bluuebunny/crossref_metadata_2025 huggingface dataset:
Acclimatizing nuclear? Climate change, nuclear power and the reframing of risk in the UK news media
Authors: Doyle Julie
Published: January 2011

In January 2008, the UK Labour government announced that new nuclear power would play a role in the generation of low carbon electricity, and thus in the mitigation of climate change. This reframing of new nuclear power as a means of tackling climate change signalled a dramatic U-turn on Labour’s commitment to decommission all existing UK nuclear power stations by 2025. In the context of the political reframing of new nuclear builds, this article examines how the UK news media contributed to the reframing of nuclear power as low carbon, and the implications this has for public understanding of nuclear power and climate change. Covering the time period from September 2005 to January 2008, a critical discourse analysis of three UK newspapers — the Daily Mirror (tabloid), the Daily Mail (mid-range) and the Independent (broadsheet) — is presented. This period covers the months leading up to the launch of the UK government’s first Energy Review in January 2006, to the publication of the government’s final White Paper on Nuclear Power in January 2008. The analysis found that the official governmental discourse on nuclear power as essential to climate change mitigation and the security of future energy supplies was variously reproduced and contested across the three newspapers. However, while the government’s rebranding of nuclear as less risky than climate change is not explicitly endorsed by any of the newspapers, it certainly provides the discursive context through which policy decisions on new nuclear have been largely accepted by the UK news media.
‘Movements that are drawn’: A history of environmental animation from The Lorax to FernGully to Avatar
Authors: Starosielski Nicole
Published: January 2011

This article surveys the history of environmental animation and charts the aesthetic possibilities it offers for environmental representation, in order to prompt a reconsideration of indexical media’s dominant role in environmental communication. Given animation’s formal capabilities, it has the potential to depict imperceptible, indeterminate and interactive environments. Distinct representational practices have emerged in animated environmental films: the visualization of environmental mutability, the representation of environmental interaction and the revelation of the environment as a construct. This article defines three periods of environmental animation: the 1960s to early 1970s, the late 1980s to early 1990s, and 2005 to the present, and analyses how these practices transformed during each cycle. Early short films pioneered the depiction of a mutable environment. In the second period, mutability became less significant, but feature films expanded the possible modes of environmental interaction. Most recently, films have begun to reflect on the environment as a visual construct.
Communicating business greening and greenwashing in global media: A multimodal discourse analysis of CNN’s greenwashing video
Authors: Maier Carmen Daniela
Published: January 2011

This article explores how knowledge about business greening and greenwashing is communicated in the specialized discourse of CNN’s Greenwashing video. Drawing upon a social semiotic approach, the article proposes a model of multimodal discourse analysis to explore how processes of knowledge selection are employed for shaping public awareness and understanding of environmental issues in the context of the greening or greenwashing efforts of businesses. Furthermore, the article discusses how environmental business identities are multimodally represented and communicated in accordance with the potential and constraints of language and images. The article also establishes which semiotic modes are given prominence in the environmental discourse by examining the complex interconnectivity and functional differentiation of these semiotic modes.
A Proposed Roadmap for Inpatient Neurology Quality Indicators
Authors: Douglas Vanja C. , Josephson S. Andrew
Published: January 2011

Background/Purpose: In recent years, there has been increasing pressure to measure and report quality in health care. However, there has been little focus on quality measurement in the field of neurology for conditions other than stroke and transient ischemic attack. As the number of evidence-based treatments for neurological conditions grows, so will the demand to measure the quality of care delivered. The purpose of this study was to review essential components of hospital performance measures for neurological disease and propose potential quality indicators for commonly encountered inpatient neurological diagnoses. Methods: We determined the most common inpatient neurological diagnoses at a major tertiary care medical center by reviewing the billing database. We then searched PubMed and the National Guidelines Clearinghouse to identify treatment guidelines for these conditions. Guideline recommendations with class I/level A evidence were evaluated as possible quality indicators. Results: We found 94 guidelines for 14 inpatient neurological conditions other than stroke and transient ischemic attack. Of these, 36 guidelines contained at least 1 recommendation with class I evidence. Based on these, potential quality indicators for intracerebral hemorrhage, subarachnoid hemorrhage, pneumococcal meningitis, coma following cardiac arrest, encephalitis, Guillain-Barre syndrome, multiple sclerosis, and benign paroxysmal positional vertigo are proposed. Conclusions: There are several inpatient neurological conditions with treatments or diagnostic test routines supported by high levels of evidence that could be used in the future as quality indicators.
Status Epilepticus
Authors: Manno Edward M.
Published: January 2011

Status epilepticus is a neurological emergency that is commonly encountered by the neurohospitalist. Successful treatment depends upon the recognition of prolonged seizure activity and the acute mobilization of available resources. Pharmacologic treatment regimens have been shown to decrease the time needed for successful control of seizures and have provided for the rapid administration of anticonvulsant medications. Treatment strategies have evolved so that clinicians can administer effective doses of medication by whatever routes of administration are immediately available. Traditional algorithms for the treatment of status epilepticus have used a stepwise approach to the administration of first-, second-, and third-order medications. More recent options have included aggressive anesthetic doses of medications while second-line medications are being titrated.
Acute Vestibulopathy
Authors: Cha Yoon-Hee
Published: January 2011

The presentation of acute vertigo may represent both a common benign disorder or a life threatening but rare one. Familiarity with the common peripheral vestibular disorders will allow the clinician to rapidly “rule-in” a benign disorder and recognize when further testing is required. Key features of vertigo required to make an accurate diagnosis are duration, chronicity, associated symptoms, and triggers. Bedside tests that are critical to the diagnosis of acute vertigo include the Dix-Hallpike maneuver and canalith repositioning manuever, occlusive ophthalmoscopy, and the head impulse test. The goal of this review is to provide the clinician with the clinical and pathophysiologic background of the most common disorders that present with vertigo to develop a logical differential diagnosis and management plan.
Neuroleptic Malignant Syndrome
Authors: Berman Brian D.
Published: January 2011

Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction to antipsychotic drugs characterized by fever, altered mental status, muscle rigidity, and autonomic dysfunction. It has been associated with virtually all neuroleptics, including newer atypical antipsychotics, as well as a variety of other medications that affect central dopaminergic neurotransmission. Although uncommon, NMS remains a critical consideration in the differential diagnosis of patients presenting with fever and mental status changes because it requires prompt recognition to prevent significant morbidity and death. Treatment includes immediately stopping the offending agent and implementing supportive measures, as well as pharmacological interventions in more severe cases. Maintaining vigilant awareness of the clinical features of NMS to diagnose and treat the disorder early, however, remains the most important strategy by which physicians can keep mortality rates low and improve patient outcomes.
The future of anti-CD20 monoclonal antibodies: are we making progress?
Authors: Alduaij Waleed , Illidge Tim M.
Published: January 2011

The anti-CD20 monoclonal antibody (mAb) rituximab has revolutionized the treatment of B-cell malignancies. This unprecedented success has not only substantially changed the mindset of the clinical community about the ability of mAb to improve outcomes but has catalyzed the interest in the pharmaceutical industry to develop the next generation of anti-CD20 mAbs. Since the introduction of rituximab 15 years ago, we have learned much about the potential mechanisms underlying the therapeutic efficacy of anti-CD20 mAbs. In parallel, many novel anti-CD20 mAbs have entered the clinic, each designed with modifications to structure aimed at further improving efficacy. On review of the newer generation of anti-CD20 mAbs entering clinical trials, it appears that the link between the novel mechanistic insights and the development of these next-generation anti-CD20 mAbs is unclear. As we move into an era of personalized medicine, it will become increasingly important for us to develop closer links between the emerging mechanistic insights and the clinical development, to further enhance the potency of anti-CD20 mAbs beyond that achieved with rituximab.
High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade
Authors: Kießling Michael K. , Oberholzer Patrick A. , Mondal Chandrani , Karpova Maria B. , Zipser Marie C. , Lin William M. , Girardi Michael , MacConaill Laura E. , Kehoe Sarah M. , Hatton Charlie , French Lars E. , Garraway Levi A. , Polier Gernot , Süss Dorothee , Klemke Claus-Detlev , Krammer Peter H. , Gülow Karsten , Dummer Reinhard
Published: January 2011

Cutaneous T-cell lymphomas (CTCLs) are malignancies of skin-homing lymphoid cells, which have so far not been investigated thoroughly for common oncogenic mutations. We screened 90 biopsy specimens from CTCL patients (41 mycosis fungoides, 36 Sézary syndrome, and 13 non–mycosis fungoides/Sézary syndrome CTCL) for somatic mutations using OncoMap technology. We detected oncogenic mutations for the RAS pathway in 4 of 90 samples. One mycosis fungoides and one pleomorphic CTCL harbored a KRASG13D mutation; one Sézary syndrome and one CD30+ CTCL harbored a NRASQ61K amino acid change. All mutations were found in stage IV patients (4 of 42) who showed significantly decreased overall survival compared with stage IV patients without mutations (P = .04). In addition, we detected a NRASQ61K mutation in the CTCL cell line Hut78. Knockdown of NRAS by siRNA induced apoptosis in mutant Hut78 cells but not in CTCL cell lines lacking RAS mutations. The NRASQ61K mutation sensitized Hut78 cells toward growth inhibition by the MEK inhibitors U0126, AZD6244, and PD0325901. Furthermore, we found that MEK inhibitors exclusively induce apoptosis in Hut78 cells. Taken together, we conclude that RAS mutations are rare events at a late stage of CTCL, and our preclinical results suggest that such late-stage patients profit from MEK inhibitors.
ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes
Authors: Mazan-Mamczarz Krystyna , Hagner Patrick R. , Zhang Yongqing , Dai Bojie , Lehrmann Elin , Becker Kevin G. , Keene Jack D. , Gorospe Myriam , Liu Zhenqui , Gartenhaus Ronald B.
Published: January 2011

Maintenance of genomic stability depends on the DNA damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell-cycle checkpoints and DNA repair after DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression posttranscriptionally. Dysregulation of this DNA damage response RNA operon is probably relevant to lymphoma development in ataxia-telangiectasia persons. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis.
Extending pathways and processes using molecular interaction networks to analyse cancer genome data
Authors: Glaab Enrico , Baudot Anaïs , Krasnogor Natalio , Valencia Alfonso
Published: January 2011

Background

Cellular processes and pathways, whose deregulation may contribute to the development of cancers, are often represented as cascades of proteins transmitting a signal from the cell surface to the nucleus. However, recent functional genomic experiments have identified thousands of interactions for the signalling canonical proteins, challenging the traditional view of pathways as independent functional entities. Combining information from pathway databases and interaction networks obtained from functional genomic experiments is therefore a promising strategy to obtain more robust pathway and process representations, facilitating the study of cancer-related pathways.

Results

We present a methodology for extending pre-defined protein sets representing cellular pathways and processes by mapping them onto a protein-protein interaction network, and extending them to include densely interconnected interaction partners. The added proteins display distinctive network topological features and molecular function annotations, and can be proposed as putative new components, and/or as regulators of the communication between the different cellular processes. Finally, these extended pathways and processes are used to analyse their enrichment in pancreatic mutated genes. Significant associations between mutated genes and certain processes are identified, enabling an analysis of the influence of previously non-annotated cancer mutated genes.

Conclusions

The proposed method for extending cellular pathways helps to explain the functions of cancer mutated genes by exploiting the synergies of canonical knowledge and large-scale interaction data.
IPRStats: visualization of the functional potential of an InterProScan run
Authors: Kelly Ryan J , Vincent David E , Friedberg Iddo
Published: January 2011

Background

InterPro is a collection of protein signatures for the classification and automated annotation of proteins. Interproscan is a software tool that scans protein sequences against Interpro member databases using a variety of profile-based, hidden markov model and positional specific score matrix methods. It not only combines a set of analysis tools, but also performs data look-up from various sources, as well as some redundancy removal. Interproscan is robust and scalable, able to perform on any machine from a netbook to a large cluster. However, when performing whole-genome or metagenome analysis, there is a need for a fast statistical visualization of the results to have good initial grasp on the functional potential of the sequences in the analyzed data set. This is especially important when analyzing and comparing metagenomic or metaproteomic data-sets.

Results

IPRStats is a tool for the visualization of Interproscan results. Interproscan results are parsed from the Interproscan XML or EBIXML file into an SQLite or MySQL database. The results for each signature database scan are read and displayed as pie-charts or bar charts as summary statistics. A table is also provided, where each entry is a signature (e.g. a Pfam entry) accompanied by one or more Gene Ontology terms, if Interproscan was run using the Gene Ontology option.

Conclusions

We present an platform-independent, open source licensed tool that is useful for Interproscan users who wish to view the summary of their results in a rapid and concise fashion.
Systematic evaluation of genome-wide methylated DNA enrichment using a CpG island array
Authors: Yang Liu , Zhang Kunlin , Dai Wei , He Ximiao , Zhao Qian , Wang Jing , Sun Zhong Sheng
Published: January 2011

Background

Recent progress in high-throughput technologies has greatly contributed to the development of DNA methylation profiling. Although there are several reports that describe methylome detection of whole genome bisulfite sequencing, the high cost and heavy demand on bioinformatics analysis prevents its extensive application. Thus, current strategies for the study of mammalian DNA methylomes is still based primarily on genome-wide methylated DNA enrichment combined with DNA microarray detection or sequencing. Methylated DNA enrichment is a key step in a microarray based genome-wide methylation profiling study, and even for future high-throughput sequencing based methylome analysis.

Results

In order to evaluate the sensitivity and accuracy of methylated DNA enrichment, we investigated and optimized a number of important parameters to improve the performance of several enrichment assays, including differential methylation hybridization (DMH), microarray-based methylation assessment of single samples (MMASS), and methylated DNA immunoprecipitation (MeDIP). With advantages and disadvantages unique to each approach, we found that assays based on methylation-sensitive enzyme digestion and those based on immunoprecipitation detected different methylated DNA fragments, indicating that they are complementary in their relative ability to detect methylation differences.

Conclusions

Our study provides the first comprehensive evaluation for widely used methodologies for methylated DNA enrichment, and could be helpful for developing a cost effective approach for DNA methylation profiling.
The genome sequence of E. coli W (ATCC 9637): comparative genome analysis and an improved genome-scale reconstruction of E. coli
Authors: Archer Colin T , Kim Jihyun F , Jeong Haeyoung , Park Jin Hwan , Vickers Claudia E , Lee Sang Yup , Nielsen Lars K
Published: January 2011

Background

Escherichia coli is a model prokaryote, an important pathogen, and a key organism for industrial biotechnology. E. coli W (ATCC 9637), one of four strains designated as safe for laboratory purposes, has not been sequenced. E. coli W is a fast-growing strain and is the only safe strain that can utilize sucrose as a carbon source. Lifecycle analysis has demonstrated that sucrose from sugarcane is a preferred carbon source for industrial bioprocesses.

Results

We have sequenced and annotated the genome of E. coli W. The chromosome is 4,900,968 bp and encodes 4,764 ORFs. Two plasmids, pRK1 (102,536 bp) and pRK2 (5,360 bp), are also present. W has unique features relative to other sequenced laboratory strains (K-12, B and Crooks): it has a larger genome and belongs to phylogroup B1 rather than A. W also grows on a much broader range of carbon sources than does K-12. A genome-scale reconstruction was developed and validated in order to interrogate metabolic properties.

Conclusions

The genome of W is more similar to commensal and pathogenic B1 strains than phylogroup A strains, and therefore has greater utility for comparative analyses with these strains. W should therefore be the strain of choice, or 'type strain' for group B1 comparative analyses. The genome annotation and tools created here are expected to allow further utilization and development of E. coli W as an industrial organism for sucrose-based bioprocesses. Refinements in our E. coli metabolic reconstruction allow it to more accurately define E. coli metabolism relative to previous models.
The exopolyphosphatase TbrPPX1 of Trypanosoma brucei
Authors: Luginbuehl Edith , Kunz Stefan , Wentzinger Laurent , Freimoser Florian , Seebeck Thomas
Published: January 2011

Background

Exopolyphosphatases and pyrophosphatases play important but still incompletely understood roles in energy metabolism, and also in other aspects of cell biology such as osmoregulation or signal transduction. Earlier work has suggested that a human exopolyphosphatase, Prune, might exhibit cyclic nucleotide phosphodiesterase activity.

Results

The kinetoplastida, a large order of unicellular eukaryotes that contains many important pathogens such as Trypanosoma brucei (human sleeping sickness), Trypanosoma cruzi (Chagas disease) or Leishmania ssp (several clinically dinstinct leishmaniases) all contain several exo- and pyrophosphatases. The current study provides a systematic classification of these enzymes, which now allows to situate the information that is already available on some of these enzymes. It then analyses the exopolyphosphatase TbrPPX1 of T. brucei in detail, using RNA interference and genetic knockouts in an attempt to define its function, and immunofluorescence microscopy to study its subcellular localization.

TbrPPX1 is an exopolyphosphatase that does hydrolyze pentasodium triphosphate, but not organic triphosphates such as ATP, pyrophosphate or long-chain polyphosphates. Finally, the study investigates the potential cyclic nucleotide phosphodiesterase activity of TbrPPX1.

Conclusions

All kinetoplastid genomes that are currently available contain genes for an exopolyphosphatase and two classes of pyrophosphatases, one associated with the acidocalcisomes and one cytoplasmic. TbrPPX1 represents the T. brucei exopolyphosphatase. It is located throughout the cytoplasm, and its genetic ablation does not produce a dramatic phenotype. Importantly, TbrPPX1 does not exhibit any cyclic nucleotide specific phosphodiesterase activity, which definitively eliminates it as an additional player in cAMP signalling of the kinetoplastida.
An overview of the Phalaenopsisorchid genome through BAC end sequence analysis
Authors: Hsu Chia-Chi , Chung Yu-Lin , Chen Tien-Chih , Lee Yu-Ling , Kuo Yi-Tzu , Tsai Wen-Chieh , Hsiao Yu-Yun , Chen Yun-Wen , Wu Wen-Luan , Chen Hong-Hwa
Published: January 2011

Background

Phalaenopsisorchids are popular floral crops, and development of new cultivars is economically important to floricultural industries worldwide. Analysis of orchid genes could facilitate orchid improvement. Bacterial artificial chromosome (BAC) end sequences (BESs) can provide the first glimpses into the sequence composition of a novel genome and can yield molecular markers for use in genetic mapping and breeding.

Results

We used two BAC libraries (constructed using theBamHI andHindIII restriction enzymes) ofPhalaenopsis equestristo generate pair-end sequences from 2,920 BAC clones (71.4% and 28.6% from theBamHI andHindIII libraries, respectively), at a success rate of 95.7%. A total of 5,535 BESs were generated, representing 4.5 Mb, or about 0.3% of thePhalaenopsisgenome. The trimmed sequences ranged from 123 to 1,397 base pairs (bp) in size, with an average edited read length of 821 bp. When these BESs were subjected to sequence homology searches, it was found that 641 (11.6%) were predicted to represent protein-encoding regions, whereas 1,272 (23.0%) contained repetitive DNA. Most of the repetitive DNA sequences were gypsy- and copia-like retrotransposons (41.9% and 12.8%, respectively), whereas only 10.8% were DNA transposons. Further, 950 potential simple sequence repeats (SSRs) were discovered. Dinucleotides were the most abundant repeat motifs; AT/TA dimer repeats were the most frequent SSRs, representing 253 (26.6%) of all identified SSRs. Microsynteny analysis revealed that more BESs mapped to the whole-genome sequences of poplar than to those of grape orArabidopsis, and even fewer mapped to the rice genome. This work will facilitate analysis of thePhalaenopsisgenome, and will help clarify similarities and differences in genome composition between orchids and other plant species.

Conclusion

Using BES analysis, we obtained an overview of thePhalaenopsisgenome in terms of gene abundance, the presence of repetitive DNA and SSR markers, and the extent of microsynteny with other plant species. This work provides a basis for future physical mapping of thePhalaenopsisgenome and advances our knowledge thereof.
The minor C-allele of rs2014355 in ACADSis associated with reduced insulin release following an oral glucose load
Authors: Hornbak Malene , Banasik Karina , Justesen Johanne M , Krarup Nikolaj T , Sandholt Camilla H , Andersson Åsa , Sandbæk Annelli , Lauritzen Torsten , Pisinger Charlotta , Witte Daniel R , Sørensen Thorkild IA , Pedersen Oluf , Hansen Torben
Published: January 2011

Background

A genome-wide association study (GWAS) using metabolite concentrations as proxies for enzymatic activity, suggested that two variants: rs2014355 in the gene encoding short-chain acyl-coenzyme A dehydrogenase (ACADS) and rs11161510 in the gene encoding medium-chain acyl-coenzyme A dehydrogenase (ACADM) impair fatty acid β-oxidation. Chronic exposure to fatty acids due to an impaired β-oxidation may down-regulate the glucose-stimulated insulin release and result in an increased risk of type 2 diabetes (T2D). We aimed to investigate whether the two variants associate with altered insulin release following an oral glucose load or with T2D.

Methods

The variants were genotyped using KASPar® PCR SNP genotyping system and investigated for associations with estimates of insulin release and insulin sensitivity following an oral glucose tolerance test (OGTT) in a random sample of middle-aged Danish individuals (n

ACADS
= 4,324; n

ACADM
= 4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (n

ACADS
= 8,313; n

ACADM
= 8,344).

Results

In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following an oral glucose load (per allele effect (β) = -3.8% (-6.3%;-1.3%), P = 0.003), reduced incremental area under the insulin curve (β = -3.6% (-6.3%;-0.9%), P = 0.009), reduced acute insulin response (β = -2.2% (-4.2%;0.2%), P = 0.03), and with increased insulin sensitivity ISIMatsuda (β = 2.9% (0.5%;5.2%), P = 0.02). The C-allele did not associate with two other measures of insulin sensitivity or with a derived disposition index. The C-allele was not associated with T2D in the case-control analysis (OR 1.07, 95% CI 0.96-1.18, P = 0.21). rs11161510 of ACADM did not associate with any indices of glucose-stimulated insulin release or with T2D.

Conclusions

In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS was associated with reduced measures of glucose-stimulated insulin release during an OGTT, a finding which in part may be mediated through an impaired β-oxidation of fatty acids.
Corticosteroid and antiviral therapy for Bell's palsy: A network meta-analysis
Authors: Numthavaj Pawin , Thakkinstian Ammarin , Dejthevaporn Charungthai , Attia John
Published: January 2011

Background

Previous meta-analyses of treatments for Bell's palsy are still inconclusive due to different comparators, insufficient data, and lack of power. We therefore conducted a network meta-analysis combining direct and indirect comparisons for assessing efficacy of steroids and antiviral treatment (AVT) at 3 and 6 months.

Methods

We searched Medline and EMBASE until September 2010 using PubMed and Elsviere search engines. A network meta-analysis was performed to assess disease recovery using a mixed effects hierarchical model. Goodness of fit of the model was assessed, and the pooled odds ratio (OR) and 95% confidence interval (CI) were estimated.

Results

Six studies (total n = 1805)were eligible and contributed to the network meta-analysis. The pooled ORs for resolution at 3 months were 1.24 (95% CI: 0.79 - 1.94) for Acyclovir plus Prednisolone and 1.02 (95% CI: 0.73 - 1.42) for Valacyclovir plus Prednisolone, versus Prednisolone alone. Either Acyclovir or Valacyclovir singly had significantly lower efficacy than Prednisolone alone, i.e., ORs were 0·44 (95% CI: 0·28 - 0·68) and 0·60 (95% CI: 0·42 - 0·87), respectively. Neither of the antiviral agents was significantly different compared with placebo, with a pooled OR of 1·25 (95% CI: 0·78 - 1·98) for Acyclovir and 0·91 (95% CI: 0·63 - 1·31) for Valacyclovir. Overall, Prednisolone-based treatment increased the chance of recovery 2-fold (95% CI: 1·55 - 2·42) compared to non-Prednisolone-based treatment. To gain 1 extra recovery, 6 and 26 patients need to be treated with Acyclovir and prednisolone compared to placebo and prednisolone alone, respectively.

Conclusions

Our evidence suggests that the current practice of treating Bell's palsy with AVT plus corticosteroid may lead to slightly higher recovery rates compared to treating with prednisone alone but this does not quite reach statistical significance; prednisone remains the best evidence-based treatment.
Provider performance in treating poor patients - factors influencing prescribing practices in lao PDR: a cross-sectional study
Authors: Syhakhang Lamphone , Soukaloun Douangdao , Tomson Göran , Petzold Max , Rehnberg Clas , Wahlström Rolf
Published: January 2011

Background

Out-of-pocket payments make up about 80% of medical care spending at hospitals in Laos, thereby putting poor households at risk of catastrophic health expenditure. Social security schemes in the form of community-based health insurance and health equity funds have been introduced in some parts of the country. Drug and Therapeutics Committees (DTCs) have been established to ensure rational use of drugs and improve quality of care. The objective was to assess the appropriateness and expenditure for treatment for poor patients by health care providers at hospitals in three selected provinces of Laos and to explore associated factors.

Methods

Cross-sectional study using four tracer conditions. Structured interviews with 828 in-patients at twelve provincial and district hospitals on the subject of insurance protection, income and expenditures for treatment, including informal payment. Evaluation of each patient's medical record for appropriateness of drug use using a checklist of treatment guidelines (maximum score = 10).

Results

No significant difference in appropriateness of care for patients at different income levels, but higher expenditures for patients with the highest income level. The score for appropriate drug use in insured patients was significantly higher than uninsured patients (5.9 vs. 4.9), and the length of stay in days significantly shorter (2.7 vs. 3.7). Insured patients paid significantly less than uninsured patients, both for medicines (USD 14.8 vs. 43.9) and diagnostic tests (USD 5.9 vs. 9.2). On the contrary the score for appropriateness of drug use in patients making informal payments was significantly lower than patients not making informal payments (3.5 vs. 5.1), and the length of stay significantly longer (6.8 vs. 3.2), while expenditures were significantly higher both for medicines (USD 124.5 vs. 28.8) and diagnostic tests (USD 14.1 vs. 7.7).

Conclusions

The lower expenditure for insured patients can help reduce the number of households experiencing catastrophic health expenditure. The positive effects of insurance schemes on expenditure and appropriate use of medicines may be associated with the long-term effects of promoting rational use of drugs, including support to active DTC work.
Science-based health innovation in sub-Saharan Africa
Authors: Al-Bader Sara , Masum Hassan , Simiyu Ken , Daar Abdallah S , Singer Peter A
Published: January 2011

In recent years emerging markets such as India, China, and Brazil have developed appropriate business models and lower-cost technological innovations to address health challenges locally and internationally. But it is not well understood what capabilities African countries, with their high disease burden, have in science-based health innovation.

This gap in knowledge is addressed by this series in BMC International Health and Human Rights. The series presents the results of extensive on-the-ground research in the form of four country case studies of health and biotechnology innovation, six studies of institutions within Africa involved in health product development, and one study of health venture funds in Africa. To the best of our knowledge it is the first extensive collection of empirical work on African science-based health innovation.

The four country cases are Ghana, Rwanda, Tanzania and Uganda. The six case studies of institutions are A to Z Textiles (Tanzania), Acorn Technologies (South Africa), Bioventures venture capital fund (South Africa), the Malagasy Institute of Applied Research (IMRA; Madagascar), the Kenyan Medical Research Institute (KEMRI; Kenya), and Niprisan’s development by Nigeria’s National Institute for Pharmaceutical Research and Development and Xechem (Nigeria).

All of the examples highlight pioneering attempts to build technological capacity, create economic opportunities, and retain talent on a continent significantly affected by brain drain. They point to the practical challenges for innovators on the ground, and suggest potentially helpful policies, funding streams, and other support systems.

For African nations, health innovation represents an opportunity to increase domestic capacity to solve health challenges; for international funders, it is an opportunity to move beyond foreign aid and dependency. The shared goal is creating self-sustaining innovation that has both health and development impacts. While this is a long-term strategy, this series shows the potential of African-led innovation, and indicates how it might balance realism against opportunity. There is ample scope to learn lessons more systematically from cases like those we discuss; to link entrepreneurs, scientists, funders, and policy-makers into a network to share opportunities and challenges; and ultimately to better support and stimulate African-led health innovation.
Science-based health innovation in Tanzania: bednets and a base for invention
Authors: Shah Ronak , Singer Peter A , Daar Abdallah S
Published: January 2011

Background

Tanzania is East Africa’s largest country. Although it is socially diverse, it has experienced general political stability since independence in 1964. Despite gradual economic development and Tanzania’s status as one of the biggest recipients of aid in Africa, health status remains poor. This paper explores Tanzania’s science-based health innovation system, and highlights areas which can be strengthened.

Methods

Qualitative case study research methodology was used. Data were collected through reviews of academic literature and policy documents, and through open-ended, face-to-face interviews with 52 people from across the science-based health innovation system over two visits to Tanzania from July to October 2007.

Results and discussion

Tanzania has a rich but complex S&T governance landscape, with the public sector driving the innovation agenda through a series of different bodies which are not well-coordinated. It has some of the leading health research on the continent at the University of Dar es Salaam, Muhimbili University of Health and Applied Sciences, the National Institute for Medical Research and the Ifakara Medical Institute, with strong donor support. Tanzania has found developing an entrepreneurial culture difficult; nevertheless projects such as the clusters initiative at the University of Dar es Salaam are encouraging low-tech innovation and overcoming knowledge-sharing barriers. In the private sector, one generics company has developed a South-South collaboration to enable technology transfer and hence the local production of anti-retrovirals. Local textile company A to Z Textiles is now manufacturing 30 million insecticide impregnated bednets a year.

Conclusions

To have a coherent vision for innovation, Tanzania may wish to address some key issues: coordination across stakeholders involved with health research, increasing graduates in health-related disciplines, and building capabilities in biological testing, preclinical testing, formulation and standardization, and related areas important to moving from basic research to applications. The private sector can be encouraged to innovate through improved access to financing, and incentives for R&D. The diaspora community represents an untapped source for partnerships and access to other developing world markets and technology. The government may wish to set up mechanisms to encourage south-south collaborations, and to bring the public and private sector together around specific projects to help realize the country’s innovation potential.
Can incubators work in Africa? Acorn Technologies and the entrepreneur-centric model
Authors: Chakma Justin , Masum Hassan , Singer Peter A
Published: January 2011

Background

Incubators are organizations that support the growth of new and typically technology-based enterprises, by providing business support services that bring together human and financial capital. Although the traditional role of incubators has been for economic development, they may also be a useful policy lever to tackle global health, by fostering the development and delivery of local health innovation.

Given its high disease burden, life sciences incubators hold particular potential for Africa. As the most industrially advanced African nation, South Africa serves as a litmus test for identifying effective incubator policies. The case study method was used to illustrate how one such publicly funded incubator founded in 2002, Acorn Technologies, helped to catalyze local health product innovation.

Discussion

Acorn helped to support twelve biomedical device firms. One of them, Real World Diagnostics, was founded by a trainee from Acorn’s innovative internship program (Hellfire). It developed rapid strip diagnostic tests for locally prevalent diseases including schistosomiasis and HIV, and reported $2 million (USD) in revenue in 2009.

Acorn achieved this success by operating as a non-profit virtual incubator with little physical infrastructure. Employing a virtual model in combination with stringent selection criteria of capital efficiency for clients proved to be effective in reducing its own fixed costs. Acorn focused on entrepreneurship training and networking, both critical at an early stage in an environment dominated by multinational biomedical device companies.

Acorn and its clients learned that employing a cross-subsidy business model allowed one to generate royalty revenue through imports to subsidize R&D for local diseases. However, funding constraints and government expectations for rapid self-sustainability forced Acorn to merge with its sister biotechnology incubator in 2009.

A key to Acorn’s achievements was identifying entrepreneurs with technologies with health and economic impact, and providing them with flexible support from an early stage. A virtual organizational model helped Acorn to focus on supporting entrepreneurs. Governments and funders may wish to consider incubation strategies that draw from these good practices. With the right policies and business models, incubators have the potential to generate both health and economic benefits for Africa.
Harnessing biodiversity: the Malagasy Institute of Applied Research (IMRA)
Authors: Puri Manveen , Masum Hassan , Heys Jennifer , Singer Peter A
Published: January 2011

Background

Biopiracy – the use of a people’s long-established medical knowledge without acknowledgement or compensation – has been a disturbing historical reality and exacerbates the global rich-poor divide. Bioprospecting, however, describes the commercialization of indigenous medicines in a manner acceptable to the local populace. Challenges facing bioprospectors seeking to develop traditional medicines in a quality-controlled manner include a lack of skilled labor and high-tech infrastructure, adapting Northern R&D protocols to Southern settings, keeping products affordable for the local population, and managing the threat of biopiracy. The Malagasy Institute of Applied Research (IMRA) has employed bioprospecting to develop new health treatments for conditions such as diabetes and burns. Because of its integration of Western science and Malagasy cultural traditions, IMRA may provide a useful example for African and other organizations interested in bioprospecting.

Discussion

IMRA’s approach to drug development and commercialization was adapted from the outset to Malagasy culture and Southern economic landscapes. It achieved a balance between employing Northern R&D practices and following local cultural norms through four guiding principles. First, IMRA’s researchers understood and respected local practices, and sought to use rather than resist them. Second, IMRA engaged the local community early in the drug development process, and ensured that local people had a stake in its success. Third, IMRA actively collaborated with local and international partners to increase its credibility and research capacity. Fourth, IMRA obtained foreign research funds targeting the “diseases of civilization” to cross-fund the development of drugs for conditions that affect the Malagasy population. These principles are illustrated in the development of IMRA products like Madeglucyl, a treatment for diabetes management that was developed from a traditional remedy.

By combining local and international research interests, IMRA has been able to keep its treatments affordable for the Malagasy population. Our analysis of IMRA’s history, strategy, and challenges suggests that other developing world institutions seeking to use bioprospecting to address issues of local access to medicines would be well-advised to treat traditional medical knowledge with respect and humility, share its benefits with the local community, and pursue strategic partnerships.
Impact of Plasmodium falciparum infection on haematological parameters in children living in Western Kenya
Authors: Maina Robert N , Walsh Douglas , Gaddy Charla , Hongo Gordon , Waitumbi John , Otieno Lucas , Jones David , Ogutu Bernhards R
Published: January 2011

Background

Malaria is the commonest cause of childhood morbidity in Western Kenya with varied heamatological consequences. The t study sought to elucidate the haemotological changes in children infected with malaria and their impact on improved diagnosis and therapy of childhood malaria.

Methods

Haematological parameters in 961 children, including 523 malaria-infected and 438 non-malaria infected, living in Kisumu West District, an area of malaria holoendemic transmission in Western Kenya were evaluated.

Results

The following parameters were significantly lower in malaria-infected children; platelets, lymphocytes, eosinophils, red blood cell count and haemoglobin (Hb), while absolute monocyte and neutrophil counts, and mean platelet volume (MPV) were higher in comparison to non-malaria infected children. Children with platelet counts of <150,000/uL were 13.8 times (odds ratio) more likely to have malaria. Thrombocytopaenia was present in 49% of malaria-infected children and was associated with high parasitaemia levels, lower age, low Hb levels, increased MPV and platelet aggregate flag. Platelet aggregates were more frequent in malaria-infected children (25% vs. 4%, p<0.0001) and associated with thrombocytopaenia rather than malaria status.

Conclusion

Children infected with Plasmodium falciparum malaria exhibited important changes in some haematological parameters with low platelet count and haemoglobin concentration being the two most important predictors of malaria infection in children in our study area. When used in combination with other clinical and microscopy, these parameters could improve malaria diagnosis in sub-patent cases.
Hepatitis C virus genotype 3a with phylogenetically distinct origin is circulating in Pakistan
Authors: Rehman Irshad-ur , Idrees Muhammad , Ali Muhammad , Ali Liaqat , Butt Sadia , Hussain Abrar , Akbar Haji , Afzal Samia
Published: January 2011

Background

Hepatitis C virus (HCV) is one of the leading causes of viral hepatitis worldwide and its genotype 3a is predominant in vast areas of Pakistan.

Findings

The present study reports the first full sequence of HCV 3a isolate PK-1 from Pakistan. This nucleotide sequence was compared with six other HCV genotype 3a full length sequences from different regions of the world by using statistical methods of phylogenetic analysis.

Conclusion

The nucleotide difference of these seven sequences shows that HCV genotype 3a of phylogenetically distinct origin is circulating in Pakistan.
Altered glycosylation profile of purified plasma ACT from Alzheimer’s disease
Authors: Ianni Manuela , Manerba Marcella , Di Stefano Giuseppina , Porcellini Elisa , Chiappelli Martina , Carbone Ilaria , Licastro Federico
Published: January 2011

Background

Alzheimer’s disease (AD) is one of the most frequent cause of neurodegenerative disorder in the elderly. Inflammation has been implicated in brain degenerative processes and peripheral markers of brain AD related impairment would be useful. Plasma levels of alpha-1-antichymotrypsin (ACT), an acute phase protein and a secondary component of amyloid plaques, are often increased in AD patients and high blood ACT levels correlate with progressive cognitive deterioration. During inflammatory responses changes in the micro-heterogeneity of ACT sugar chains have been described.

Methods

N-Glycanase digestion from Flavobacterium meningosepticum (PNGase F) was performed on both native and denatured purified ACT condition and resolved to Western blot with the purpose to revealed the ACT de-glycosylation pattern.

Further characterization of the ACT glycan profile was obtained by a glycoarray; each lectin group in the assay specifically recognizes one or two glycans/epitopes. Lectin-bound ACT produced a glyco-fingerprint and mayor differences between AD and controls samples were assessed by a specific algorithms.

Results

Western blot analysis of purified ACT after PNGase F treatment and analysis of sugar composition of ACT showed significantly difference in “glyco-fingerprints” patterns from controls (CTR) and AD; ACT from AD showing significantly reduced levels of sialic acid. A difference in terminal GlcNac residues appeared to be related with progressive cognitive deterioration.

Conclusions

Low content of terminal GlcNac and sialic acid in peripheral ACT in AD patients suggests that a different pattern of glycosylation might be a marker of brain inflammation. Moreover ACT glycosylation analysis could be used to predict AD clinical progression and used in clinical trials as surrogate marker of clinical efficacy.