bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustained virological responses following standard anti‐viral therapy in decompensated HCV‐infected cirrhotic patients
Authors: IACOBELLIS A. , SICILIANO M. , ANNICCHIARICO B. E. , VALVANO M. R. , NIRO G. A. , ACCADIA L. , CARUSO N. , BOMBARDIERI G. , ANDRIULLI A.
Published: April 2009

Background  Little data is available about predictors of sustained virological response (SVR) during anti‐viral therapy of patients with decompensated HCV cirrhosis.

Aims  To determine whether rapid and early virological responses (RVR and EVR) could predict SVR and help optimize treatment in these patients.

Methods  A total of 94 cirrhotics underwent treatment with peg‐interferon alfa‐2b (1.5 μg/kg weekly) and ribavirin (800/1200 mg daily) for 48 or 24 weeks for genotypes 1/4 or genotypes 2/3, respectively.

Results  Overall, SVR was achieved in 33 patients (35.1%), 16% with genotype 1/4 and 56.8% with genotype 2/3 (P < 0.01). At treatment week 4, 34 patients had undetectable HCV‐RNA, 10 with genotype 1/4 and 24 with genotype 2/3. Of RVR patients, 24 achieved SVR (70.5%), 6 and 18 with genotypes 1 and non‐1. At the multivariate analysis, only EVR, genotypes 2 and 3, and adherence to full course and dosage of therapy retained their independent predictive power, with corresponding ORs of 25.5 (95% CI 3.0–217.3), 4.2 (95% CI 1.2–15.3) and 9.1 (95% CI 2.2–38.0), respectively.

Conclusion  In decompensated cirrhotic patients, anti‐viral therapy with current regimens is feasible and associated with an overall SVR rate of 35.1%. Treatment ought to be pursued among patients who attain an EVR, and maintain a full course and dosage of therapy.
Stratigraphic evolution of the upper slope and shelf edge in the Karoo Basin, South Africa
Authors: Wild R. , Flint S. S. , Hodgson D. M.
Published: April 2009

The Permian Ecca Group of the Karoo Basin, South Africa preserves an extensive well‐exposed siliciclastic basin floor, slope and shelf‐edge delta succession. The Kookfontein Formation includes multiple sedimentary cycles that display clinoform geometries and are interpreted to represent the deposits of a slope to shelf succession. The succession exhibits progradational followed by aggradational stacking of deltaic cycles that is related to a change in shelf‐edge trajectory, and lies within two depositional sequences. Sediment was transferred to the slope via overextension of deltas onto and over the shelf edge, resulting in failure and re‐adjustment of local slope gradients. The depositional facies and architecture of the Kookfontein Formation record the change from a bypass‐ to accretion‐dominated margin, which is interpreted to reflect a decrease in sediment transport efficiency as the slope gradient decreased, slope length increased and shelf‐edge trajectory rose. During this time the delivery system changed from point‐sourced basin‐floor fans fed by slope channels to starved basin‐floor with sand‐rich slope clinoforms. This is an example of a progradational margin in which the younger slope system is interpreted to be of a different style to the older slope system that fed the underlying sand‐rich basin floor fans.
Chitinases and chitinase‐like proteins: potential therapeutic targets for the treatment of T‐helper type 2 allergies
Authors: Sutherland T. E. , Maizels R. M. , Allen J. E.
Published: April 2009

Mammalian chitinase and chitinase‐like proteins (CLPs) are a family of mediators increasingly associated with infection, T cell‐mediated inflammation, wound healing, allergy and asthma. Although our current knowledge of the function of mammalian chitinases and CLPs is very limited, important information can be deduced from research carried out in lower organisms, and in different immunopathological conditions. Enzymatically active mammalian chitinase proteins may have evolved to degrade the copious amounts of chitin mammals are exposed to on a daily basis, and to form an innate barrier to chitin‐containing organisms. CLPs are homologous to chitinases but lack the ability to degrade chitin. It is most striking that both chitinases and CLPs are up‐regulated in T‐helper type 2 (Th2)‐driven conditions, and the first evidence is now emerging that these proteins may accentuate Th2 reactivity, and possibly contribute to the repair process that follows inflammation. Following studies demonstrating that chitinase inhibition leads to an attenuated allergic response, several strategies are being used to develop enzyme inhibitors for therapeutic use in human diseases. In this review, we will summarize recent insights into the effects of chitinases and CLPs in the context of Th2‐dominated pathology with particular focus on allergy and asthma, discussing whether chitinase enzyme inhibitors may be of therapeutic value.
Establishing the incidence and prevalence of clinician‐diagnosed allergic conditions in children and adolescents using routinely collected data from general practices
Authors: Punekar Y. S. , Sheikh A.
Published: April 2009

Background
There remains a need to better characterize the epidemiology of allergic disorders, particularly in relation to describing the incidence, natural history and co‐morbidity of allergic conditions.

Objectives
To estimate the incidence and prevalence of clinician‐diagnosed eczema, asthma and rhinitis, alone and in combination, in children and adolescents in the United Kingdom.

Methods
Using the national General Practice Research Database (GPRD) – one of the largest validated databases of routinely collected healthcare data in the world aggregating 3.6 million individuals – we constructed a retrospective birth cohort of 43 473 children born in the year 1990 and registered with a UK general practice within a year of birth. The cohort was followed until 2008 or the longest available follow‐up period to determine the cumulative and age‐specific incidence and prevalence rates of clinician‐diagnosed eczema, asthma and rhinitis, and an 18‐year prevalence of these conditions, alone and in combination.

Results
Eczema had the highest incidence density of 226.9 per 10 000 person‐years [95% confidence interval (CI): 225.8–228.0] followed by asthma [136.6;(95% CI: 135.7–137.5)] and rhinitis [61.4;(95% CI: 60.8–62.0)], by the age of 18 years. The incidence densities of suffering from one, two or all three allergic conditions were 323.2 (95% CI: 322.0–324.4), 206.4 (95% CI: 205.7–207.1) and 141.9 (95% CI: 141.4–142.4) per 10 000 person‐years, respectively. Among the 24 112 children with a complete 18‐year follow‐up, eczema had the highest 18‐year prevalence of clinician‐diagnosed condition at 36.5% (95% CI: 35.9–37.2%) followed by asthma [22.9;(95% CI: 22.3–23.4%)] and rhinitis[11.4;(95% CI: 11.0–11.8%)]. The 18‐year prevalence of more than one and all three conditions was 16.1% (95% CI: 15.6–16.6%) and 2.5% (95% CI: 2.4–2.8%), respectively.

Conclusions
This is one of the first studies to provide national estimates on the age‐specific incidence and age‐specific prevalence of the major allergic disorders showing clinician‐diagnosed eczema, asthma and rhinitis to have high incidence rates in early childhood. A significant proportion of children experience and are diagnosed with multiple allergic conditions in early childhood.
Relationship of peak growth hormone to cardiovascular parameters, waist circumference, lipids and glucose in HIV‐infected patients and healthy adults
Authors: Lo Janet , You Sung M. , Wei Jeffrey , Canavan Bridget , Grinspoon Steven
Published: April 2009

Objective  Relative growth hormone (GH) deficiency is highly prevalent in patients with HIV. The purpose of this study was to investigate relationships of GH to metabolic and anthropometric parameters in HIV patients and non‐HIV controls.

Design  Peak GH and metabolic parameters were assessed in a cross‐sectional study of 191 HIV patients and 62 age and BMI‐matched healthy controls.

Methods  Peak GH was assessed by GHRH/arginine stimulation testing.

Results  HIV patients demonstrated similar BMI, but increased waist circumference (WC) and reduced peak GH to GHRH/arginine compared with control subjects [median = 12·4 (interquartile range: 6·3–24·8) vs. 21·3 (8·8, 34·5) μg/l, P = 0·006, HIV vs. control]. Among HIV and non‐HIV groups, peak GH was inversely associated with WC (rho = −0·44, P < 0·0001; rho = −0·63, P < 0·0001; HIV patients and controls, respectively), blood pressure (rho = −0·17, P = 0·02; rho = −0·36, P = 0·004), triglycerides (rho = −0·37, P < 0·0001; rho = −0·43, P = 0·001), glucose (rho = −0·34, P < 0·0001; rho = −0·30, P = 0·02), insulin (rho = −0·43, P < 0·0001; rho = −0·60, P < 0·0001) and CRP (rho = −0·29, P < 0·0001; rho = −0·59, P < 0·0001). Among HIV patients, the inverse association between peak GH and fasting glucose remained significant (β = −0·006 mmol/l change in glucose per μg/l change in GH, P = 0·004) controlling for age, gender, race, BMI, WC, protease inhibitor (PI) and nucleoside reverse transcriptase inhibitors. Similarly, the inverse association between peak GH and triglycerides remained significant (β = −0·01 mmol/l change in triglycerides per μg/l change in GH, P = 0·02) controlling for age, gender, race, BMI, WC, PI and lipid‐lowering medications. HIV men with peak GH < 7·5 μg/l demonstrated higher BMI, WC, SBP, triglycerides, glucose and CRP.

Conclusions  Reduced GH secretion is independently associated with dyslipidaemia and higher glucose, among HIV patients with abdominal fat accumulation.
Impaired endothelial‐ and nonendothelial‐mediated vasodilation in patients with acute or chronic hypothyroidism
Authors: Napoli Raffaele , Guardasole Vincenzo , Zarra Emanuela , D’Anna Carolina , De Sena Antonietta , Lupoli Gelsy Arianna , Oliviero Ugo , Matarazzo Margherita , Lupoli Giovanni , Saccà Luigi
Published: April 2009

Objective  Vascular dysfunction and accelerated atherosclerosis are prominent features of hypothyroidism. The relative roles of thyroid hormone (TH) deficiency and the associated vascular risk conditions are still unclear. We studied the impact of acute and chronic hypothyroidism on vascular reactivity.

Patients  We studied 12 patients with chronic primary hypothyroidism (cHY; TSH: 52 ± 14 mU/l), seven patients with acute hypothyroidism secondary to total thyroidectomy (aHY; TSH: 97 ± 24) and 13 healthy subjects (TSH: 1·2 ± 0·5).

Measurements  We measured forearm blood flow (FBF) using plethysmography during intra‐brachial infusion of: acetylcholine (ACh), sodium nitroprusside (NP) and norepinephrine (NE). We also measured serum C‐reactive protein (CRP), TNF‐alpha, asymmetric dimethylarginine (ADMA) and the forearm balance of nitric oxide (NO) during ACh infusion.

Results  As compared with the controls, the vasodilatory response to ACh was reduced in cHY (P = 0·001) and aHY (P = 0·04), as was the forearm release of NO (P < 0·05). During NP infusion, FBF rose to 24 ± 2 ml/dl/min in the controls and to significantly lower values in cHY (12 ± 1; P = 0·001) and aHY (15 ± 2; P = 0·004). NE‐induced vasoconstriction was similar in the controls and aHY, but blunted in cHY. Serum CRP, TNF‐alpha and ADMA were not different in the three groups.

Conclusions  (i) Hypothyroidism associates with endothelial and nonendothelial mediated vascular dysfunction; (ii) these defects are evident even after short‐term hypothyroidism, indicating that TH deficiency per se is sufficient to alter vascular homeostasis; and (iii) chronic, but not acute, hypothyroidism impairs the vasoconstrictory effect of NE in the resistance vessels.
Identification of the shallow subsurface succession and investigation of the seawater invasion to the Quaternary aquifer at the northern part of El Qaa plain, Southern Sinai, Egypt by transient electromagnetic data
Authors: Massoud Usama , Santos Fernando , El Qady Gad , Atya Magdy , Soliman Mamdouh
Published: April 2009

The phenomenon of seawater invasion is a very common and widespread environmental problem that is present in the majority of Egyptian coastal aquifers. Saltwater intrusion may occur due to human activities and by natural events such as climate change and sea level rise. El Qaa plain is a structural depression trending NNW‐SSE, parallel to the main rift system of the Gulf of Suez. The Quaternary aquifer in El Qaa plain is the main source for water supply in this region. So, this study has been conducted to shed more light on the description of the subsurface section and marking out the invasion of seawater to this aquifer at the northern part of El Qaa plain. In this concern, transient electromagnetic data were measured at 52 stations arranged along 2 parallel profiles, 10 km apart, trending NE‐SW to cross the major course of the plain and to be approximately perpendicular to the coast line of the Suez Gulf. In addition, information from a nearby borehole was used to confirm the results of transient electromagnetic data interpretation. Two apparent resistivity pseudosections and two geoelectrical cross‐sections were constructed along the selected profiles. Investigation of these sections revealed that four geoelectrical layers could be detected in the shallow subsurface medium at the studied area and the Quaternary aquifer has been affected by seawater invasion at the western and middle parts. Besides, three faults striking approximately NW‐SE parallel to the major track of the plain were inferred from this study. These faults may be controlling the groundwater accumulation and flow in this area.
More pieces in the promoter jigsaw: recognition of −10 regions by alternative sigma factors
Authors: Busby Stephen J. W.
Published: April 2009

Two papers in this issue of Molecular Microbiology from Carol Gross and colleagues describe experiments that investigate how two alternative Escherichia coliσ proteins recognize target promoter −10 regions. A combination of genetics, biochemistry and bioinformatics is used to show that determinants in two adjacent domains of the σ proteins contact discrete sequence elements in the −10 regions.
Relationship between gastro‐oesophageal reflux pattern and severity of mucosal damage
Authors: Bredenoord A. J. , Hemmink G. J. M. , Smout A. J. P. M.
Published: April 2009

Abstract  The aim of the study is to compare the characteristics of reflux episodes in controls and in patients with various degrees of oesophagitis and Barrett’s oesophagus. Ambulatory 24‐h impedance‐pH tracings were analysed from healthy volunteers, patients with non‐erosive reflux disease (NERD), patients with grade A oesophagitis, grade B oesophagitis, grade C or D oesophagitis and patients with a short segment (<2 cm) of Barrett’s metaplasia. The number of acid and weakly acidic reflux episodes increased from 25.9 ± 3.9 to 17.9 ± 1.5 in the controls, 39.9 ± 6.3 to 33.4 ± 5.7 in the patients with NERD, 46.6 ± 6.2 to 40.4 ± 9.2 in grade A, 68.2 ± 9.2 to 49.2 ± 12.3 in grade B, 79.8 ± 15.6 to 47.4 ± 4.6 in grade C/D and 75.1 ± 7.9 to 37.3 ± 8.5 in the patients with Barrett. The proportion of reflux episodes that is acidic or alkaline was similar all groups. Comparison with normal values revealed that none of the controls, 40% of the patients with NERD, 50% of the patients with grade A, 80% of the patients with grade B and all patients with grade C/D or Barrett’s oesophagus had an abnormally high total number of reflux episodes. In the patients with severe oesophagitis a significantly higher percentage of reflux episodes reached the proximal oesophagus (43.8%) compared to the patients with Barrett’s oesophagus (19.2%). With increasing degrees of oesophagitis, patients have more reflux episodes but a large overlap between the groups exists making comparison with normal values of limited relevance. In patients with Barrett’s oesophagus fewer reflux episodes reach the proximal oesophagus which might explain their low sensitivity to reflux.
Eosinophilic oesophagitis in adults
Authors: Gonsalves N. , Kahrilas P. J.
Published: April 2009

Abstract  Previously considered a rare condition, eosinophilic oesophagitis (EoE) has become increasingly recognized as an important cause of dysphagia and food impactions in adults. This is likely attributable to a combination of an increasing incidence of EoE and a growing awareness of the condition. EoE may occur in isolation or in conjunction with eosinophilic gastroenteritis. However, the burgeoning field is likely attributable to the variant that uniquely affects the oesophagus. Adults classically present with symptoms of dysphagia, food impactions, and heartburn. Typical endoscopic features include concentric mucosal rings, linear furrowing, white plaques or exudates and a narrow caliber oesophagus. In some cases, the endoscopic features may appear normal. For years, EoE went unrecognized because eosinophilic infiltration was accepted as a manifestation of reflux, which continues to be a confounding factor in some patients. Current consensus is that the diagnosis of EoE is established by 1) the presence of symptoms, especially dysphagia and food impactions in adults, 2) ≥15 eosinophils per high power field in oesophageal tissue, and 3) exclusion of other disorders with similar presentations such as GERD. Current understanding of EoE pathophysiology and natural history are limited but the entity has been increasingly linked to food allergies and aeroallergens. The main treatment options for EoE are proton pump inhibitors, dietary manipulation, and topical or oral glucocorticoids. This review highlights recent insights into EoE in adults although, clearly, much of the available data overlap with pediatrics and, occasionally, with eosinophilic gastroenteritis.
Assessment of donor steatosis in liver transplantation: is it possible without liver biopsy?
Authors: Cucchetti Alessandro , Vivarelli Marco , Ravaioli Matteo , Cescon Matteo , Ercolani Giorgio , Piscaglia Fabio , Gaudio Massimo Del , Grazi Gian Luca , Ridolfi Lorenza , Pinna Antonio Daniele
Published: April 2009

Abstract:  Background:  Macrovesicular steatosis of the liver is associated with early dysfunction or poor function of the graft after transplantation; however, it can be quantified accurately only through a liver biopsy that sometimes may not be available and whose result is anyway known when the recipient has already been selected. It would, therefore, be helpful to be able to predict the degree of steatosis, on the basis of non‐invasive readily available variables.

Methods:  Data from 374 deceased liver donors from whom a liver biopsy had been taken were analyzed with the receiver operating characteristic area [area under the curve (AUC)] to identify variables that could predict the degree of macrovesicular steatosis classified as: absent to mild (0–30%) and moderate to severe (>30%).

Results:  Steatosis was associated significantly with donor age, increased body mass index (BMI), presence of type II diabetes, ultrasonographic features, heavy alcohol consumption, transaminases [aspartate‐aminotransferase and alanine‐aminotransferase (ALT)], gamma‐glutamyl‐transpeptidase, and glucose blood levels. The combination of BMI, elevation of ALT, presence of type II diabetes, history of heavy alcohol consumption, and ultrasonography signs of steatosis could identify steatosis >30% accurately with an AUC of 0.86 (95% CI = 0.81–0.91).

Conclusion:  Fatty infiltration in liver donors can be estimated based on clinical and biochemical parameters.
A critical component that activates the left inferior prefrontal cortex during interference resolution
Authors: Jimura Koji , Yamashita Ken‐ichiro , Chikazoe Junichi , Hirose Satoshi , Miyashita Yasushi , Konishi Seiki
Published: April 2009

Previous studies of proactive interference (PI) have revealed the involvement of the left inferior frontal gyrus (IFG) in resolution of PI during working memory/item recognition. PI resolution is thought to require: (1) inhibition of inappropriate attribution of familiarity to the probe and resultant inappropriate response tendencies; and (2) inhibition of PI per se regardless of the appropriateness of the attribution of familiarity. It is not clear, however, whether the IFG supports inhibition of inappropriate response tendencies or inhibition of PI per se. In the present functional magnetic resonance imaging study, we dissociate these possibilities using a recency judgment paradigm. Recency judgments, judgments of the relative temporal order of two studied items, provided an opportunity of examining three types of trials that differed in the way PI influenced the current trials: the trials where PI from previous trials was congruent with the current trials (C‐PI trials); the trials where PI was incongruent with the current trials (I‐PI trials); and the trials where no PI influenced the current trials (N‐PI trials). Relative to the N‐PI trials, the I‐PI trials elicited the significant left IFG activation associated with PI resolution, consistent with previous studies using working memory/item recognition. We found that the IFG activation was related not to inhibition of inappropriate response tendencies (I‐PI vs. C‐PI), but to inhibition of PI per se (C‐PI vs. N‐PI). These results indicate that the left IFG plays its control role regardless of whether or not PI is congruent with correct performance of current trials.
Impact of high‐fat /low‐carbohydrate, high‐, low‐glycaemic index or low‐caloric meals on glucose regulation during aerobic exercise in Type 2 diabetes
Authors: Ferland A. , Brassard P. , Lemieux S. , Bergeron J. , Bogaty P. , Bertrand F. , Simard S. , Poirier P.
Published: April 2009

Aims  A decrement in blood glucose (BG) may be observed in patients with Type 2 diabetes (T2DM) when exercise is performed after a meal, in contrast to fasting. We determined the impact of different pre‐exercise meal macronutrient compositions with modulation of the glycaemic index (GI) on glucose regulation during exercise in patients with T2DM.

Methods  Using a randomized, single‐blind crossover design, 10 sedentary men performed five exercise sessions, once after an overnight fast, and also after each of four test meals, consisting of a high‐fat/low‐carbohydrate meal, a high‐GI meal, a low‐GI meal, and a low‐calorie meal.

Results  Pre‐exercise BG and insulin levels were comparable for all four meals. Exercise decreased BG and insulin levels during all meal conditions (all P < 0.001) compared with the fasting state in which BG levels did not change. The magnitude of BG and insulin decrements was similar after consuming the low‐calorie, the high‐GI and the high‐fat/low‐carbohydrate meals, whereas the low‐GI meal induced the lowest BG fall. Adrenaline response was higher after consumption of the high‐, the low‐GI and the low‐caloric meals compared with the high‐fat/low‐carbohydrate meal and with the fasting state (P < 0.05).

Conclusions  This study underlines the beneficial effect of low‐GI foods and the differential impact of pre‐exercise meal macronutrient composition on BG decrease. This may protect against exercise‐induced hypoglycaemia, and reiterates the safety of exercising while fasting in T2DM patients.
Continuous subcutaneous insulin infusion is more effective than multiple daily insulin injections in preventing albumin excretion rate increase in Type 1 diabetic patients
Authors: Lepore G. , Bruttomesso D. , Bonomo M. , Dodesini A. R. , Costa S. , Meneghini E. , Corsi A. , Nosari I. , Trevisan R.
Published: April 2009

Aims  To compare the effect of continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) on albumin excretion rate (AER) in Type 1 diabetic patients.

Methods  In a 3‐year multicentre retrospective observational study, 110 Type 1 diabetic patients treated with CSII were compared with 110 patients treated with MDI matched at baseline for age, sex, diabetes duration and HbA1c. At entry, 90 patients in each group had normal AER and 20 persistent microalbuminuria. AER, estimated glomerular filtration rate (eGFR), HbA1c, lipids and blood pressure were assessed.

Results  HbA1c was lower in the CSII than in the MDI group (8.1 ± 0.9 vs. 8.4 ± 1.3%; P < 0.005 after 3 years). Blood pressure and eGFR were similar during the study. AER [median (95% confidence interval)], similar at baseline [6.0 μg/min (9, 21) in the CSII group vs. 4.4 (8, 16) in the MDI group, NS] was significantly lower in the patients treated with CSII both at year 2 and at year 3 of follow‐up [4.7 μg/min (6, 12) vs. 6.4 (13, 29), P < 0.002]. This difference was observed even when normo‐ and microalbuminuric patients were analysed separately. Nine patients progressed to microalbuminuria in the MDI group and only one in the CSII group. Nine patients regressed to normoalbuminuria in the CSII group, whereas only two regressed to normoalbuminuria in the MDI group.

Conclusions  Despite a small benefit in terms of improved glycaemic control, CSII therapy may be useful in decreasing the progressive increase in AER in Type 1 diabetic patients.
Australia’s national trends in the incidence of Type 1 diabetes in 0–14‐year‐olds, 2000–2006
Authors: Catanzariti L. , Faulks K. , Moon L. , Waters A.‐M. , Flack J. , Craig M. E.
Published: April 2009

Aims  To determine the national incidence of Type 1 diabetes in children aged 0–14 years and examine trends in incidence between 2000 and 2006 by age, sex and calendar year.

Methods  Case ascertainment was from the Australian National Diabetes Register, a prospective population‐based incidence register established in 1999, with two sources of ascertainment: the National Diabetes Services Scheme and the Australasian Paediatric Endocrine Group’s state‐based registers. Denominator data were from the Australian Bureau of Statistics.

Results  There were 6350 new cases of Type 1 diabetes (3323 boys and 3027 girls). Case ascertainment was 97.1% complete using the capture–recapture method. The mean adjusted incidence rate for 2000–2006 was 21.6 per 100 000 person‐years [95% confidence interval (CI) 21.0, 22.1], and increased from 19.8 in 2000 to 23.4 per 100 000 in 2006, an average increase of 2.8% (95% CI 1.5, 4.1) per year. Mean incidence for the 7‐year period increased with age, and was significantly higher in boys aged 0–4 years and 10–14 years than in girls of the same age.

Conclusions  The incidence of Type 1 diabetes among 0–14‐year‐olds in Australia is very high compared with available data from many other countries. The rate of increase observed globally in the last decade has continued well into this decade in Australia. The rising incidence cannot be explained by changes in genetic susceptibility; there is an urgent need to examine the environmental factors that have contributed to this increase. The findings of this study also have important implications for resource planning.
Optimizing TILLING populations for reverse genetics in Medicago truncatula
Authors: Le Signor Christine , Savois Vincent , Aubert Grégoire , Verdier Jérôme , Nicolas Marie , Pagny Gaelle , Moussy Françoise , Sanchez Myriam , Baker Dave , Clarke Jonathan , Thompson Richard
Published: April 2009

Medicago truncatula has been widely adopted as a model plant for crop legume species of the Vicieae. Despite the availability of transformation and regeneration protocols, there are currently limited tools available in this species for the systematic investigation of gene function. Within the framework of the European Grain Legumes Integrated Project (http://www.eugrainlegumes.org), chemical mutagenesis was applied to M. truncatula to create two mutant populations that were used to establish a TILLING (targeting induced local lesions in genomes) platform and a phenotypic database, allowing both reverse and forward genetics screens. Both populations had the same M2 line number, but differed in their M1 population size: population 1 was derived from a small M1 population (one‐tenth the size of the M2 generation), whereas population 2 was generated by single seed descent and therefore has M1 and M2 generations of equal size. Fifty‐six targets were screened, 10 on both populations, and 546 point mutations were identified. Population 2 had a mutation frequency of 1/485 kb, twice that of population 1. The strategy used to generate population 2 is more efficient than that used to generate population 1, with regard to mutagenesis density and mutation recovery. However, the design of population 1 allowed us to estimate the genetically effective cell number to be three in M. truncatula. Phenotyping data to help forward screenings are publicly available, as well as a web tool for ordering seeds at http://www.inra.fr/legumbase
Strategies to mitigate transgene–promoter interactions
Authors: Gudynaite‐Savitch Loreta , Johnson Douglas A. , Miki Brian L. A.
Published: April 2009

The expression pattern of tissue‐specific promoters in transgenes can be influenced by promoter/enhancer elements employed for the expression of selectable marker genes or elements found in DNA flanking the insertion site. We have developed an analytical system in Arabidopsis thaliana to investigate strategies useful in blocking or reducing nonspecific interactions. These experiments confirm that the DNA configuration and the insertion of spacer DNA aid in the appropriate expression of tissue‐specific promoters. It is also demonstrated that the novel tobacco cryptic promoter (tCUP), when used to replace the cauliflower mosaic virus (CaMV) 35S promoter/enhancer, does not show nonspecific interactions. Furthermore, it is shown that insulators isolated from yeast and animals may have potential application in plants. Our results may allow the design of strategies that, individually or in combination, can be used to minimize nonspecific interactions and to design vectors for individual tissue‐specific promoters.
Developmental differences in memory for cross‐modal associations
Authors: Pirogovsky Eva , Murphy Claire , Gilbert Paul E.
Published: April 2009

Associative learning is critical to normal cognitive development in children. However, young adults typically outperform children on paired‐associate tasks involving visual, verbal and spatial location stimuli. The present experiment investigated cross‐modal odour–place associative memory in children (7–10 years) and young adults (18–24 years). During the study phase, six odours were individually presented and paired with one of 12 spatial locations on a board. During the test phase, participants were presented with the six stimuli individually and were asked to place each stimulus on the correct spatial location. Children committed significantly more errors on the odour–place task than did young adults. However, item recognition memory for the odours or spatial locations involved in the odour–place associative memory task was similar between children and young adults. Therefore, poor odour–place associative memory in children did not result from impaired memory for the individual odours or spatial locations involved in the associations. The results suggest that cross‐modal associative memory is not fully developed in children.
Children perseverate to a human's actions but not to a robot's actions
Authors: Moriguchi Yusuke , Kanda Takayuki , Ishiguro Hiroshi , Itakura Shoji
Published: April 2009

Previous research has shown that young children commit perseverative errors from their observation of another person’s actions. The present study examined how social observation would lead children to perseverative tendencies, using a robot. In Experiment 1, preschoolers watched either a human model or a robot sorting cards according to one dimension (e.g. shape), after which they were asked to sort according to a different dimension (e.g. colour). The results showed that children’s behaviours in the task were significantly influenced by the human model’s actions but not by the robot’s actions. Experiment 2 excluded the possibility that children’s behaviours were not affected by the robot’s actions because they did not observe its actions. We concluded that children’s perseverative errors from social observation resulted, in part, from their socio‐cognitive ability.
Bad Drives Psychological Reactions, but Good Propels Behavior
Authors: Wang Cynthia S. , Galinsky Adam D. , Murnighan J. Keith
Published: April 2009

Research across disciplines suggests that bad is stronger than good and that individuals punish deception more than they reward honesty. However, methodological issues in previous research limit the latter conclusion. Three experiments resolved these issues and consistently found the opposite pattern: Individuals rewarded honesty more frequently and intensely than they punished deception. Experiment 2 extended these counterintuitive findings by revealing a divergence between evaluation and behavior: Evaluative reactions to deception were stronger than those to honesty, but behavioral intentions in response to honesty were stronger than those in response to deception. In addition, individuals wanted to avoid deceivers more than they wanted to approach honest actors. Experiment 3 found that punishment, but not reward, frequencies were sensitive to costs. Moderated-mediation tests revealed the role of different psychological mechanisms: Negative affect drove punishments, whereas perceived trustworthiness drove rewards. Overall, bad appears to be stronger than good in influencing psychological reactions, but good seems to be stronger than bad in influencing behavior.
The Enhancement of Visuospatial Processing Efficiency Through Buddhist Deity Meditation
Authors: Kozhevnikov Maria , Louchakova Olga , Josipovic Zoran , Motes Michael A.
Published: April 2009

This study examined the effects of meditation on mental imagery, evaluating Buddhist monks' reports concerning their extraordinary imagery skills. Practitioners of Buddhist meditation were divided into two groups according to their preferred meditation style: Deity Yoga (focused attention on an internal visual image) or Open Presence (evenly distributed attention, not directed to any particular object). Both groups of meditators completed computerized mental-imagery tasks before and after meditation. Their performance was compared with that of control groups, who either rested or performed other visuospatial tasks between testing sessions. The results indicate that all the groups performed at the same baseline level, but after meditation, Deity Yoga practitioners demonstrated a dramatic increase in performance on imagery tasks compared with the other groups. The results suggest that Deity meditation specifically trains one's capacity to access heightened visuospatial processing resources, rather than generally improving visuospatial imagery abilities.
Low genetic diversity in the masked palm civet Paguma larvata (Viverridae)
Authors: Patou M.‐L. , Chen J. , Cosson L. , Andersen D. H. , Cruaud C. , Couloux A. , Randi E. , Zhang S. , Veron G.
Published: April 2009

The masked palm civet is distributed through south‐east Asia, China and the Himalayas. Because of its potential role in the severe acute respiratory syndrome (SARS) epidemic, it has become important to gather information on this species, and notably to provide a tool to determine the origin of farm and market animals. For this purpose, we studied the genetic variability and the phylogeographic pattern of the masked palm civet Paguma larvata. First, two portions of mitochondrial genes, cytochrome b and the control region, were sequenced for a total of 76 individuals sampled from China, the Indochinese region and the Sundaic region. Results indicated a low genetic variability and suggested a lack of a phylogeographic structure in this species, which do not allow inferring the geographic origin of samples of unknown origin, although it is possible to distinguish individuals from China and the Sundaic region. This low variation is in contrast to the well‐marked morphological differentiation between the populations in the Sundaic and Chinese–Indochinese regions. We also used five microsatellite loci to genotype 149 samples from two wild and four farmed populations in China, where the masked palm civet is farmed and where the SARS coronavirus was isolated. These analyses also showed a reduced variability in Chinese civets and showed that farmed populations did not exhibit a lower genetic diversity than wild populations, suggesting frequent introductions of wild individuals into farms.
Understanding Sierra Leone in Colonial West Africa: A Synoptic Socio‐Political History
Authors: Bangura Joseph
Published: April 2009

Sierra Leone played a pivotal role in the success of the British colonial project in West Africa in the 19th century. In 1866, it served as the administrative headquarters for the colonies of Lagos, the Gold Coast now Ghana and Bathurst Gambia. Professionals, clergymen, and intellectuals from Sierra Leone, particularly Creoles, served as civil servants, engineers, and medical doctors in Nigeria, Ghana, and the Gambia in the 18th and 19th centuries. Sierra Leone also educated one of the first crops of Western‐educated elites in West Africa. In short, despite experiencing a devastating civil war, evidently Sierra Leone is gradually regaining its quintessential role as one of the oldest, peaceful, and democratic states in West Africa.
Literature, History, Periodization, and the Pleasures of the Latin Literary History of Late Antiquity
Authors: Shanzer Danuta
Published: April 2009

This survey aims to look back on, and to serve as an invitation to, the study of the Latin literature of Late Antiquity. While Late Antiquity has now emerged and been validated as an important subject for historians, the same cannot be said for philologists, literary historians, and literary critics. Paradigms of decadence, degeneration, and decline still reign in the minds of many classicists (from whose ranks many ‘late antiques’ will ultimately be recruited), while many historians who come to Late Antiquity from the Middle Ages will remain just that, namely historians, and may not have the chance to acquire the linguistic formation to study Late Antique texts closely; perhaps not even the will to do so, for the study of medieval history through literary texts (as opposed to documents) is comparatively recent.1 The classical canon is restrictive, excluding, as it does, Christian and Jewish texts. The available larger scale literary histories may not be doing much to make scholars want to read texts from the late 2nd through the 7th century. They range from the dismissive acceleration through ‘fly‐over’ territory to the learned, objective, exhaustive, but dry. From the early 20th century the effete and decadent Des Esseintes's Late Latin reading list in Huysmans's A rebours still seems rather more stimulating. A much broader, but gradual approach, acknowledging that one cannot do everything, will ultimately be most constructive. Late Antiquity has an enormous amount of new and emerging material for study as well as great and complicated old problems to contemplate. Special pleasures include the study of the literary history of specific provinces, learning to work with hagiography, reading ‘substandard’ Latin (including papyrological and epigraphic texts), contemplating the long trajectory of the evolution from Latin to Romance, reading authors with highly distinctive voices, learning to love exegesis, and more. Self‐identification as ‘textual’ rather than purely ‘literary’ specialists is particularly empowering.
Understanding herb and dietary supplement use in patients with epilepsy
Authors: Kaiboriboon Kitti , Guevara Marie , Alldredge Brian K.
Published: April 2009

Objective:  To determine the prevalence of herb and dietary supplement use and to provide a comprehensive analysis of factors influencing the use of these products in patients with epilepsy.

Methods:  We performed a cross‐sectional study using self‐administered questionnaires in a selected group of patients who were receiving care at a tertiary epilepsy center. Logistic regression was used to measure the association between the demographic variables and herb and dietary supplement use. In addition, we performed a MEDLINE search for each of the herb and dietary products used by our patients to determine the effect of these products on seizures and on their potential for interactions with other drugs metabolized by the liver.

Results:  One hundred eighty‐seven patients completed the survey. Fifty‐six percent of this group of patients with epilepsy used herbs and dietary supplements at the time of the survey. A considerable portion (71%) of these patients reported the use of these products to their physician, and most of them relied on their physicians as the primary source of information. Most of the patients used dietary supplement for health promotion rather than to specifically benefit their epilepsy condition. Approximately one‐third of patients used herb or dietary supplements that had the potential to increase seizures (16%) or to interact with hepatically metabolized drugs (19%). The most powerful independent predictors of herb and dietary supplement use were partial epilepsy [odds ratio (OR) 3.36; 95% confidence interval (CI) 1.27–8.88] and Caucasian race (OR 3.55; 95% CI 1.11–11.34).

Conclusion:  Patients with epilepsy commonly used dietary supplements along with their antiepileptic medications. The majority of these patients used herb and dietary supplements for health promotion rather than because of dissatisfaction with conventional treatment. It is important that physicians involved in the care of patients with epilepsy routinely inquire about the use of dietary supplements and that they make use of reliable resources to assess the safety of these products with regard to modification of seizure risk and the potential for interactions with antiepileptic drugs.
Design and Analysis of Bioenergy Networks
Authors: Kempener Ruud , Beck Jessica , Petrie Jim
Published: April 2009

This article presents a new methodology for designing industrial networks and analyzing them dynamically from the standpoint of sustainable development. The approach uses a combination of optimization and simulation tools. Assuming “top‐down” overarching control of the network, we use global dynamic optimization to determine which evolutionary pathways are preferred in terms of economic, social, and environmental performance. Considering the autonomy of network entities and their actions, we apply agent‐based simulation to analyze how the network actually evolves. These two perspectives are integrated into a powerful multiscale modeling framework for evaluating the consequences of new policy instruments or different business strategies aimed at stimulating sustainable development as well as identifying optimal leverage points for improved performance of the network in question. The approach is demonstrated for a regional network of interdependent organizations deploying a set of bioenergy technologies within a developing‐economy context.
Depressive Symptoms and Incident Cognitive Impairment in Cognitively Well‐Functioning Older Men and Women
Authors: Ng Tze Pin , Niti Mathew , Zaw Min Htet , Kua Ee Heok
Published: April 2009

OBJECTIVES: To investigate whether the effect of depressive symptoms on the risk of cognitive decline and incident cognitive impairment (CI) in cognitively well‐functioning older persons differed between men and women and whether sex differences in cerebrovascular factors might explain this.

DESIGN: Prospective cohort study.

SETTING: General community.

PARTICIPANTS: One thousand four hundred eighty‐seven well‐functioning Chinese older adults (Mini‐Mental State Examination (MMSE) score ≥24) assessed at baseline for the presence of depressive symptoms (Geriatric Depression Scale score ≥5), and covariates (age, apolipoprotein E ɛ4, education, smoking, alcohol drinking, and vascular risk factors and diseases).

MAIN OUTCOME MEASURES: Incident CI and change in MMSE were assessed at 2‐year follow‐up.

RESULTS: In the whole sample, participants with depression showed significantly more incident CI than those without (5.7% vs 2.6%, P=.04; adjusted odds ratio (OR)=2.29, 95% confidence interval (CI)=1.05–5.00. Significantly higher OR was observed only in men (OR=4.75, 95% CI=1.22–18.5) and not for women (OR=1.29). There was a correspondingly greater rate of cognitive decline in participants with depressive symptoms that was observed to be marked only in men and not in women. The association was accentuated in subgroups with hypertension or vascular factors, but the sex differences in association were consistently observed.

CONCLUSION: The association between depressive symptoms and risk of cognitive decline was observed only in men and was not explained by sex differences in vascular factors. The comorbid presence of underlying cerebral vascular pathology or multi‐infarct disease was possibly not a mediating factor but might amplify the process of cognitive decline.
Potentially Inappropriate Medications and Functional Decline in Elderly Hospitalized Patients
Authors: Corsonello Andrea , Pedone Claudio , Lattanzio Fabrizia , Lucchetti Maria , Garasto Sabrina , Di Muzio Massimo , Giunta Sergio , Onder Graziano , Di Iorio Angelo , Volpato Stefano , Corica Francesco , Mussi Chiara , Antonelli Incalzi Raffaele ,   on behalf of the Pharmacosur Veillance in the Elderly Care Study Group
Published: April 2009

OBJECTIVES: To verify whether the use of potentially inappropriate medications (PIMs) is associated with loss of independence in elderly in‐patients by promoting adverse drug reactions (ADRs).

DESIGN: Prospective observational study.

PARTICIPANTS: Five hundred six patients aged 65 and older admitted to 11 acute care medical wards.

MEASUREMENTS: In‐hospital loss of one or more activities of daily living (ADLs) and three or more ADLs. PIMs were identified according to diagnosis‐independent Beers criteria and ascertained by study physicians based on daily review of medical and nurse records. The relationship between risk factors and outcomes was assessed using logistic regression.

RESULTS: Overall, 104 patients (20.6%) were taking at least one PIM at the time of admission (baseline users), and 49 (9.7%) were newly prescribed at least one PIM during their hospital stay. The loss of one or more ADLs occurred in 9.6% of baseline users, 16.3% of new users, and 8.5% of nonusers (P=.21) and that of three or more ADLs in 7.7% of baseline users, 12.2% of new users, and 4.8% of nonusers (P=.10). The lack of association was confirmed after correction for potential confounders, including ADRs. The occurrence of ADRs was strongly associated with both outcomes (odds ratio (OR)=7.80, 95% confidence interval (CI)=3.53–17.3 for the loss of ≥1 ADLs; OR=3.98, 95% CI=1.50–10.5 for the loss of ≥3 ADLs), but PIMs caused only six of 106 ADRs.

CONCLUSIONS: ADRs to any drugs more than the use of PIMs might be associated with functional decline in elderly hospitalized patients, but because the power of this study was too limited to definitively exclude a direct relationship between PIMs and functional decline, this merits further investigation.