bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of C‐reactive protein with mild cognitive impairment
Authors: Roberts Rosebud O. , Geda Yonas E. , Knopman David S. , Boeve Bradley F. , Christianson Teresa J.H. , Pankratz V. Shane , Kullo Iftikhar J. , Tangalos Eric G. , Ivnik Robert J. , Petersen Ronald C. 
Published: September 2009

BackgroundInflammation is proposed to play a role in the development of Alzheimer's disease, and may also be involved in the pathogenesis of mild cognitive impairment (MCI). This study examined the association of inflammatory markers in serum or plasma with prevalent MCI and MCI subtypes in a population‐based sample.MethodsOlmsted County, MN, residents aged 70–89 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Information ascertained for each participant was reviewed by an expert panel of neuropsychologists, physicians, and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by consensus. C‐reactive protein (CRP), interleukin‐6 (IL‐6), tumor necrosis alpha (TNFα), and adiponectin were measured at baseline.ResultsAmong 313 subjects with MCI and 1570 cognitively normal subjects, a CRP level in the upper quartile (>3.3 mg/L) was significantly associated with MCI (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.00–2.01) and with nonamnestic MCI (OR, 2.05; 95% CI, 1.12–3.78) after adjusting for age, sex, and years of education. However, there was no association with amnestic MCI (OR, 1.21; 95% CI, 0.81–1.82). No association was observed with the other inflammatory markers.ConclusionsPlasma CRP is associated with prevalent MCI and with nonamnestic MCI in elderly, nondemented persons in a population‐based setting. These findings suggest the involvement of inflammation in the pathogenesis of MCI.
Severe Impairment Battery Language scale: A language‐assessment tool for Alzheimer's disease patients
Authors: Ferris Steven , Ihl Ralf , Robert Philippe , Winblad Bengt , Gatz Gudrun , Tennigkeit Frank , Gauthier Serge 
Published: September 2009

BackgroundCommunication problems are common in Alzheimer's disease (AD) patients, but instruments to assess these symptoms are limited. Our objective was to create a new scale, based on the language subscale of the Severe Impairment Battery (SIB), as a sensitive and reliable measurement of treatment effects on language performance.MethodsAll 24 items of the SIB language subscale were chosen for analysis. Baseline scores of 1320 moderate‐to‐severe patients (Mini‐Mental State Examination [MMSE] score, <15), from a combined AD database of four Memantine clinical trials (Study Codes: IE‐2101, MEM‐MD‐01, MEM‐MD‐02, and MRZ‐9605), were used for item reduction according to a standard principal components factor analysis. All items with loadings >0.5 on the identified factors were selected for inclusion in the new language scale. Correlations with existing AD scales were examined.ResultsThe analysis indicated six factors, with 21 of 24 items showing loadings >0.5. The resulting 21‐item SIB Language (SIB‐L) scale exhibited high internal consistency (Cronbach's α = 0.809). The maximal SIB‐L score was 41 points, with a measurement error of 3.7 points. The stratification of baseline SIB‐L scores (mean, 31.7; SD, 8.4) by MMSE scores (mean, 9.7; SD, 3.3) showed a high variance in SIB‐L scores. This confirms that patients with a low MMSE score can possess preserved language abilities. The SIB‐L scale did not exhibit substantial floor‐and‐ceiling effects.ConclusionsThe new SIB‐L is a fast (<15 minutes) and easily administered scale with favorable psychometric characteristics for assessing language impairment and treatment effects on the language performance of patients with moderate to severe AD.
Treatment effects of Memantine on language in moderate to severe Alzheimer's disease patients
Authors: Ferris Steven , Ihl Ralf , Robert Philippe , Winblad Bengt , Gatz Gudrun , Tennigkeit Frank , Gauthier Serge 
Published: September 2009

BackgroundLanguage impairment is one of the most troublesome manifestations of Alzheimer's disease (AD). The objective of this post hoc analysis was to assess the treatment effects of Memantine on language in patients with moderate to severe AD, using the recently developed Severe Impairment Battery‐Language (SIB‐L) scale.MethodsFrom a combined database including four Memantine clinical trials in moderate‐to‐severe AD, we analyzed 801 patients with SIB‐L scores of <38 and Mini‐Mental State Examination scores of <15. Patients were treated with either 20 mg Memantine per day or placebo. Mean changes in SIB‐L scores from baseline were calculated. For responder analyses, a change in SIB‐L score greater than or equal to the SIB‐L measurement error of 3.7 points was considered a clinically relevant response.ResultsThe mean change from baseline in SIB‐L score at week 12 and weeks 24/28 (study end) significantly favored Memantine over placebo treatment (P < .0001 and P = .0182, respectively). Overall, more Memantine‐treated patients than placebo‐treated patients benefited from treatment. The effect was especially pronounced in patients with substantial language impairment on the SIB‐L (baseline score, ≤20). At weeks 24/28, significantly more Memantine‐treated patients experienced a clinically relevant improvement (25.4% vs. 10.8%, P = .0414), and significantly fewer patients experienced clinically relevant worsening (32.8% vs. 60.0%, P = .0029).ConclusionsMemantine treatment of AD patients results in significant benefits for language function. Our results suggest that it is worth considering this therapeutic option, even for AD patients with marked language impairment.
Alzheimer's disease drug development and the problem of the blood‐brain barrier
Authors: Pardridge William M. 
Published: September 2009

Alzheimer's disease (AD) drug development is limited by the presence of the blood‐brain barrier (BBB). More than 98% of all small‐molecule drugs, and ∼100% of all large‐molecule drugs, do not cross the BBB. Although the vast majority of AD drug candidates do not cross the BBB, the present‐day AD drug‐development effort is characterized by an imbalance wherein >99% of the drug‐development effort is devoted to central nervous system (CNS) drug discovery, and <1% of drug development is devoted to CNS drug delivery. Future AD drug development needs a concerted effort to incorporate BBB sciences early in the CNS drug discovery process. This goal can be achieved by a reallocation of resources, and an expansion of research efforts in the pure science of BBB biology and the applied science of brain drug‐targeting technology.
Current Alzheimer's disease clinical trials: Methods and placebo outcomes
Authors: Schneider Lon S. , Sano Mary 
Published: September 2009

BackgroundEighteen‐month‐long randomized, placebo‐controlled clinical trials are common for phase II and phase III drug development for Alzheimer's disease (AD). Yet, no 18‐month trial has shown statistically significant outcomes favoring the test drug. We examined characteristics and underlying assumptions of these trials by assessing the placebo groups.MethodsWe searched the clinicaltrials.gov registry for randomized, placebo‐controlled clinical trials for AD of at least 18‐month duration and extracted demographic, clinical, and trials characteristics, and change in main outcomes from the placebo groups. We obtained additional information from presentations, abstracts, publications, and sponsors.ResultsOf 23 trials identified, 11 were completed and had baseline data available; nine had follow‐up data available; 17 were phase III. General inclusion criteria were very similar except that minimum Mini‐Mental State Examination (MMSE) scores varied from 12 to 20. Sample sizes ranged from 402 to 1,684 for phase III trials and 80 to 400 for phase II. Cholinesterase inhibitor use was from 53% to 100%, and memantine use was from 13.5% to 78%. The AD Assessment Scale‐cognitive (ADAS‐cog) was the co‐primary outcome in all trials; and activities of daily living, global severity, or global change ratings were the other co‐primaries. APOE ɛ4 genotype carriers ranged from 58% to 67%; mean baseline ADAS‐cog was 17.8 to 24.2. ADAS‐cog worsening in the placebo groups during 18 months ranged from 4.34 to 9.10, with standard deviations from 8.17 to 9.39, increasing during 18 months.ConclusionsInclusion criteria are essentially similar to earlier 6‐month and 12‐month trials in which cholinesterase inhibitors were not allowed, as were mean ADAS‐cog rates of change. Yet increasing variability and relatively little change overall in the ADAS‐cog placebo groups, eg, about 25% of patients do not worsen by more than 1 point, might make it more unlikely than previously assumed that a modestly effective drug can be reliably recognized, especially when the drug might work only to attenuate decline in function and not to improve function. These observations would be strengthened by pooling individual trials data, and pharmaceutical sponsors should participate in such efforts.
“Below average” self‐assessed school performance and Alzheimer's disease in the Aging, Demographics, and Memory Study
Authors: Mehta Kala M. , Stewart Anita L. , Langa Kenneth M. , Yaffe Kristine , Moody‐Ayers Sandra , Williams Brie A. , Covinsky Kenneth E. 
Published: September 2009

BackgroundA low level of formal education is becoming accepted as a risk factor for Alzheimer's disease (AD). Although increasing attention has been paid to differences in educational quality, no previous studies addressed participants' own characterizations of their overall performance in school. We examined whether self‐assessed school performance is associated with AD beyond the effects of educational level alone.MethodsParticipants were drawn from the population‐representative Aging, Demographics, and Memory Study (ADAMS, 2000‐2002). The ADAMS participants were asked about their performance in school. Possible response options included “above average,” “average,” or “below average.” The ADAMS participants also underwent a full neuropsychological battery, and received a research diagnosis of possible or probable AD.ResultsThe 725 participants (mean age, 81.8 years; 59% female; 16% African‐American) varied in self‐assessed educational performance: 29% reported “above average,” 64% reported “average,” and 7% reported “below average” school performance. Participants with a lower self‐assessed school performance had higher proportions of AD: 11% of participants with “above average” self‐assessed performance had AD, as opposed to 12% of participants with “average” performance and 26% of participants with “below average” performance (P < 0.001). After controlling for subjects' years in school, a literacy test score (Wide‐Range Achievement Test), age, sex, race/ethnicity, apolipoprotein E‐ɛ4 status, socioeconomic status, and self‐reported comorbidities, respondents with “below average” self‐assessed school performance were four times more likely to have AD compared with those of “average” performance (odds ratio, 4.0; 95% confidence interval, 1.2–14). “Above average” and “average” self‐assessed school performance did not increase or decrease the odds of having AD (odds ratio, 0.9; 95% confidence interval, 0.5–1.7).ConclusionsWe suggest an association between “below average” self‐assessed school performance and AD beyond the known association with formal education. Efforts to increase cognitive reserve through better school performance, in addition to increasing the number of years of formal education in early life, may be important in reducing vulnerability throughout the life course.
Habit persistence, impediments to production factor adjustments, and asset returns in general equilibrium models with self‐fulfilling expectations
Authors: Gershun Natalia 
Published: September 2009

AbstractI examine asset returns in the context of real dynamic stochastic general equilibrium economies with multiple equilibria (indeterminacy) that allow for aggregate fluctuations due to non‐fundamental belief shocks. The two models include habit formation in preferences. Model 1 combines restrictions on factor mobility and adjustment costs in a one‐sector economy. Model 2 uses restrictions on factor mobility in a two‐sector economy. Results demonstrate that Model 1 fails to match the stylized financial facts. Model 2 replicates the low risk‐free rate and the standard deviation of the return on the risk‐free asset, but underestimates the equity premium and standard deviation of the return on equity.
Separation of genetic influences on attention deficit hyperactivity disorder symptoms and reaction time performance from those on IQ
Authors: Wood A. C. , Asherson P. , van der Meere J. J. , Kuntsi J. 
Published: September 2009

BackgroundAttention deficit hyperactivity disorder (ADHD) shows a strong phenotypic and genetic association with reaction time (RT) variability, considered to reflect lapses in attention. Yet we know little about whether this aetiological pathway is shared with other affected cognitive processes in ADHD, such as lower IQs or the generally slower responses (mean RTs). We aimed to address the question of whether a shared set of genes exist that influence RT variability, mean RT, IQ and ADHD symptom scores, or whether there is evidence of separate aetiological pathways.MethodMultivariate structural equation modelling on cognitive tasks data (providing RT data), IQ and ADHD ratings by parents and teachers collected on general population sample of 1314 twins, at ages 7–10 years.ResultsMultivariate structural equation models indicated that the shared genetic influences underlying both ADHD symptom scores and RT variability are also shared with those underlying mean RT, with both types of RT data largely indexing the same underlying liability. By contrast, the shared genetic influences on ADHD symptom scores and RT variability (or mean RT) are largely independent of the genetic influences that ADHD symptom scores share with IQ.ConclusionsThe finding of unique aetiological pathways between IQ and RT data, but shared components between mean RT, RT variability and ADHD symptom scores, illustrates key influences in the genetic architecture of the cognitive and energetic processes that underlie the behavioural symptoms of ADHD. In addition, the multivariate genetic model fitting findings provide valuable information for future molecular genetic analyses.
Early maternal and paternal bonding, childhood physical abuse and adult psychopathic personality
Authors: Gao Y. , Raine A. , Chan F. , Venables P. H. , Mednick S. A. 
Published: September 2009

BackgroundA significant gap in the literature on risk factors for psychopathy is the relative lack of research on parental bonding.MethodThis study examines the cross-sectional relationship between maternal and paternal bonding, childhood physical abuse and psychopathic personality at age 28 years in a community sample of 333 males and females. It also assesses prospectively whether children separated from their parents in the first 3 years of life are more likely to have a psychopathic-like personality 25 years later.ResultsHierarchical regression analyses indicated that: (1) poor parental bonding (lack of maternal care and low paternal overprotection) and childhood physical abuse were both associated with a psychopathic personality; (2) parental bonding was significantly associated with psychopathic personality after taking into account sex, social adversity, ethnicity and abuse; (3) those separated from parents in the first 3 years of life were particularly characterized by low parental bonding and a psychopathic personality in adulthood; and (4) the deviant behavior factor of psychopathy was more related to lack of maternal care whereas the emotional detachment factor was related to both lack of maternal care and paternal overprotection.ConclusionsFindings draw attention to the importance of different components of early bonding in relation to adult psychopathy, and may have potential implications for early intervention and prevention of psychopathy.
Outbreak of giardiasis associated with a community drinking-water source
Authors: DALY E. R. , ROY S. J. , BLANEY D. D. , MANNING J. S. , HILL V. R. , XIAO L. , STULL J. W. 
Published: September 2009

SUMMARYGiardiasis is a common waterborne gastrointestinal illness. In 2007, a community giardiasis outbreak occurred in New Hampshire, USA. We conducted a cohort study to identify risk factors for giardiasis, and stool and environmental samples were analysed. Consuming tap water was significantly associated with illness (risk ratio 4·7, 95% confidence interval 1·5–14·4). Drinking-water samples were coliform-contaminated and a suspectGiardiacyst was identified in a home water filter. One well was coliform-contaminated, and testing indicated that it was potentially under the influence of surface water. The well was located 12·5 m from aGiardia-contaminated brook, although the genotype differed from clinical specimens. Local water regulations require well placement at least 15 m from surface water. This outbreak, which caused illness in 31 persons, represents the largest community drinking-water-associated giardiasis outbreak in the USA in 10 years. Adherence to well placement regulations might have prevented this outbreak.
Palatal lift prosthesis for palatopharyngeal closure in Wilson's disease
Authors: Koidis PT , Topouzelis N 
Published: September 2009

AbstractThis is a report of our work on a female patient with Wilson's disease who was treated for speech improvement. A palatal lift prosthesis was constructed to displace the soft palate superiorly and posteriorly and partially restore the functional deficiencies of palatopharyngeal insufficiency. Cephalometric radiographs confirm the association between the displacement of the soft palate and speech improvement.
The Use of a Selective Staphylococcal Broth v Direct Plating for the Recovery of Staphylococcus aureus
Authors: Sautter R.L. , Brown W.J. , Mattman L.H. 
Published: September 2009

AbstractNine hundred seventy-two cultures taken from the external nares and the vaginal vestibules of 54 women for the isolation of Staphylococcus aureus were studied. The swabs were plated directly to a trypticase soy agar plate containing 5% sheep blood and were then placed into a selective staphylococcal broth. Both culture methods were compared for the ability to recover S aureus.Twenty percent (26/131) and 66% (38/58) of the S aureus-positive cultures taken from the nares and vagina respectively were cultured from the selective broth only. We believe that a selective staphylococcal broth should be used in addition to routine culture techniques to isolate S aureus from infection control surveillance cultures.
The Multi-lumen Catheter: Proposed Guidelines for Its Use
Authors: Farber Bruce F. 
Published: September 2009

Infusion therapy for the administration of blood products, fluids, and parenteral nutrition are essential parts of medical practice. The risks associated with such therapy are well documented but frequently unappreciated. Intravascular infusions are the single most common cause of nosocomial bacteremia.’ Many studies have focused on the epidemiology, microbiology, and pathophysiology of these infections.In recent years, several companies have introduced a multi-lumen intravenous catheter that is placed through the subclavian or internal jugular vein. Unlike a multi-lumen pulmonary artery catheter, the multi-lumen intravenous catheter is designed solely for intravenous access. The first of these catheters was introduced in 1983, and it was soon followed by several others. These catheters have been designed to allow multiple infusions to be given simultaneously. In addition, one of the ports can be used for venous access. The advantages of these catheters are obvious. The clinician is given three ports for use instead of one. The catheter may be used to simplify infusion therapy. In some instances, cut-downs and other invasive procedures (Hickmans, Broviacs, Mediports) may be avoided. It is not surprising that the use of these catheters has grown. In many institutions, multi-lumen catheters account for a majority of all centrally placed catheters, and in some intensive care units, they are used almost exclusively. The enormous growth of the use of the multi-lumen catheter has occurred despite minimal data regarding risk, cost, and the proper procedures needed for its care.
Increased Incidence of Infections in Intravenous Drug Users
Authors: Horsburgh Charles R. , Anderson Judith R. , Boyko Edward J. 
Published: September 2009

AbstractTo ascertain the incidence of infections in intravenous users of illicit drugs, we performed a retrospective study of 270 intravenous drug users (IVDUs) and 562 controls who did not use drugs over a seven-year period from 1978-1985. IVDUs had an increased overall incidence of infections (P <0.00l) compared to controls, which was explained to a large degree by an increased incidence of hepatitis. Endocarditis and disseminated gonococcal infection were seen with increased frequency in IVDUs (P <0.05), but abscess and cellulitis were not. Neither acquired immunodeficiency syndrome (AIDS), tuberculosis, Pneumocystis pneumonia, nor disseminated viral or fungal infection were seen in IVDUs or controls. Heroin users, but not other IVDUs, had an increased incidence of infections not thought to be associated with needle use, suggesting impaired immunity. This study demonstrates that IVDUs have an increased incidence of infection compared to control subjects, but the kinds of infections have changed substantially over the past two decades. The presence of opportunistic pathogens in these patients should suggest concurrent infection with human immunodeficiency virus (HIV).
Pseudoepidemic of Urinary Tract Infections due to Trichosporon beigelii
Authors: Stone Judy , Manasse Robert 
Published: September 2009

AbstractDuring the period April, 1985 to March, 1986, Trichosporon beigelii was isolated from the urine of 15 intensive care unit patients. All of these patients had Foley catheters in place at the time of T beigelii isolation. None of them had urinary tract infections on admission, and it was initially felt that this organism was a source of infection in these critically ill individuals. Subsequent investigation revealed this to be a pseudoepidemic secondary to contamination of the urinary catheter drainage system. Urine obtained by gravity drainage from the outlet port of urimeters yielded growth of T beigelii, whereas urines obtained concurrently from the proximal tubing sampling port were negative. T beigelii was isolated from the drainage port as well as from various items used in the collection and sampling of urine specimens. It is felt that these items were the source of perpetuation of this pseudoepidemic due to the repeated contamination and colonization of the distal portion of the urine catheter collection system. In-services to nursing and housekeeping personnel in the proper collection of urine specimens and cleaning of potentially contaminated items, the replacement of metal urine graduates with disposable plastic ones and increased monitoring of personnel's activities stopped the outbreak abruptly.