bluuebunny/crossref_metadata_2025_split huggingface dataset:
FFPopSim: an efficient forward simulation package for the evolution of large populations
Authors: Zanini Fabio , Neher Richard A. 
Published: October 2012

Abstract
Motivation: The analysis of the evolutionary dynamics of a population with many polymorphic loci is challenging, as a large number of possible genotypes needs to be tracked. In the absence of analytical solutions, forward computer simulations are an important tool in multi-locus population genetics. The run time of standard algorithms to simulate sexual populations increases as 8L with the number of loci L, or with the square of the population size N.
Results: We have developed algorithms to simulate large populations with arbitrary genetic maps, including multiple crossovers, with a run time that scales as 3L. If the number of crossovers is restricted to at most one, the run time is reduced to L2L. The algorithm is based on an analogue of the Fast Fourier Transform (FFT) and allows for arbitrary fitness functions (i.e. any epistasis). In addition, we include a streamlined individual-based framework. The library is implemented as a collection of C++ classes and a Python interface.
Availability: http://code.google.com/p/ffpopsim/.
Contact: richard.neher@tuebingen.mpg.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Influence of Host Chloroplast Proteins on Tobacco mosaic virus Accumulation and Intercellular Movement
Authors: Bhat Sumana , Folimonova Svetlana Y. , Cole Anthony B. , Ballard Kimberly D. , Lei Zhentian , Watson Bonnie S. , Sumner Lloyd W. , Nelson Richard S. 
Published: October 2012

Abstract
Tobacco mosaic virus (TMV) forms dense cytoplasmic bodies containing replication-associated proteins (virus replication complexes [VRCs]) upon infection. To identify host proteins that interact with individual viral components of VRCs or VRCs in toto, we isolated viral replicase- and VRC-enriched fractions from TMV-infected Nicotiana tabacum plants. Two host proteins in enriched fractions, ATP-synthase γ-subunit (AtpC) and Rubisco activase (RCA) were identified by matrix-assisted laser-desorption ionization time-of-flight mass spectrometry or liquid chromatography-tandem mass spectrometry. Through pull-down analysis, RCA bound predominantly to the region between the methyltransferase and helicase domains of the TMV replicase. Tobamovirus, but not Cucumber mosaic virus or Potato virus X, infection of N. tabacum plants resulted in 50% reductions in Rca and AtpC messenger RNA levels. To investigate the role of these host proteins in TMV accumulation and plant defense, we used a Tobacco rattle virus vector to silence these genes in Nicotiana benthamiana plants prior to challenge with TMV expressing green fluorescent protein. TMV-induced fluorescent lesions on Rca- or AtpC-silenced leaves were, respectively, similar or twice the size of those on leaves expressing these genes. Silencing Rca and AtpC did not influence the spread of Tomato bushy stunt virus and Potato virus X. In AtpC- and Rca-silenced leaves TMV accumulation and pathogenicity were greatly enhanced, suggesting a role of both host-encoded proteins in a defense response against TMV. In addition, silencing these host genes altered the phenotype of the TMV infection foci and VRCs, yielding foci with concentric fluorescent rings and dramatically more but smaller VRCs. The concentric rings occurred through renewed virus accumulation internal to the infection front.
Consumer Communication and Organisational Strategies for Animal Welfare by the Food and Retail Industries in Italy
Authors: Mancini Maria Cecilia , Arfini Filippo 
Published: October 2012

SummaryConsumer Communication and Organisational Strategies for Animal Welfare by the Food and Retail Industries in ItalyThe treatment of animals used in production processes involves ethical principles as well as food safety and has become increasingly a focus of debate. Based on survey evidence, this article examines consumer communication and organisational strategies regarding animal welfare (AW) by food processors and retailers in Italy. It identifies three levels of commitment to animal welfare: full sensitivity with regard to ethical issues and products; animal welfare seen solely as an aspect of product quality; and indifference where animal welfare is considered purely a legal obligation. This classification could be a starting point for institutional intervention. ‘Active’ behaviour shows that AW can be used as a means of organisational renewal of supply chain mechanisms and thus could be supported by public institutions. At the same time, an effective implementation of EU AW policy requires public intervention to ensure that consumers receive the information they need to shop with awareness of AW issues. It is only through greater awareness of AW friendly techniques and their implications that willingness to pay among Italian consumers will increase. This in turn will provide the incentives for producers, processors and retailers to show more interest in AW‐friendly techniques.
A Family with Recurrent Sudden Death and No Clinical Clue
Authors: Arad Michael , Glikson Michael , El‐Ani Dalia , Monserrat‐Inglesias Lorenzo 
Published: October 2012

Background: Sudden cardiac death of a child is a devastating event for the family and an enormous challenge for the attending physician.Methods and Results: We report a family with repeat events of sudden cardiac death and recurrent ventricular fibrillation in a teenage girl, where autopsy data and clinical investigations were inconclusive. The diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was established only following finding a gene mutation in the cardiac ryanodine receptor.Conclusions: Interpretation of autopsy data, provocation testing and genetic testing in victims of sudden death and family members are discussed to correctly identify the cause and properly manage asymptomatic carriers in such families.
The impact of ‘being assessed’ by a disabled children's team: a personal reflective account
Authors: Wilkins David 
Published: October 2012

AbstractThe body of ‘service user’ literature confirms the value of parental perceptions of child and family social work and the insight parents and others can offer. This paper lends my voice to the literature regarding parental perceptions, inspired by the work of Pamela Davies, who provided a personal account of the impact of a child protection investigation. This paper draws upon my experiences of being a father of two ‘disabled children’ and undergoing an assessment of need. This paper seeks to draw attention to issues of choice, power imbalances and the role of expertise. My personal experience of undergoing an assessment was that it was an emotionally fraught process, for the duration of the assessment, our family stress increased and we had a sense of having to ‘battle’ for the support we needed. As such, my personal experience fits well with the wider body of literature, which highlights the increased stress of caring for children with additional needs, the challenges of ‘fitting’ disabled children into the frameworks used to assess all children and the difficulty for parents and professionals in distinguishing between ‘normal’ parenting responsibilities and the additional responsibilities of caring for a disabled child.
Kinship care in Spain: messages from research
Authors: Montserrat Carme 
Published: October 2012

AbstractKinship foster care has experienced significant growth within the Spanish child protection system and now carries considerable weight. Over 40% of children in the public care system are formally fostered by relatives, equalling, and in some areas exceeding, the percentage of those in residential homes. This increase is not the result of a pre‐designed global programme or clearly pre‐established objectives in the system itself. Its current weight within the system has made it the focus of attention of researchers, politicians and protection system practitioners alike. The results of research carried out in Spain have revealed more positives than negatives in this type of fostering, giving rise to an in‐depth reflection on care systems, questioning the determinism of theories anchored in the intergenerational repetition of abuse and making room for perspectives more associated with resilience and children's rights. Positive results are related to fewer breakdowns, more stability, permanency beyond the age of 18, children agreeing with their placement, academic results similar to those with non‐relatives and better results after leaving care. The negatives relate to the lack of economic, educational and psychosocial support, which generally goes with this type of fostering. The experience of support programmes for these placements contributes to the debate.
The Neuroprotective Effect of Losartan through Inhibiting AT1/ASK1/MKK4/JNK3 Pathway Following Cerebral I/R in Rat Hippocampal CA1 Region
Authors: Zhang Tian‐Ling , Fu Jian‐Liang , Geng Zhi , Yang Jia‐Jun , Sun Xiao‐Jiang 
Published: October 2012

SummaryAimsIt has been well documented that angiotensin II type 1 (AT1) receptor blockers (ARBs) are known to attenuate neural damage and the c‐Jun N‐terminal protein kinase 3 (JNK3) pathway and caspase‐3 signal are involved in neuronal cell death following cerebral ischemia/reperfusion (I/R). In this study, we first showed that losartan could protect neurons against cerebral I/R‐induced injury.MethodsCerebral ischemia model was induced by four‐vessel occlusion. Antisense oligodeoxynucleotides (ODNs) against AT1 receptor and losartan were used to detect whether the AT1 receptor implicated in cerebral I/R. Immunoprecipitation (IP) and immunoblotting (IB) were used to detect the interactions between β‐arrestin‐2 and AT1/apoptosis signal‐regulating kinase 1 (ASK1)/MAP kinase kinase 4 (MKK4) signaling module following cerebral I/R.ResultsFirst, losartan decreased cerebral I/R‐induced neuronal death. Second, losartan depressed the β‐arrestin‐2‐assembled AT1/ASK1/MKK4 signaling module. Third, losartan depressed the activation of c‐jun, JNK3, Bcl‐2, caspase‐3 and the release of cytochrome c from mitochondria to cytoplasm.ConclusionTaken together, losartan could attenuate neural damage following the cerebral I/R via inhibiting the β‐arrestin‐2‐assembled AT1/ASK1/MKK4 signaling module and depressing the activation of c‐jun, JNK3, and caspase‐3 and the release of cytochrome c.
Combination Therapy for Manic Phases: A Critical Review of a Common Practice
Authors: Geoffroy Pierre Alexis , Etain Bruno , Henry Chantal , Bellivier Frank 
Published: October 2012

SummaryAll relevant guidelines recommend monotherapy as the initial treatment for manic phases of bipolar disorder (BD), with combination therapy reserved for severe cases or as a subsequent choice. However, in routine practice, monotherapy is often not sufficiently effective for acute and/or maintenance therapy. As a consequence, most patients are given combination therapies. An extensive search concerning combination treatment for manic episodes was conducted for relevant international randomized controlled studies, treatment guidelines and comprehensive reviews published since 1980. The scientific literature is sufficiently rich to validate the superiority of combination therapy over monotherapy in the manic phase in terms of efficacy and prevention of relapse; its safety profile is acceptable. Side effects are more frequent with combination therapy as a whole than with monotherapy, and discontinuation rates due to adverse events are higher. Continued administration of antipsychotics after a manic phase is controversial: drug classification, the course of the disease and the predominant polarity should all be considered before treatment is continued. Combinations including olanzapine and asenapine and to a lesser extent risperidone are associated with weight gain, those including quetiapine, haloperidol and asenapine with sedation, and those including aripiprazole with akathisia. This review of literature leads us to suggest that combination therapy including an atypical antipsychotic with lithium or valproate may be considered as a first‐line approach. An appropriate algorithm for making decisions about combination treatment needs to be developed and included in future guidelines.
Vascular and platelet responses to aspirin in patients with coronary artery disease
Authors: Blann Andrew D. , Kuzniatsova Nadya , Lip Gregory Y. H. 
Published: October 2012

AbstractBackgroundVariability in the response to aspirin (sometimes known as aspirin resistance) in modulating platelet activity is a potentially important clinical issue in coronary artery disease (CAD), but may be also be important in other areas of pathophysiology.Materials and methodsTesting the hypothesis of a relationship between aspirin resistance and vascular function, inflammation and coagulation, we recruited 175 stable CAD outpatients taking 75 mg aspirin daily. Indices were compared to 58 controls not taking aspirin. Platelet activity was assessed by light transmission aggregometry (LTA) to 0·5 mg/mL arachidonic acid (AA), plasma markers soluble P selectin and thromboxane (ELISA), and resting and AA stimulated membrane P selectin and PAC‐1 expression (flow cytometry). Vascular function was assessed by arterial stiffness (Sphygmocor system), von Willebrand factor and soluble E selectin (ELISA), inflammation by high sensitivity CRP and interleukin‐6, and coagulation by tissue factor and fibrin d‐dimers levels (all immunoassay).ResultsThe 5‐min LTA response AA was superior to flow cytometry in discriminating the response of platelets to aspirin. Using the cut‐off of 20% LTA response to AA, 32·6% of patients were aspirin resistant. The latter had higher soluble P selectin (P = 0·03), CRP (P = 0·029) and fibrin d‐dimers (P = 0·01) compared to those who were aspirin sensitive. There was no relationship between aspirin response status and any vascular index.ConclusionWe conclude that LTA is a more sensitive marker of aspirin resistance than is flow cytometry for P‐selectin and PCA‐1, and that aspirin response has no influence on vascular function.
Rapid and complete reconstitution of autologous haemopoiesis after cord blood infusion in treatment‐naive patients with severe aplastic anemia receiving high‐dose cyclophosphamide/ATG therapy
Authors: Li Yanxiang , Sheng Zhixin , Niu Shaona , Ge Lifu , Ren Cuiai , Zou Yandun 
Published: October 2012

AbstractAlthough high‐dose cyclophosphamide seems to achieve durable complete remission, there are still concerns about its too much early toxicity. So, we designed a clinical study to investigate the effects of high‐dose cyclophosphamide/ATG combined with cord blood infusion as first‐line therapy for patients with severe aplastic anemia. Patients and Method: Between January 2003 and September 2007, we treated 16 treatment‐naive patients with severe aplastic anemia with cord blood infusion after high‐dose cyclophosphamide (50 mg/kg/d × 2) and rabbit antithymocyte globulin (3 mg/kg/d × 5) therapy. Results: Although only one patient had durable full donor engraftment, 14 of the enrolled 16 patients had rapid autologous hematopoietic recovery. The median recovery time for neutrophils and platelets was only 23 and 37 d after infusion of cord blood. Of the 15 responding patients, all patients achieved treatment‐free remission: nine patients met the criteria for a complete remission; six patients achieved a partial remission. Conclusion: Infusion of cord blood after high‐dose cyclophosphamide/ATG resulted in a rapid autologous hematologic recovery and a high response rate in patients with treatment‐naive patients with severe aplastic anemia. These promising results merit further investigation and confirmation on a larger number of patients.
Cognitive impairment in HIV infection is associated with MRI and CSF pattern of neurodegeneration
Authors: Steinbrink F. , Evers S. , Buerke B. , Young P. , Arendt G. , Koutsilieri E. , Reichelt D. , Lohmann H. , Husstedt I.‐W. ,   the German Competence Network HIV/AIDS
Published: October 2012

Background and purposeBiomarkers as indicators for the progression of human immunodeficiency virus (HIV)‐associated neurocognitive disorders (HAND) remain still elusive. We performed a cross‐sectional study to analyze the correlation between cognitive impairment, abnormalities in magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) markers of neurodegeneration in HIV‐infected patients.MethodsWe enrolled 94 patients (82 men and 12 women; mean age 45 ± 10 years) with HIV infection, but without opportunistic infections of the CNS. All patients underwent MRI and CSF analysis. The global pattern of white matter signal intensity abnormalities, the index of atrophy, the severity of periventricular white matter abnormalities, and the severity of basal ganglia signal changes were analyzed. We measured CSF markers of neurodegeneration (total tau, phospho‐tau, beta‐amyloid). The findings of this evaluation were correlated with demographic and infection parameters of the patients in blood and CSF.ResultsWe found a highly significant correlation between the severity of global brain atrophy, basal ganglia signal changes, and cognitive impairment in HIV‐infected patients. Furthermore, cognitive impairment was significantly correlated with total tau, but not with phospho‐tau or A‐beta‐amyloid in CSF analysis.ConclusionsOur results confirm the significant correlation between MRI changes and cognitive impairment in HIV infection. Furthermore, we could show that global brain atrophy and signal changes in basal ganglia are the typical MRI pattern in HAND. The correlation between cognitive impairment and total tau, but not phospho‐tau, supports the hypothesis that HAND are not a subtype of Alzheimer's dementia.
Prevalence and prognostic impact of comorbidities in amyotrophic lateral sclerosis
Authors: Körner S. , Kollewe K. , Ilsemann J. , Müller‐Heine A. , Dengler R. , Krampfl K. , Petri S. 
Published: October 2012

Background and purposeAmyotrophic lateral sclerosis (ALS) is characterized by rapidly progressive paralysis of striated muscles due to the loss of upper and lower motor neurons. The disease leads to death within 2–5 years, mainly due to respiratory failure. The pathogenesis of ALS is still unexplained for the most part. In this study, we aimed to determine the prevalence of different cardiovascular, metabolic, and neuropsychiatric comorbidities in a large ALS cohort and to evaluate their influence on the disease course.MethodsA cohort of 514 patients with ALS of our ALS outpatient clinic was investigated retrospectively with reference to known prognostic factors and comorbidities. The prevalence of concomitant diseases was compared with the data from the German general population. Uni‐ and multivariate survival analyses were performed using the Cox proportional hazards model and Kaplan–Meier analysis.ResultsThe prevalence of cardiovascular diseases and cardiovascular risk factors was significantly lower in patients with ALS compared to the German general population, whilst the prevalence of dementia, parkinsonism, and depressive symptoms was significantly higher in the ALS cohort. None of the investigated comorbidities had an influence on the disease course or on the survival of patients.ConclusionsPersons with cardiovascular diseases or risk factors seem to be at lower risk of ALS. Although these diseases are apparently somehow protective regarding ALS susceptibility, their presence did not modify disease progression and survival in patients with ALS. Our study further confirms the well‐known continuum between ALS and dementia. It also suggests a link with other neurodegenerative diseases such as Parkinson's disease.
Critical determinants of the epilepsy treatment gap: A cross‐national analysis in resource‐limited settings
Authors: Meyer Ana‐Claire L. , Dua Tarun , Boscardin W. John , Escarce José J. , Saxena Shekhar , Birbeck Gretchen L. 
Published: October 2012

SummaryPurpose:  Epilepsy is one of the most common serious neurologic disorders worldwide. Our objective was to determine which economic, health care, neurology, and epilepsy‐specific resources were associated with untreated epilepsy in resource‐constrained settings.Methods:  A systematic review of the literature identified community‐based studies in resource‐constrained settings that calculated the epilepsy treatment gap, the proportion with untreated epilepsy, from prevalent active epilepsy cases. Economic, health care, neurology, and epilepsy‐specific resources were taken from existing datasets. Poisson regression models with jackknifed standard errors were used to create bivariate and multivariate models comparing the association between treatment status and economic and health resource indicators. Relative risks were reported.Key Findings:  Forty‐seven studies of 8,285 individuals from 24 countries met inclusion criteria. Bivariate analysis demonstrated that individuals residing in rural locations had significantly higher risks of untreated epilepsy (relative risk [RR] 1.63; 95% confidence interval [CI] 1.26–2.11). Significantly lower risks of untreated epilepsy were observed for higher physician density (RR 0.65, 95% CI 0.55–0.78), presence of a lay (RR 0.74, 95% CI 0.60–0.91) or professional association for epilepsy (RR 0.73, 95% CI 0.59–0.91), or postgraduate neurology training program (RR 0.67, 95% CI 0.55–0.82). In multivariate models, higher physician density maintained significant effects (RR 0.67; 95% CI 0.52–0.88).Significance:  Even among resource‐limited regions, people with epilepsy in countries with fewer economic, health care, neurology, and epilepsy‐specific resources are more likely to have untreated epilepsy. Community‐based epilepsy care programs have improved access to treatment, but in order to decrease the epilepsy‐treatment gap, poverty and inequalities of health care, neurology, and epilepsy resources must be dealt with at the local, national, and global levels.
Frontal lobe function and structure in juvenile myoclonic epilepsy: A comprehensive review of neuropsychological and imaging data
Authors: Wandschneider Britta , Thompson Pamela J. , Vollmar Christian , Koepp Matthias J. 
Published: October 2012

SummaryJuvenile myoclonic epilepsy is the most common idiopathic epilepsy syndrome and is considered a benign seizure disorder that responds well to antiepileptic drug treatment, in particular sodium valproate. By definition, routine brain imaging shows no abnormalities, but advanced imaging studies have identified functional and structural abnormalities in the frontal cortex and thalamus. Neuropsychological studies revealed subtle cognitive deficits in patients with JME, mainly implicating the frontal lobes. These findings are in keeping with anecdotal reports of behavioral problems in JME. Cognitive dysfunction in otherwise healthy siblings of patients with JME and a high heritability support the concept of a genetically determined thalamo‐frontocortical network dysfunction, accounting for the cognitive impairment and cognitively triggered “motor seizures.”