of cases. Early identification of patients who will not respond is desirable because treatment might be stopped, thereby avoiding the expense and inconvenience of unnecessary therapy. We examined the accuracy of different degrees of viral inhibition during the early weeks of treatment (early virologic response [EVR]) with pegylated interferon alfa–2b and ribavirin (PEG/R) in identifying patients who would not respond to therapy. The best definition of EVR was a reduction in hepatitis C virus (HCV) RNA by at least 2 logs after the first 12 weeks of treatment compared with baseline. Between 69% and 76% of patients achieved this threshold, depending on the treatment regimen, and sustained virologic response (SVR) occurred in 67% to 80% of these patients. Patients who did not reach EVR did not respond to further therapy. If treatment had been stopped in patients without EVR, drug costs would have been reduced by more than 20%. In conclusion, early confirmation of viral reduction following initiation of antiviral therapy for chronic hepatitis C is worthwhile. It provides a goal to motivate adherence during the first months of therapy and a milepost at which to reassess the need for continued treatment. Most patients who are able to complete the first 12 weeks of therapy achieve EVR and have a high probability of SVR. Patients who fail to achieve EVR will not clear virus even if an additional 9 months of therapy is received. Therapy can be confidently discontinued in those cases.
Cyclooxygenase–2 Promotes Hepatocellular Carcinoma Cell Growth Through Akt Activation: Evidence for Akt Inhibition in Celecoxib–Induced Apoptosis
Authors: Leng Jing , Han Chang , Demetris Jake A. , Michalopoulos George K. , Wu Tong
Published: September 2003

Cyclooxygenase–2 (COX–2)–controlled prostaglandin (PG) metabolism recently has been implicated in the pathogenesis of hepatocellular carcinoma (HCC). However, the biologic role and molecular mechanism of COX–2–mediated PGs in the control of liver cancer growth have not been established. This study was designed to examine the direct effect of COX–2 and its inhibitor celecoxib on the growth control of liver cancer cells. Human HCC cell lines Hep3B and HepG2 transfected with COX–2 expression vector showed increased cell growth and enhanced phosphorylation of serine/threonine protein kinase B (Akt). The level of COX–2 expression and Akt phosphorylation is correlated positively in cultured HCC cells and human liver cancer tissues. Inhibition of Akt activation by phosphatidylinositol 3–kinase (PI3–kinase) inhibitor LY294002 significantly decreased the viability of Hep3B and HepG2 cells (P < .01). These results reveal a novel role of Akt activation in COX–2–induced HCC cell survival. Furthermore, HCC cells treated with the COX–2 inhibitor celecoxib showed significant reduction of Akt phosphorylation and marked morphologic and biochemical characteristics of apoptosis. Overexpression of COX–2 or addition of exogenous PGE2 partially prevented celecoxib–induced apoptosis (P < .01). In conclusion, our results suggest the involvement of COX–2–dependent and –independent mechanisms in celecoxib–mediated HCC cell apoptosis.
Upper Digestive Bleeding in Cirrhosis. Post–Therapeutic Outcome and Prognostic Indicators
Authors: D'Amico Gennaro , De Franchis Roberto
Published: September 2003

Several treatments have been proven to be effective for variceal bleeding in patients with cirrhosis. The aim of this multicenter, prospective, cohort study was to assess how these treatments are used in clinical practice and what are the posttherapeutic prognosis and prognostic indicators of upper digestive bleeding in patients with cirrhosis. A training set of 291 and a test set of 174 bleeding cirrhotic patients were included. Treatment was according to the preferences of each center and the follow–up period was 6 weeks. Predictive rules for 5–day failure (uncontrolled bleeding, rebleeding, or death) and 6–week mortality were developed by the logistic model in the training set and validated in the test set. Initial treatment controlled bleeding in 90% of patients, including vasoactive drugs in 27%, endoscopic therapy in 10%, combined (endoscopic and vasoactive) in 45%, balloon tamponade alone in 1%, and none in 17%. The 5–day failure rate was 13%, 6–week rebleeding was 17%, and mortality was 20%. Corresponding findings for variceal versus nonvariceal bleeding were 15% versus 7% (P = .034), 19% versus 10% (P = .019), and 20% versus 15% (P = .22). Active bleeding on endoscopy, hematocrit levels, aminotransferase levels, Child–Pugh class, and portal vein thrombosis were significant predictors of 5–day failure; alcohol–induced etiology, bilirubin, albumin, encephalopathy, and hepatocarcinoma were predictors of 6–week mortality. Prognostic reassessment including blood transfusions improved the predictive accuracy. All the developed prognostic models were superior to the Child–Pugh score. In conclusion, prognosis of digestive bleeding in cirrhosis has much improved over the past 2 decades. Initial treatment stops bleeding in 90% of patients. Accurate predictive rules are provided for early recognition of high–risk patients.
Infection with chronic hepatitis C virus and liver transplantation: A role for interferon therapy before transplantation
Authors: Thomas Ryan M. , Brems John J. , Guzman-Hartman Grace , Yong Sherri , Cavaliere Patricia , Van Thiel David H.
Published: September 2003

An analysis of the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplant Registry data shows that the greater the viral load at the time of transplantation, the more rapidly clinically evident posttransplantation hepatitis C virus (HCV) disease recurs. These data suggest that aggressive pretransplantation treatment of HCV might delay recurrent posttransplantation HCV disease and enhance posttransplantation survival. We have taken an aggressive approach to treating HCV infection pretransplantation with the use of high-dose (5 MU) daily interferon α2b in an effort to clear the virus before transplantation. A total of 27 patients with HCV-induced cirrhosis were seen and underwent transplantation at Loyola University Medical Center (Maywood, IL) between February 1997 and December 2001. There were 22 men and five women, with a mean age of 56 ± 2 years. The majority had genotype 1 disease (67%). Of the 27 patients, 7 had a baseline platelet count <50,000/mm3 and were excluded from interferon therapy. The remaining 20 were treated for a mean of 14 ± 2.5 (range, 0.5 to 33.5) months before orthotopic liver transplantation (OLT). Twelve (60%) responded to the therapy with serologic clearance of HCV before OLT. The mean time from initiation of therapy to the first negative qualitative polymerase chain reaction was 4.5 ± 1.5 (range, 0.5 to 12) months. Four of the 12 patients in whom the virus cleared did not have evidence of HCV recurrence after OLT, representing 20% of those treated and 33% of those who had HCV clearance before OLT. The duration of post-OLT freedom from HCV infection in these individuals has been 33.6 ± 11.3 (range, 0 to 47.4) months. These data suggest that with careful supervision, cirrhotic patients can tolerate high-dose interferon. In addition, a viral clearance can be achieved in a significant number of cirrhotic patients with high-dose interferon. One third of patients, in whom the HCV cleared before OLT, did not have evidence of disease recurrence after OLT. It is thus anticipated that with early and aggressive pre-OLT HCV therapy, possibly with the use of pegylated interferon, even better results may be obtained.
Liver transplantation with allografts from hepatitis B core antibody-positive donors: A new approach
Authors: Fábrega Emilio , García-Suarez Covadonga , Guerra Armando , Orive Aitor , Casafont Fernando , Crespo Javier , Pons-Romero Fernando
Published: September 2003

The enduring shortfall of organ donors has inspired the widespread utilization of hepatic allografts from donors with hepatitis B core antibodies in spite of the potential risk of transmitting hepatitis B virus (HBV) infection to the recipient. Here we report a protocol of naive recipients receiving livers from hepatitis B core antibody-positive donors. From November, 1999 to March, 2002, 77 liver transplantations were performed in 73 patients at our institution, 7 of whom received livers from hepatitis B core antibody-positive donors. All recipients received 10,000 U/d of intravenous HBIg for 7 days and 100 mg/d of lamivudine until we could obtain the HBV-DNA from the donor samples (serum and liver tissue). If the results of the HBV-DNA from the donor samples were positive, the patient would continue with prophylaxis and if they were negative we would finish the combined prophylaxis. After transplantation, HBV serologic markers and HBV-DNA by polymerase chain reaction (PCR) in serum and lymphocytes were tested in the recipients on the seventh, fifteenth, thirtieth, and ninetieth days as well as every 3 months after transplantation. All seven donor organs were negative for HBV-DNA in serum and liver tissue. Thus, we stopped the combined prophylaxis in all recipients (range, 7 to 10 days). None of the 7 patients developed de novo HBV infection over the 3-year study period (range, 9 to 36 months). Our approach is reasonably safe, and it appears to be very effective in the prevention of de novo HBV infection after liver transplantation
Compact covering mappings between Borel sets and the size of constructible reals
Authors: Debs Gabriel , Raymond Jean
Published: September 2003

We prove that the topological statement: “Any compact covering mapping between two Borel sets is inductively perfect" is equivalent to the set-theoretical statement:

“

∀
α
∈

ω
ω

,

ℵ
1

L
(
α
)

>

ℵ
1

“\,\forall \alpha \in \omega ^\omega ,\; \aleph _1^{L(\alpha )}>\aleph _1

".
Framings of knots satisfying differential relations
Authors: Hebda James , Tsau Chichen
Published: September 2003

This paper introduces the notion of a differential framing relation for knots in a three-dimensional manifold. There is a canonical map from the space of knots that satisfy a framing relation into the space of framed knots. Under reasonable assumptions this canonical map is a weak homotopy equivalence.
Eigenvalue and gap estimates for the Laplacian acting on 𝑝-forms
Authors: Guerini Pierre , Savo Alessandro
Published: September 2003

We study the gap of the first eigenvalue of the Hodge Laplacian acting on

p
p

-differential forms of a manifold with boundary, for consecutive values of the degree

p
p

. We first show that the gap may assume any sign. Then we give sufficient conditions on the intrinsic and extrinsic geometry to control it. Finally, we estimate the first Hodge eigenvalue of manifolds whose boundaries have some degree of convexity.
Asymptotics of the transition probabilities of the simple random walk on self-similar graphs
Authors: Krön Bernhard , Teufl Elmar
Published: September 2003

It is shown explicitly how self-similar graphs can be obtained as ‘blow-up’ constructions of finite cell graphsC^\hat C. This yields a larger family of graphs than the graphs obtained by discretising continuous self-similar fractals. For a class of symmetrically self-similar graphs we study the simple random walk on a cell graphC^\hat C, starting at a vertexvvof the boundary ofC^\hat C. It is proved that the expected number of returns tovvbefore hitting another vertex in the boundary coincides with the resistance scaling factor. Using techniques from complex rational iteration and singularity analysis for Green functions, we compute the asymptotic behaviour of thenn-step transition probabilities of the simple random walk on the whole graph. The results of Grabner and Woess for the Sierpiński graph are generalised to the class of symmetrically self-similar graphs, and at the same time the error term of the asymptotic expression is improved. Finally, we present a criterion for the occurrence of oscillating phenomena of thenn-step transition probabilities.
Semi-linear homology 𝐺-spheres and their equivariant inertia groups
Authors: Lü Zhi
Published: September 2003

This paper introduces an abelian group

H

Θ
V
G

H\Theta _V^G

for all semi-linear homology

G
G

-spheres, which corresponds to a known abelian group

Θ
V
G

\Theta _V^G

for all semi-linear homotopy

G
G

-spheres, where

G
G

is a compact Lie group and

V
V

is a

G
G

-representation with

dim
⁡

V
G

>
0

\dim V^G>0

. Then using equivariant surgery techniques, we study the relation between both

H

Θ
V
G

H\Theta _V^G

and

Θ
V
G

\Theta _V^G

when

G
G

is finite. The main result is that under the conditions that

G
G

-action is semi-free and

dim
⁡
V
−
dim
⁡

V
G

≥
3

\dim V-\dim V^G\geq 3

with

dim
⁡

V
G

>
0

\dim V^G >0

, the homomorphism

T
:

Θ
V
G

⟶
H

Θ
V
G

T: \Theta _V^G\longrightarrow H\Theta _V^G

defined by

T
(
[
Σ

]
G

)
=
⟨
Σ

⟩
G

T([\Sigma ]_G)=\langle \Sigma \rangle _G

is an isomorphism if

dim
⁡

V
G

≠
3
,
4

\dim V^G\not =3,4

, and a monomorphism if

dim
⁡

V
G

=
4

\dim V^G=4

. This is an equivariant analog of a well-known result in differential topology. Such a result is also applied to the equivariant inertia groups of semi-linear homology

G
G

-spheres.
Slopes of vector bundles on projective curves and applications to tight closure problems
Authors: Brenner Holger
Published: September 2003

We study different notions of slope of a vector bundle over a smooth projective curve with respect to ampleness and affineness in order to apply this to tight closure problems. This method gives new degree estimates from above and from below for the tight closure of a homogeneous

R
+

R_+

-primary ideal in a two-dimensional normal standard-graded algebra

R
R

in terms of the minimal and the maximal slope of the sheaf of relations for some ideal generators. If moreover this sheaf of relations is semistable, then both degree estimates coincide and we get a vanishing type theorem.
Backward stability for polynomial maps with locally connected Julia sets
Authors: Blokh Alexander , Oversteegen Lex
Published: September 2003

We study topological dynamics on unshielded planar continua with weak expanding properties at cycles for which we prove that the absence of wandering continua implies backward stability. Then we deduce from this that a polynomial

f
f

with a locally connected Julia set is backward stable outside any neighborhood of its attracting and neutral cycles. For a conformal measure

μ
\mu

this easily implies that one of the following holds: 1. for

μ
\mu

-a.e.

x
∈
J
(
f
)

x\in J(f)

,

ω
(
x
)
=
J
(
f
)

\omega (x)=J(f)

; 2. for

μ
\mu

-a.e.

x
∈
J
(
f
)

x\in J(f)

,

ω
(
x
)
=
ω
(
c
(
x
)
)

\omega (x)=\omega (c(x))

for a critical point

c
(
x
)

c(x)

depending on

x
x

.
Ideals of the cohomology rings of Hilbert schemes and their applications
Authors: Li Wei-Ping , Qin Zhenbo , Wang Weiqiang
Published: September 2003

We study the ideals of the rational cohomology ring of the Hilbert scheme

X

[
n
]

X^{[n]}

of

n
n

points on a smooth projective surface

X
X

. As an application, for a large class of smooth quasi-projective surfaces

X
X

, we show that every cup product structure constant of

H
∗

(

X

[
n
]

)

H^*(X^{[n]})

is independent of

n
n

; moreover, we obtain two sets of ring generators for the cohomology ring

H
∗

(

X

[
n
]

)

H^*(X^{[n]})

. Similar results are established for the Chen-Ruan orbifold cohomology ring of the symmetric product. In particular, we prove a ring isomorphism between

H
∗

(

X

[
n
]

;

C

)

H^*(X^{[n]}; \mathbb {C})

and

H

orb

∗

(

X
n

/

S
n

;

C

)

H^*_\textrm {orb}(X^n/S_n; \mathbb {C})

for a large class of smooth quasi-projective surfaces with numerically trivial canonical class.
Binding of the EssentialSaccharomyces cerevisiaeKinetochore Protein Ndc10p to CDEII
Authors: Espelin Christopher W. , Simons Kim T. , Harrison Stephen C. , Sorger Peter K.
Published: September 2003

Chromosome segregation at mitosis depends critically on the accurate assembly of kinetochores and their stable attachment to microtubules. Analysis of Saccharomyces cerevisiae kinetochores has shown that they are complex structures containing ≥50 protein components. Many of these yeast proteins have orthologs in animal cells, suggesting that key aspects of kinetochore structure have been conserved through evolution, despite the remarkable differences between the 125-base pair centromeres of budding yeast and the Mb centromeres of animal cells. We describe here an analysis of S. cerevisiae Ndc10p, one of the four protein components of the CBF3 complex. CBF3 binds to the CDEIII element of centromeric DNA and initiates kinetochore assembly. Whereas CDEIII binding by Ndc10p requires the other components of CBF3, Ndc10p can bind on its own to CDEII, a region of centromeric DNA with no known binding partners. Ndc10p-CDEII binding involves a dispersed set of sequence-selective and -nonselective contacts over ∼80 base pairs of DNA, suggesting formation of a multimeric structure. CDEII-like sites, active in Ndc10p binding, are also present along chromosome arms. We propose that a polymeric Ndc10p complex formed on CDEII and CDEIII DNA is the foundation for recruiting microtubule attachment proteins to kinetochores. A similar type of polymeric structure on chromosome arms may mediate other chromosome–spindle interactions.
Human Immunodeficiency Virus-1 Nef Expression Induces Intracellular Accumulation of Multivesicular Bodies and Major Histocompatibility Complex Class II Complexes: Potential Role of Phosphatidylinositol 3-Kinase
Authors: Stumptner-Cuvelette Pamela , Jouve Mabel , Helft Julie , Dugast Marc , Glouzman Anne-Sophie , Jooss Karin , Raposo Graça , Benaroch Philippe
Published: September 2003

Nef alters the cell surface expression of several immunoreceptors, which may contribute to viral escape. We show that Nef modifies major histocompatibility complex class II (MHC II) intracellular trafficking and thereby its function. In the presence of Nef, mature, peptide-loaded MHC II were down-modulated at the cell surface and accumulated intracellularly, whereas immature (invariant [Ii] chain-associated) MHC II expression at the plasma membrane was increased. Antibody internalization experiments and subcellular fractionation analyses showed that immature MHC II were internalized from the plasma membrane but had limited access to lysosomes, explaining the reduced Ii chain degradation. Immunoelectron microscopy revealed that Nef expression induced a marked accumulation of multivesicular bodies (MVBs) containing Nef, MHC II, and high amounts of Ii chain. The Nef-induced up-regulation of surface Ii chain was inhibited by LY294002 exposure, indicating the involvement of a phosphatidylinositol 3-kinase, whose products play a key role in MVB biogenesis. Together, our results indicate that Nef induces an increase of the number of MVBs where MHC II complexes accumulate. Given that human immunodeficiency virus recruits the MVB machinery for its assembly process, our data raise the possibility that Nef is involved in viral assembly through its effect on MVBs.