bluuebunny/crossref_metadata_2025 huggingface dataset:
Consumer understanding of sugars claims on food and drink products
Authors: Patterson N. J. , Sadler M. J. , Cooper J. M.
Published: May 2012

Consumer understanding of nutrition and health claims is a key aspect of current regulations in the European Union (EU). In view of this, qualitative and quantitative research techniques were used to investigate consumer awareness and understanding of product claims in the UK, focusing particularly on nutrition claims relating to sugars. Both research methods identified a good awareness of product claims. No added sugars claims were generally preferred to reduced sugars claims, and there was a general assumption that sweeteners and other ingredients would be added in place of sugars. However, there was little awareness of the level of sugar reduction and the associated calorie reduction in products when reduced sugars claims were made on pack. In focus groups, participants felt deceived if sugar reduction claims were being made without a significant reduction in calories. This was reinforced in the quantitative research which showed that respondents expected a similar and meaningful level of calorie reduction to the level of sugar reduction. The research also identified consumer confusion around the calorie content of different nutrients, including over‐estimation of the calorie content of sugars. This is crucial to consumers' expectations as they clearly link sugar to calories and therefore expect a reduction in sugar content to deliver a reduction in calorie content.
Hypothalamic obesity in children
Authors: Bereket A. , Kiess W. , Lustig R. H. , Muller H. L. , Goldstone A. P. , Weiss R. , Yavuz Y. , Hochberg Z.
Published: May 2012

Hypothalamic obesity is an intractable form of obesity syndrome that was initially described in patients with hypothalamic tumours and surgical damage. However, this definition is now expanded to include obesity developing after a variety of insults, including intracranial infections, infiltrations, trauma, vascular problems and hydrocephalus, in addition to acquired or congenital functional defects in central energy homeostasis in children with the so‐called common obesity. The pathogenetic mechanisms underlying hypothalamic obesity are complex and multifactorial. Weight gain results from damage to the ventromedial hypothalamus, which leads, variously, to hyperphagia, a low‐resting metabolic rate; autonomic imbalance; growth hormone‐, gonadotropins and thyroid‐stimulating hormone deficiency; hypomobility; and insomnia. Hypothalamic obesity did not receive enough attention, as evidenced by rarity of studies in this group of patients. A satellite symposium was held during the European Congress of Obesity in May 2011, in Istanbul, Turkey, to discuss recent developments and concepts regarding pathophysiology and management of hypothalamic obesity in children. An international group of leading researchers presented certain aspects of the problem. This paper summarizes the highlights of this symposium. Understanding the central role of the hypothalamus in the regulation of feeding and energy metabolism will help us gain insights into the pathogenesis and management of common obesity.
Psychological Safety, Knowledge Sharing, and Creative Performance in Healthcare Teams
Authors: Kessel Maura , Kratzer Jan , Schultz Carsten
Published: May 2012

We examined how psychological safety fosters knowledge‐sharing processes and enables team creative performance. Using a multi‐respondent design, we tested our hypotheses using survey data collected from 73 patient‐centred healthcare teams working in the field on rare diseases. The data were analysed using latent class regression analysis. We confirmed that a high level of psychological safety within the team is a significant predictor of creative team performance and is mediated by the sharing of two types of knowledge: information and know‐how.
The Ethical Dilemma of Information Asymmetry in Innovation: Reputation, Investors and Noise in the Innovation Channel
Authors: Millar Carla , Udalov Yuri , Millar Hartley
Published: May 2012

A sufficient and steady stream of innovations is widely seen as a basis for healthy modern economies. Governments divert substantial resources from other purposes in society to increase innovation. Yet the failure rate among innovative SMEs is high, suggesting that resources are wasted. Avoiding such waste is a challenge for both governments and investors, but also raises a question for the innovative company, namely how to build and fund the enterprise on an ethical basis. The dilemma of giving in to temptations to ‘cut corners’ clearly exists, for example to exploit the inevitable asymmetry of information arising in innovation and potentially deploy this in support of misleading claims about specific capabilities and/or the unjustified creation and exploitation of reputation. This is consistent with Olaf Fisscher's finding that entrepreneurs starting new ventures tend to exhibit an inherent bias towards compromising their own values in order to succeed at any cost. When the innoSME's aspirations are unrealistic or the proposed innovations are of marginal value, the ethical issues are broader and extend also to those who are potential financiers. Noting this as a gap in the ethics literature, we argue that the current situation fails to match economic and ethical ideals and that work is needed to develop tools which allow those who provide finance and support for innovation to target it more effectively at those who have a prospect of successfully launching genuine innovations and thus reduce the ‘noise’ in the innovation field.
Corporate Social Responsibility in Innovation: Insights from two Cases of Syngenta's Activities in Genetically Modified Organisms
Authors: Weisenfeld Ursula
Published: May 2012

Corporate social responsibility (CSR) implies that companies have collective responsibility beyond legal requirements. This ‘beyond’ can be described along the ‘triple bottom line’ of sustainability (social, environmental and economic dimensions). Dealing with these dimensions is under discussion in societies and some propose the stakeholder concept as a framework for companies to identify their responsibilities. However, who counts as a key stakeholder and what is a legitimate stake are difficult to determine. This article discusses reasons, possibilities and difficulties of managing responsibility in innovation, taking two cases of genetically modified organisms as examples. It is argued that the stakeholder approach is necessary to provide different perspectives, but is not enough or even completely unsuitable for defining responsibilities. Moral responsibility involves judgement that differs between stakeholders and might vary over time, owing to emerging insights and changing priorities. Therefore, pursuing or abandoning a particular project does not constitute a responsible organization; rather, it is the preparation of decisions, accountability and the resulting pattern of behaviour that renders an organization responsible. The various notions of responsibility set the scene for discussion but do not provide a clear answer to the questions of right or wrong and good or ill intent. Key conclusions are that companies need to organize for responsibility and that responsibility needs to be complemented with accountability.
Does Median Voter Income Matter? The Effects of Inequality and Turnout on Government Spending
Authors: Barnes Lucy
Published: May 2012

This article examines the relationship between economic inequality, electoral turnout and redistributive spending. I use the Current Population Survey to create direct measures of the income of the median voter to investigate its effect on spending and its relationship with inequality and turnout. In the 50 US states from 1978 to 2002, I find little effect of these direct measures on redistributive outcomes; nor do the individual characteristics of the median voter appear to mediate the effects of turnout and inequality measured at the state level. Thus I find no support for the contention that turnout affects government spending via increasing the political representation of the poor. In contrast to cross-national findings, across US states the income of the median voter is not strongly affected by turnout, but rather by other state characteristics.
A true simulation study of three estimators at equal protection of respondents in randomized response sampling
Authors: Singh Sarjinder , Sedory Stephen A.
Published: May 2012

In this study, three different estimators for estimating the proportion of a sensitive attribute in survey sampling are compared at equal protection of the respondents. The three estimators considered are due to Odumade and Singh (2009, Comm. Statist. Theory Methods), Singh and Sedory (2011, Sociological Methods and Research) and a new estimator obtained by minimizing a chi‐squared distance. A SAS Macro is developed to compare these three estimators using a simulation study at equal protection of the respondents. A set of data from a real face‐to‐face interview was collected using two decks of cards and has been analyzed. The results are discussed.
Direct Linearization of Extended Lattice BSQ Systems
Authors: Zhang D.‐J. , Zhao S.‐L. , Nijhoff F. W.
Published: May 2012

The direct linearization structure is presented of a “mild” but significant generalization of the lattice BSQ system. Some of the equations in this system were recently discovered in [1] through a search of a class of three‐component systems obeying the property of multidimensional consistency. We show that all the novel equations arising in this class follow from one and the same underlying structure. Lax pairs for these systems are derived and explicit expressions for the N‐soliton solutions are obtained from the given structure.
Alien finance and the development of the English economy, 1285–13111
Authors: NIGHTINGALE PAMELA
Published: May 2012

The contribution of alien, particularly Italian, investment to the development of the medieval English economy has provoked opposing views which hitherto have had to rely chiefly on customs records and evidence of Italian loans to the state for statistical evidence. These, though, vary in their coverage and do not record the inland trade. This article uses the Statute Merchant certificates of debt from 1285 to analyse changing levels of commercial investment by alien and denizen merchants throughout all areas of the kingdom. It shows that Italian investment was declining from the 1280s in line with falling imports of foreign silver. It discusses the causes of this decline, and the effect on alien and denizen credit of imports of counterfeit sterling coins produced by European mints. It relates these financial developments in England, France, and Flanders to the sequence of events which led to English merchants increasing their numbers and mercantile capital at the beginning of the fourteenth century when they were first able to establish their domination of the country's export trade in wool.
Law and credit constraints in transition economies1
Authors: Skosples Goran
Published: May 2012

Using a survey of over 4,000 firms in 21 transition economies, this paper investigates how legal extensiveness (law on the books) and legal effectiveness (law in practice) affect availability of bank finance. Our findings suggest that both law on the books and law in practice are important, but that they impact firms of different sizes differently. Small firms appear to be the most credit constrained in countries with weak creditor rights and with weak contract enforcement, while large firms are the most credit constrained in countries with weak courts and unclear and inconsistent laws pertaining to firms’ business operations.
Outlay equivalence analysis of child gender bias in household expenditure data
Authors: Parpiev Ziyodullo , Yusupov Kakhramon , Yusupov Nurmukhammad
Published: May 2012

This article reports the results of an empirical analysis of gender‐based discrimination among children based on household consumption data from Uzbekistan. We employ the outlay equivalence methodology to examine whether the entry of a new child leads to different effects in the decrease of adult good consumption for boys and for girls. We use a semi‐parametric estimation method to address the so‐called ‘zero consumption problem’, the statistical problem that arises because some households have zero consumption on a budget line in the period prior to the survey date. The results indicate that alcohol and tobacco reveal the incidence of discrimination against girls, while other groups of adult goods do not.
Diagnosing HIV infection in patients presenting with glandular fever‐like illness in primary care: are we missing primary HIV infection?
Authors: Hsu DTS , Ruf M , O'Shea S , Costelloe S , Peck J , Tong CYW
Published: May 2012

Objectives

The aim of the study was to examine the prevalence of HIV infection in patients presenting in primary care with glandular fever (GF)‐like illness.

Methods

Samples from primary care submitted for a GF screen between April 2009 and June 2010 were identified. Samples without an HIV request were anonymized and retrospectively tested using a 4th‐generation HIV antigen/antibody screening test. Reactive samples were further confirmed by an HIV antibody only test, with or without a p24 antigen assay. Antibody avidity testing based on the Recent HIV Infection Testing Algorithm (RITA) was used to identify individuals with evidence of recent acquisition (within 4–5 months).

Results

Of 1046 GF screening requests, concomitant HIV requests were made in 119 patients. Excluding one known positive patient, 2.5% (three of 118) tested HIV positive. Forty‐five (4.3%) had a subsequent HIV test through another consultation within 1 year; of these, 4.4% (two of 45) tested positive. Of the remaining 882 patients, 694 (78.7%) had samples available for unlinked anonymous HIV testing, of which six (0.9%) tested positive. The overall HIV prevalence was 1.3% (11 of 857), with 72.7% (eight of 11) of cases missed at initial primary care presentation. Four of the nine (44.4%) available positive samples had evidence of recent acquisition, with three (75.0%) missed at initial primary care presentation.

Conclusion

Low levels of HIV testing in patients presenting in primary care with GF‐like illness are resulting in a significant number of missed HIV and seroconversion diagnoses. Local policy should consider adopting an opt‐out strategy to include HIV testing routinely within the GF‐screening investigation panel.
Determinants of epidermal nerve fibre density in antiretroviral‐naïve HIV‐infected individuals
Authors: Shikuma CM , Gerschenson M , Ananworanich J , Valcour VG , Teeratakulpisarn N , Jadwattanakul T , DeGruttola V , Liang C‐Y , McArthur JC , Ebenezer GJ , Chomchey N , Praihirunkit P , Hongchookiath P , Mathajittiphun P , Nakamoto B , Hauer P , Phanuphak P , Phanuphak N ,   the SEARCH 003 protocol team
Published: May 2012

Objectives

Distal leg epidermal nerve fibre density (ENFD) is a validated predictor of small unmyelinated nerve fibre damage and neuropathy risk in HIV infection. As pre‐existing damage may increase the risk of neuropathy following antiretroviral (ARV) therapy, particularly when the regimen contains stavudine (d4T), we assessed the relationship between ENFD and various parameters including mitochondrial factors in HIV‐infected Thai individuals naïve to ARV therapy.

Methods

Distal leg and proximal thigh ENFDs were quantified in HIV‐infected Thai individuals without neuropathy prior to randomization to a HIV clinical trial that focused on mitochondrial toxicity issues. We assessed their association with various clinical and immunovirological parameters as well as with peripheral blood mononuclear cell (PBMC) mitochondrial (mt) DNA copies/cell, oxidative phosphorylation (OXPHOS) complex I (CI) and complex IV (CIV) enzyme activities, and mt 8‐oxo‐deoxyguanine (8‐oxo‐dG) break frequencies.

Results

In 132 subjects, the median (interquartile range) ENFD (fibres/mm) values were 21.0 (16.2–26.6) for the distal leg and 31.7 (26.2–40.0) for the proximal thigh. By linear regression, lower CD4 count (P < 0.01), older age (P < 0.01), increased body mass index (BMI) (P = 0.04), increased height (P = 0.02), and higher PBMC OXPHOS activity as measured by CIV activity (P = 0.02) were associated with lower distal leg ENFD.

Conclusions

Older age, increased height, higher BMI, poorer immunological status and higher PBMC OXPHOS activity are associated with lower distal leg ENFD in HIV‐infected subjects free of neuropathy prior to initiation of first‐time ARV therapy.
A difficult conversation? The views and experiences of parents and professionals on the consent process for perinatal postmortem after stillbirth
Authors: Heazell AEP , McLaughlin M‐J , Schmidt EB , Cox P , Flenady V , Khong TY , Downe S
Published: May 2012

Please cite this paper as: Heazell A, McLaughlin M, Schmidt E, Cox P, Flenady V, Khong T, Downe S. A difficult conversation? The views and experiences of parents and professionals on the consent process for perinatal postmortem after stillbirth. BJOG 2012;119:987–997.

Objective  To describe the experiences, knowledge and views of both parents and professionals regarding the consent process for perinatal postmortem.

Design  Internet‐based survey.

Setting  Obstetricians, midwives and perinatal pathologists currently working in the UK. Parents who have experienced a stillbirth in the UK in the previous 10 years.

Sample  Obstetricians, midwives and perinatal pathologists registered with their professional bodies. Parents who accessed the Sands website or online forum.

Methods  Online self‐completion questionnaire with both fixed‐choice and open‐ended questions.

Results  Responses were analysed from 2256 midwives, 354 obstetricians, 21 perinatal pathologists and 460 parents. The most common reason for parents to request postmortem examination was to find a cause for their baby’s death; the prevention of stillbirths in others also ranked highly. Perinatal pathologists possessed greatest knowledge of the procedure and efficacy of postmortem, but were unlikely to meet bereaved parents. The majority of professionals and parents ranked emotional distress and a lengthy wait for results as barriers to consent. The majority of staff ranked workload, negative publicity, religion and cultural issues as important barriers, whereas most parents did not. Almost twice as many parents who declined postmortem examination later regretted their decision compared with those who accepted the offer (34.4 versus 17.4%).

Conclusion  Emotional, practical and psychosocial issues can act as real or perceived barriers for staff and bereaved parents. Education is required for midwives and obstetricians, to increase their knowledge to ensure accurate counselling, with due regard for the highly individual responses of bereaved parents. The contribution of perinatal pathologists to staff education and parental decision‐making would be invaluable.
Taxonomy versus phylogeny: evolutionary history of marsh rabbits without hopping to conclusions
Authors: Tursi Rosanna M. , Hughes Phillip T. , Hoffman Eric A.
Published: May 2012

Aim

To evaluate whether population genetic structure reflects taxonomic recognition of the endangered Lower Keys marsh rabbit (
Sylvilagus palustris hefneri) and the two mainland subspecies.

Location

Southeastern United States.

Methods

We inferred phylogenetic relationships, population structure and genetic diversity within
S. palustris using a mitochondrial gene (cytochrome b) and 10 microsatellite loci.

Results

The cytochrome b sequence data revealed taxonomy‐phylogeography incongruence, and microsatellite data revealed moderate structure (
F

ST = 0.22) with two genetic clusters recovered: one grouping the western Lower Keys, and the second grouping the eastern Lower Keys together with the mainland. Furthermore, island genetic diversity was not reduced relative to mainland populations (cyt b: π: t = −0.6952, P = 0.5651; h: t = −1.2053, P = 0.4305; microsatellite:
H

E: t = −4.1201, P = 0.1313;
AR
: t = −2.3113, P = 0.2441).

Main conclusions

The taxonomy‐phylogeny disparity reveals unknown aspects of the evolutionary history including an absence of contemporary dispersal barriers between the mainland subspecies and a more recent Lower Keys isolation than originally thought. Moreover, diversity patterns indicate that undocumented man‐mediated transfers may contribute to current genetic structure between eastern Lower Keys and the mainland. Although subspecies designations were not confirmed, these findings support recognition of western Lower Keys populations as a distinct population segment under the Endangered Species Act.
Exceptionally well‐preserved isolated eyes from Cambrian ‘Orsten’ fossil assemblages of Sweden
Authors: CASTELLANI CHRISTOPHER , HAUG JOACHIM T. , HAUG CAROLIN , MAAS ANDREAS , SCHOENEMANN BRIGITTE , WALOSZEK DIETER
Published: May 2012

Abstract: Eyes other than those of trilobites are rarely preserved in the fossil record. We describe here a set of six tiny, isolated, three‐dimensionally preserved compound eyes. These secondarily phosphatized eyes were etched from ‘Orsten’ limestone nodules dated to theAgnostus pisiformisBiozone from the Cambrian Alum Shale Formation of Sweden. The ovoid eyes arise from an elongated stalk, their surface being covered by a mosaic of regular and hexagonal‐shaped facets representing the surface of ommatidia. Facet size and pattern change within the same specimen from the posterior to the anterior end. With regard to some morphological criteria, we grouped the material in two different morphotypes, type A and B, the first being represented by specimens of two different developmental stages. From stage to stage, mostly growth in overall size and addition of new ommatidia was noticed. Among the meiobenthic ‘Orsten’ arthropods, only the crustaceanHenningsmoenicaris scutulahas been described as possessing stalked eyes, but the eyes of the largest specimen with preserved eyes of this species are much smaller than the new eyes and do not display any kind of ommatidia on their visual surface. However, fragments of larger specimens ofH. scutulaand the co‐occurrence of this species with the new isolated eyes in the sieving residues make it likely that the latter belong to this species but belong to more advanced stages than those described previously ofH. scutula. Ontogenetically, the eye stalks of this fossil crustacean elongate progressively, while the regular hexagonal facets, lacking in early stages, appear later on.
Cost‐Effectiveness of an Electronic Medical Record Based Clinical Decision Support System
Authors: Gilmer Todd P. , O'Connor Patrick J. , Sperl‐Hillen JoAnn M. , Rush William A. , Johnson Paul E. , Amundson Gerald H. , Asche Stephen E. , Ekstrom Heidi L.
Published: May 2012

Background and Objective

Medical groups have invested billions of dollars in electronic medical records (EMRs), but few studies have examined the cost‐effectiveness of EMR‐based clinical decision support (CDS). This study examined the cost‐effectiveness of EMR‐based CDS for adults with diabetes from the perspective of the health care system.

Data Sources/Setting

Clinical outcome and cost data from a randomized clinical trial of EMR‐based CDS were used as inputs into a diabetes simulation model. The simulation cohort included 1,092 patients with diabetes with A1c above goal at baseline.

Study Design

The United Kingdom Prospective Diabetes Study Outcomes Model, a validated simulation model of diabetes, was used to evaluate remaining life years, quality‐adjusted life years (QALYs), and health care costs over patient lifetimes (40‐year time horizon) from the health system perspective.

Principal Findings

Patients in the intervention group had significantly lowered A1c (0.26 percent, p = .014) relative to patients in the control arm. Intervention costs were $120 (SE = 45) per patient in the first year and $76 (SE = 45) per patient in the following years. In the base case analysis, EMR‐based CDS increased lifetime QALYs by 0.04 (SE = 0.01) and increased lifetime costs by $112 (SE = 660), resulting in an incremental cost‐effectiveness ratio of $3,017 per QALY. The cost‐effectiveness of EMR‐based CDS persisted in one‐way, two‐way, and probabilistic sensitivity analyses.

Conclusions

Widespread adoption of sophisticated EMR‐based CDS has the potential to modestly improve the quality of care for patients with chronic conditions without substantially increasing costs to the health care system.
Function and expression of the proton‐coupled amino acid transporter PAT1 along the rat gastrointestinal tract: implications for intestinal absorption of gaboxadol
Authors: Broberg ML , Holm R , Tønsberg H , Frølund S , Ewon KB , Nielsen AL , Brodin B , Jensen A , Kall MA , Christensen KV , Nielsen CU
Published: May 2012

BACKGROUND AND PURPOSE Intestinal absorption via membrane transporters may determine the pharmacokinetics of drug compounds. The hypothesis is that oral absorption of gaboxadol (4,5,6,7‐tetrahydroisoxazolo [5,4‐c] pyridine‐3‐ol) in rats occurs via the proton‐coupled amino acid transporter, rPAT1 (encoded by the gene rSlc36a1). Consequently, we aimed to elucidate the in vivo role of rPAT1 in the absorption of gaboxadol from various intestinal segments obtained from Sprague‐Dawley rats.

EXPERIMENTAL APPROACH The absorption of gaboxadol was investigated following its administration into four different intestinal segments. The intestinal expression of rSlc36a1 mRNA was measured by quantitative real‐time PCR. Furthermore, the hPAT1‐/rPAT1‐mediated transport of gaboxadol or L‐proline was studied in hPAT1‐expressing Xenopus laevis oocytes, Caco‐2 cell monolayers and excised segments of the rat intestine.

KEY RESULTS The absorption fraction of gaboxadol was high (81.3–91.3%) following its administration into the stomach, duodenum and jejunum, but low (4.2%) after administration into the colon. The pharmacokinetics of gaboxadol were modified by the co‐administration of L‐tryptophan (an hPAT1 inhibitor) and L‐proline (an hPAT1 substrate). The in vitro carrier‐mediated uptake rate of L‐proline in the excised intestinal segments was highest in the mid jejunum and lowest in the colon. The in vitro uptake and the in vivo absorption correlated with the expression of rSlc36a1 mRNA along the rat intestine.

CONCLUSIONS AND IMPLICATIONS These results suggest that PAT1 mediates the intestinal absorption of gaboxadol and therefore determines its oral bioavailability. This has implications for the in vivo role of PAT1 and may have an influence on the design of pharmaceutical formulations of PAT1 substrates.
Retinoids: novel immunomodulators and tumour‐suppressive agents?
Authors: Carratù MR , Marasco C , Mangialardi G , Vacca A
Published: May 2012

Retinoids play important roles in the transcriptional activity of normal, degenerative and tumour cells. Retinoid analogues may be promising therapeutic agents for the treatment of immune disorders as different as type I diabetes and systemic lupus erythematosus. In addition, the use of retinoids in cancer treatment has progressed significantly in the last two decades; thus, numerous retinoid compounds have been synthesized and tested. In this paper, the actual or potential use of retinoids as immunomodulators or tumour‐suppressive agents is discussed.
Evaluation of bone marrow aspirates from multiple sites for staging of canine lymphoma and mast cell tumours
Authors: Aubry O. A. , Spangler E. A. , Schleis S. E. , Smith A. N.
Published: May 2012

Abstract

This prospective study evaluated the utility of bone marrow aspirates (BMAs) obtained from multiple sites for staging of canine lymphoma (LSA) and mast cell tumours (MCTs). Forty dogs (LSA, n = 24; MCTs, n = 16) were enrolled, but only 33 (82.5%) had diagnostic bone marrow (BM) aspirates obtained from two sites for inclusion in the study. Nineteen dogs with LSA were included, and 6 (31.6%) had BM involvement. Neoplastic lymphocytes were present in BM from both sites in all of these dogs. Fourteen dogs with MCTs were included, and 3 (21.4%) had BM involvement. Neoplastic mast cells were present at both sites in two dogs and at only one site in the third. These results indicate that BMAs from multiple sites may not be needed for accurate staging of canine LSA patients, but more studies evaluating the pattern of BM infiltration in dogs with high‐grade MCTs are warranted.
Patterns of altered functional connectivity in mesial temporal lobe epilepsy
Authors: Pittau Francesca , Grova Christophe , Moeller Friederike , Dubeau François , Gotman Jean
Published: May 2012

Purpose: In mesial temporal lobe epilepsy (MTLE) the epileptogenic area is confined to the mesial temporal lobe, but other cortical and subcortical areas are also affected and cognitive and psychiatric impairments are usually documented. Functional connectivity methods are based on the correlation of the blood oxygen level dependent (BOLD) signal between brain regions, which exhibit consistent and reproducible functional networks from resting state data. The aim of this study is to compare functional connectivity of patients with MTLE during the interictal period with healthy subjects. We hypothesize that patients show reduced functional connectivity compared to controls, the interest being to determine which regions show this reduction.

Methods: We selected electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) resting state data without EEG spikes from 16 patients with right and 7 patients with left MTLE. EEG‐fMRI resting state data of 23 healthy subjects matched for age, sex, and manual preference were selected as controls. Four volumes of interest in the left and right amygdalae and hippocampi (LA, RA, LH, and RH) were manually segmented in the anatomic MRI of each subject. The averaged BOLD time course within each volume of interest was used to detect brain regions with BOLD signal correlated with it. Group differences between patients and controls were estimated.

Key Findings: In patients with right MTLE, group difference functional connectivity maps (RMTLE − controls) showed for RA and RH decreased connectivity with the brain areas of the default mode network (DMN), the ventromesial limbic prefrontal regions, and contralateral mesial temporal structures; and for LA and LH, decreased connectivity with DMN and contralateral hippocampus. Additional decreased connectivity was found between LA and pons and between LH and ventromesial limbic prefrontal structures. In patients with left MTLE, functional connectivity maps (LMTLE − controls) showed for LA and LH decreased connectivity with DMN, contralateral hippocampus, and bilateral ventromesial limbic prefrontal regions; no change in connectivity was detected for RA; and for RH, there was decreased connectivity with DMN, bilateral ventromesial limbic prefrontal regions, and contralateral amygdala and hippocampus.

Significance: In unilateral MTLE, amygdala and hippocampus on the affected and to a lesser extent on the healthy side are less connected, and are also less connected with the dopaminergic mesolimbic and the DMNs. Changes in functional connectivity between mesial temporal lobe structures and these structures may explain cognitive and psychiatric impairments often found in patients with MTLE.
Epilepsy and psychiatric comorbidity: A nationally representative population‐based study
Authors: Rai Dheeraj , Kerr Michael P. , McManus Sally , Jordanova Vesna , Lewis Glyn , Brugha Traolach S.
Published: May 2012

Purpose:  In a nationally representative population‐based study in England, we estimated the burden of psychiatric and neurodevelopmental comorbidities in people with epilepsy. We investigated whether any overrepresentation of comorbidities could be explained by epilepsy being a chronic medical or neurologic condition, or by the confounding effect of demographic and socioeconomic factors or other health conditions.

Methods:  The Adult Psychiatric Morbidity Survey 2007 comprised detailed interviews with 7,403 individuals living in private households in England. Doctor‐diagnosed epilepsy (and asthma, diabetes, and migraine, chronic conditions for comparison) was ascertained by self‐report, and extensive diagnostic and screening interviews were used to assess psychiatric and neurodevelopmental conditions.

Key Findings:  The estimated lifetime prevalence of epilepsy in the adult (≥16 years old) population of England was 1.2% (95% confidence interval [CI] 1.0–1.5). Almost one‐third of the people with epilepsy had an International Classification of Diseases, Tenth Revision (ICD‐10) anxiety or depressive disorder (compared with one in six people without epilepsy). Among these, social phobia and agoraphobia, generalized anxiety disorder, depression, and measures of suicidality had strong associations with epilepsy, which remained robust after accounting for potential confounders. These associations were consistently stronger than those in people with asthma or diabetes, and similar to those in people reporting migraine or chronic headaches. Epilepsy was also strongly associated with autism spectrum disorders (odds ratio [OR] 7.4, 95% CI 1.5–35.5) and possible eating disorders, and these associations were not evident in people with asthma, diabetes, or migraine.

Significance:  Psychiatric and neurodevelopmental conditions were overrepresented in people with epilepsy. These associations were stronger than with other nonneurologic chronic conditions, and not explained by confounding. Some overlap in the psychopathology observed in epilepsy and migraine cannot rule out the presence of common pathways of psychiatric comorbidity in neurologic conditions. However, associations of epilepsy with conditions such as autism spectrum disorders point to comorbidities specific to epilepsy that may not be shared by other neurologic conditions.
Fast evaluation of interictal spikes in long‐term EEG by hyper‐clustering
Authors: Scherg Michael , Ille Nicole , Weckesser Dieter , Ebert Arndt , Ostendorf Andrea , Boppel Tobias , Schubert Susanne , Larsson Pål G. , Henning Oliver , Bast Thomas
Published: May 2012

Purpose:  The burden of reviewing long‐term scalp electroencephalography (EEG) is not much alleviated by automated spike detection if thousands of events need to be inspected and mentally classified by the reviewer. This study investigated a novel technique of clustering and 24‐h hyper‐clustering on top of automated detection to assess whether fast review of focal interictal spike types was feasible and comparable to the spikes types observed during routine EEG review in epilepsy monitoring.

Methods:  Spike detection used a transformation of scalp EEG into 29 regional source activities and adaptive thresholds to increase sensitivity. Our rule‐based algorithm estimated 18 parameters around each detected peak and combined multichannel detections into one event. Similarity measures were derived from equivalent location, scalp topography, and source waveform of each event to form clusters over 2‐h epochs using a density‐based algorithm. Similar measures were applied to all 2‐h clusters to form 24‐h hyper‐clusters. Independent raters evaluated electroencephalography data of 50 patients with epilepsy (25 children) using traditional visual spike review and optimized hyper‐cluster inspection. Congruence between visual spike types and epileptiform hyper‐clusters was assessed on a sublobar level using three‐dimensional (3D) peak topographies.

Key Findings:  Visual rating found 126 different epileptiform spike types (2.5 per patient). Independently, 129 hyper‐clusters were classified as epileptiform and originating in separate sublobar regions (2.6 per patient). Ninety‐one percent of visual spike types matched with hyper‐clusters (temporal lobe spikes 94%, extratemporal 89%). Conversely, 11% of hyper‐clusters rated epileptiform had no corresponding visual spike type. Numbers were comparable in adults and children. On average, 15 hyper‐clusters had to be inspected and rated per patient with an evaluation time of around 5 min.

Significance:  Hyper‐clustering over 24 h provides an independent tool for rapid daily evaluation of interictal spikes in long‐term video‐EEG monitoring. If used in addition to routine review of 2–5 min EEG per hour, sensitivity and reliability in noninvasive diagnosis of focal epilepsy increases.
Finding a better drug for epilepsy: The mTOR pathway as an antiepileptogenic target
Authors: Galanopoulou Aristea S. , Gorter Jan A. , Cepeda Carlos
Published: May 2012

The mammalian target of rapamycin (mTOR) signaling pathway regulates cell growth, differentiation, proliferation, and metabolism. Loss‐of‐function mutations in upstream regulators of mTOR have been highly associated with dysplasias, epilepsy, and neurodevelopmental disorders. These include tuberous sclerosis, which is due to mutations in TSC1 or TSC2 genes; mutations in phosphatase and tensin homolog (PTEN) as in Cowden syndrome, polyhydramnios, megalencephaly, symptomatic epilepsy syndrome (PMSE) due to mutations in the STE20‐related kinase adaptor alpha (STRADalpha); and neurofibromatosis type 1 attributed to neurofibromin 1 mutations. Inhibition of the mTOR pathway with rapamycin may prevent epilepsy and improve the underlying pathology in mouse models with disrupted mTOR signaling, due to PTEN or TSC mutations. However the timing and duration of its administration appear critical in defining the seizure and pathology‐related outcomes. Rapamycin application in human cortical slices from patients with cortical dysplasias reduces the 4‐aminopyridine–induced oscillations. In the multiple‐hit model of infantile spasms, pulse high‐dose rapamycin administration can reduce the cortical overactivation of the mTOR pathway, suppresses spasms, and has disease‐modifying effects by partially improving cognitive deficits. In post–status epilepticus models of temporal lobe epilepsy, rapamycin may ameliorate the development of epilepsy‐related pathology and reduce the expression of spontaneous seizures, but its effects depend on the timing and duration of administration, and possibly the model used. The observed recurrence of seizures and epilepsy‐related pathology after rapamycin discontinuation suggests the need for continuous administration to maintain the benefit. However, the use of pulse administration protocols may be useful in certain age‐specific epilepsy syndromes, like infantile spasms, whereas repetitive‐pulse rapamycin protocols may suffice to sustain a long‐term benefit in genetic disorders of the mTOR pathway. In summary, mTOR dysregulation has been implicated in several genetic and acquired forms of epileptogenesis. The use of mTOR inhibitors can reverse some of these epileptogenic processes, although their effects depend upon the timing and dose of administration as well as the model used.
Tetanus neurotoxin–induced epilepsy in mouse visual cortex
Authors: Mainardi Marco , Pietrasanta Marta , Vannini Eleonora , Rossetto Ornella , Caleo Matteo
Published: May 2012

Tetanus neurotoxin (TeNT) is a metalloprotease that cleaves the synaptic protein VAMP/synaptobrevin, leading to focal epilepsy. Although this model is widely used in rats, the time course and spatial specificity of TeNT proteolytic action have not been precisely defined. Here we have studied the biochemical, electrographic, and anatomic characteristics of TeNT‐induced epilepsy in mouse visual cortex (V1). We found that VAMP cleavage peaked at 10 days, was reduced at 21 days, and completely extinguished 45 days following TeNT delivery. VAMP proteolysis was restricted to the injected V1 and ipsilateral thalamus, whereas it was undetectable in other cortical areas. Electrographic epileptiform activity was evident both during and after the time window of TeNT effects, indicating development of chronic epilepsy. Anatomic analyses found no evidence for long‐term tissue damage, such as neuronal loss or microglia activation. These data show that TeNT reliably induces nonlesional epilepsy in mouse cortex. Due to the excellent physiologic knowledge of the visual cortex and the availability of mouse transgenic strains, this model will be useful for examining the network and cellular alterations underlying hyperexcitability within an epileptic focus.
How Acute and Chronic Alcohol Consumption Affects Brain Networks: Insights from Multimodal Neuroimaging
Authors: Schulte Tilman , Oberlin Brandon G. , Kareken David A. , Marinkovic Ksenija , Müller‐Oehring Eva M. , Meyerhoff Dieter J. , Tapert Susan
Published: May 2012

Background

Multimodal imaging combining 2 or more techniques is becoming increasingly important because no single imaging approach has the capacity to elucidate all clinically relevant characteristics of a network.

Methods

This review highlights recent advances in multimodal neuroimaging (i.e., combined use and interpretation of data collected through magnetic resonance imaging [MRI], functional MRI, diffusion tensor imaging, positron emission tomography, magnetoencephalography, MR perfusion, and MR spectroscopy methods) that leads to a more comprehensive understanding of how acute and chronic alcohol consumption affect neural networks underlying cognition, emotion, reward processing, and drinking behavior.

Results

Several innovative investigators have started utilizing multiple imaging approaches within the same individual to better understand how alcohol influences brain systems, both during intoxication and after years of chronic heavy use.

Conclusions

Their findings can help identify mechanism‐based therapeutic and pharmacological treatment options, and they may increase the efficacy and cost effectiveness of such treatments by predicting those at greatest risk for relapse.
Impact of Altered Methylation in Cytokine Signaling and Proteasome Function in Alcohol and Viral‐Mediated Diseases
Authors: Kharbanda Kusum K. , Bardag‐Gorce Fawzia , Barve Shirish , Molina Patricia E. , Osna Natalia A.
Published: May 2012

Data from several laboratories have shown that ethanol (EtOH) feeding impairs many essential methylation reactions that contribute to alcoholic liver disease (ALD). EtOH is also a comorbid factor in the severity of hepatitis C virus–induced liver injury. The presence of viral proteins further exacerbates the methylation defects to disrupt multiple pathways that promote the pathogenesis of liver disease. This review is a compilation of presentations that linked the methylation reaction defects with proteasome inhibition, decreased antigen presentation, and impaired interferon (IFN) signaling in the hepatocytes and dysregulated TNFα expression in macrophages. Two therapeutic modalities, betaine and S‐adenosylmethionine, can correct methylation defects to attenuate many EtOH‐induced liver changes, as well as improve IFN signaling pathways, thereby overcoming viral treatment resistance.
Plasma transfusion for patients with severe hemorrhage: what is the evidence?
Authors: Callum Jeannie L. , Rizoli Sandro
Published: May 2012

The following review will detail the current knowledge in massive hemorrhage with regard to the pathophysiology of the coagulation disturbance, the role of plasma, the role of alternatives to plasma, and the clinical value of having a massive transfusion protocol. The coagulation disturbance in trauma patients is more than just the result of consumption of clotting factors at sites of injury and dilution from the infusion of intravenous fluids and red blood cells (RBCs). Even before substantial amounts of fluid resuscitation and RBC transfusion, one‐quarter of trauma patients already have abnormal coagulation variables. There is an apparent role for the activation of protein C, hypofibrinogenemia, and fibrin(gen)olysis in the coagulation disturbance after trauma and massive hemorrhage. None of these three disturbances would be completely mitigated by the use of plasma alone, suggesting that there may be an opportunity to improve care of these patients with alternative strategies, such as fibrinogen concentrates and antifibrinolytics. Despite numerous retrospective cohort studies evaluating 1:1 plasma to RBC formula–driven resuscitation, the overall clinical value of this approach is unclear. Studies have even raised concerns regarding a potential increase in morbidity associated with this approach, particularly for patients overtriaged to 1:1 where a massive transfusion is unlikely. We also do not have sufficient evidence to recommend either goal‐directed therapy with thromboelastography or early use of fibrinogen replacement, with either cryoprecipitate or fibrinogen concentrates. We have high‐quality data that argue against the role for recombinant Factor VIIa that should prompt removal of this strategy from existing protocols. In contrast, we have high‐level evidence that all bleeding trauma patients should receive tranexamic acid as soon as possible after injury. This therapy must be included in hemorrhage protocols. If we are to improve the care of massively bleeding patients on a firm scientific ground, we will need large‐scale randomized trials to delineate the role of coagulation replacement and the utility of laboratory monitoring. But even until these trials are completed, it is clear that a massive transfusion protocol is needed in all hospitals that manage bleeding patients, to ensure a prompt and coordinated response to hemorrhage.
Plasma and plasma derivatives in therapeutic plasmapheresis
Authors: McLeod Bruce C.
Published: May 2012

In therapeutic plasmapheresis, patient plasma is withdrawn and a colloid replacement solution is infused in its place. A 4% to 5% human serum albumin solution in saline is the preferred replacement solution in most instances, even though this practice causes transient mild deficiencies of most plasma proteins. Albumin solutions are pasteurized for viral inactivation, are very unlikely to cause a febrile or allergic reaction, and are convenient to store and administer. Single‐donor plasma must be type specific, which requires advance knowledge of patient blood type, and must be ordered and usually thawed before use. It also carries a higher risk of reactions. On the plus side, it replaces all plasma constituents and is appropriate for patients with thrombotic thrombocytopenic purpura or an existing coagulopathy. Neither cryosupernatant plasma, which is relatively deficient in the proteins in cryoprecipitate, nor plasma derived from pools that have been virally inactivated with detergents and organic solvents has been shown to produce better outcomes than fresh frozen plasma for any indication.