Hepatitis B virus (HBV) infection has persisted as a major public health problem due to the lack of an effective treatment for those chronically infected. Therapeutic vaccination holds promise, and targeting HBV polymerase is pivotal for viral eradication. In this research, a computational approach was employed to predict suitable HBV polymerase targeting multi-peptides for vaccine candidate selection. We then performed in-depth computational analysis to evaluate the predicted epitopes’ immunogenicity, conservation, population coverage, and toxicity. Lastly, molecular docking and MHC-peptide complex stabilization assay were utilized to determine the binding energy and affinity of epitopes to the HLA-A0201 molecule. Criteria-based analysis provided four predicted epitopes, RVTGGVFLV, VSIPWTHKV, YMDDVVLGA and HLYSHPIIL. Assay results indicated the lowest binding energy and high affinity to the HLA-A0201 molecule for epitopes VSIPWTHKV and YMDDVVLGA and epitopes RVTGGVFLV and VSIPWTHKV, respectively. Regions 307 to 320 and 377 to 387 were considered to have the highest probability to be involved in B cell epitopes. The T cell and B cell epitopes identified in this study are promising targets for an epitope-focused, peptide-based HBV vaccine, and provide insight into HBV-induced immune response. HBV infection is a major public health problem with at least 250 million chronically infected individuals. More than 686,000 people die every year due to complications of hepatitis B that include cirrhosis and hepatocellular carcinoma . AlthougResearch has shown that HBV hinders the liver’s innate immune responses, which are necessary in triggering adaptive immune responses . AnotherHBV therapeutic vaccines aim to stimulate patients’ innate and adaptive immune response to effectively eliminate the virus. Poor clinical responses to therapeutic vaccines are probably due to the exhausted T cells not responding correctly to therapeutic vaccination . The keyHigh HBV antigen levels, especially HBsAg, contribute to specific T cell exhaustion and limit the immunological response to therapeutic vaccination . PersistHBV DNA polymerase contains four domains and plays a vital part in HBV replication . TherefoPolymerase function is inhibited when nucleos(t)ide analogues incorporate into the elongating DNA chain and act as chain terminators, due to their lack of a 3’-OH, during HBV reverse transcription. Guanosine and adenosine analogs, such as entecavir and tenofovir, also impair protein priming . HBV repIn recent years, bioinformatics has garnered much scientific attention. Vaccines developed through bioinformatics are safer, more convenient, more efficacious, and less expensive than traditional vaccines . Our preDifferent genotype protein sequences of HBV polymerase were obtained from GenBank of National Center for Biotechnology Information (NCBI). We selected complete sequences of all gene subtypes and excluded the sequences that constituted different genotypes. Sequences only containing partial sequences of genotypes were also excluded. Thirteen complete sequences, constituted by only one genotype, were selected . The lengths of these sequences ranged from 831aa to 845aa. . All sequences were stored in FASTA format. Since the B genotype is the most prominent genotype in China, the B genotype sequence was recorded for MHC-I binding, proteasomal C cleavage, TAP transport, immunogenicity, conservancy, toxin, population coverage, and B cell epitope analysis. A graphical representation predicting T cell and B cell epitopes is shown in To confirm whether the epitope could be presented on the surface of cells, the epitope prediction tools were used. Potential epitopes of HBV polymerase were predicted by T cell epitope prediction tools: IEDB MHC-I processing predictions, MHC-NP, netCTLpan1.1, RANKPEP, and netMHCpan3.0. Since HLA-A0201 was the most popular MHC allele and most MHC-I epitopes were nonapeptides, we selected the HLA-A0201 MHC allele and nonapeptide. Other parameters of each prediction tools were set to default.http://tools.immuneepitope.org/processing/).The IEDB MHC-I processing predictions website aims to identify MHC-I ligands. This website provides approach of predicting peptides that are naturally processed from proteins and presented by MHC class I molecules. The MHC-I binding predictions were made on 12 June 2016 using the IEDB analysis resource consensus , which chttp://tools.immuneepitope.org/mhcnp/) [The MHC-NP server is designed for prediction of peptides naturally presented by the MHC molecules. This website employs data obtained from MHC elution experiments in order to assess the probability that a given peptide is naturally processed and binds to a given MHC molecule (/mhcnp/) .http://www.cbs.dtu.dk/services/NetCTLpan/) [The netCTLpan1.1 server is designed for predicting cytotoxic lymphocyte (CTL) epitopes in protein sequences. This website integrates predicted peptide MHC-I binding, proteasomal C terminal cleavage performed using artificial neural networks (ANN), and TAP transport efficiency, which was predicted using weight matrix (CTLpan/) .http://imed.med.ucm.es/Tools/rankpep.html) [RANKPEP server aims to predict epitopes of class I and class II MHC molecules based on protein sequences. This method predicts epitopes using position-specific scoring matrices (PSSMs) (ep.html) ,26,27.http://www.cbs.dtu.dk/services/NetMHCpan/) [NetMHCpan3.0 server is designed for predicting ability of peptide-MHC class I binding. This website predicts epitope binding to any MHC molecule using ANN (MHCpan/) ,29.The top 50 predicted epitopes  were chosen, and epitopes which were predicted by at least four prediction methods were selected for further analysis.http://tools.immuneepitope.org/immunogenicity/) [Immunogenicity prediction tools was used to predict the ability of the epitope/MHC complex to elicit an immune response. The IEDB class I immunogenicity server is designed to predict the immunogenicity of a peptide MHC complex (nicity/) . Epitopehttp://tools.immuneepitope.org/tools/conservancy/iedb_input) [In order to assess the conservancy level of epitopes within different genotype protein sequences, IEDB conservancy analysis was used. This analysis aims to calculate the degree of conservancy of epitopes within a given protein sequence (b_input) . The seqhttp://www.imtech.res.in/raghava/toxinpred/index.html) [To confirm the specific immune responses induced by epitopes that targets only the virus rather than the host tissue, the ToxinPred website was used to confirm epitopes’ nontoxicity (ex.html) . This wehttp://www.cbs.dtu.dk/services/NetMHC/) [http://tools.immuneepitope.org/tools/population/iedb_input) [HBV is a worldwide pandemic disease. To cover most chronic infected individuals, the IEDB population coverage method was carried out to estimate the rate of coverage of epitopes in regions with high HBV prevalence. Before estimating population coverage, the MHC-I alleles that would interact with epitopes were required. Therefore, epitopes were subjected to NetMHC4.0 server to predict the interacting MHC-I alleles. NetMHC4.0 server is designed for predicting ability of peptide-MHC class I binding and affinity between epitopes and MHC-I molecules using ANNs by detecting all MHC-I alleles. The MHC allele was set to HLA-A0201 and peptide length was set to nonapeptide. The threshold for strong binders and weak binders were respectively set to 0.5% and 2% rank (NetMHC/) ,33, and NetMHC/) ,35, we sb_input) .http://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD/) [http://www.rcsb.org/pdb/home/home.do). The structure 4UQ3 of this database was the crystal structure of HLA-A0201 in complex with an azobenzene-containing peptide [For the sake of ascertaining the binding affinities between the epitopes and MHC-I molecular structures, molecule docking was used. The epitope sequences were subjected to PEP-FOLD2.0 (P-FOLD/) ,38, a we peptide . HLA-A02 peptide . The cenTo determine the binding affinity of selected peptides to the HLA-A0201 molecule, we detected the upregulation of peptide-inducing HLA-A0201 molecules on T2 cells using flow cytometry. The transporter associated with the antigen processing (TAP)-deficient T2 cell line was purchased from American Type Culture Collection (ATCC) and maintained in complete RPMI-1640 medium. Candidate epitopes were synthesized and purified to greater than 99% purity . The MHC-peptide complex stabilization assay was performed in accordance with the method described by Duan et al. , brieflyThe goal of B cell epitope prediction was to determine the antigen recognized by B lymphocytes and initiate humoral immunity. To identify the B cell epitopes, IEDB B-cell epitope prediction was used. This website server is designed for prediction of B-cell epitope, which consisted of BepiPred linear epitope prediction ,43,44, CIn a preselected environment, the IEDB recommend, MHC-NP, netCTLpan1.1, RANKPEP and netMHCpan3.0 server predicted the potent epitopes from the HBV polymerase sequence. To improve the accuracy of epitope prediction, we selected epitopes which were predicted by at least four tools. In total, 30 epitopes were selected. Results are shown in Besides the epitope prediction, the binding affinity between peptide/MHC complex and TCR should be further analyzed. A high immunogenicity score was deemed to have high ability to stimulate naive T cells and induce cellular immunity. The epitopes selected using the above methods were subjected to IEDB immunogenicity prediction. The epitopes’ immunogenicity scores ranged from 0.22707 to −0.3485. Fifteen peptides with positive value scores were selected for further analysis. The results are depicted in To determine the conservancy status of selected peptides among the HBV polymerase proteins, multiple sequence alignments were carried out using IEDB conservancy analysis. Our analysis showed that two epitopes  were 100% conserved in 12 other genotype sequences; epitope VSIPWTHKV scored 83.3%. Three epitopes  showed 75% conservancy. Our data is shown in A qualified vaccine should have the ability to induce a specific immune response that targets only the virus rather than the host tissue. To confirm that inducement of cellular immunity by epitopes did not damage host tissue, we used a bioinformatics tool to predict the toxicity of epitopes; the data is depicted in To cover most chronic infected individuals, the IEDB population coverage method was used. The netMHC4.0 server was utilized to acquire MHC alleles with high epitope-binding force. The MHC alleles and binding ranks were shown in The epitopes selected by the above methods were validated by molecular docking. The binding energy between each structure and the HLA-A0201 molecule was calculated and ranked. Docking results are shown in Along with cellular immunity, humoral immunity is also required for viral elimination. B cell epitope identification was based on sequence characteristics of the antigen using amino acid scales, and different analysis methods were used to predict linear B cell epitopes.To predict B-cell epitopes, we should first identify the location of linear B-cell epitopes. Therefore, BepiPred linear epitope prediction was carried out using a hidden Markov model and propensity scale method. The result indicated that the average score is −0.026, with the minimum being −2.495 and the maximum, 2.197. The graph is shown in The Kolaskar–Tongaonkar antigenicity scale was used to predict antigenic determinants on proteins based on the physicochemical properties of amino acid residues. The frequency of occurrence in experimentally known segmental epitopes was also taken into consideration. The average antigenic propensity of the sequence was 1.049, with a minimum of 0.904 and maximum of 1.214. The highest score region was from 334 to 344 amino acid sequences. The result is shown in To be an epitope, surface accessibility was also taken into consideration. The Emini surface accessibility scale was carried out, with an average score of 1.000, a minimum of 0.065, and a maximum of 6.664. The highest surface-accessible region was between 158 and 165 amino acid sequences. The graph is shown in Experimental evidence has found that the beta turn and flexibility of proteins are also critical to B-cell epitope prediction. Hence, we implemented the Chou–Fasman beta turn prediction and the Karplus–Schulz flexibility scale to estimate the beta turn and flexibility of the proteins. The result of Chou–Fasman was an average score of 1.007, a minimum of 0.676, a maximum of 1.406, and the generated outcomes’ most recognized regions were from 308 to 316 amino acid sequences. The Karplus–Schulz result was an average score of 0.993, a minimum of 0.867, and a maximum of 1.144. The region between 307 and 320 amino acid sequences was considered the most favorable region in the flexibility prediction. The two graphs are shown in Finally, hydrophilicity should be analyzed. Hence the Parker hydrophilicity prediction was used to constructed a hydrophilic scale based on peptide retention times during high-performance liquid chromatography (HPLC) on a reversed-phase column. The result revealed an average score of 0.952, a minimum of −5.157, and a maximum of 6.100. The most hydrophilic region was from 785 to 794 amino acid sequences. The graph is shown in These six B cell epitope prediction tools divide sequences into different regions, and rank these regions based on probability of inducing B cell immune response. The top 2% of regions were selected to analyze the B cells’ epitope regions. We selected the regions predicted by at least four prediction tools for further analysis. We found that regions 307–320 and 377–387 contained overlapped regions predicted by at least four tools and were considered to have the highest probability to be involved in B cell epitopes. Our study predicted and selected four T cell epitopes, RVTGGVFLV, VSIPWTHKV, YMDDVVLGA, and HLYSHPIIL, on the basis of their immunogenicity, conservancy, toxicity, and population coverage. Epitopes VSIPWTHKV and YMDDVVLGA were found to have the lowest binding energy to the HLA-A0201 molecule, while epitopes RVTGGVFLV and VSIPWTHKV were found to have high affinity to the HLA-A0201 molecule. Regions 307–320 and 377–387 were considered to have the highest probability to be involved in B cell epitopes. Our research employed all criteria regarding epitope selection in an effort to obtain quality predictions. These four T cell epitopes and two regions involved in B cell epitopes will be validated by in vivo and in vitro experience in our subsequent research, and eventually we expect these epitopes will be found to constitute the basis of a HBV polymerase therapeutic vaccine.There are many novel therapies for an HBV cure under investigation, including direct acting anti-virals (DAA) and host targeting agents (HTA). DAAs directly target the virus, and include entry inhibitors, polymerase inhibitors, site-specific cleavage of DNA agents, inhibitors of relax-circular DNA to cccDNA conversion, inhibitors of nucleocapsid assembly, capsid inhibitors, agents that knock down HBV RNA, viral proteins and HBV DNA, and agents that block HBsAg secretion. HTAs, which act by improving host immune ability, include therapeutic vaccines, immune checkpoint inhibitors, stimulators of exogenous interferon, and agents that induce APOBEC3A and APOBEC3B. These novel therapies are undergoing pre-clinical or clinical testing, and their effects should be further investigated ,52.There has been considerable development in the various types of therapeutic vaccines in recent years. The HBV surface-and-core-antigens-formulated vaccine Nasvac was proven to be able to stimulate both B and T cells in vitro . An autoIn conclusion, numerous HBV therapeutic vaccines have been developed and subjected to clinical trials, including core antigen, e antigen, surface antigen, and recombined vaccines, but vaccines constructed only by polymerase have not been reported. Theoretically, the crucial role of polymerase in HBV replication and infection suggest that a polymerase antigen vaccine may be more effective than other vaccines . TherapeIn recent years, bioinformatic analysis has been carried out as a significant approach to designing vaccines, including numerous methods and databases for designing subunit vaccines and epitope-based immunotherapy. Compared to the traditional approach, which administrates whole pathogens and raises several safety issues, the in silico tool is convenient and time saving . ComputaThe benefits of epitopes and vaccines designed by bioinformatics technology have been validated by appreciable research. A study in regard to glypican-1 (GPC3), which is a new prognostic factor for early hepatocellular carcinoma (HCC), showed that epitopes selected by technical websites have the ability to bind to T2 cells . In anotIt is crucial that epitopes identified through in silico analysis should be validated in vivo and/or in vitro experiments to certify their immunogenicity ,75,76. AOur research provides a novel and promising pathway to designing an HBV therapeutic vaccine. It is possible that a vaccine design based on this research will specially target HBV polymerase and inhibit HBV replication, which may achieve an effect comparable to nucleos(t)ide analogues, but without drug resistance. Furthermore, individuals with chronic HBV infections may be liberated from the inconvenience and financial burden of a lifelong medication regimen.


The online Journal of Applied Clinical Medical Physics (JACMP) has moved editorial operations to Rochester, Minnesota. I am being ably assisted by Sarah D. Evers, who will become known to many of you as “Manuscript Manager.” Four issues are planned for 2003, which is Volume 4, with this Winter issue being the first. A 10‐paper minimum per‐issue goal was set, and this was exceeded. The “pipeline” of articles under consideration is staying steady at about 20. We are discussing with AIP their service to put accepted manuscripts online the instant a final copy is submitted so an issue will “build.” This could cut availability time down by up to three months and certainly adds value to potential authors.I would be very remiss if I did not specifically acknowledge the work of Peter Almond (Editor‐in‐Chief for Volumes 1‐3), as well as Georgeanne Moore (Manuscript Manager for Volumes 1‐3). As I am finding out, there is a ton of little details that have to be attended to. The fact that the Journal has grown (about 60% per year) and thrived under their “watch” is a testimony to their dedication to the task. The ACMP and the worldwide medical physics community owe them a debt of gratitude that really cannot be repaid adequately.It became painfully obvious after taking over the helm that additional Associate Editors (AE) were needed. Four new Associate Editors have been added. In the area of Therapy Physics we have added John Gibbons, Tim Solberg, and Gino Fallone. We are also extremely pleased that Walter Huda has agreed to join the Diagnostic Imaging AE “team.” Editorial Board members and reviewers are to be thanked profusely for volunteering their expertise to insure a consistent and high‐ quality product. I have been very pleased to see the effort that goes into the AE and their reviewer's deliberations. This is a truly peer‐reviewed journal.JACMP is available free to a worldwide audience, and is now an official publication of the International Organization of Medical Physics (IOMP). As such, the Editorial Board is developing strategies to increase international submissions and online access numbers. Informal discussions are underway to see whether there could be a role for JACMP in placing online nonjournal published Tech‐ nical Reports from some major medical physics societies, increasing worldwide availability and helping carry out their international scientific mission(s).As I jot down these “musings,” I am heading to an Online Electronic Journal Publishing Meeting at AIP in College Park. It will be interesting to learn of others' experiences. I am particularly interested in being updated on the changes to the electronic submission system. The current one is quirky and had certain features I find suboptimal (like the authors get to preselect the Associate Editor!).The principal goal of the Editorial Board (below) remains that JACMP be the first choice source of rapidly published and thoroughly peer‐reviewed information for immediately useful clinical medical physics information. JACMP is seeking high‐ quality papers that deal with the application of the observations, data, and/or procedures in the clinic. Class examples include technology, information systems, treatment techniques, quality assurance, and procedure guidelines. Immediate usefulness in the clinic should be the hallmark of a JACMP sub‐ mission. Please consider JACMP for some of your future manuscripts. We promise fair and speedy review as well as the ability to reach a wide international audience.ecmc@mayo.edu) with any suggestions for how the Journal can better serve your needs as a reader or, better still, an author!!I look forward to visiting you next time in the “Editorial.” Please feel free to email me (Edwin C. McCulloughEditor‐in‐Chief


The great fallacy is the wisdom of old men. They do not grow wise. They grow careful.A Farewell to Arms, Ernest Hemingway 1899–1961) [899–1961 At a certain moment in life everyone has to make important decisions with direct implications for their future. This time has now arrived and I would like to announce that, as of 1 January 2017, I will be stepping down as Editor-in-Chief of the Netherlands Heart Journal (NHJ). Formally, the appointment of an Editor-in-Chief is a matter for both the Publisher and the Netherlands Society of Cardiology (NVVC). Together they arrive at the decision on who is the most appropriate candidate for this position at this moment.At the 2016 autumn meeting of the NVVC it was officially announced that from 1 January 2017 Professor Jan J. Piek  will take over the position of Editor-in-Chief of NHJ, for a well-defined period of time. He will be assisted by local deputy editors. Further details will be given in the NHJ Editor’s Comment of January 2017.We hope that you really appreciate our efforts to make the Netherlands Heart Journal a new platform for cardiovascular research in a broadest sense of the word’! [It was 15 years ago, on 1 April 2001, that the Netherlands Heart Journal was founded. It was the offspring of the journal entitled ‘Nederlands Tijdschift voor Cardiologie’ (founded in 1987) and its successor ‘Cardiologie’ (founded in 1994), both journals predominantly publishing in the Dutch language. However, at the turn of this century it was thought wise and timely, by both the Chief Editors and the Publisher, to completely change to the English language and to mainly focus on original and review articles. At that time, the first Editorial Comment in April 2001 ended with the phrase ‘e word’! , 4.Let us briefly go over the main events and achievements of NHJ since 2001. On 1 January 2005, our journal changed its publishing company from Mediselect BV to Bohn, Stafleu & van Loghum , which over time became a division of the Springer Verlag Concern, Germany.www.pubmedcentral.gov) [www.pubmed.gov). PubMed has now retroactively listed all NHJ articles  from its very start in April 2001. In 2008, NHJ was indexed by WOS and received its first impact factor in 2009, which was 1.392 at that time and by 2015 it had increased to 2.062 [In 2006, NHJ was adopted by PubMed Central  , 5, whicto 2.062 .These major achievements were not given to us for free. It has cost much effort and many years for NHJ to enter the international arena. Once getting there, we have had to battle to stay there and it requires an ongoing fighting spirit to preserve and, more importantly, to improve the scientific level of our journal. This achievement has been made possible, and continues to be possible, through the cooperation and support of many institutions and individuals. In particular the Publisher (predominantly represented by Lieda Meester) together with my former Chief Editors, Professors de Boer, Doevendans, Wilde and Zijlstra, laid the basis for these martial accomplishments. Furthermore, over the years we have received support from the NVVC , 13, theGreat is the art of beginning, but greater is the art of ending’ the American poet Henry Wadsworth Longfellow (1807–1882) once said. A new editorial period will begin and I am fully confident that NHJ will continue to thrive. In the style of Ernest Hemingway, I say farewell to arms with one of his quotes; ‘it is now hard to leave the country but it is in no way impossible’ [‘ngfellow 807–1882


Clostridium thermocellum is a leading candidate for the consolidated bioprocessing of lignocellulosic biomass for the production of fuels and chemicals. A limitation to the engineering of this strain is the availability of stable replicating plasmid vectors for homologous and heterologous expression of genes that provide improved and/or novel pathways for fuel production. Current vectors relay on replicons from mesophilic bacteria and are not stable at the optimum growth temperature of C. thermocellum. To develop more thermostable genetic tools for C. thermocellum, we constructed vectors based on the hyperthermophilic Caldicellulosiruptor bescii replicon pBAS2. Autonomously replicating shuttle vectors based on pBAS2 reproducibly transformed C. thermocellum at 60 °C and were maintained in multiple copy. Promoters, selectable markers and plasmid replication proteins from C. bescii were functional in C. thermocellum. Phylogenetic analyses of the proteins contained on pBAS2 revealed that the replication initiation protein RepL is unique among thermophiles. These results suggest that pBAS2 may be a broadly useful replicon for other thermophilic Firmicutes. •C. thermocellum.Intergeneric replication of a hyperthermophilic plasmid replicon in •Transformation efficiencies >3000 colony forming units per µg of plasmid DNA.•C. thermocellum.Plasmid maintained at ~20 copies per chromosome in •Caldicellulosiruptor proteins and promoters function in C. thermocellum.•The pBAS2 RepL replication initiation protein is unique among thermophilic proteins. C. thermocellum secretes proteins that form an extracellular organelle, called a cellulosome , that confers thiamphenicol resistance; and neomycin acetyl transferase (neo), that confers neomycin resistance. Counter-selectable markers include pyrF, that confers sensitivity to 5-fluoroorotic acid (5-FOA); tdk, that confers sensitivity to 5-fluoro-2′-deoxyuridine (FUdR); and hpt, that confers sensitivity to toxic purine analogs such as 8-azahypoxanthine (8AZH)  . CounterC. thermocellum. Early work in mesophilic Gram-positive bacteria identified several such replicons. Staphylococcus aureus plasmid pC194, that replicates by a rolling circle mechanism  twice in succession for 45 min at 37 °C and ligated with the FastLite ligation kit  according to the manufacturer’s instructions. Plasmid pJGW37 was constructed by amplifying a 7.467 kb fragment from pDCW196 using primers JG024 and JG099, digesting with XbaI (New England Biolabs) and ligating as described above to circularize the linear fragment. All plasmid sequences were verified by Sanger DNA sequencing (Genewiz). All primers are listed in All PCR reactions for cloning were performed with Q5 polymerase  according to the manufacturer's instructions . Plasmid pDCW196 was constructed by ligating r pDCW89  to the cr pMU612 . Primers2.3C. thermocellum DSM 1313 ΔpyrF was grown at 60 °C to mid-exponential phase in defined CTFUD medium  set at 1.8 kV, 25 μF, and 350 Ω, and placed immediately into 60 °C CTFUD+C medium , and placed immediately into warm CTFUD+C medium for 6 h at 60 °C, after which they were serially diluted onto CTFUD plates containing yeast extract (0.1% w/v) and 10 µg/mL thiamphenicol . Colonies appeared after 4–5 days of growth at 60 °C under an atmosphere of 85% nitrogen, 10% CO2, and 5% Hydrogen. Transformation efficiency was calculated in CFU/µg of plasmid DNA, and experiments were performed in biological triplicate.A 10 mL starter culture of D medium . This cu2.5600~0.4 for C. thermocellum ΔpyrF, ~0.7 for C. thermocellum Δhpt) and 5 mL of culture was harvested at 4 °C at 6100×g. The pellet was resuspended in 200 µL 40 mM EDTA, 50 mM Tris–HCl, 25% sucrose (w/v) with 30 mg/mL lysozyme  and 1 µL/mL RNase A (Qiagen), and incubated for 30 min at 37 °C. Cells were frozen and thawed five times using a dry ice–ethanol slurry and a 37 °C water bath. 500 µL 6 M Guanidine-HCl pH 8.5  was immediately added to the cell lysate and allowed to incubate at 75 °C for 10 min. The lysate was washed twice with Phenol:chloroform:isoamyl alcohol and once with chloroform. To the aqueous layer, 3 M sodium acetate pH 5.2 was added, and DNA was precipitated at −80 °C for 3 h, washed with cold 70% ethanol and resuspended in 10 mM Tris–HCl. Total DNA for C. thermocellum transformants containing pJGW37 was visualized on a 1% agarose gel  stained with ethidium bromide  inoculum was grown without shaking at 60 °C. 2% (v/v) samples were removed for qPCR analysis at the indicated time points . For pla bromide C.2.6C. thermocellum transformants as template. Reactions were performed with primers DC091 and DC508 according to the manufacturer's instructions . PCR products were visualized on a 1% agarose gel with an NEB 1 kb Ladder for size verification . To verify structural stability in C. thermocellum, total DNA was electrotransformed into E. coli BL21 with a BioRad Gene Pulser  using an exponential pulse in a 2mm cuvette . Selection in E. coli was performed with 50 µg/mL apramycin, and colonies were screened for the presence of the plasmid by performing restriction digests with EcoRI and ApaLI .Taq polymerase  was used for PCR reactions to confirm presence of the plasmid using total DNA purified from 2.7C. thermocellum chromosome  were used to compute relative copy number of the plasmid to the chromosome. The formula for this calculation was PCN=2^| Ctchromosome−Ctplasmid |. Four replicate reactions for each primer set were performed, and the average of the two primer sets on each sample was used to calculate the plasmid copy number in each serial subculture  with LightCycler 480 SYBR Green I master mix (Roche). Cycle thresholds resulting from amplification with two independent sets of primers specific to either the pJGW07 plasmid  or the bculture  accordin2.8http://tree.bio.ed.ac.uk/ software/figtree/) was used to visualize the phylogenetic trees generated by MRBAYES. MEME was used for motif analysis  and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to search for homologous proteins to the ORFs on plasmid pBAS2. Amino acid similarity was also determined with the NCBI Basic Local Alignment Search Tool (BLAST). Clustal Omega was used for multiple sequence alignment with default settings . ProtTesanalysis , searchianalysis . CodonO analysis  was used33.1As noted previously , the proThermoanaerobacter and Thermoanaerobacterium . There were no plasmid-encoded thermophilic homologs, and very few Firmicute homologs A. Cbes27g domain B, althouresidues , and wheresidues . These fy groups  making tCyanothece sp. PCC 8802 MarR2/RepL and Sodalis glossinidius RepL are encoded on plasmids that encode Xer-like recombinases, reminiscent of the arrangement of RepL and XerD on pBAS2. In fact, the use of portions of pBAS2 to construct other vectors revealed that the XerD recombinase is required for plasmid replication in C. bescii  gene for selection of transformants in C. thermocellum strains that are wild type at the pyrF locus.Two pBAS2-derived plasmids were used for testing transformation of d pDCW89 A was preid pBAS2     , allowinse (hpt)  selectinse (hpt) . The ΔhpC. thermocellum transformants containing pDCW89 or C. thermocellum transformants containing pJGW37 was used to back-transform E. coli. Two different restriction endonuclease digests performed on plasmid DNA purified from nine independent E. coli colonies (3 shown) resulted in identical banding patterns relative to the original plasmid , demonstrating that the pBAS2 origin of replication can efficiently transform is~51 °C .C. thermocellum transformants were passaged in both selective and non-selective media five times, and the copy number was measured using quantitative polymerase chain reaction (qPCR), as described by To assess plasmid stability and copy number, individual 3.4C. bescii pyrF wild type allele and this gene functions to complement the pyrF deletion in C. thermocellum. The PyrF proteins have 45% amino acid sequence identity. The G+C content of the C. bescii pyrF gene is 35.7%, and that of the C. thermocellum pyrF gene is 39.9%. In fact, CodonO software (C. bescii and C. thermocellum genomes is not statistically significant with a p value of >0.33. Both pDCW89 and pJGW37 rely on a C. bescii ribosomal protein promoter (pyrF gene in pDCW89 and the cat gene in pJGW37. While we have no direct evidence for the efficiency of these promoters at this time, they clearly function at a level sufficient to allow selection. No promoter from C. bescii has been characterized experimentally so the transcription start site and RNA polymerase binding site for this promoter is unknown, but the sequence does contain a prototypical RNA polymerase binding site sequence for growth phase dependent transcription in Gram-positive bacteria.Plasmid pDCW89 contains the software  indicatepromoter  to direcpromoter , the pyr4C. bescii can replicate in C. thermocellum at its optimal growth temperature of 60 °C. This expansion of the genetic tools available for C. thermocellum will facilitate more rapid genetic engineering toward the goal of developing an organism for the efficient conversion of lignocellulosic biomass to fuels and chemicals. Further, the demonstration of stable, autonomous replication of the C. bescii pBAS2 replicon in C. thermocellum suggests that this replicon might serve as a new tool for plasmid-based expression in other thermophiles, as well.While many plasmid origins of replication are derived from mesophilic sources, genetic tools for thermophiles must function at elevated temperatures. The use of thermophilic sources offers a solution to this issue, and we have demonstrated that plasmid origin pBAS2 from thermophile C. thermocellum.LL has an equity interest in Enchi Corporation, a biofuel start-up company with a financial interest in


The American Society of Tropical Medicine and Hygiene (ASTMH) was established in 1951 with the merger of the American Society of Tropical Medicine, formed by 28 American physicians in Philadelphia in 1903, and The National Malaria Committee (later Society), formed by 29 charter members in 1916. The focus of the originating societies was necessarily international from the onset. Indeed, a driving force for establishment of the American Society of Tropical Medicine was the acquisition by the United States of possessions in the Caribbean and Pacific near the turn of the twentieth century, with consequent challenges of tropical diseases such as yellow fever and malaria. Now, more than 100 years after the formation of the parent societies, and 65 years after the formation of the ASTMH, it is useful to reflect on the international scope of our Society. More than ever, our Society extends beyond the borders of the United States and welcomes contributions from those around the world interested in tropical medicine and global health.The membership of ASTMH has grown steadily over the decades, reaching about 2,700 members in the first decade of the twenty-first century. Recently, the Society leadership took specific steps to increase participation of two key constituencies: trainees  and international members, particularly those from low and lower-middle income countries (LMICs). Although these constituencies were well-represented at the Annual Meeting, many attendees were not ASTMH members. For example, in 2013, 33% of Annual Meeting attendees, but only 21% of members, were from Africa, Asia, Latin America, and Europe. Thus, in 2011, the ASTMH Council voted to decrease membership dues from $65 to $15 for undergraduates and from $95 to $25 for post-doctoral students, residents, and fellows. The Council then focused on facilitating membership for international colleagues, voting in 2013 to decrease dues for members from LMICs from $230 to $25. As a likely consequence, total membership for 2016 rose to over 4,000, with trainees comprising 25% (compared with 13% prior to the dues change), and international members 35%  to bring three Cuban scientists to the 2015 Annual Meeting to participate in a special symposium entitled “Building Bridges Through Science and Global Health,” with participation of the National Institutes of Health Fogarty International Center, the PAHO Department of Communicable Diseases and Health Analysis, and the United States Assistant Secretary for Global Affairs. The Cuban participants were among the first to receive visas through the newly opened United States Embassy in Havana and to make formal scientific presentations in the United States in over half a century.The ASTMH has been an international society since its inception, and it continues to strive to enhance participation by members from around the globe; increase discourse between attendees from all countries at the ASTMH Annual Meeting; build on ASTMH sponsored forums in South America, Africa, and Asia; encourage contributions to the AJTMH; and work with international partners to strengthen contributions to global scientific discourse, education, and diplomacy. We encourage our members from around the globe and contributors to ASTMH meetings and publications to spread the word. We are eager to embrace the international public health and research communities in our shared agendas to work toward a world free of tropical infectious diseases.


Engineers can learn from nature for inspirations to create new designs. The internal structure of lotus roots with several oval holes was studied in this paper for engineering inspirations. The structural performance of lotus roots under outside water pressure was simulated and compared with various cross-sectional areas. The distribution of stresses in the cross-sectional area of lotus roots was analysed and presented. It was found that the maximum compressive stresses in the cross-sectional area of lotus roots were occurring at the long axis ends of the holes. This was very different from that of circular holes. Further analysis on the triaxiality factors revealed that the cross-sectional area of the lotus root resulted in large areas of high triaxiality factors. The resulting hydrostatic stress in the cross-sectional area of lotus root ranges from zero to 2.7 times the applied outside pressure. In contrast, the hydrostatic stress in a cylindrical cross-sectional area is a fixed value. The study showed that the lotus root and the orientation of the oval holes could be mimicked in the design of new structures, for example, underwater pipes and vessels. Through evolution, nature has learned to achieve maximal performance by using minimum resources. It has evolved and optimized a large number of materials and structured surfaces with rather unique characteristics . TherefoStructural optimization is very important in the design of mechanical systems in industry. Shape optimization of engineering components can follow the design rules of nature; for example, Mattheck  studied In this paper, lotus roots with large and small holes under external water pressures will be studied to extract nature's design principles. Lotus roots are found buried in anaerobic sediment and are characterised by having oval holes for obtaining oxygen. Mevi-schutz and Grosse  conducteDominy et al.  have stuVincent  reportedThe study of the effect of holes on the strain distribution in Campaniform Sensilla by Vincent et al.  showed tThe lotus root has a unique geometry with its canals regularly aligned. Through the study of the lotus root's porosity and orderly arranged pores, the lotus root has already provided engineering inspirations for the designs of a multibore hollow fibre membrane  and a poChen and Zhang  reportedMaterial properties can be affected by hydrostatic stress in material deformations. Triaxiality is mainly used to describe the forming limit of materials and ductile fracture criteria. The triaxiality factor (TF) in a material is a ratio of the hydrostatic stress and the von Mises stress resulted from loading. Bridgman  reportedThe novelty of this paper is to analyse and reveal the effects of the layout and orientation of the large and small holes on the stress distribution in the cross-sectional area of lotus roots through finite element simulations. To this end, the hydrostatic stress and triaxiality in the cross-sectional area of lotus with oval holes will be analysed and compared with the cross-sectional areas of various artificial arrangements of holes. From this, the natural design principles of the lotus root is extracted and applied to solve an engineering problem as a proof of concept.The fresh lotus root shown in 2. The total area of large holes numbered from 1 to 10 is 506 mm2, with a mean value of 50.6 mm2 and a standard deviation of 26.7 mm2. The total area of the small holes labelled alphabetically from a to k is 28 mm2, with a mean value of 2.5 mm2 and a standard deviation of 1.1 mm2. The total area of all the holes and the solid area is 2672 mm2. Therefore, the porosity of the cross-sectional area of the lotus root is 20%.The area of each hole in the lotus root shown in ANSYS  finite eWhen the cross-sectional area of the lotus root is equivalently represented as a cylindrical cross section as shown in To understand the influence of hole shape, the actual holes in the cross-sectional area were replaced with 10 circular holes for comparison. Each circular hole has a diameter of 4.12 mm to create the same porosity in the modified cross sections when compared to the actual lotus root. One circular hole is located at the centre of the lotus root cross section and the other nine circular holes are equally distributed along the circumference of a “planetary” circle with its centre coinciding with the centre of the lotus root. The locations of the nine outer circular holes are varied by changing the diameter of the planetary circle and the effects on stress distributions are studied. The diameter of the planetary circle is varied from 22 mm, 20 mm, 17 mm, and 14 mm to 13 mm. These five cases are labelled as (a) to (e) as shown in Figures 4(a)In From the compressive stress plot in Tensile stresses in the cross-sectional area of the lotus root are presented in The von Mises criterion or maximum distortion energy criterion is associated with the change in shape of the material and is normally applied to ductile materials like metals. However, because lotus roots are subjected to water pressure acting on the external surfaces, it is considered useful that the von Mises stress is discussed in this paper.The von Mises stress distributions in the actual cross-sectional area of the lotus root (case 1) and with circular holes (case c) are shown in 2, which is 32.3% of the solid area of the cross-sectional area of the lotus root. Comparing case 1 and case 2 in In order to compare the von Mises stress distribution, von Mises stresses between 0.008 MPa and 0.012 MPa were studied, that is, 80% to 120% of the applied outside pressure. These stresses are shown in Influence of holes on the triaxiality factors in the cross-sectional area shown in r, ri, and ν are the outside, inside radius and Poisson's ratio, respectively:With an outside water pressure load of 0.01 MPa, the triaxiality factors in the cross-sectional area of the lotus root and the cylindrical cross-sectional area is shown in ν as 0.3, since ri/r ≈ 1, for a thin walled circular cross-sectional area, then TF = −0.49, when ri = 0, TF = −2.17.Taking In order to show the difference between triaxiality factors in the cross-sectional areas shown in To compare and analyse hydrostatic stress, an internal hydrostatic stress pressure factor (HPF) is introduced here; it is the hydrostatic stress developed in the cross-sectional area divided by the applied outside pressure. For example, the HPF in the cylindrical cross-sectional area shown in Lotus roots are normally subjected to outside water pressures, and the formation of oval/elliptical holes in cross-sectional area is interesting to engineers; this research work can provide an inspiration for design ideas of underwater vessels and other structures having several compartments. To illustrate the advantage of using oval holes like that in the lotus roots, von Mises stress distributions of two cross-sectional areas are shown in Figures Because of the oval holes in lotus roots, large compressive stresses in the cross-sectional area of the lotus root occurred at the major axis ends of the actual holes. When the oval holes were simulated as circular holes, the maximum compressive stress locations were changed to where the short axis of the oval holes was located. Under the outside water pressure, the oval holes in the cross-sectional area of the lotus roots resulted in more areas having the von Mises stress close to the outside water pressure than the circular holes. Very small or negligible tensile stresses occurred in the cross-sectional areas of lotus roots under outside water pressures.Under the outside water pressure, the cross-sectional area of the lotus root showed that the hydrostatic stress is varying. This is different from the constant hydrostatic stress values in the cross-sectional area of cylinder. The analysis also showed that large areas of high triaxiality factors occurred in the cross-sectional area of the lotus root, and all the triaxiality factors are negative. Because the shape of holes in the lotus root can change the stress states, the creation of new materials and structures can be inspired by lotus roots.


Temporal trends in source normalized impact per paper (SNIP) values for the three top-ranking nursing journals were analyzed and compared to explore whether predicting future SNIP values based on trend analysis could be an innovative service provided by librarians.International Journal of Nursing Studies, Journal of Nursing Scholarship, and Journal of Advanced Nursing were the three top-ranked nursing journals according to 2015 SNIP values. SNIP values for the selected journals were retrieved from the Scopus database, and extracted data were exported to Joinpoint trend analysis software to perform trend analysis.The International Journal of Nursing Studies was the most stable and positive, whereas the trend in SNIP values for the Journal of Advanced Nursing was the most negative. The annual percentage change of the most recent trend line, which is the best indicator for predicting future SNIP values, was the largest for the International Journal of Nursing Studies.The trend in SNIP values for the Predictions of journal metrics based on statistical joinpoint regression may not be completely accurate. Using this technique, however, a librarian can reasonably claim which journal will retain or even improve its prestige in the future and thus safely advise prospective authors on where to publish their research. The rapid development in information and communication technology has triggered a need for librarians to constantly adapt to the requirements of ever-changing information environments. Bibliometrics is an emerging field in information science, and its increasing importance provides opportunities for librarians to develop and provide innovative services and thus aid their customers in an academic environment more effectively . AdditioResearch success assessment relies strongly on the status of the journals in which the research is published . The impIn this study, temporal trends in source normalized impact per paper (SNIP) values  for the International Journal of Nursing Studies (IJNS), Journal of Nursing Scholarship (JNS), and Journal of Advanced Nursing (JAN) were the 3 top-ranked journals in the “Nursing ” category according to SNIP in 2015. SNIP values for the 3 selected journals for the period 1999–2015 were retrieved from the Scopus database  using the Scopus Analyze and Export services. Extracted data were exported to Joinpoint (JP) trend analysis software, version 4.4.0.0, open license software that is available from the National Cancer Institute website [The  website . A joinp website . JP softThe models were validated by training them on SNIP data for the period 1999–2014, using the models to predict SNIP values for 2015, and then comparing these values to the actual SNIP values in 2015. After validation, models were built on SNIP data for the entire period 1999–2015 and used to estimate SNIP values for 2016 and 2017.IJNS, the predicted SNIP value for 2015 was 1.89, based on an APC of 3.62 for the last trend line during 1999–2014, whereas the actual SNIP value for 2015 was 2.13. For JNS, the predicted SNIP value was 1.51, based on an APC of –1.71, whereas the actual SNIP value was 1.61. For JAN, the predicted SNIP value was 1.58, based on an APC of 2.21, whereas the actual SNIP value was 1.41. The accuracy of predictions was 89% for JAN and IJNS and 94% for JNS. The trend models for 1999–2015 are shown in For IJNS SNIP trend was the most stable of the 3 journals, with just 2 slightly negative trend lines . This negative trend was followed by a very steep rise, which was interrupted in 2010 with a still positive but more modest positive trend. Due to these large fluctuations, predictions of SNIP values cannot be as accurate as those for IJNS. The very low APC for the last five years suggests that SNIP values may stay in the range of its 2015 value in the near future.The end line , althougJAN was the most chaotic  and 2017 (to be published in mid-2018) are as follows:IJNS: 2.29 for 2016 and 2.46 for 2017JNS: 1.61 for 2016 and 1.62 for 2017JAN: 1.39 for 2016 and 1.37 for 2017IJNS is the safest option for prospective authors to publish their research, as its SNIP value will probably increase and the journal will likely retain its prestigious status in the future.These values are only predictions based on statistical joinpoint regression. However, a librarian could reasonably claim that the


Individuals may stand with a range of ankle angles. Furthermore, shoes or floor surfaces may elevate or depress their heels. Here we ask how these situations impact ankle stiffness and balance. We performed two studies (each with 10 participants) in which the triceps surae, Achilles tendon and aponeurosis were stretched either passively, by rotating the support surface, or actively by leaning forward. Participants stood freely on footplates which could rotate around the ankle joint axis. Brief, small stiffness-measuring perturbations  were applied at intervals of 4–5 s. In study 1, participants stood at selected angles of forward lean. In study 2, normal standing was compared with passive dorsiflexion induced by 15 deg toes-up tilt of the support surface. Smaller perturbations produced higher stiffness estimates, but for all perturbation sizes stiffness increased with active torque or passive stretch. Sway was minimally affected by stretch or lean, suggesting that this did not underlie the alterations in stiffness. In quiet stance, maximum ankle stiffness is limited by the tendon. As tendon strain increases, it becomes stiffer, causing an increase in overall ankle stiffness, which would explain the effects of leaning. However, stiffness also increased considerably with passive stretch, despite a modest torque increase. We discuss possible explanations for this increase. In quiet standing the ankles play a crucial role in connecting the long, nearly vertical body to the feet, which are used to apply gravitational counteractive torque against the ground. This torque is used to stabilize the inherently unstable body. Ankle torque is produced by passive and active mechanisms. The passive mechanism consists of the visco-elastic forces produced by the stretch of the muscles, tendons and ligaments acting around the ankle, and this operates with zero delay. This is the intrinsic ankle stiffness. The active mechanism is the modulation of ankle muscle activity by the nervous system. Responses to unforeseeable disturbances will be delayed, but usually in quiet standing neural prediction minimizes the delay . IntrinsHere we investigate intrinsic ankle stiffness for anterior-posterior sway . The two main contributors to intrinsic ankle stiffness are the Achilles tendon and the triceps surae muscles, which act as springs arranged in series. During quiet standing, the stretch sizes are normally very small and ankle torque is relatively low . Ankle sThe muscle can be stiffened either by the active contraction of its fibres or by passive means. Passive means include changes in muscle length through stretch and altering the immediate history of muscle movement (e.g. leaving the muscle still for 5–10 s), which can produce thixotropic increases in stiffness –17.In vivo measurement of stiffness of whole bundles of tendons and muscles acting in combination was much facilitated with the introduction of the ultrasound technique [Tendon stiffness is dependent on the linkage between the collagen molecules, cross-linked end-to-end within a fibril . This isechnique . For theechnique –33.The function of the Achilles tendon is to connect the triceps surae muscles to the calcaneous bone. Therefore, it can be elongated in two different ways; either by shortening of the calf muscle fibers connected to it through active muscle contraction, or by passive dorsiflexion of the ankles. Both modes of elongation can act to increase tendon stiffness. This implies that, in standing, ankle stiffness should increase as ankle torque increases. Ankle torque can be increased by leaning forward or by dorsiflexion of the foot. However, it is important to note that in standing the underlying ankle torque is directly proportional to the angle of inclination of the body so that ankle torque cannot be arbitrarily altered without changing body lean. A further possible way of increasing ankle stiffness may be by co-contraction, although co-contraction is unusual in standing.-1). In freely standing individuals, mean plantarflexing ankle torque can only be increased by leaning forwards. Casadio et al. [Two contradictory results for ankle stiffness have been reported for upright human subjects. Loram & Lakie  applied o et al.  applied In an attempt to resolve these conflicting observations, we carried out two experiments to further investigate how intrinsic standing stiffness can be affected by ankle torque or angle. In study 1, intrinsic stiffness was measured at various mean levels of forward lean using a range of perturbation amplitudes. In study 2, intrinsic stiffness was measured while standing normally with increased ankle dorsiflexion .The intention was to compare the effects of two conditions in which tendon tension was varied. In one it was varied mainly by muscle activation (forward body leaning) and in the other it was varied mainly by passive stretch (ankle dorsiflexion). Of course, active and passive sources of ankle torque are inevitably entangled during quiet stance, but our objective here was to maximize the contribution of either source using these two interventions. We were also able to investigate whether changes in stiffness were critically dependent on the perturbation amplitude used to make the measurement. In addition, we investigated how sway size and velocity were altered by leaning and dorsiflexion. To our knowledge, no previous study has investigated the effect of Achilles tendon tension on postural sway.For each study, 10 healthy volunteers ; height 1.68±0.1 m; weight 65.9±8.3 kg)  gave written informed consent and participated in this study, which was approved by the local human ethics committee at the University of Birmingham .medial gastrocnemius and tibialis anterior muscles (Delsys Bagnoli). Only measurements of the left lower limb were used for the stiffness estimation. The methodology specific to the two studies is described below . Within the data of a single participant, it varied by as little as 0.013 deg SD for 0.1 deg perturbation, 0.013 deg SD for 0.3 deg perturbation and 0.017 deg SD for 0.7 deg perturbation. The whole experimental procedure consisted of one session of approximately 1 ½ hours.We asked the participants to manipulate the amount of forward shift of their COP by monitoring the average baseline torque applied by the feet against the footplate. Before the experiment, participants did at least one familiarization trial per condition to establish the level of torque that they could sustain at each level of leaning. Due to individual variation of weight and height, it was not possible to establish a common target torque for all participants. For example, during the forward leaning condition, we asked the participants to lean as far forward as they could, comfortably for the duration of the trial. We averaged these torque traces and established this value as an individual target trace they had to maintain. It was displayed on a screen located at eye level during the actual trials. They performed three different levels of forward leaning:Normal: standing at their spontaneously chosen position;Vertical: standing with the COP shifted backwards in relation to their normal condition. Participants were asked to reduce torque applied against the footplate, as much as possible without compromising their free standing balance control;Lean: standing with the COP shifted forwards in relation to their normal condition. Participants were asked to increase torque applied against the footplate to a level that was still comfortable and sustainable for the duration of the 3 min trials.For obvious reasons, it was relatively easier for individuals to follow a target torque in normal condition . It was more difficult to maintain proximity with the target torque in vertical and lean conditions . Nevertheless, the participants were able to maintain a reasonable amount of accuracy, considering that they were freely standing.There were 3 conditions of COP shift  and 3 different perturbation amplitudes , resulting in a total of 9 conditions. Given that 30 perturbations were applied per condition, altogether 270 events were recorded for each participant. The timing, conditions, perturbation amplitudes and directions were pseudo-randomized so that they could not be predicted by the participants.For this experiment the main objective was to increase ankle dorsiflexion with minimal change in baseline ankle torque. Participants performed standing trials with perturbations of the same shape and time-window intervals as in the previous experiment, but only with amplitudes of 0.1 or 0.7 deg. There were two different conditions:Normal: standing at their spontaneously chosen position with footplates horizontal;Dorsiflexion: standing with the footplate rotated upwards by 15 deg. As it was an angular measure, it was common to all subjects (unlike the torque in study 1). 15 deg was chosen because it was close to the maximum that the participants could comfortably maintain.The whole experimental procedure consisted of one session of approximately 1 hour. There were 2 ankle positions and 2 perturbation amplitudes and 32 perturbations were recorded for each condition, resulting in a total of 128 events from each participant. Normal standing was investigated prior to the dorsiflexion trials. Perturbation amplitudes and directions were pseudo-randomized.We assumed that the calf muscles, the Achilles tendon, aponeurosis and foot act as a mass-spring-damper system ,39 respoθ = angle (deg) -1), -2), K = stiffness (Nm deg-1), B = viscosity (Nm s deg-1) and I = moment of inertia of the foot (kg m2).Where: T = torque (Nm), During normal standing, the gravitational torque exerted by the body COM is closely related to the COM rotation around the ankle joint ,43,44. TWe assessed the amount of leaning as the increase in total ankle torque. This was calculated from the mean total ankle torque during a 70 ms time window prior to each perturbation onset. The amount of ankle dorsiflexion and body inclination were calculated as the mean ankle angle  and body angle  over a 2 s time window prior to each perturbation onset. We normalized each participant’s data to their normal standing condition, described here as 0 deg for body angle and 90 deg for ankle angle. Thus we discounted their actual elected standing position, which corresponds to a variable 1.5–4 deg forward leaning in relation to the earth [The effect of the different conditions upon stability and control of movement was assessed with measurements of anterior-posterior body sway and muscle activity. Body sway was quantified as the average root-mean-square (RMS) ankle angle and velocity. The mean value over a 2 s time window prior to each perturbation onset was subtracted. Muscle activity was calculated as the integral of the rectified EMG activity of the medial gastrocnemius and tibialis anterior muscles over a 70 ms time window envelope prior to each perturbation onset. To compare changes within conditions, we normalized all participants’ EMG data as a ratio of normal standing data.st and 2nd studies) and stimulus amplitude  upon ankle stiffness. Two-tailed paired samples t-tests and one-way ANOVA were used to verify differences in mean ankle and body angle, ankle torque, body sway and EMG activity between conditions. P<0.05 was considered statistically significant for all tests.Repeated-measures ANOVA was used to determine effects of condition , 16.4±4.7 Nm  and 31±5.7 Nm (lean). A one-way ANOVA revealed a significant difference between different leaning conditions  ((9) = -2.4; p<0.05)  and ankle  mean angles  = -17.6; p<0.001) ((9) = -1.7; p = 0.12) (Rotating the platform toes-up by 15 deg was enough to produce a large increase in ankle dorsiflexion in study 2 (tversus toes-down) on stiffness, for either study . Therefore, we combined perturbations of both directions for the final calculation. For the first experiment (left graph), values ranged from 37% to 97%. There was a systematic increase in stiffness  from vertical to normal and from normal to lean . There was no interaction between condition and amplitude . Ankle dorsiflexion also produced a significant increase in stiffness (mean 29%) , also without any interaction between condition and amplitude  (right graph). The results obtained from the normal condition in both experiments were very similar , making comparisons between both experiments easier to interpret.For both studies, average intrinsic ankle stiffness is presented as a percentage of toppling torque per unit angle (% mgh) in 2,18 = 13.4; p<0.001; second study: F1,9 = 12.8; p = 0.006). Viscosity was also significantly affected by the degree of forward leaning  but not by passive stretch . Moment of inertia was dependent on degree of forward leaning and amplitude in the first study ; it was dependent on passive stretch but not amplitude in the second study .As the duration of all perturbation sizes was the same (140 ms), the peak velocity was higher for larger perturbations, and we found a significant increase in viscosity with perturbation amplitude . Dorsiflexion also has no significant effect on sway size or velocity (t(9) = -1.3; p = 0.225 and t(9) = 1.2; p = 0.267, respectively) (right panels).Body sway size is described in vertical condition), the medial gastrocnemius (GM) activity is reduced, but there is a large increase in tibialis anterior (TA) activity. When leaning forwards, there is a considerable increase in GM activity accompanied by a trivial increase in TA activity  (left graph). In the dorsiflexion condition (right graph), there is a significant increase in TA activity and decrease in GM activity (GM t(9) = 3.6; p = 0.006; TA t(9) = -2.5; p = 0.032).The analysis of EMG activity confirms that changing the level of body leaning either backwards or forwards from normal stance will alter the neural activation. In this paper we attempt to understand how intrinsic ankle stiffness can be altered by changes in normal standing conditions. To complement previous research on standing individuals ,34, two vertical to lean, Firstly, active ankle torque was altered by asking the participants to lean at different angles. Intrinsic stiffness was shown to correlate positively with increasing levels of forward leaning which produced increasing levels of active ankle torque , confirm Casadio et al.’s  significThus, a change from normal standing position to forward lean produced an average torque rise of ~ 15 Nm  and an aThe results from study 1 were also comparable to those previously derived from recumbent individuals , which aBecause the different results found by Loram & Lakie  and CasaUnusually, in the paper by Loram and Lakie, the authors measured both foot stiffness and ankle stiffness. They reported  .It is possible to compare our data with those from Mirbagheri et al. . In thatConsequently, this increase is stiffness is associated with ankle angle rather than ankle torque so an alternative explanation for the rise in stiffness is necessary. This could be a consequence of either coactivation of antagonist muscles, increase of calf muscle moment arm, unmeasured change in knee angle acting on the biarticular gastrocnemius muscle or increased resistance of other tissues crossing the ankle.Activity of the muscles is shown in If dorsiflexion increases the moment arm of the calf muscles, a given rotation of the ankle will cause a larger linear displacement of the tendon and muscle and, consequently, measured angular stiffness will rise. However, as has been pointed out by –50, momeIn leaning forward, there might have been a slight, unintended and unmeasured extension of the knee joint. This would pull on the biarticular gastrocnemius muscle and potentially contribute to increased ankle stiffness. Similarly, during dorsiflexion the toes were moved upwards and there was an alteration in body conformation, as indicated by the sketched image in Given that changes in co-contraction, moment arm and knee angle do not fully explain changes in stiffness found by these studies, a remaining possibility is that the rise in stiffness is due to stretching or compression of other tissues which bridge the ankle joint.The calf muscle-tendon complex can generate tension in two ways. First, with active contraction (as in the lean condition) there is a tendency for muscle to shorten and expand. This has the effect of straining the serially-arranged tendon. Series elastic structures in muscles are not limited to the extramuscular free tendon. Most muscles with a long free tendon also have a sheet-like aponeurosis that serves as a broad tendinous insertion for muscle fibers . Thus, tSecond, the calf muscle can be passively pulled to a long length (as in the dorsiflexion experiment). This has the effect of considerably straining the aponeurosis, and because it now generates substantial passive tension at this longer length, the free tendon is similarly strained . The effEven though significant, the change in inertia in study 1 caused by condition and amplitude was very small (8.1%). Such changes are much smaller than the observed changes in stiffness, and could be accounted for simply by errors in the estimation process, since all three parameters are allowed to vary . For study 2, the changes were higher (14.1%), with dorsiflexion being associated with greater inertia. These apparent changes in inertia may also be due to variation in the model fitting process. Alternatively, it is concievable they are attributable to additional muscle mass being moved during the perturbation. This would be consistent with our assertion that dorsiflexion increases the stiffness of the tendon which would, in turn, cause greater muscle movement. Whether this added moving mass would be sufficient to cause the increased inertia is uncertain. Again, measurement with ultrasound would help confirm this.In a previous paper , we showIntrinsic stiffness is a stabilizing feature because in partly offsetting gravitational acceleration it reduces the size and the speed of necessary neural interventions. However, the changes that we produced did not systematically alter sway size or velocity. It is possible that by requiring subjects to stand in unusual configurations, as here, the normally stabilizing role of intrinsic stiffness is vitiated by the unfamiliarity of the task and standing is dominated by active neural control so that any departure from normal tends to increase sway size.Because both processes stretch elastic tendon structures, muscle activity and dorsiflexion can, in principle, contribute to the ankle torque required to stand. Weiss et al. ,55 showeOur results show that intrinsic ankle stiffness in standing individuals increases considerably in conditions of increased forward lean and dorsiflexion. Even though stiffness is changed, body sway is little affected. Since during normal standing there is relatively small potential for changes in ankle angle compared with larges changes in ankle torque, we believe that intrinsic ankle stiffness is mostly affected by the latter.


Dementia & Neuropsychologia reaches the end of its second year ofpublication, jostling to find its place among the high quality journals of its kind,while abiding by the stringent rules of the indexation systems. This issue includesthree papers from abroad, testimony to the faith which members of the internationalscientific community place in this journal’s future.Besides its four regular issues for the year, one supplement was also published in 2008,containing the abstracts of the Sixth Congress of Rehabilitation promoted by theBrazilian Society of Neuropsychology. The opening of the journal to carry abstracts ofmeetings in its areas of interest has been a important function of the journal from itsoutset. Abstracts of the Brazilian Congress on Brain, Behavior and Emotions were alsopublished both in 2007 and 2008, while abstracts of the Brazilian Meeting on Alzheimer’sDisease and Related Disorders as well as the Second International and Ninth BrazilianCongress from the Brazilian Society of Neuropsychology were published in 2007. It is theintention of the editorial board to continue in this vein, and to carry supplements orabstracts of international meetings.Dementia & Neuropsychologia is nearing implementation of its home page,a significant achievement for the journal. It is available at: demneuropsy.com.br.The home page will facilitate the search for papers using key words, furnish informationon number of visitors to each article, and follow the interest of the scientificcommunity in Dementia & Neuropsychologia. A newsletter system, a keystrategy to promote and disseminate recently published papers, is now being prepared.The goal is for this newsletter to reach a vast array of neurologists, psychologists,psychiatrists, speech therapists, geriatricians and basic scientists.Instructions to authors have been changed to include the mission of thejournal as follows: Dementia & Neuropsychologia is a quarterly journaldedicated to publishing research in cognitive and behavioral sciences, focusing onclinical epidemiology, basic and applied neurosciences, and cognitive tests devised oradapted for populations with heterogeneous educational and socioeconomic backgrounds.Dementia & Neuropsychologia is particularly involved in publishingresearch relevant to developing countries, and also seeks to disseminate reviews andcase reports that are important contributions to neurological, psychiatric, geriatric,neuropsychological, speech therapy, and related fields. The editorial board considersthat with this mission Dementia & Neuropsychologia clearly states thatit is not simply another journal, but that it has a specific role and niche among thejournals in the area. The editorial board is also confident that these new achievementswill pave the way for indexing of the journal in the forthcoming months.The To tie up the edition of this issue and on behalf of the editorial board, I wish toexpress our gratitude to the scientific community, not only within Brazil, but alsoacross all Latin American countries and beyond, who have generously submitted papers andinvested time in the peer-reviewing process. I also thank all our colleagues from backoffice, the copydesk, printers and English language consultation and extend to them, ourreaders and sponsors, our wishes for a Prosperous and Happy 2009.Ricardo NitriniEditor-in-Chief


Splitting a liver for utilization in adult/pediatric recipients has been shown to decrease mortality on the wait list without increasing the overall risk of long-term graft failure compared to a whole graft. However, splitting a single donor organ for two adult recipients, full-right-full-left split liver transplantation (FRFLSLT), to overcome organ shortage is still considered controversial.This study assessed the outcome of FRFLSLT comparing full-right (FR) and full-left (FL) with whole liver (WL) allografts in adults (1998–2010) using UNOS standard transplant analysis and research (STAR) file.Methods: Unadjusted allograft and patient survival were estimated using Kaplan-Meier survival curves. Adjusted analyses of survival were conducted controlling for propensity for WL allograft.There were 83,313 cases of WL, 651 FR and 117 FL. Significant differences were evident in the unadjusted cohort between recipients who received FR and FL including donor, cold ischemic time, and days on transplant waiting list. Use of FL allograft resulted in a trend toward lower graft and patient survival compared to WL and FR, which was not statistically significant (p=0.07). In the matched cohort, FL hemiliver allograft had no detrimental effect on the allograft or patient survival after split liver transplantation when compared to FR and WL.After adjusting for donor and recipient characteristics, there was no difference in allograft or patient survival with the use of FL, FR, or WL after liver transplantation in adults. FRFLSLT is a valuable and safe option to expand the donor pool.  The number of liver transplantations being performed each year is ultimately limited by graft availability. Despite the increasing demand for orthotopic liver transplantation (OLT), supply of deceased donor organs has persisted as the barrier for patients awaiting transplantation. In 2013, there were 6256 liver transplantations performed in the USA. That same year, 10,143 patients were added to the waiting list and 3002 either died or became too sick to undergo transplantation [Procurement of marginal organs, living donor transplantation and split liver transplantation (SLT) are three innovative ways that the transplant community has tried to meet the expanding demand for more organs. In 1988, the first descriptions of SLT were reported , 3. InitJust as pediatric-adult SLT was controversial in its infancy; there is concern that FRFLSLT has inferior results when compared to adult/child SLT or whole liver transplant (WLT). Early reports of success with FRFLSLT have been published, however, numbers have been limited -17. ThesStudent’s t tests for continuous variables, and χ2 for categorical variables, were considered statistically significant at α=0.017 (Bonferroni correction). Patient and graft survival were compared between the graft types using Kaplan-Meier survival analysis. The log-rank test was used to test for equality of survival distributions between the curves for each graft type.The data were collected from the UNOS as reported between 1998 and 2010. Patients with WL, FR, or FL hemiliver allograft were included in the analysis. Pediatric patients and SLT using right trisegment allografts were excluded from the analysis. Means and SDs were given for continuous variables as they were normally distributed, and percentages were provided for categorical variables. To control for multiple pairwise comparisons between graft types, p values from Propensity analysis  was condvs. 72 kg, respectively). Transplant recipient weight was highest for WL patients (82 kg) when compared to FR (72 kg) and FL (69 kg). Those with WL had less time on the liver waiting list than FR and FL . FL recipients had shorter cold ischemic time than FR and WL  and were less likely to be male . MELD scores were similar for FR and FL  and significantly lower when comparing FR to WL (21). DRI scores were comparable in FR and FL groups (3.9) and significantly higher than WL (2.7).We found that during 1998–2010, a total of 768 adult patients underwent SLT using FR or FL allografts; 651 FR, and 117 FL. At the same time period, 83,313 adult patients received WL allograft . The demThe unadjusted patient survival of all graft typesis shown in Propensity scores were obtained for patients using multiple logistic regression predicting WL transplant. The c-statistic for the model was 0.99, which illustrated the model discriminated well. The matched patients were divided into quintiles of propensity for WL graft. After stratifying by propensity quintile, most of the differences in characteristics between recipients of different graft types were no longer statistically significant . This alSLT for two adult patients usually consists in the generation of a full-right graft  and a full-left graft  -17. ConvWe report a series of SLTs for two adult recipients performed at US centers. Although unadjusted results of SLT using FL allografts in adults were inferior to FR, propensity matched analysis showed comparable allograft and patient survival. This experience showed that FRFLSLT can be safely applied in adult patients with acceptable outcomes being anticipated.vs. FR) is an advantage of our study. Propensity scores reduce the entire collection of observed background characteristics to a single variable that appropriately summarizes that characteristics [The use of propensity scores to create a risk-adjusted, demographically matched cohort based on allograft status  observed in deceased donor WLT are most probably amplified in the SLT group and should be taken into account. SLT represents a potentially underutilized resource in the USA. Factors such as high recipient MELD score and extended CIT may have negative effects on results in SLT and therefore, deter surgeons from performing this procedure. A different allocation system for these grafts that takes into consideration CIT and recipient MELD score should be considered .vs FL graft, graft weight and quality, surgical details, techniques employed to alleviate small-for-size syndrome, center and surgeon volume/experience were not available in the database. Biliary complications are done well captured in the database either.A limitation of this study is its being a retrospective analysis of UNOS data. We recognize both potential advantages and limitations of such a large national database. The large sample size provides sufficient power to detect meaningful risk factors that may be missed by single-center studies. However, as with any analysis utilizing the UNOS database, our conclusions rely on the assumption that there is no systematic bias generated by reporting error or missing data. The groups are obviously unequal in size and selection criteria for one or the other procedure are not known. However, the primary endpoint for this analysis was allograft and patient survival, which is reliably captured in the UNOS database. Residual or unmeasured confounders that could impact allograft and patient survival include surgical technique and skill level, differences in immunosuppression protocols, the fat content/quality of the allografts, and center-specific practices. Other important determinants of success with SLT such as recipient and donor selection, choice of RL Second, we did not have much data on the donor and the quality or size of the allograft. Third, the study did not look at the potential impact of the portal inflow and the hepatic vein outflow modulation in smaller grafts. Fourth, we were not able to analyzed center-specific outcomes. There is a size difference between FR (n=651) and FL (n=117). This would be due to the fact that some of FLs were used in a child or been discarded.In summary, FRFLSLT in adults can expand the donor pool and provide reasonable outcomes in two adults using FR and FL hemiliver allografts.


We examined a sense of personal control as one such confound—specifically, whether the association between free will belief (FWB) and subjective well-being is based, in part, on the degree to which an individual feels a sense of personal control over their life. In Study, 1 trait-level belief in personal control significantly uniquely predicted satisfaction with life and stress, over and above the contribution of FWB. In Study 2, within-person daily fluctuations in stress and depression were not significantly predicted by daily changes in FWB over and above the contribution of personal control/choice. The findings provide new insight into the relationship between FWB and subjective well-being.The extent to which an individual believes in free will is associated with a number of positive life outcomes, including their own subjective well-being. However, it is not known whether the belief that one has free will  A growing body of evidence has shown that believing in free will is associated with a variety of positive life outcomes, including feeling grateful for past events , better per se is associated with positive life outcomes or whether some third variable is driving these associations remains to be explored. One possibility is that the relationship between free will beliefs (FWBs) and positive life outcomes, such as satisfaction with one’s life, might be confounded by a sense of personal control. Indeed, it is well-established that a sense of personal control is positively associated with many of the same positive life outcomes that relate to FWB, including subjective well-being . Demographic information was not collected (but see n = 6) or failing a basic attention check item (n = 13). A power analysis showed that our sample size had 80% power to detect “small-to-medium” effect sizes  in our multiple regression analysis.Participants from the United States were recruited through Amazon’s Mechanical Turk (no belief in free will) to 100 (absolute belief in free will), and the starting position of the slider was set to the mid-point of the scale. This measure has been shown to have good convergent . The scale ranged from 0  to 5 (strongly agree). Higher scores indicate a greater sense of personal control.Participants’ sense of personal control was gauged using a five-item measure  and therefore averaged to form a composite measure of perceived stress.Participants’ perceived stress was measured using two items: “In the past year, how would you rate the amount of stress in your life (at home and at work)?” (1 = strongly disagree to 7 = strongly agree). Alpha reliabilities for all measures with more than one item are shown in Table 1.Participants’ life satisfaction was measured using Table 1 presents descriptive statistics, alpha reliabilities, and correlations among the measures. All of the measures correlated significantly in the expected directions. FWB positively correlated with sense of personal control, and both correlated positively with SWL and negatively with perceived stress.b = 0.85, β = 0.49, SE = 0.098, t(281) = 8.65, p < 0.001, sr2 = 0.20, but not FWB, b = 0.003, β = 0.05, SE = 0.004, t(281) = 0.81, p = 0.42, sr2 = 0.002, uniquely predicted scores on the SWLS. Likewise, personal control, b = -0.67, β = -0.443, SE = 0.090, t(281) = -7.42, p < 0.001, sr2 = 0.20, but not FWB, b = 0.003, β = 0.04, SE = 0.004, t(281) = 0.73, p = 0.46, sr2 = 0.002, uniquely predicted perceived stress.A multiple regression analysis showed that sense of personal control, Because confounding relationships are a special case of indirect relationships , we testlavaan package in R .These results suggest that the associations between FWB and SWL and FWB and perceived stress are largely due to co-variation between FWB and a sense of personal control. One limitation, however, is that our multiple regression approach fails to take measurement unreliability into account, which age in R , we specMage = 24.18, SDage = 6.50; 77% female) who participated in exchange for a monetary reward  and the chance to win gift cards. Two additional participants completed measures during an initial session but did not complete any of our focal daily measures. The final sample size was determined by how many participants we could recruit within our monetary budget and time constraints.The final sample of participants were 88 staff or students from the University of Essex , but all data from participants who completed at least one daily survey were retained for analysis. Along with several questions unrelated to the current research interests, participants completed the following daily measures:no belief in free will today) to 100 (absolute belief in free will today).We measured participants’ daily FWB using a single-item, graphical slider scale . The scale ranged from 0  to 100 (complete control/complete choice today). Scores on these two daily measures were averaged to form a composite control/choice variable . Scores could range from 0 . Depression is an element of the unpleasant affect component of subjective well-being  and daily depression  using four-point scales , analyses were performed using multilevel modeling . AnalyseSD = 3.75) of the 14 daily surveys . Table 3 shows descriptive statistics and the proportion of variance at the within- and between-person levels for each of the measures we employed.On average participants completed 10.74 . Shown in Table 4, both daily FWBs and daily choice/control beliefs significantly predicted daily fluctuations in stress and depression when modeled alone. However, when daily FWBs and daily choice/control were modeled together to predict daily stress and depression, only daily choice/control emerged as a significant predictor. Put differently, at the within-person level, daily changes in FWBs did not account for significant variability in daily stress and depression over and above the contributions of daily changes in choice/control. Figure 1 shows the means of FWB, choice/control, stress, and depression across the 14 days.As expected, daily fluctuations in choice/control were significantly associated with daily fluctuations in participants’ FWB, Z = -2.77, p = 0.006, 95% Monte Carlo CI: -0.007, -0.001) and daily FWB and daily depression  were significantly reduced from their zero-order relationships when statistically controlling for a sense of personal control.Like in Study 1, we tested whether there was a significant decrease in the regression weight for daily FWB when modeled with daily choice/control to predict each of daily stress and daily depression compared to when FWB was modeled alone. We used These findings are consistent with our trait-level findings reported in Study 1: associations between participants’ subjective well-being  and FWBs appear to be due to the co-variation between FWB and beliefs about having control and being able to choose.Across two studies we investigated the role of personal control and choice in the relationship between FWB and subjective well-being. Previous research has provided evidence for the predictive value of FWB on such outcomes e.g., . Here, wPrevious research has shown that the association between FWB and judgments of others’ morality/blame is due to perceived capacity for choice . The curMuch recent research has investigated the role of FWBs in a number of life outcomes, as well as psychological well-being. Here, we provide evidence for the role of personal control/choice in explaining why FWB predicts stress and depression. For laypeople, belief in free will fundamentally means having the capacity to make choices and control one’s life , and ourAlthough we show that the predictive utility of FWB on personal life outcomes is abolished when controlling for personal choice, it remains possible that FWB does have unique predictive utility in other contexts. Indeed, the modest correlation between FWB and personal control suggests that FWB and personal control are not precisely the same thing. Nonetheless, recent work  shows thFurther research should also attempt to identify the direction of these relationships. For instance, much research on FWB assumes that belief or disbelief in free will drives life outcomes and personal well-being. However, while control beliefs influence how someone copes with a stressful event, this coping also feeds back into the individual’s sense of personal control . As suchEthical approval was granted by the University of Essex Faculty of Science and Health Ethics Sub-Committee . Prior to testing, all participants were informed of their right to withdraw from the research at any time. All participants signaled their consent to participate.The research was conducted online and analyzed by PG and MC. All three authors conceived of and designed the studies, contributed to writing the manuscript, and approved the final version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


It is with my deepest sorrow that I announce the untimely death of the passing of Dr Dimitri Tassiopoulos.Dr Dimitri Tassiopoulos was a Chief Research Manager with Social Aspects of HIV/AIDS Research Alliance (SAHARA) within the HIV/AIDS, STIs and TB (HAST) research programme of the HSRC. He held a BA (Hons.) degree in Political Science from the University of Stellenbosch, and obtained an MBA and PhD in Management and Administration from the University of Stellenbosch Business School in South Africa.Before joining the HSRC in May 2011, he was an Associate Director at the School of Tourism and Hospitality at the Walter Sisulu University (WSU) in East London, South Africa. He spent the majority of his academic career as a head of a School or as a Departmental Chairperson. After 1993, he was involved in various national and international tourism research projects, of a multidisciplinary and multi-institutional nature, concerning agritourism, event, cultural and wine tourism, amongst others. In 2004 he was appointed as a member of the South African Qualifications Authority’s Standards Generating Body (SGB) for Travel, Tourism and Events, and was appointed as its chairperson. He was the vice president of the Tourism and Hospitality Education Providers of South Africa (THEPSA). This Federation represents further (FET) and higher education (HET) institutions offering the spectrum of qualifications related with the management of the tourism industry. He was also the chairperson of the Tourism and Events Educators Chamber of South Africa (TEECSA), an association representing higher education travel, tourism and events related programme providers.Dr Tassiopoulos successfully supervised post-graduate mini-theses/theses/dissertations and served as an external examiner for post-graduate theses at various universities in South Africa. Dr Tassiopoulos was a board member of a number international peer-reviewed research journals. The evidence of Dr Tassiopoulos’s work is reflected in his publication record that spans the authoring and co-authoring of more than 16 presentations, at local, regional and international conferences, and, nine scientific publications in peer-reviewed journals. He was awarded six grants for research, published six books, published 33 chapters in books, has been involved in seven commissioned research projects. He has been rated a C3 researcher by the National Research Foundation. He served as a book reviewer for a number of publishers and as a proposal reviewer for the National Research Foundation.Tourism Today: published annually by the College of Tourism and Hotel Management, Nicosia, Cyprus (ISSN 1450-0906) (http://www.cothm.ac.cy/research.htm), and European Journal of Tourism Research: an academic refereed journal published bi-annually by International University College, Bulgaria (ISSN: 1994-76580) (http://ejtr.vumk.eu/). He was a regular reviewer of articles submitted to the prestigious Tourism Management Journal for publication.Dr Tassiopoulos was involved as an International Reviewer for the European Council on Hotel, Restaurant and Institutional Education (EuroCHRIE), Dubai 2008 Conference. He was involved as a session chair for the 2008 International Council for Small Business (ICSB) Conference, Halifax, NS, Canada; and, the 7th International Conference for Consumer Behaviour and Retailing Research (CIRCLE), Estoril Higher Institute for Tourism and Hotel Studies (ESHTE), Estoril, Portugal. He served on the following journal editorial boards as a board member of a number international peer-reviewed research journals. In particular, SAHARA-J: Journal of Social Aspects of HIV/AIDS (SAHARAJ). He successfully, while working closely together with Prof. Phaswana-Mafuya, managed to bring the journal under the Taylor & Francis Online stable with Routledge Press. SAHARAJ’s impact factor has risen during his leadership. Dr Tassiopoulos also managed the SAHARA Conference.Among some of his achievements since joining HSRC Dr Tassiopoulos served as Managing Editor of Dr Tassiopoulos was involved in collaborating in cross-disciplinary research projects. He was involved in researching the effects of HIV and AIDS within higher education and the management of this syndrome that is afflicting the higher education population. More recently, he was involved in co-editing and publishing a book entitled non-communicable diseases in developing countries. Most recently, he led both international and South African research in the field of HIV and the World of Work Initiatives.Dr Dimitri Tassiopoulos made a significant contribution to South Africa’s social science capital and his bright mind, dedication and passion will be missed. I take this opportunity again to convey my condolences to all of you who have known and worked with Dr Dimitri Tassiopoulos.


Computational Psychiatry! We are delighted to present a new open access journal devoted to “original research articles and reviews that involve the application, analysis, or invention of theoretical, computational and statistical approaches to mental function and dysfunction.” As a field, Computational Psychiatry is the modern pursuit of a new understanding of mental dysfunction, but it also has the goal of understanding broadly the sustenance of healthy mental function.Welcome to Three obvious questions come to mind: Why this field? Why now? Why start a journal?There is now widespread recognition of the critical importance of mental health and ill health to personal development and suffering, and to society and the economy . Like others, we think that novel ways of understanding psychiatric disease, accelerated by radically new sources of personal and social data, offer the possibility for revolutionary progress. However, we are also well aware that computational psychiatry is a nascent field that is still only taking its first baby steps. Nevertheless, it is by bringing together the understanding, methods, principles and enthusiasm of a thoroughly multi-disciplinary collection of experimental, theoretical and clinical scientists, that breakthroughs can be made.Right now is the ideal time to set out on this venture. The field started more than 30 years ago, including pioneers such as the late Ralph Hoffman, and Steven Grossberg and particularly Jonathan Cohen. Over a decade ago, the first centre devoted to the topic was launched at Baylor College of Medicine. However, more recently, a number of other centres, institutes, units and courses have been created in response to the scientific interest and the broad-based demand. The many successes of the tightly-coupled experimental and theoretical field of neural reinforcement learning are providing a normative foundation for the study of dysfunctional decision-making. The resulting multi-level understanding matches well the move away from symptom-based characterizations for research and towards more fundamental information processing, cognitive and neural primitives. Equally, our new-found constant deliberate and incidental collection and leakage of personal data via smart-phones and the like offers the computationally-minded radically new paradigms to for assessing, predicting and decomposing disease.It might not seem obvious to start a journal, even an open-access one, given the woefully increasing noise to signal ratio in academic publishing. However, we hope that rigorous reviewing, and the high standards of our publication partner, MIT Press, will prevent us from approaching too close to any unfortunate frontier. We hope the journal will also help nucleate a wider community.We have many people to thank for helping us get to this point. These include Deanna Barch, Peter Fonagy, Helen Mayberg and Steve Hyman for forming our Advisory Board; a fantastic group of editors who span the whole field and more, and the reviewers whom they recruit and who are the backbone of any journal. A special thanks to Michael Frank and Tiago Maia for their support of the effort and the first international meeting on Computational Psychiatry in Miami in 2013. Lastly, a hearty thanks to the brave authors of the superb first submissions to the journal; Nick Lindsay and his colleagues at MIT Press for their engagement and involvement; and Cassie Carrin and before her, Justin King, for their firmly gentle steering as managing editors.We look forward to many future papers; but most especially to making a difference.