bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bidirectional Corridor in the Sahel‐Sudan Belt and the Distinctive Features of the Chad Basin Populations: A History Revealed by the Mitochondrial DNA Genome
Authors: Černý V. , Salas A. , Hájek M. , Žaloudková M. , Brdička R.
Published: January 2007

The Chad Basin was sparsely inhabited during the Stone Age, and its continual settlement began with the Holocene. The role played by Lake Chad in the history and migration patterns of Africa is still unclear. We studied the mitochondrial DNA (mtDNA) variability in 448 individuals from 12 ethnically and/or economically (agricultural/pastoral) different populations from Cameroon, Chad, Niger and Nigeria. The data indicate the importance of this region as a corridor connecting East and West Africa; however, this bidirectional flow of people in the Sahel‐Sudan Belt did not erase features peculiar to the original Chad Basin populations. A new sub‐clade, L3f2, is described, which together with L3e5 is most probably autochthonous in the Chad Basin. The phylogeography of these two sub‐haplogroups seems to indicate prehistoric expansion events in the Chad Basin around 28,950 and 11,400 Y.B.P., respectively. The distribution of L3f2 is virtually restricted to the Chad Basin alone, and in particular to Chadic speaking populations, while L3e5 shows evidence for diffusion into North Africa at about 7,100 Y.B.P. The absence of L3f2 and L3e5 in African‐Americans, and the limited number of L‐haplotypes shared between the Chad Basin populations and African‐Americans, indicate the low contribution of the Chad region to the Atlantic slave trade.
New polymorphic microsatellite loci for rodents of the genus Mastomys using PCR multiplexing, and cross‐species amplification in Myomys and Praomys
Authors: LOISEAU A. , KONEČNÝ A. , GALAN M. , BRYJA J. , COSSON J. F. , BROUAT C.
Published: January 2007

The Praomys complex contains some of the most important agricultural pests of Africa, including Mastomys species. We describe the development of nine supplementary microsatellite markers isolated from Mastomys huberti. We show the potential utility of M. huberti microsatellites as population markers for two other species of Mastomys, and two other species of the Praomys complex, Myomys daltoni and Praomys cf. rostratus.
TREES SIFTER 1.0: an approximate method to estimate the time to the most recent common ancestor of a sample of DNA sequences
Authors: MARDULYN PATRICK
Published: January 2007

trees sifter1.0 implements an approximate method to estimate the time to the most recent common ancestor (TMRCA) of a set of DNA sequences, using population evolution modelling. In essence, the program simulates genealogies with a user‐defined model of coalescence of lineages, and then compares each simulated genealogy to the genealogy inferred from the real data, through two summary statistics: (i) the number of mutations on the genealogy (Mn), and (ii) the number of different sequence types (alleles) observed (Kn). The simulated genealogies are then submitted to a rejection algorithm that keeps only those that are the most likely to have generated the observed sequence data. At the end of the process, the accepted genealogies can be used to estimate the posterior probability distribution of the TMRCA.
THE SYSTEMATICS AND PHYLOGENETIC RELATIONSHIPS OF VETULICOLIANS
Authors: ALDRIDGE RICHARD J. , XIAN‐GUANG HOU , SIVETER DAVID J. , SIVETER DEREK J. , GABBOTT SARAH E.
Published: January 2007

Abstract: Vetulicolians have variously been considered to be unusual arthropods, stem‐group deuterostomes or relatives of the tunicates. They are known from a number of Cambrian Lagerstätten, and are particularly diverse in the Chengjiang biota of Yunnan Province, China. We recognize two classes, Vetulicolida and Banffozoa, which together form a monophyletic group. Within the Chinese collections we also identify two new species and recognize one new genus:Vetulicola monilesp. nov. andBullivetula variolagen. et sp. nov. The evidence from new and previously described specimens is used to undertake a phylogenetic analysis and to evaluate a range of hypotheses for the affinities of vetulicolians. Given the difficulties of interpreting features in enigmatic fossils and the apparently contradictory set of characters possessed by vetulicolians, it is not possible on current evidence to reach an unequivocal conclusion regarding the phylogenetic position of the group. One possibility is that they are a sister group of arthropods that lost limbs but gained gill structures analogous to those of deuterostomes, but several features remain unexplained by this model. If they are protostomes, a more generally parsimonious position is close to the kinorhynchs. An alternative is that they are deuterostomes, although a placement at the base of the clade is not supported by the evidence. If they are deuterostomes, it is more likely that they are close to the tunicates.
CARBONATE DEPOSITIONAL ENVIRONMENTS, SEQUENCE STRATIGRAPHY AND EXCEPTIONAL SKELETAL PRESERVATION IN THE MUCH WENLOCK LIMESTONE FORMATION (SILURIAN) OF DUDLEY, ENGLAND
Authors: RAY DAVID C. , THOMAS ALAN T.
Published: January 2007

Abstract:  The Much Wenlock Limestone Formation of the Dudley inliers, West Midlands, contains one of the world's richest and most exquisitely preserved Silurian marine biotas. However, for most museum specimens, little is known of their exact provenance and mode of preservation. Detailed comparisons between outcrops and museum collections allow the identification of five faunal‐lithological associations and numerous horizons of exceptional skeletal preservation. The associations are interpreted as a series of transient carbonate mid‐platform environments extending from below storm wave‐base to above fair‐weather wave‐base. Erosive surfaces, condensed sections, flooding surfaces and the stacking patterns of genetically related bed‐sets (parasequences) have allowed the formation to be interpreted as a single third‐order sequence stratigraphic cycle of sea‐level change. The articulated preservation of taxa such as pelmatozoan echinoderms and trilobites can be attributed to either rapid burial by obrution deposits close to fair‐weather wave‐base or smothering by storm sequestered muds in slightly deeper‐water settings. Such intervals of exceptional preservation are commonly associated with flooding surfaces, presumably reflecting reduced likelihood of reworking once rapid burial had taken place.
CRANIAL MORPHOLOGY OF THE LATE TRIASSIC SOUTH AMERICAN ARCHOSAUR NEOAETOSAUROIDES ENGAEUS: EVIDENCE FOR AETOSAURIAN DIVERSITY
Authors: DESOJO JULIA BRENDA , BÁEZ ANA MARIA
Published: January 2007

Abstract:  The cranial anatomy of Neoaetosauroides engaeus Bonaparte, 1969 from the upper part of the Los Colorados Formation, western Argentina, is addressed herein. This description is based on material collected recently, which permits a complete restoration of the skull; previously, a partial lower jaw and premaxillary and maxillary fragments were the only cranial remains known. Unlike other aetosaurs for which the premaxillary dentition is known, in N. engaeus the upper tooth row extends anteriorly to reach near the expanded tip of the snout; this condition is not compatible with the presence of a keratinous beak previously suggested for other aetosaurs. The conical shape of the teeth of N. engaeus differs from the slightly compressed teeth of Desmatosuchus, Stagonolepis and Typothorax, and the distinctly recurved teeth of Aetosaurus and Aetosauroides. This diversity of dental morphology suggests a variety of food‐item preferences among aetosaurs.
AUTECOLOGY AND THE FILLING OF ECOSPACE: KEY METAZOAN RADIATIONS
Authors: BAMBACH RICHARD K. , BUSH ANDREW M. , ERWIN DOUGLAS H.
Published: January 2007

Abstract: All possible combinations of six tiering positions in relation to the substratum/water interface, six motility levels and six feeding strategies define a complete theoretical ecospace of 216 potential modes of life for marine animals. The number of modes of life actually utilized specifies realized ecospace. Owing to constraints of effectiveness and efficiency the modern marine fauna utilizes only about half the potential number of modes of life, two‐thirds of which (62 of 92) are utilized by animals with readily preserved, mineralized hard parts. Realized ecospace has increased markedly since the early evolution of animal ecosystems. The Ediacaran fauna utilized at most 12 modes of life, with just two practised by skeletal organisms. A total of 30 modes of life are recorded in the Early and Middle Cambrian, 19 of which were utilized by skeletal organisms. The other 11 are documented from soft‐bodied animals preserved in the Chengjiang and Burgess Shale Konservat‐Lagerstätten. The number of modes of life utilized by skeletal organisms increased by more than 50 per cent during the Ordovician radiation to a Late Ordovician total of 30. Between the Late Ordovician and the Recent the number of utilized modes of life has doubled again. The autecological and taxonomic diversity histories of the marine metazoa appear to be broadly parallel, and future studies of theoretical ecospace utilization should provide more detailed tests of pattern and process in the ecological history of the metazoa.
HOW DID LIFE BECOME SO DIVERSE? THE DYNAMICS OF DIVERSIFICATION ACCORDING TO THE FOSSIL RECORD AND MOLECULAR PHYLOGENETICS
Authors: BENTON MICHAEL J. , EMERSON BRENT C.
Published: January 2007

Abstract: The long‐term diversification of life probably cannot be modelled as a simple equilibrial process: the time scales are too long, the potential for exploring new ecospace is too large and it is unlikely that ecological controls can act at global scales. The sum of many clade expansions and reductions, each of which happens according to its own dynamic, probably approximates more a damped exponential curve when translated into a global‐scale species diversification curve. Unfortunately, it is not possible to plot such a meaningful global‐scale species diversification curve through time, but curves at higher taxonomic levels have been produced. These curves are subject to the vagaries of the fossil record, but it is unlikely that the sources of error entirely overwhelm the biological signal. Clades radiate when the external and internal conditions are right: a new territory or ecospace becomes available, and the lineage has acquired a number of characters that open up a new diet or mode of life. Modern high levels of diversity in certain speciose clades may depend on such ancient opportunities taken. Dramatic climatic changes through the Quaternary must have driven extinctions and originations, but many species responded simply by moving to more favourable locations. Ecological communities appear to be no more than merely chance associations of species, but there may be real interactions among species. Ironically, high species diversity may lead to more speciation, not, as had been assumed, less: more species create more opportunities and selective pressures for other species to respond to, rather than capping diversity at a fixed equilibrium level. Studies from the scale of modern ecosystems to global long‐term patterns in the fossil record support a model for the exponential diversification of life, and one explanation for a pattern of exponential diversification is that as diversity increases, new forms become ever more refinements of existing forms. In a sense the world becomes increasingly divided into finer niche space. Organisms have a propensity to speciate freely, species richness within ecosystems appears to generate opportunities for more speciation, clades show all kinds of patterns from sluggish speciation rates and constant diversity through time to apparently explosive speciation, and there is no evidence that rapidly speciating clades have reached a limit, nor that they are driving other clades to extinction. A corollary of this view is that current biodiversity must be higher than it has ever been. Limits to infinite growth are clearly local, regional, and global turnover and extinction events, when climate change and physical catastrophes knock out species and whole clades, and push the rising exponential curve down a notch or two.
THE MACROEVOLUTIONARY CONSEQUENCES OF ECOLOGICAL DIFFERENCES AMONG SPECIES
Authors: McPEEK MARK A.
Published: January 2007

Abstract: In this paper, I examine the dynamics of species richness in a model system in which multiple species compete in a metacommunity (multiple patches linked by dispersal). Patches lie along an environmental gradient, and new species are introduced into the system by speciation of existing species. This model is used to explore how the ecological similarity of species influences the patterns in community structure that result and to determine whether patterns in fossil and systematics data may be signatures for different types of community structure. Making species more similar overall along the entire gradient or making new species that have more similar optimal positions along the gradient to their progenitor both increase the time required to drive species extinction. As a result, making species more similar ecologically to one another increases overall species richness because of an increased frequency of transient species in the system. Having more transient species in systems shifted the longevity distributions of species in the fossil record towards having a greater frequency of shorter duration species, and the age distribution of extant species that would be estimated from molecular phylogenies also had a higher frequency of younger aged species. Comparisons of these results with species longevity distributions extracted from two data sets and with species ages derived from species‐level molecular phylogenies strongly suggest that transient species are an important component of real biological communities.
THE EFFECTS OF SAMPLING BIAS ON PALAEOZOIC FAUNAS AND IMPLICATIONS FOR MACROEVOLUTIONARY STUDIES
Authors: TARVER JAMES E. , BRADDY SIMON J. , BENTON MICHAEL J.
Published: January 2007

Abstract:  Trilobites, a dominant component of marine faunas during the Cambrian and Ordovician and which survived until the end of the Permian (542–251 Ma) have been used in many macroevolutionary analyses. Here, we use a discovery curve to document the sampling history of trilobites, which we consider a proxy for Palaeozoic faunas in general. At higher taxonomic ranks, orders, suborders and superfamilies, the fossil record has been completely sampled, while the family rank also shows a high level of sampling completeness, having reached an asymptote in 1970. Importantly, this levelling‐off occurred even though worker effort continued to increase. However, at genus level the sampling record is incomplete, indicating that families should not be used as a proxy for genera. There is little variation among the different subsets of generic data, with the sampling history of different stratigraphic periods and among different orders being very similar. However, there is noticeable variation among geographical regions, caused by variations in worker effort, and this could cause problems when comparing speciation and diversity patterns across faunal provinces. The role of synonyms on sampling history has had little effect.
EDIACARAN AND CAMBRIAN INDEX FOSSILS FROM SONORA, MEXICO
Authors: SOUR‐TOVAR FRANCISCO , HAGADORN JAMES W. , HUITRÓN‐RUBIO TOMÁS
Published: January 2007

Abstract:  The Cambrian index fossil Treptichnus pedum is reported from the Puerto Blanco Formation near Pitiquito, Sonora, Mexico, and new occurrences of the Neoproterozoic index fossil Cloudina are reported from the underlying La Ciénega Formation. Considered together, these fossils constrain the location of the Ediacaran/Cambrian boundary in Mexico. The suite of fossils in this sequence is important because it provides an independent biostratigraphic datum for constraining the position of Laurentia during the onset of metazoan diversification, for testing proposed lithostratigraphic correlations among western North American Neoproterozoic–Cambrian successions, and for testing regional tectonic paradigms such as the Mojave‐Sonora Megashear hypothesis.
The Early History (1909–1961) ofEpilepsia, the Journal of the International League Against Epilepsy, and Its Echoes Today
Authors: Shorvon Simon
Published: January 2007

Summary: This paper records the history ofEpilepsia, the journal of the International League Against Epilepsy, from its inception in 1908/1909 until the beginning of its fourth series in 1961. During this time, publication was interrupted on three occasions and so the journal appeared in four series, with a complex numbering system. Over the years, the content and format of the journal has varied. Its role has changed over the years, at times primarily as a scientific organ and at other times as a source of ILAE news and reports. Concerns throughout its history have included its role as an historical record, its international representation, financial vicissitude, quality of papers, the balance between basic and clinical science, the value of clinical papers, and issues of overspecialization.Epilepsiais today the leading clinical epilepsy journal; but these are still significant concerns, and a knowledge of the history ofEpilepsiais important for understanding the current position of the journal.
Alcohol and Hepatitis C Mortality Among Males and Females in the United States: A Life Table Analysis
Authors: Chen Chiung M. , Yoon Young‐Hee , Yi Hsiao‐ye , Lucas Diane L.
Published: January 2007

Objective:Evidence from previous studies suggests that heavy alcohol use (HAU) exacerbates the rate of fibrosis progression in the liver and results in increased probability for premature death among patients with hepatitis C virus (HCV) infection. The current study uses population‐based mortality data to investigate whether heavy drinking affects the age of death among individuals with HCV and, if so, whether this effect differs between men and women.

Methods:A total of 7,263,163 death records in the United States between 2000 and 2002 were drawn from the Multiple Cause of Death (MCD) public‐use data files compiled by the National Center for Health Statistics (NCHS). International Classification of Diseases, Tenth Revision (ICD‐10) codes were used to identify the presence of HCV (B17.1 and B18.2) and HAU (as indicated by alcohol‐induced medical conditions, F10 and K70) either as the underlying cause or as one of the contributing causes of death. The deaths were divided into 4 distinctive cause‐of‐death categories: HCV without HAU, HAU without HCV, HCV plus HAU, and all others. The mean ages of death and the cumulative probabilities of death derived from multiple‐cause life table were compared across these categories.

Results:Hepatitis C virus deaths showed an excessive prevalence of HAU when compared with non‐HCV deaths. Compared with deaths of HCV without HAU, the mean age of death was shortened for deaths of HCV plus HAU (from 55.1 to 50.0 years among males, and from 61.0 to 49.1 years among females). The cumulative probability of death before age 65 was much higher for the latter than the former group (0.91 vs 0.68 among males, and 0.88 vs 0.47 among females). While HCV alone showed a disproportionate effect on premature death in males, HAU presented a stronger effect in females, resulting in a “catching‐up” effect that diminished the gender difference in age of HCV death.

Conclusions:This study provides mortality‐based evidence to further establish heavy alcohol consumption as one of the key risk factors contributing to premature deaths from HCV in the United States. More importantly, this study, for the first time, presents empirical evidence that alcohol consumption affects men and women differently in HCV mortality.
In Vivo Dysfunction of the Term Alveolar Macrophage After in Utero Ethanol Exposure
Authors: Ping Xiao‐Du , Harris Frank L. , Brown Lou Ann S. , Gauthier Theresa W.
Published: January 2007

Background: The effects of in utero alcohol exposure on the immune function of the newborn remain under investigation. Fetal ethanol (ETOH) exposure increases oxidative stress in the developing lung, in part due to decreased availability of the antioxidant glutathione (GSH). We have previously shown that in utero ETOH impairs alveolar macrophage phagocytosis and viability in the premature pup, while maintaining GSH availability with maternal supplementation of S‐adenosyl‐methionine (SAM) during ETOH ingestion improves macrophage function and viability. We hypothesized that dysfunction of the neonatal alveolar macrophage exposed to ETOH in utero would persist at term gestation.

Methods: Using a guinea‐pig model of fetal ETOH exposure, timed‐pregnant guinea‐pigs were pair‐fed ETOH±the GSH precursor SAM and the diet continued until spontaneous delivery. Term alveolar macrophages were evaluated using fluorescent microscopy for phagocytosis and apoptosis after in vitro incubation with Staphalococcus aureus. Using an in vivo model of intranasal Staph. aureus inoculation, the in vivo function of the term alveolar macrophage was also investigated using confocal fluorescent analysis.

Results: In utero ETOH exposure increased oxidant stress in the alveolar macrophage and decreased phagocytosis and viability in vitro and in vivo. Confocal analysis of phagocytosis in vivo demonstrated a marked impairment of internalization of the bacteria by the ETOH‐exposed alveolar macrophage. The addition of SAM during maternal ETOH ingestion prevented loss of alveolar macrophage function and viability in vitro and in vivo.

Conclusions: In utero ETOH exposure impairs alveolar macrophage function and viability in vitro and in vivo even at term gestation. The ETOH‐induced changes in macrophage function and viability can be ablated with maternal SAM supplementation. Further investigations are required to identify the mechanisms of ETOH‐induced derangement of phagocytosis in the neonatal alveolar macrophage and the clinical ramifications of altered immune function after in utero alcohol exposure for the newborn.
Alcohol Consumption Is Enhanced After Naltrexone Treatment
Authors: Juárez Jorge , Eliana Barrios De Tomasi
Published: January 2007

Background: It is well known that alcohol increases opioid activity, which can contribute to the reinforcing effect of alcohol. Clinical studies have supported reductions in alcohol consumption among alcoholic patients during treatment with opioid antagonists (OAs) and its use is recommended for this purpose. Experimental studies have demonstrated opioid receptor up‐regulation after several days of OA treatment, which increases the availability of these receptors. On this basis, the physiological conditions in the period immediately after the OA treatment could increase the reinforcing value of alcohol and in this way enhance alcohol consumption.

Methods: To test this hypothesis, 2 groups of Wistar male rats were used in the present study. After assessing the baseline of voluntary alcohol (10% v/v) consumption, subjects were treated with either the OA naltrexone (Ntx), (2 mg/kg/d/rat) or a saline solution (0.2 mL/d/male) for 7 days. Subsequently, all subjects were given a free choice between ethanol (10%) and water for 5 days. To study a possible cumulative effect, this procedure was sequentially repeated 4 times with each group. Water and food were available ad libitum throughout the experiment.

Results: After each period of 7 days of Ntx use, alcohol consumption increased significantly with respect to the baseline and each equivalent period in the control group. When the subjects were exposed to alcohol again 1 week after the last of the 4 sequential periods, alcohol drinking was higher than the baseline in the Ntx group, but not in the control group. Water consumption was decreased during Ntx treatment in the control group in periods 1, 2, and 4. Food intake and body weight did not show differences between groups throughout the study; however, a decrease in food intake was observed over time regardless of treatment.

Conclusion: These results show that alcohol intake may increase after the Ntx treatment, particularly when alcohol is not available during treatment with the OA, and that this may be due to a higher availability of opioid receptors in that period.
Spatial Competition in Variety and Number of Stores
Authors: Peng Shin‐Kun , Tabuchi Takatoshi
Published: January 2007

We propose location‐then‐variety competition for a multiproduct and multi‐store oligopoly, in which the number of firms, the number of stores and their location, and the number of varieties are endogenously determined. We show that as compared to price‐then‐variety and quantity‐then‐variety competition, location‐then‐variety competition with multistores yields a much richer set of equilibrium outcomes, such as market segmentation, interlacing, sandwich, and enclosure.
The Effectiveness and Cost‐Effectiveness of Respite for Caregivers of Frail Older People
Authors: Mason Anne , Weatherly Helen , Spilsbury Karen , Golder Su , Arksey Hilary , Adamson Joy , Drummond Michael
Published: January 2007

The proportion of frail elderly people in the industrialized world is increasing. Respite care is a potentially important way of maintaining the quality of life for these people and their caregivers. The objective of this systematic review was to determine the effectiveness and cost‐effectiveness of different models of community‐based respite care for frail older people and their caregivers. To identify relevant studies, 37 databases were searched, and reference checking and citation searches were undertaken. Well‐controlled effectiveness studies were eligible for inclusion, with uncontrolled studies admissible only in the absence of higher‐quality evidence. Studies assessed the effect of community‐based respite on caregivers of frail elderly people relative to usual care or to another support intervention. Eligible economic evaluations also addressed costs. Where appropriate, data were synthesized using standard meta‐analytic techniques. Ten randomized, controlled trials, seven quasi‐experimental studies and five uncontrolled studies were included in the review. For all types of respite, the effects upon caregivers were generally small, with better‐controlled studies finding modest benefits only for certain subgroups, although many studies reported high levels of caregiver satisfaction. No reliable evidence was found that respite care delays entry to residential care or adversely affects frail older people. The economic evaluations all assessed day care, which tended to be associated with similar or higher costs than usual care. Given the increasing numbers of frail elderly people and the lack of up‐to‐date, good‐quality evidence for all types of respite care, better‐quality evidence is urgently needed to inform current policy and practice.
Effect of Depression Treatment on Depressive Symptoms in Older Adulthood: The Moderating Role of Pain
Authors: Mavandadi Shahrzad , Ten Have Thomas R. , Katz Ira R. , Durai U. Nalla B. , Krahn Dean D. , Llorente Maria D. , Kirchner JoAnn E. , Olsen Edwin J. , Van Stone William W. , Cooley Susan L. , Oslin David W.
Published: January 2007

OBJECTIVES: To investigate whether pain severity and interference with normal work activities moderate the effects of depression treatment on changes in depressive symptoms over time in older adults in primary care.

DESIGN: Patient‐randomized, clinical trial.

SETTING: Multisite: three clinics located in Veterans Affairs Medical Centers.

PARTICIPANTS: Adults aged 60 and older (n=524) who screened positive for depression and participated in the Primary Care Research in Substance Abuse and Mental Health for the Elderly Study.

INTERVENTION: Integrated care versus enhanced specialty referral care.

MEASUREMENTS: Pain severity, the degree to which pain interferes with work inside and outside of the home, and depressive symptoms were examined at baseline and 3, 6, and 12 months.

RESULTS: Intention‐to‐treat analyses revealed that both treatment groups showed reduced depressive symptoms over time, although self‐reported pain moderated reductions in depressive symptoms. At higher levels of pain severity and interference with work activities, improvements in depressive symptoms were blunted. Furthermore, pain interference appeared to have a greater effect on depressive symptoms than did pain severity; in individuals with major depression, pain interference fully accounted for the moderating effects of pain severity on changes in depressive symptoms over time.

CONCLUSION: Pain and its interference with functioning interfere with recovery from depression. Findings highlight the importance of addressing multiple domains of functioning (e.g., physical and social disability) and the degree to which pain and other forms of physical comorbidity may hinder or minimize treatment‐related improvements in depressive symptoms.
Combination of Oral Antidiabetic Agents with Basal Insulin Versus Premixed Insulin Alone in Randomized Elderly Patients with Type 2 Diabetes Mellitus
Authors: Janka Hans U. , Plewe Gerd , Busch Klaus
Published: January 2007

OBJECTIVES: To compare initiation of insulin therapy by adding once‐daily insulin glargine to oral antidiabetic agents (OADs) with switching patients to premixed 30% regular, 70% human neutral protamine hagedorn insulin (70/30) without OADs.

DESIGN: A 24‐week, multicenter, open, randomized (1:1), parallel study.

SETTING: Three hundred sixty‐four poorly controlled patients with type 2 diabetes mellitus were treated with once‐daily morning insulin glargine with continued OADs (glimepiride+metformin) (glargine+OAD) or twice‐daily 70/30 alone. Insulin dosage in each group was titrated to target fasting blood glucose (FBG) of 100 mg/dL or less (≤5.6 mmol/L) using a weekly titration algorithm.

PARTICIPANTS: This planned subgroup analysis of the original study was based on 130 insulin‐naive patients aged 65 and older with FBG of 120 mg/dL or greater (≥6.7 mmol/L) and hemoglobin (Hb)A1c levels between 7.5% and 10.5% on OADs (glargine+OAD, n=67; 70/30, n=63).

MEASUREMENTS: HbA1c, FBG, hypoglycemia, insulin dose, and adverse events were recorded.

RESULTS: HbA1c decreased from baseline to endpoint for both glargine+OAD (from 8.8% to 7.0%) and 70/30 (from 8.9% to 7.4%); adjusted mean HbA1c decrease for glargine+OAD and 70/30 was −1.9% and −1.4%, respectively (P=.003). More patients reached HbA1c of 7.0% or less without confirmed nocturnal hypoglycemia with glargine+OAD (n=37, 55.2%) than with 70/30 (n=19, 30.2%) (P=.006). FBG decreased significantly more with glargine+OAD (−57 mg/dL (−3.2 mmol/L)) than with 70/30 (−40 mg/dL (−2.2 mmol/L)) (P=.002). Patients treated with glargine+OAD experienced fewer episodes of any hypoglycemia (3.68/patient–year) than did those treated with 70/30 (9.09/patient–year) (P=.008).

CONCLUSION: In elderly patients, addition of once‐daily morning glargine+OAD is a simple regimen to initiate insulin therapy, restoring glycemic control more effectively and with less hypoglycemia than twice‐daily 70/30 alone.
Improving Vision to Prevent Falls in Frail Older People: A Randomized Trial
Authors: Cumming Robert G. , Ivers Rebecca , Clemson Lindy , Cullen John , Hayes Maggie F. , Tanzer Michael , Mitchell Paul
Published: January 2007

OBJECTIVES: To determine the efficacy of vision and eye examinations, with subsequent treatment of vision problems, for preventing falls and fractures in frail older people.

DESIGN: Randomized, controlled trial.

SETTING: Community in Sydney, Australia.

PARTICIPANTS: Six hundred sixteen men and women aged 70 and older (mean age 81) recruited mainly from people attending outpatient aged care services.

INTERVENTIONS: The intervention group received comprehensive vision and eye examinations conducted by a study optometrist. The optometrist arranged for new eyeglasses for 92 subjects and referred 24 for a home visit with an occupational therapist, 17 for glaucoma management, and 15 for cataract surgery. The control group received usual care.

MEASUREMENTS: Falls and fractures during 12 months of follow‐up were ascertained according to self‐report using a monthly postcard system.

RESULTS: Fifty‐seven percent of subjects fell at least once during follow‐up. Falls occurred more frequently in the group randomized to receive the vision intervention (65% fell at least once; 758 falls in total) than in the control group (50% fell at least once; 516 falls in total). The falls rate ratio using the negative binomial model was 1.57 (95% confidence interval (CI)=1.20–2.05, P=.001). Fractures were also more frequent in the intervention group (31 fractures) than the control group (18 fractures; relative risk from proportional hazards model 1.74, 95% CI=0.97–3.11, P=.06).

CONCLUSION: In frail older people, comprehensive vision and eye assessment, with appropriate treatment, does not reduce, and may even increase, the risk of falls and fractures.
Alcohol Use, Physical Performance, and Functional Limitations in Older Men
Authors: Cawthon Peggy M. , Fink Howard A. , Barrett‐Connor Elizabeth , Cauley Jane A. , Dam Thuy‐Tien , Lewis Cora E. , Marshall Lynn M. , Orwoll Eric S. , Cummings Steven R. ,   for the Osteoporotic Fractures in Men Research Group
Published: January 2007

OBJECTIVES: To describe associations between recent alcohol intake, physical performance, and functional limitations in older men.

DESIGN: Cross‐sectional study.

SETTING: Six U.S. clinical centers.

PARTICIPANTS: Five thousand nine hundred sixty‐two men aged 65 and older.

MEASUREMENTS: Self‐reported functional limitations; problem drinking history (≥2 positive responses on the CAGE questionnaire); history of sustained excessive drinking (history of consumption of ≥5 drinks/day on most days); and alcohol intake categorized by drinks/week (0=abstainers, n=2,116; < 1=intermittent, n=739); 1 to <7= light, n=1,563; 7 to <14=low‐moderate, n=848; 14 to <21 =high‐moderate, n=459; and ≥21=heavy, n=237). Grip strength, leg power, chair stand, and walking tests were completed during a standard examination.

RESULTS: After age adjustment, men with low‐moderate or high‐moderate intake generally performed 3% to 5% better on physical performance tests than abstainers; heavy drinkers performed similarly to abstainers. These associations lessened yet tended to remain significant after multivariate adjustment. Men with low‐moderate alcohol intake had the lowest odds of reporting a limitation in instrumental activities of daily living (multivariate‐adjusted odds ratio (OR)=0.52, 95% confidence interval (CI)=0.39–0.69) compared to abstainers; similar odds were seen for high‐moderate and heavy use. The association between alcohol intake and self‐reported physical limitation was U‐shaped, with the highest odds of physical limitation in abstainers (OR=1.0, referent) and heavy users (OR=0.88, 95% CI=0.58–1.36) and the lowest odds in low‐moderate users (OR=0.62, 95% CI=0.46–0.95).

CONCLUSION: Moderate alcohol intake was associated with modestly better physical performance and lower odds of reporting a functional limitation in older men.
Epidemiology of Medicare Abuse: The Example of Power Wheelchairs
Authors: Goodwin James S. , Nguyen‐Oghalai Tracy U. , Kuo Yong‐Fang , Ottenbacher Kenneth J.
Published: January 2007

OBJECTIVES: To determine the effect of neighborhood ethnic composition on power wheelchair prescriptions.

DESIGN: The 5% noncancer sample of Medicare recipients in the Surveillance, Epidemiology and End Results (SEER)‐Medicare linked database, from 1994 to 2001.

SETTING: SEER regions.

PARTICIPANTS: Individuals covered by Medicare living in SEER regions without a cancer diagnosis.

MEASUREMENTS: Individual characteristics (age, sex, ethnicity, justifying diagnosis, and comorbidity), primary diagnoses, neighborhood characteristics (percentage black, percentage Hispanic, percentage with <12 years education, and median income), and SEER region.

RESULTS: The rate of power wheelchair prescriptions was 33 times greater in 2001 than in 1994, with a shift over time from justifying diagnoses more closely tied to mobility impairment, such as strokes, to less‐specific medical diagnoses, such as osteoarthritis. In multilevel, multivariate analyses, individuals living in neighborhoods with higher percentages of blacks or Hispanics were more likely to receive power wheelchairs (odds ratios=1.09 for each 10% increase in black residents and 1.23 for each 10% increase in Hispanic residents) after controlling for ethnicity and other characteristics at the individual level.

CONCLUSION: These results support allegations that marketers promoting power wheelchairs have specifically targeted minority neighborhoods.
The Relationship of Indwelling Urinary Catheters to Death, Length of Hospital Stay, Functional Decline, and Nursing Home Admission in Hospitalized Older Medical Patients
Authors: Holroyd‐Leduc Jayna M. , Sen Saunak , Bertenthal Dan , Sands Laura P. , Palmer Robert M. , Kresevic Denise M. , Covinsky Kenneth E. , Seth Landefeld C.
Published: January 2007

OBJECTIVES: To determine the association between indwelling urinary catheterization without a specific medical indication and adverse outcomes.

DESIGN: Prospective cohort.

SETTING: General medical inpatient services at a teaching hospital.

PARTICIPANTS: Five hundred thirty‐five patients aged 70 and older admitted without a specific medical indication for urinary catheterization.

INTERVENTION: Indwelling urinary catheterization within 48 hours of admission.

MEASUREMENTS: Death, length of hospital stay, decline in ability to perform activities of daily living (ADLs), and new admission to a nursing home.

RESULTS: Indwelling urinary catheters were placed in 76 of the 535 (14%) patients without a specific medical indication. Catheterized patients were more likely to die in the hospital (6.6% vs 1.5% of those not catheterized, P=.006) and within 90 days of hospital discharge (25% vs 10.5%, P<.001); the greater risk of death with catheterization persisted in a propensity‐matched analysis (hazard ratio (HR)=2.42, 95% confidence interval (CI)=1.04–5.65). Catheterized patients also had longer lengths of hospital stay (median, 6 days vs 4 days; P=.001); this association persisted in a propensity‐matched analysis (HR=1.46, 95% CI=1.03–2.08). Catheterization was not associated (P>.05) with decline in ADL function or with admission to a nursing home.

CONCLUSION: In this cohort of older patients, urinary catheterization without a specific medical indication was associated with greater risk of death and longer hospital stay.
Blood Pressure and Survival in the Oldest Old
Authors: Oates Daniel J. , Berlowitz Dan R. , Glickman Mark E. , Silliman Rebecca A. , Borzecki Ann M.
Published: January 2007

OBJECTIVES: To determine the relationship between blood pressure (BP) and all‐cause mortality in subjects aged 80 and older with hypertension.

DESIGN: Retrospective cohort study with 5 years of follow‐up.

SETTING: Ten Veterans AFFAIRS (VA) sites.

PARTICIPANTS: Four thousand seventy‐one ambulatory patients aged 80 and older with hypertension.

MEASUREMENTS: The outcome measure was likelihood of survival during the follow‐up period. Vital status was obtained from VA and Social Security files. Variables collected for adjustment in Cox regression models were baseline BP, medications, demographics, diagnoses, and health‐related quality of life (HRQoL); HRQoL information was available on 1,289 subjects based on Veterans Health Study Short From‐36 (SF‐36) questionnaire scores.

RESULTS: Subjects with higher BP (up to a systolic BP (SBP) of 139 mmHg and a diastolic BP (DBP) of 89 mmHg) were less likely to die during follow‐up than subjects with lower BP. After baseline adjustments, the hazard ratio for a 10‐point increase in SBP was 0.82 (95% confidence interval (CI)=0.74–0.91), up to a SBP of 139 mmHg, and for DBP was 0.85 (95% CI=0.78–0.92), up to a DBP of 89 mmHg. There was no significant association between survival and BP levels in subjects with uncontrolled hypertension.

CONCLUSION: In a cohort of very old, hypertensive veterans, in subjects with controlled BPs, subjects with lower BP levels had a lower 5‐year survival than those with higher BPs. This suggests that clinicians should use caution in their approach to BP lowering in this age group.
Effects of Statin Use on Muscle Strength, Cognition, and Depressive Symptoms in Older Adults
Authors: Agostini Joseph V. , Tinetti Mary E. , Han Ling , McAvay Gail , Foody JoAnne M. , Concato John
Published: January 2007

OBJECTIVES: To determine the relationship between hydroxymethyl glutaryl coenzyme A reductase inhibitor (statin) use and proximal muscle strength, cognition, and depression in older adults.

DESIGN: Observational cohort study.

SETTING: Outpatient primary care clinics.

PARTICIPANTS: Seven hundred fifty‐six community‐dwelling veterans aged 65 and older.

MEASUREMENTS: Timed chair stands (a measure of proximal muscle strength), Trail Making Test Part B (a measure of cognition), and the Center for Epidemiologic Studies Depression Scale score were measured at baseline and 1‐year follow‐up. Participants were assessed for statin prescriptions (and indications for or contraindications to their use), concomitant medication use, comorbidities, and other potential confounders.

RESULTS: Statin users (n=315) took a mean 6.6 medications, versus 4.6 for nonusers (n=441), and had a median duration of statin use of 727 days. Statin users were more likely to be white and had (as expected) more cardiac, cerebrovascular, and peripheral vascular disease. Based on multivariable models adjusting for pertinent covariates, statin users performed modestly better than nonusers for timed chair stands (−0.5 seconds; P=.04), Trail Making Test Part B (−7.7 seconds; P=.08), and depression scores (−0.2 points; P=.49) at follow‐up. Of potentially high‐risk participants (based on age, comorbidity, and number of medications), statin users also showed similar 1‐year changes as nonusers, although worsened depression scores were found in those with greater comorbidity (+0.88 points; P=.10).

CONCLUSION: Older, community‐dwelling male participants taking maintenance statin therapy had similar outcomes to those of nonusers in tests of muscle strength, cognition, and depression, but further examination of benefits and harms in different subgroups is warranted.
Adding an Alcohol‐Related Risk Score to an Existing Categorical Risk Classification for Older Adults: Sensitivity to Group Differences
Authors: Wilson Sandra R. , Fink Arlene , Verghese Shinu , Beck John C. , Nguyen Khue , Lavori Philip
Published: January 2007

OBJECTIVES: To evaluate a new alcohol‐related risk score for research use.

DESIGN: Using data from a previously reported trial of a screening and education system for older adults (Computerized Alcohol‐Related Problems Survey), secondary analyses were conducted comparing the ability of two different measures of risk to detect postintervention group differences: the original categorical outcome measure and a new, finely grained quantitative risk score based on the same research‐based risk factors.

SETTING: Three primary care group practices in southern California.

PARTICIPANTS: Six hundred sixty‐five patients aged 65 and older.

MEASUREMENTS: A previously calculated, three‐level categorical classification of alcohol‐related risk and a newly developed quantitative risk score.

RESULTS: Mean postintervention risk scores differed between the three experimental conditions: usual care, patient report, and combined report (P<.001). The difference between the combined report and usual care was significant (P<.001) and directly proportional to baseline risk. The three‐level risk classification did not reveal approximately 57.3% of the intervention effect detected by the risk score. The risk score also was sufficiently sensitive to detect the intervention effect within the subset of hypertensive patients (n=112; P=.001).

CONCLUSION: As an outcome measure in intervention trials, the finely grained risk score is more sensitive than the trinary risk classification. The additional clinical value of the risk score relative to the categorical measure needs to be determined.
Development of proficiency testing for detection of bacterial contamination of platelet products
Authors: Easley Samantha , Yomtovian Roslyn A. , Sullivan Patricia , Jacobs Michael R.
Published: January 2007

BACKGROUND: Accrediting agencies now require quality control for minimizing platelet (PLT) bacterial contamination (PBC). A proficiency testing (PT) strategy for PBC testing was developed.

STUDY DESIGN AND METHODS: During Phase 1, validation of the pH meter and an enhanced bacteria detection system (Pall eBDS)—methods used in our blood bank—was accomplished with two aliquots of an apheresis PLT unit inoculated with Escherichia coli (ATCC 25922, 70 CFU/mL) or Staphylococcus aureus (ATCC 27217, 46 CFU/mL) with an uninoculated aliquot serving as a negative control. Quantitative plate culture was the reference method. PLTs were stored on a rotator at 22°C. Units were sampled in duplicate at 0, 24, and 48 hours. pH testing was considered positive when the pH value was less than 6.6. eBDS was positive when the oxygen concentration was less than 9.4 percent. During Phase 2, synchronized PT of pH and eBDS was performed at four independent sites. PLT samples were inoculated and incubated as above, and aliquots were removed at Time 0 for eBDS testing and at 48 hours for pH testing.

RESULTS: In Phase 1, on inoculated bags eBDS was positive at all time periods but pH was positive only at 48 hours. In Phase 2, synchronized results showed positive eBDS at Time 0 and positive pH at 48 hours on inoculated bags with agreement between paired sites.

CONCLUSIONS: This strategy may serve as a useful model for developing PT materials for PBC detection. eBDS was able to identify low levels of PBC, and pH testing, only much higher levels. It is important to carefully coordinate and standardize handling of PT materials and reporting of results.
Impact of transfection with total RNA of K562 cells upon antigen presenting, maturation, and function of human dendritic cells from peripheral blood mononuclear cells
Authors: Gao Li , Fan Hua‐hua , Lu Hua‐zhong , Nie Xiao‐xuan , Liu Yan , Yang Yi‐ming , Qian Kai‐cheng , Gao Feng
Published: January 2007

BACKGROUND: Vaccination of dendritic cells (DCs) with tumor antigens is a potential strategy to induce tumor‐specific immunity in tumor‐bearing patients. The purpose of this study was to investigate whether human monocyte‐derived DCs were able to present P210Bcr‐Ab1 protein and induce antigen‐specific cytotoxic T lymphocyte (CTL) responses in vitro after transfected with total RNA of K562 cells (K562‐RNA).

STUDY DESIGN AND METHODS: DCs derived from human peripheral blood mononuclear cells were transfected with K562‐RNA with electroporation or DOTAP lipofection. The successful transfection was determined by reverse transcription‐polymerase chain reaction and Western blot. The phenotypes of the DCs were analyzed by flow cytometry (FCM), and cytotoxicity of CTL was assessed by propidium iodide staining followed by FCM analysis. The CD1a expression and purity of DCs were measured by FCM.

RESULTS: The Bcr‐Abl fusion gene was detected in the DCs with 24 hours after the transfection. The transfected cell expressed increased levels of CD80, CD83, CD86, and HLA‐DR. Moreover, the transfected DCs strongly stimulated the T lymphocytes to gain cytotoxic activity against K562 cells. Culture medium containing 1 percent human plasma was the most effective for DC growth.

CONCLUSION: Human DCs transfected with K562‐RNA effectively induce specific immune responses. This method can be used to induce tumor‐specific immune response and may have potential application in immunotherapy of tumors.