D∞) ranged from 52.58 to 102.13 g/100 g dry starch, while the hydrolysis index (HI) ranged from 41.55% to 76.93% and high average glycemic index (GIavg) ranged from 65.97 to 94.14. The results showed that there are differences in grain quality of Algerian sorghum cultivars. The starch fractions have acceptable nutritional value with good in vitro digestibility characteristics suitable for human health and nutrition.This work aims to evaluate starch digestion in whole sorghum grains. Nine sorghum cultivars were sampled from the Sahara of Algeria. The structural characteristics of sorghum grains were measured. Total starch (TS) varied between 67.67% and 74.82%, digestible starch (DS) between 64.34% and 69.70%, and resistant starch (RS) ranged from 2.55% to 7.98%. The kinetic of starch digestion displayed first-order model. For all sorghum cultivars, starch were digested with different extents, DS at infinite time ( Sorghum is a staple food crop for many of the world's poorest people in Africa and Asia. Many studies showed that it will become the alternative for wheat in the future  is an in vitro measurement based on glycemic response to carbohydrate-containing foods, and allows ranking of food on the basis of the rate of digestion and absorption of carbohydrates that they contain , a hyperarid region, known to have temperatures ranging from 7.8 to 45.2°C, a very low annual rainfall rate (16.9 mm), and irrigation is done with saline water. In addition, these environmental factors affect the starch properties in different sorghum genotypes  Moench] cultivars were harvested from different localities from Tidikelt region in Algerian Sahara; Taarankoukou, In salah, El Malah, Foggaret Ezzoua, and Djafou. The samples were characterized by various colors and different harvest years . The sorghum grains were cleaned, representative 100 g sorghum samples were prepared and stored in a fridge at 4°C until used. The crops were grounded to flour in IKA Labotechik A10  sample mill. The obtained flours were manually sieved over a 500-μm sieve. All the reagents were of analytical grade.Nine samples of local sorghum [Some physical properties of sorghum grains  were determined by descriptors  were added, and the mixture was introduced in a water bath at 60°C for 45 min with occasional shaking. A volume of 1 mL of the obtained solution was diluted to 10 mL with distilled water to obtain a glucose concentration lower than 100 μg/mL. Glucose concentrations were determined using glucose oxidase–peroxidase Kit . The absorbance was measured at a wavelength of 500 nm and the concentration of starch was obtained by multiplying the concentration of glucose by 0.9.Total starch (TS) was determined enzymatically according to the modified method of Goni et al. . The weiα-amylase type VI.B from porcine pancreas . The sample was centrifuged  and the supernatant discarded, 3 mL of distilled water was then added to the residue. Then, 3 mL of 4 mol/L KOH mix was added and left for 30 min at room temperature with constant shaking. Approximately 5 mL of HCl solution (2 mol/L) was added and 4 mL of sodium acetate buffer solution  containing 0.833 μL of amyloglucosidase from A. niger  were added. Afterwards, it was mixed well and left for 45 min in water bath at 60°C with constant shaking, and set to centrifuge . The residue was washed at least once with 10 mL of distilled water, centrifuged again, and the supernatant was combined to obtain a glucose concentration lower than 100 μg/mL, the solution was extended to 100 mL. Glucose concentration was determined using glucose oxidase–peroxidase (Biomaghreb) Kit. The absorbance was measured at a wavelength of 500 nm and glucose concentration was converted into RS content by multiplying it with the factor 0.9. The DS was calculated by the difference between TS and RS.Resistant starch (RS) and digestible starch (DS) was likewise determined according to the modified method described by Goni et al. . 100 mg α-amylase (2 × 10−4 mg/mL) type VI.B from porcine pancreas  was added. The prepared mixture was incubated at 37°C for 3 h with constant shaking. Aliquots of 0.2 mL were taken every 30 min for 3 h. α-Amylase was inactivated immediately by placing the tubes in a boiling water bath for 5 min. Then, 0.6 mL of 0.4 mol/L sodium acetate buffer solution (pH 4.75), and 0.2 mL of an enzyme solution containing 0.833 μL of amyloglucosidase from A. niger  were added. In order to hydrolyze digested starch into glucose, sample was incubated at 60°C for 45 min. Finally, the volume was adjusted to 20 mL with distilled water and glucose concentration in the digesta was measured within the range (25–100 μg/mL) using the oxidase–peroxidase Kit . Digested starch at time t (Dt) (g/100 g dry starch) was calculated by equation ; 0.9, represents stoichiometric constant of glucose content conversion into starch; 1/1000, the conversion from μg to mg; V, volume of digesta (mL); Ws, weight of sample (mg); TS (%), the total starch expressed as percentage in dry matter.where Dt in this model.The first-order exponential model in kinetic study has been used to estimate starch hydrolysis or glycemic indices in food and feed studies ; K, constant rate (min−1); t, time (min).where K and D∞ were determined by LOS method “log of slope” described by , which is obtained by integrating Eq. (t0 = 0 min and tf = 180 min getting Eq. (The glycemic and hydrolysis indices use the area under the hydrolysis curve (min g/100 g dry starch) (AUCting Eq.  between ting Eq. :exp of the sample from 0 to 180 min to the area under the hydrolysis curve of white bread (∼15500 min g/100 g dry starch), was used in calculating GI using an equation (GIHI = 39.51 + 0.570 HI) adapted from  was also obtained from  at 90 min; subscripts th and exp are, respectively, theoretical and experimental values. Consequently, an average GIavg, was defined as (GIHI + GIH90)/2.The hydrolysis index (HI), expressed as the ratio of the AUCAll the parameters of sorghum grain quality and starch analysis were measured in three replicates and expressed as mean ± SD. The data analyses were performed with the SigmaPlot V.10.0  for Windows.Grain colors were white, red, and mixed (white and red), this characteristic is controlled genetically and modified by environmental conditions during and after maturation  content of sorghum flour ranged from 67.67% to 74.82% db with a mean value of 71.78% Table . The graSome nutritionally important starch fractions in the grains are shown in Table The resistant starch value (RS) obtained in samples: SB10AS, SM10AS, SB11TA, SB10TA, SB11MA, SB12FE, SR12DJ was found to be from 2.5% to 5%, which is considered intermediate, while it ranged from 5% to 15% in SR10AS and SR12AS which is considered high, according to the classification of resistant starch content as suggested by  , digestibility between 60% and 80% (D180 60–80) , and digestibility lower than 60% (D180 < 60) .The starch hydrolysis curves for grain samples are shown in Fig. . The reaD∞, K, the hydrolysis index HI, and GIavg. The digested starch at infinite time D∞ varied from 52.58 to 102.13 (g/100 g dry starch), K ranged between 0.011 and 0.0245 min−1, and the hydrolysis index (HI) ranged from 41.55% to 76.93%  was found to be 110, while in maize (Zea mays) was about 85, in flour made into chapatti (India) was 60 ± 8 and 94 for brown rice (Canada). (Mani et al. According to the classification of GI content as suggested by (Brand-Miller et al. avg values of sorghum flours grown in Algeria were much higher, possibly due to differences in genetic source, growing conditions, and the employed methods to determine HI and GIavg. This result suggests that there are good opportunities for utilization of sorghum grain, grown in Sahara of Algeria, for human health and nutrition purposes.The HI and GIThis study pointed out that the differences in structural, physical, and biochemical properties of sorghum grains demonstrated the diversity of genotype in local sorghum cultivars in Algeria. Moreover, the measure of in vitro starch digestibility showed that the nine local cultivars exhibited high digestibility up to 90%. First-order model can assess the modeling starch digestion of uncooked sorghum flours. Nutritionally important starch fractions and starch digestion can be affected by many factors including genotype, environmental conditions, structure of starch, and nonstarch components. Finally, the digestibility properties of the Algerian sorghum cultivars showed a high diversity and might have implications for human health and nutrition.


Plasmodium vivax merozoite invasion of reticulocytes is a rapid process that involves a series of specific, sequential interactions. These interactions are crucial for invasion and continued blood-stage infection, thus representing attractive targets for vaccine development. The Duffy binding protein (DBP) is a vital microneme protein associated with the decisive, irreversible step of junction formation during the later stages of the invasion process. The ligand domain of DBP, known as region II (DBPII), binds the Duffy Antigen Receptor for Chemokines (DARC) by dimerization of two DBP and two DARC molecules forming a heterotetrameric structure. Naturally acquired antibodies to DBPII are prevalent in residents of areas where vivax malaria is endemic. These antibodies can inhibit DBPII binding and merozoite invasion of human reticulocytes; however, they tend to be poorly inhibitory, strain-specific, and short-lived. Remarkably, strain-specific serologic activity can be altered by even single amino acid substitutions found in allelic variants of DBPII. While strain-transcending, broadly neutralizing antibodies are less prevalent, there is a significant correlation of their antibody reactivity to certain epitopes and inhibition of DBPII-receptor function. Our data indicate epitopes at or near the dimer interface of DBPII represent the primary targets of naturally occurring protective anti-DBPII antibodies that can inhibit merozoite invasion of host erythrocytes. However, these epitopes also contain most of the prevalent variable residues resulting from DBP allelic diversity. These data are consistent with the hypothesis that DBP variation is an immune evasion mechanism responsible for strain-specific immunity and stable, broadly neutralizing immunity is achieved when antibodies target functionally-conserved epitopes, thereby blocking DBP dimerization and inhibiting invasion. To overcome the natural tendency for eliciting a strain-specific response, synthetic DBPII alleles were evaluated for their ability to broaden efficacy of strain-transcending inhibition against diverse DBPII alleles. In an effort to identify potential conserved, protective epitopes we have prepared and evaluated a panel of anti-DBPII murine monoclonal antibodies. Inhibitory activities of these monoclonal antibodies were characterized with in vitro functional assays for DBPII and their respective minimal epitopes were mapped using phage display. These targets of putative strain-transcending inhibition identify epitopes that may be targeted for vaccine-induced anti-DBPII inhibitory antibodies.


Background. An adequate blood flow is directly related to graft survival in living donor liver transplantation. However, in some cases, unfavorable conditions prevent the use of the hepatic artery for arterial reconstruction. Herein, we report a case in which the recipient right gastroepiploic artery was used as an option for arterial reconstruction in adult-to-adult living donor liver transplantation. Case Report. A 62-year-old woman, with cirrhosis due to hepatitis B associated with hepatocellular carcinoma, was submitted to living donor liver transplantation. During surgery, thrombosis of the hepatic artery with intimal dissection until the celiac trunk was observed, which precluded its use in arterial reconstruction. We decided to use the right gastroepiploic artery for arterial revascularization of the liver graft. Despite the discrepancy in size between donor hepatic artery and recipient right gastroepiploic artery, anastomosis was performed successfully. Conclusions. The use of the right gastroepiploic artery as an alternative for arterial revascularization of the liver graft in living donor liver transplantation should always be considered when the hepatic artery of the recipient cannot be used. For performing this type of procedure, familiarity with microsurgical techniques by the surgical team is necessary. An adequate blood flow is directly related to graft survival and prevention of postoperative complications in living donor liver transplantation (LDLT). However, in some cases, unfavorable conditions prevent the use of the recipient hepatic artery for arterial reconstruction. In these cases, an alternative source for arterial inflow is necessary. Herein, we report a case in which the right gastroepiploic artery (RGEA) was used as an option for arterial reconstruction in adult-to-adult LDLT.A 62-year-old woman, with cirrhosis due to hepatitis B associated with hepatocellular carcinoma, was submitted to adult-to-adult LDLT, using a right liver graft. Recipient, donor, and graft weight were 51 Kg, 72 Kg, and 774 g, respectively. Graft to recipient weight ratio was 1.52%. During recipient's hepatectomy, thrombosis of the hepatic artery with extensive subintimal dissection until celiac trunk was observed. The use of hepatic artery for graft revascularization was judged impossible. We decided to use the RGEA for arterial reconstruction. The artery was released from the gastric greater curvature, mobilized under the gastric pylorus, and approximated without tension to the liver graft. Despite the discrepancy in size between the donors right hepatic artery and the recipient RGEA, arterial anastomosis was performed successfully in an end-to-end fashion using separate 8–0 Prolene sutures. Magnification loupes (6x) were worn by surgeons. A parallel bulldog clamp was used to approximate the arteries during anastomosis Figures . During The first description of RGEA as an alternative for liver graft revascularization in orthotopic liver transplantation was made by Radermecker et al. in 1993 considering a whole liver transplantation from deceased donor  reportedWith the development of liver transplantation, especially in transplant centers in Asia, other arteries have been described as alternative for arterial anastomosis in LDLT, such as splenic, left gastric, right gastric, middle colic, cystic, and gastroduodenal . Still, In the case presented here, as soon as we realized that the recipient right hepatic artery had severe thrombosis with wall dissection to the celiac trunk, we chose to use the RGEA for arterial reconstruction. The RGEA showed approximately 2 mm in diameter, slightly thinner than the recipient right hepatic artery. Despite the difference in size, arterial anastomosis was performed successfully using microsurgery techniques.Liver transplantation teams ought to be prepared for unexpected situations during surgery. Right gastroepiploic artery should always be considered as an alternative for arterial reconstruction when the hepatic artery cannot be used. For performing this type of procedure, knowledge of microsurgical techniques by the surgical team is necessary.


Methods for identifying physiologically relevant T-cell epitopes are critically important for development of vaccines and the design of therapeutic proteins. As the number of proteins that are being evaluated for putative immunogenicity expands, rapid and accurate tools are in great demand. Several methods to identify T-cell epitopes have been developed, the most recent of which is a cell free system consisting of a minimal set of proteases incubated with HLA DRB1*0101, HLA-DM and whole antigen. Isolation and sequencing of the HLA bound peptides using mass spectrometry allows for the prospective identification of immunodominant T-cell epitopes.We present here, a comparison of this cell free in vitro antigen processing system to an immunoinformatics approach using the EpiMatrix algorithm. Our comparison reveals that in addition to identifying a similar set of epitopes to the cell-free system, the immunoinformatics approach prospectively identifies more HLA-DRB1*0101 epitopes and can simultaneously analyze multiple HLA alleles.Although the cell-free system incorporates antigen processing and MHC binding, the immunoinformatics approach identifies many validated epitopes with a very high degree of accuracy and can be performed much faster with far fewer resources. Methods for the prospective identification of physiologically relevant T-cell epitopes are critically important for development of vaccines and for the design of therapeutic proteins. A cell free system (CFS) for prospectively identifying T-cell epitopes from whole antigens was recently described and applied to the identification of influenza epitopes . As descin silico approach using EpiMatrix and the CFS approach, in terms of epitopes identified and the relative speed, effort required and cost of the two methods.The publication of the CFS method provided an opportunity for comparing a purely immunoinformatics approach based entirely on MHC binding affinity (EpiMatrix) to an in vitro system that involves both antigen processing and presentation . We hypo306–318) appended to the C-terminus; (2) Collagen type II; (3) influenza H5N1 (A/Vietnam/1203/2004) HA and (4) Liver stage malaria antigen. The resulting peptide-DR1 complexes were isolated by immunoprecipitation and the bound peptides were eluted under acidic conditions. These eluted peptides were then analyzed on a matrix-assisted laser desorption ionization (MALDI) mass spectrometer.The CFS approach to finding immunodominant epitopes, as published in reference Results for the CFS method were obtained using a single allele HLA-DRB1*0101) [*0101 [1]298–317) were eluted from peptide-DR1 complexes. T cell proliferation assays using peripheral blood mononuclear cells (PBMC) obtained from HLA DRB*0101 transgenic mice immunized with rHA1 showed a strong dose dependent response to the A/Texas/1/77 single epitope identified by the cell free assay and a weaker but still significant response to the A/PR/8/34 peptide. The sum of proliferative responses (ex vivo) to these two epitopes approached the magnitude of the response to whole rHA1.For example, recombinant HA1 (rHA1), engineered to include a published epitope, was incubated in the cell free system. After isolating HLA DRB1*0101 complexes, the genetically-linked A/Texas/1/77 known immunodominant epitope and only one other peptide  was used to test the epitope identification system. CII is a major component of cartilage and is the main suspected auto-antigen in rheumatoid arthritis in DR1+ individuals . A core The CFS was also used to prospectively identify immunodominant DR1 epitopes from HA1 protein of influenza A/Vietnam/1203/2004 (H5N1) and LSA-NRC, a recombinant modified version of a protein expressed exclusively in malaria-infected hepatocytes at a preerythrocytic stage, which was designed as a vaccine against preerythrocytic stage malaria. Several new epitopes  were ideImmunoinformatics (I) and the CFS (C) approaches.The sequences of the four antigens evaluated in the CFS were obtained from GenBank and then analyzed using EpiMatrix . Standard criteria  were used for epitope identification . A list All four I/C epitopes scored among the top 5 HLA DRB1*0101 EpiMatrix scores for the antigens . Of these 13 epitopes, eight (62%) were previously confirmed as human T cell epitopes, according to IEDB; validation is not yet recorded the remaining five epitopes.Epitope sequences identified by both the CFS and EpiMatrix method were cross-referenced against the Immune Epitope Database (IEDB) of published T cell epitopes and MHC ligands using the substring parameter. Further, all T cell responses and MHC binding results available on IEDB were compiled for each input antigen. If IEDB is taken as the reference standard for validation of epitopes predicted by either method, EpiMatrix prospectively identified five more ‘validated’ epitopes that the CFS method did not identify. CFS identified two epitopes that were not identified by EpiMatrix, and although these are published in IEDB, they have been published for alternative alleles. If more stringent criteria are applied, (restriction by HLA DRB1*0101 and publication in IEDB), EpiMatrix correctly identified three of the three (100%) HLA DRB1*0101-restricted epitopes. This significant reduction is due in part to the limited HLA-restriction references available on IEDB; of the four test antigens, only H5N1 Vietnam had references qualified as HLA-DRB1*0101-restricted. As we will discuss in greater detail below, the single HLA DRB1*0101-restricted epitope prospectively identified by the CFS (I/C-CII5), was only validated as a result of querying the EpiMatrix-identified core.The single PR epitope that was identified by both the CFS and EpiMatrix, I/C-PR1, was ranked first of all PR-derived HLA DRB1*0101 epitopes by EpiMatrix, and was extracted from the same amino acid locus 306–318) as the influenza HA epitope control peptide (I/C-Tex1) that was fused to the A/PR/8/34 antigen. The two epitopes also identified by EpiMatrix have high DRB1*0101 scores (I/C-PR1 and I/C-Tex1) and contain an epitope bar (or EpiBar) –318 as t, a featu259–274) to test for immunodominance in T cell proliferation assays, cytokine production assays, and tetramer staining assays. EpiMatrix analysis shows that the shorter HA most likely has a truncated terminal HLA DRB1*0101 HLA binding motif. The peptide only has one EpiBar at the C-terminal end of the sequence and the N-terminal end of the peptide, which is devoid of predicted HLA binding motifs, would interfere with binding, in vitro, and with immunogenicity. The properly centered peptide would have been identified prospectively using EpiMatrix.When the full length HA1 from H5N1 A/Vietnam/1203/2004 was analyzed in the CFS, two unique peptide species were identified; both shared the same core sequence (C-VN45). The authors selected the shorter of these two peptides  are equally likely if not more likely to be HLA DRB1*0101-restricted, however this would have to be tested prospectively in T cell assays as was done for the CFS epitopes.273–305 contains the same epitope that is predicted by EpiMatrix, however its sequence is elongated and the probable HLA binding motif is almost obscured by the extended flanks that were eluted with the core sequence. When queried against the IEDB, the CFS-eluted sequence returned no results, whereas the EpiMatrix-identified core sequence was published as a DRB1*0101-restriced epitope. In other words, immunoinformatics analysis using EpiMatrix can rapidly and accurately identify a core HLA binding epitope, whereas the CFS does not. EpiMatrix identified three additional epitopes in Cll that are likely to be immunogenic . One was previously reported in IEDB but not confirmed in HLA transgenic mice nor in human T cell assays.It is notable that the single collagen epitope (I/C-CII5) identified by the CFS was also confirmed by EpiMatrix. It was the 5th ranked peptide for HLA DRB1*0101, which is not unexpected considering the greater length of the CII sequence compared to other proteins examined in the CFS. The peptide has a maximum DR1 EpiMatrix score of 2.66, putting it in the top 1% of peptides expected to bind to DR1, a rank that would have normally led to selection by EpiMatrix. The sequence of the CFS eluted peptide CIIFinally, the single LSA epitope identified by both the Immunoinformatics approach and the CFS method contains a strong EpiMatrix-scoring peptide, and was the only LSA epitope to be validated in T cell assays. The weaker LSA epitope (C-LSA11) was also identified by the immunoinformatics approach, but the EpiMatrix score was slightly below the normal cut off for selection. Two additional epitopes, I-LSA1 and I-LSA3 were identified using EpiMatrix, of which one (I-LSA1) is found in IEDB for an unreported Class II HLA allele.The CFS method described by Hartman et al. is a novel approach for identification of T cell epitopes that involves a significant amount of effort, reagents, and highly technical expertise in the use of MALDI mass-spectrometry. One advantage of CFS is that the method could, in theory, be applied to additional antigens and alleles for which immunoinformatics approaches do not yet exist. In comparison to the immunoinformatics approach, EpiMatrix, it appears to be both time- and cost-intensive. Many of the same epitopes are identified using the two approaches. Additionally, previously validated epitopes are identified using EpiMatrix that appear to be missed by the CFS , as are several epitopes that appear likely to be immunogenic based on their rank and EpiMatrix score. Thus antigen-processing as performed using the CFS may have destroyed peptides that might otherwise have been presented by DR1. Two epitopes were identified using the CFS that would not have been selected by EpiMatrix. Neither of these epitopes would qualify as high quality targets based on information obtained from IEDB.Epitopes identified using the CFS were not compared to epitopes that have already been published. Instead, in vivo methods were used to validate sequences. Epitopes were considered to be validated if, following immunization of HLA-DRB1*0101 mice with whole antigen, T cells were induced to proliferate, cytokine production was increased, or tetramer-stained cells could be detected, or some combination of the three. These methods are useful for validation regardless of the epitope selection method – and have been used for the validation of T cell epitopes identified using EpiMatrix  and may have application to organisms with little to no information on peptide-MHC interactions. A much more extensive (and perhaps cost-prohibitive) comparison would have to be performed, prospectively validating the epitopes discovered using EpiMatrix alongside epitopes discovered using the CFS, before either method is proven to be superior to the other. At the very least, they appear to be somewhat complementary.http://www.cbs.dtu.dk/services/NetMHCII/).It should be mentioned that there are a range of epitope prediction tools available, however each tool may provide slightly different results . For exain vitro reagents, and MALDI mass spectrometer costs). Thus immunoinformatics approaches with algorithms such as EpiMatrix provide a clear cost and time advantage over CFS.Immunoinformatics provides a rapid means of analyzing protein sequences for multiple HLA alleles at the same time. EpiMatrix prospectively identified more HLA-DRB1*0101 epitopes than the CFS, of which almost all are present in IEDB. In addition to providing an analysis of multiple alleles at once (not just HLA DRB1*0101) and highlighting promiscuous epitopes , this gap grows exponentially wider.Adding antigen-processing to epitope selection in vitro does not improve prospective class II antigen identification. In this comparison of two methods for T cell epitope identification, the in vitro antigen-processing and MHC-elution method (CFS) obscured two of three externally validated, HLA-DRB1*0101-restricted epitopes, whereas the immunoinformatics approach (EpiMatrix) correctly identified all published epitopes restricted by DRB1*0101, and prospectively identified many additional epitopes that have yet to be validated. While the CFS approach may enable identification of epitopes from MHC for which there is little to no published information, the advantages of the immunoinformatics method, which include a very high degree of accuracy, high throughput, rapidity, and low cost, are clear.Proteins analyzed by EpiMatrix are parsed into 9-mers that overlap each other by 8 amino acids. Each of these 9-mers is then scored individually (and simultaneously) for predicted binding affinity against a panel of eight common Class II HLA alleles  that collectively cover over 95% of the human population [


Biologic grafts have been shown to support tissue regeneration in various animal models. Very few reports in the literature exist to show tissue remodeling in patients after placement of a biologic graft.We report the case of a 69-year-old Caucasian man with a history of small bowel carcinoid resection and concurrent recurrent ventral hernia repair with component separation and underlay biologic graft placement who underwent re-operation for metastatic carcinoid tumor to his liver. Complete incorporation of the biologic graft was observed. Tissue analysis of the incised midline fascia revealed tissue remodeling at the site of the previous abdominal wall defect.Placement of a biologic graft in ventral hernia repair supports tissue regeneration similar to that previously reported in animal models. The use of biologic graft materials in complex abdominal wall reconstruction over the last several decades has significantly increased, especially in contaminated cases where synthetic mesh is relatively contraindicated. Two important potential complications after complex abdominal wall reconstruction are recurrence and infection. Several studies have shown that although recurrence rates are slightly lower in patients who have received synthetic mesh than in those who have received biologic graft material, the complication rates, especially the incidence of infection, are higher . The morA recent study evaluating biologic graft biopsies obtained during re-exploration for ventral hernia recurrence revealed that the duration of time the biologic graft had been implanted was directly correlated with the degree of constructive remodeling. The human dermis scaffolds that had been implanted longer showed decreased numbers of inflammatory cells and fibrous encapsulation, increased extracellular matrix deposition and neovascularization, increased cellular penetration to the center of the biopsy, and nearly complete scaffold degradation .Animal studies utilizing either porcine or human acellular dermal matrices showed that after several weeks, the tensile strength measurements of the abdominal wall at the biologic graft-to-musculofascia interface were not less, and in some cases were greater, than the adjacent unwounded fascia -6. In adA 69-year-old Caucasian man presented with recurrent metastatic carcinoid tumor to his liver. His past surgical history included gunshot wounds to his abdomen, resulting in an exploratory laparotomy in 1979. Four years later, a ventral hernia developed that was repaired primarily. His hernia recurred another 5 years later and was repaired with a polypropylene mesh.In 2009, he developed gastrointestinal symptoms of intermittent bloating, epigastric pain, abdominal cramps, and alternating episodes of diarrhea and constipation. With increased frequency and severity of symptoms, he subsequently developed a third recurrence of his ventral hernia in late 2010. A small bowel mass was visualized on a computed tomography scan in 2011 along with the recurrent ventral hernia , and a ventral hernia repair were performed.®, Cook Medical, Bloomington, IN, USA) and secured with transfascial O Ethibond sutures . The fascia edges were approximated primarily over the biologic graft with #1 polydioxanone (PDS) and drains were placed in the subcutaneous layers. He recovered uneventfully.Thirty months after the carcinoid resection and liver tumor ablation, a repeat surveillance octreotide scan revealed a suspicious 1.9cm lesion on segment 1 of his liver that was confirmed with magnetic resonance imaging. Good fascial approximation at the site of the prior recurrent ventral hernia repair was also noted  are several types of materials used in prosthetic mesh. The mechanism by which prosthetic mesh strengthens hernia repair is by inciting an intense inflammatory response to the foreign body with resultant development of a strong scar plate. The inflammatory changes around the alloplastic material used in abdominal wall defect repair can persist for many years . This inThe various types of biologic graft materials consist of a decellularized collagen matrix derived from either porcine, bovine or human sources. Typically obtained from either dermal or non-dermal sources these graft materials have undergone significant processing to remove the cells and antigenic components, resulting in a highly purified collagen architecture and surrounding extracellular matrix. Depending on the graft, the resulting product may or may not be cross-linked . The theCommon hernia mesh implant complications include recurrence, infection, seroma formation, integumentary necrosis, chronically draining sinuses, enterocutaneous fistulas, and intestinal obstruction . Both clAlthough a retrospective study assessing single-stage ventral hernia repairs with lightweight polypropylene mesh implants in clean-contaminated and contaminated cases has shown some favorable results, re-operation was 12% and the incidence of surgical site occurrences  was 30% . A systeAnimal studies of various biologic graft materials on physicomechanical properties , immunolSeveral animal studies have shown that biologic grafts induce the expression of extracellular matrix components, remodeling enzymes, and inflammatory cytokines, and promote fibroblast infiltration and migration into the matrices. Our current observation suggests that tissue regeneration in humans may mirror that of the animal model. Improved tissue regeneration with implantation of biologic graft materials in animals may also be seen in humans.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.CT scan: Computed tomography; MRI: Magnetic resonance imaging.The authors declare that they have no competing interests.EH performed the clinical follow-up of the patient. EH performed the surgery. KN and EH have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data. Furthermore, all authors have been involved in revising the manuscript critically for important intellectual content, and have read and approved the final manuscript. VZ provided the histologic pictures and analysis.


The recent release of Impact Factors 2013 by Journal Citation Reports (JCR) 2013 confirmed the physiological and progressive growth of The Journal of Headache and Pain, untied from geo-political totems or classification duties.Also this year the growth has been remarkable, over 18% compared to the past year, matching the one of the headache area journal ranked first on the grid line. The Journal of Headache and Pain, in a global editorial scenario, has now upgraded of one position and is second overall between the four journals dedicated to this area of the clinical medicine. Full details are presented as Additional file The Open Access strategic option, as cornerstone of a past editorial choice and strictly connected to the introduction of the Article Processing Charge, has proved us to be the right decision helping the Journal to reach these important results .The global trend is evidently towards Open Access and this is out of any doubt, just like the results obtained from every journal that has made this choice at the right time . In factCircumstances require us to be cautious, but we have to note a general trend of growth of the four area journals and this tells us that, despite the miserable pipeline of headache drugs and the reduction/unification of scientific events on headache, a huge cultural request towards this area still exists and is rising.The Journal of Headache and Pain will keep witnessing the opening needs to new research groups who are entering the headache editorial world, preferring it to more generalist journals, with a loyal readership composed by a mixed audience not always interested in headache disorders.An incoming newness is Transparent Peer Review (TPR), as last strategy that will soon be in our hands and before the readers’ eyes: the reviewers’ reports will be fully readable alongside with the published papers. In times of editorial scandals, just to cite the one that brought disgrace on 66 scientific journals , TPR wilIf every actor of this success, Authors, Reviewers, affiliated scientific societies – European Headache Federation and Lifting The Burden, my multi-localized Editorial Office and obviously Springer Publisher will keep working with the same enthusiasm and passion as ever, of which I am certain, we will be able to meet again at the next stop and share the joy of being helpful to the headache scientific community.At the end of this year the Editorial Boards will expire and then will be refreshed on the basis of the proved scientific contribution. All headache scientists willing to be on-board for the next term are invited to offer their expertise.The Journal of Headache and Pain - 2013.Click here for file


Obesity, insulin resistance, and type 2 diabetes are associated with a substantially increased prevalence of vascular fibrosis and stiffness, with attendant increased risk of cardiovascular and chronic kidney disease. Although the underlying mechanisms and mediators of vascular stiffness are not well understood, accumulating evidence supports the role of metabolic and immune dysregulation related to increased adiposity, activation of the renin angiotensin aldosterone system, reduced bioavailable nitric oxide, increased vascular extracellular matrix (ECM) and ECM remodeling in the pathogenesis of vascular stiffness. This review will give a brief overview of the relationship between obesity, insulin resistance and increased vascular stiffness to provide a contemporary understanding of the proposed underlying mechanisms and potential therapeutic strategies. Vascular stiffness is a consequence of pathophysiological alterations involving endothelial cells (ECs), vascular smooth muscle cells (VSMCs), extracellular matrix (ECM), and other functional elements of the vessel wall  analysis of pulse transit time; (2) wave contour of the arterial pulse; and (3) direct measurement of arterial geometry and pressure that corresponds to regional, systemic, and local determination of stiffness  and sympathetic nervous (SNS) systems are all components of the cardiorenal metabolic syndrome, which is associated with vascular stiffness Sowers, . DysreguExcess adipose tissue, in particular abdominal adipose tissue, has been closely linked to the development of vascular stiffness and cardiovascular disease , and vasoconstrictor substances, such as angiotensin II (Ang II), and thromboxane A2  has a vasodilatory effect and anti-atherogenic properties, including inhibition of VSMC proliferation and migration, platelet activation and adhesion and leukocyte adhesion and migration  and connective tissue growth factor (CTGF) are well-known profibrotic factors that can stimulate synthesis of ECM proteins, such as fibronectin and collagens, under conditions of obesity, insulin resistance, and T2D  expression on the EC surface leading to reduced NO production that is associated with increases in cortical stiffness of the cytoskeleton  oxidase activity and reduction of NO bioavailability, thereby promoting oxidative stress and vascular dysfunction  can protect the vascular cells by immunosuppression, cell contact–dependent suppression, and functional modification or killing of activated protein C (He et al., Vascular stiffness is associated with chronic inflammatory disease in the vessel wall characterized by an activation of both the innate and adaptive immune systems, which are composed of diverse cellular components, including granulocytes, mast cells, monocytes, macrophages, and natural killer cells (Aroor et al., Non-diabetic premenopausal women exhibit lower incidence of cardiovascular complications compared to age matched men. However, this protection is lost under the setting of obesity and T2D (Manrique et al., Although the mechanisms that contribute to vascular stiffness in obese premenopausal women are poorly understood, upregulation of RAAS signaling may be important in this regard (Aroor et al., Vascular stiffness is increased in conditions of insulin resistance and obesity and independently increases the risk of developing hypertension, coronary heart disease, and CVD morbidity and mortality. The underlying pathophysiology of vascular stiffness in insulin resistance and obesity involves activation of RAAS, adipocyte inflammation, abnormalities in vascular cells, ECM and maladaptive immune responses, all of which increase the risk of vascular stiffness associated CVD events Figure . Future 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.


The passive stiffness of the calf muscles contributes to standing balance, although the properties of muscle tissue are highly labile.We investigated the effect of sway history upon intrinsic ankle stiffness and demonstrated reductions in stiffness of up to 43% during conditions of increased baseline sway.This sway dependence was most apparent when using low amplitude stiffness‐measuring perturbations, and the short‐range stiffness component was smaller during periods of high sway.These characteristics are consistent with the thixotropic properties of the calf muscles causing the observed changes in ankle stiffness.Periods of increased sway impair the passive stabilization of standing, demanding more active neural control of balance.vs. 0.6 deg). Furthermore, torque responses exhibited a biphasic pattern, consisting of an initial steep rise followed by a shallower increase. This transition occurred earlier during increased levels of ankle sway. These results are consistent with a movement‐dependent change in passive ankle stiffness caused by thixotropic properties of the calf muscle. The consequence is to place increased reliance upon active neural control during times when increased sway renders ankle stiffness low.Quiet standing is achieved through a combination of active and passive mechanisms, consisting of neural control and intrinsic mechanical stiffness of the ankle joint, respectively. The mechanical stiffness is partly determined by the calf muscles. However, the viscoelastic properties of muscle are highly labile, exhibiting a strong dependence on movement history. By measuring the effect of sway history upon ankle stiffness, the present study determines whether this lability has consequences for the passive stabilization of human standing. Ten subjects stood quietly on a rotating platform whose axis was collinear with the ankle joint. Ankle sway was increased by slowly tilting this platform in a random fashion, or decreased by fixing the body to a board. Ankle stiffness was measured by using the same platform to simultaneously apply small, brief perturbations  at the same time as the resulting torque response was recorded. The results show that increasing sway reduces ankle stiffness by up to 43% compared to the body‐fixed condition. Normal quiet stance was associated with intermediate values. The effect was most apparent when using smaller perturbation amplitudes to measure stiffness (0.1  The passive stiffness of the calf muscles contributes to standing balance, although the properties of muscle tissue are highly labile.We investigated the effect of sway history upon intrinsic ankle stiffness and demonstrated reductions in stiffness of up to 43% during conditions of increased baseline sway.This sway dependence was most apparent when using low amplitude stiffness‐measuring perturbations, and the short‐range stiffness component was smaller during periods of high sway.These characteristics are consistent with the thixotropic properties of the calf muscles causing the observed changes in ankle stiffness.Periods of increased sway impair the passive stabilization of standing, demanding more active neural control of balance. COMcentre of massEMGelectromyogramSRECshort‐range elastic componentet al. et al. et al. et al. et al. a). To our knowledge, however, the source and significance of these differences has not been clarified fully. In the present study, we investigate these within‐subject differences.In quiet standing, the body's centre of mass is situated forward of the ankle joint, and so continuous ankle torque is required to prevent it from falling forwards  previously investigated the effect of amplitude in standing individuals and reported that ankle stiffness is indeed less for larger movements  were recruited for this non‐invasive experiment , we applied four different rotation sizes of 0.1, 0.2, 0.4 and 0.6 deg, intended to span the range of the muscle short‐range elastic component  movement.C).Wobble: participants were standing freely at the same time as the footplates were continuously rotated by a randomly‐varying waveform, generated by applying a 1 Hz low‐pass filter to white noise. The root‐mean‐square amplitude of the waveform was 0.6 ± 0.02 deg (mean ± SD). This was sufficient to increase ankle movement without endangering balance, and no subject found this condition to be challenging in the least. The stiffness measuring perturbations were summed with this waveform Fig. C.To determine how baseline motion of the ankle joint would affect its stiffness we artificially manipulated the degree of ankle movement in three ways:The three conditions of baseline ankle movement  combined with the four different perturbation sizes  resulted in a total of 12 conditions. Forty‐eight perturbations were applied per condition, resulting in a total of 576 for each participant.et al. et al. et al. Platform angular displacement, velocity and acceleration, along with ankle torque, were used to estimate stiffness of the ankle joint. Torque was measured by two miniature load cells . These were horizontally mounted between the platform and footplates and placed directly above their axis of rotation. The foot was firmly placed on the footplate, and angular displacement was recorded with a precision Hall effect potentiometer  located on the platform axis. A laser‐reflex sensor , placed at the left mid‐tibia level (150–250 mm away from the shin), was used to record shin linear displacement, which was converted to angular rotation by taking the inverse tangent of laser distance over height. This signal was subtracted from the footplate angle to provide the ankle angle. A second laser  was used to record an approximation of the centre of mass (COM) angular position and was directed at the umbilicus. This laser was used for the estimation of the gravitational toppling torque (see below). A 3 g linear accelerometer  measured footplate acceleration. This was attached underneath the left footplate at a distance of 0.22 m from its axis, and the signal was converted to angular acceleration. Signals were low‐pass filtered by a fourth‐order Butterworth filter with a cut‐off frequency at 40 Hz. Velocity was calculated by integrating angular acceleration. Muscle activity evoked by the perturbation (e.g. stretch reflexes) could affect our calculations of joint stiffness  and θ¨ is angular acceleration (deg s−2); K is stiffness (Nm deg−1); B is viscosity (Nm s deg−1) and I is moment of inertia of the foot (kg m2).We assumed that the ankle joint acted as a rotating mass‐spring‐damper system .The reliability of the estimation process was monitored by correlating the estimated torque with the actual torque  and body angle . For convenience, we refer to toppling torque as ‘mgh’. Torque and body angle were recorded during 30 s of voluntary sway, when subjects were instructed to sway very gently about the ankle joint, minimizing any hip or knee motion. As expected, this value correlated strongly with subject mass  and height .During quiet standing, body sway amplitude is below 6 deg  and stimulus amplitude  upon ankle stiffness. Pearson's correlation was used to investigate the relationship between baseline ankle torque and stiffness. P < 0.05 was considered statistically significant for all tests.A), normal  and wobble . Within the 5.4 s period shown for each condition, two ankle perturbations can be identified. The traces illustrate the wide range of spontaneous ankle movement and torque observed across conditions; the average baseline results are summarized in the bar graphs . Although footplate rotation induced by the perturbation was identical between board and normal, baseline ankle movement and torque was greater for the latter. The minor fluctuations that occurred in the board condition represented the limitations of our ability to immobilize the subject. During the wobble condition, when a randomized waveform was applied to the footplates, ankle motion was inevitably much greater, as was the intention. Mean pre‐stimulus ankle movement exhibited a significant difference between conditions, approximately doubling in value between board and normal, with a much larger increase again for wobble  . This confirmed that our interventions were successful in manipulating the degree of baseline ankle motion prior to each stiffness‐measuring perturbation.Figure mal Fig. B and woble Fig. C. Withiphs Fig. D and E.01) Fig. D. This vs. toes‐down) upon stiffness, viscosity or inertia . Both directions were therefore combined for all further analysis. Figure A–C depicts mean ankle stiffness, viscosity and inertia for all conditions and perturbation amplitudes. The estimated inertia of the combined foot and footplate remained similar across perturbation amplitudes . However, there was a significant influence of condition upon inertia, reflecting slightly higher values with increasing baseline ankle movement . Viscosity increased with perturbation amplitude  and became larger with increasing ankle movement . Crucially, neither inertia, nor viscosity exhibited an interaction between amplitude and condition (P > 0.11), in contrast to ankle stiffness, which is reported below.There was no effect of perturbation direction . Figure C depicts mean ankle stiffness for all conditions and perturbation amplitudes, reported here as a percentage of toppling torque per unit angle (‘% mgh’). Values ranged between 31% and 78% mgh. For both the normal and board conditions, there was a systematic non‐linear reduction in ankle stiffness with increasing perturbation amplitude. This effect was absent for the wobble condition, where stiffness was relatively low, and remained low (31–49% mgh) across all amplitudes. These observations are confirmed by a significant interaction between condition and amplitude . This effect of wobble is consistent with our hypothesized effect of prior muscle movement upon joint stiffness. By contrast to our hypothesis, however, stiffness was slightly but significantly lower in the board compared to normal condition, across all perturbation amplitudes. We speculated that changes in baseline torque between conditions may underlie the difference.Because we were primarily interested in estimating passive ankle stiffness, we first needed to exclude the possibility of an active contribution to the ankle torque as a result of the perturbation (e.g. stretch reflexes). We therefore compared mean EMG activity of the lateral gastrocnemius between 70 ms time windows pre‐ and post‐stimulus but found no significant difference (pre E). Values were almost identical between normal and wobble (∼33 Nm) but were ∼36% less for board . We then verified the correlation between torque and stiffness. We restricted this analysis to the wobble condition because it was the only one in which stiffness was not affected by perturbation amplitude. Figure −1) . We therefore normalized stiffness values by dividing them by baseline ankle torque. The result is shown in Fig. To test this speculation, we compared baseline torque during a 70 ms pre‐stimulus window Fig. E. ValueTo identify changes in stiffness throughout the time course of each perturbation, we examined the relationship between ankle torque and position during the first 70 ms of each stimulus. Figure et al. et al. et al. K were well below this value, ranging from between 31% and 78% mgh . Such amplitude‐dependence has previously been demonstrated in both the wrist and ankle joints , their perturbation was around half the magnitude of our smallest perturbation (0.055 vs. 0.1 deg). The results from Loram et al. et al. K using long slow continuous stretches, they estimated 30–40% for 1 deg perturbations, as opposed to our estimates of 31% for 0.6 deg. In their study, the stimulus velocity was much lower than the velocity used here (∼0.35 vs. 5–22 deg s–1), suggesting that amplitude is the key stimulus property affecting estimates of K.In addition to manipulating the level of baseline ankle sway, we also measured stiffness across a range of stimulus amplitudes. For both the normal and board conditions, there was a non‐linear reduction in  & Lakie  observedK would be inversely related to ankle sway. This hypothesis is based upon the well‐established thixotropic property of muscle tissue . This would explain the consistently lower values of stiffness in board compared to normal condition, across all amplitudes. It also suggests that in leaning forward, when more torque is required, stiffness will increase, potentially increasing stability. This is a possible reason for not standing strictly at the vertical equilibrium point. However, other reasons might include minimizing the range of backward COP movement and/or involvement of the dorsal flexors. After factoring out differences in baseline torque, the data fully confirmed our hypothesis  at the largest amplitude  where c is normalized stiffness, I is moment of inertia, m is mass, h is height and g is acceleration as a result of gravity. If the moment of inertia is written as I = kmh2 where k is a shape factor of value ∼1.3 g. If we assume the COM is positioned at 55% of our subjects’ height (1.75 m), this equates to an h of 0.96 m. During normal standing, c ranged from 0.46 to 0.78, at 0.6 and 0.1 deg of stimulus amplitude, respectively. Therefore, these stiffness values equate to time constants of 491 and 756 ms. This shows that the behaviour of the standing subject and the size and timing of their neural response are all sensitive to the size of the perturbations applied. During the wobble condition, the time constant was always ∼490 ms. This suggests that greater control alacrity is required in situations where sway size is large, such as when standing in moving vehicles.The potential consequence of reduced ankle stiffness is to increase reliance upon active neural intervention to maintain balance. This would not only involve more torque modulation, but also faster modulation. Loram et al. (et al. (The results reported in the present study suggest that individuals with less stiffness may be less stable. To our knowledge, only Fitzpatrick et al.  has inve (et al.  did not For an ankle stiffness dependent on the history of movement, the implication is that the demand for neural intervention to stabilize standing will not be constant but, instead, will vary continuously. For control of limb movement, a reduction in stiffness as movement occurs is favourable because it allows muscles to economically control both posture and movement. For standing, it may be less beneficial because an increased sway will lead to a reduction in ankle stiffness and stability and thus, potentially, to collapse unless there is additional neural intervention.The authors declare that they have no competing interests.TS, ML and RR contributed to all aspects of the work, including the conception of the experiments, the experimental design and collection and assembly of data, analysis and interpretation of data, drafting of the article, and critical revision for important intellectual content. All authors approved the final version of the manuscript, all persons designated as authors qualify for authorship, and all those who qualify for authorship are listed.This work was supported by the University of Birmingham Brazil Scholarship for Research Excellence and BBSRC grant BB/L02103X/1.


The design is based on the use of a pixelated CdTe Schottky detector to have optimal energy and spatial resolution. An individual read-out channel is dedicated for each detector voxel of size 1 × 1 × 2 mm3 using an application-specific integrated circuit (ASIC) which the VIP project has designed, developed and is currently evaluating experimentally.The Voxel Imaging PET (VIP) Pathfinder project intends to show the advantages of using pixelated semiconductor technology for nuclear medicine applications to achieve an improved image reconstruction without efficiency loss. It proposes designs for Positron Emission Tomography (PET), Positron Emission Mammography (PEM) and Compton gamma camera detectors with a large number of signal channels  Multiphysics COMSOL software package has been used to simulate the behaviour of signal charge carriers in CdTe and extract values for the expected charge sharing depending on the impact point and bias voltage. The results on charge sharing obtained with COMSOL are combined with GAMOS, a Geant based particle tracking Monte Carlo software package, to get a full evaluation of the amount of charge sharing in pixelated CdTe for different gamma impact points. However for PET –5), we u for PET ) to esti for PET  to numerϕ is applied to the detector, the charge carriers move towards the oppositely charged electrodes, creating an electrical signal that is amplified and measured. The value for the electric potential within the semi-conductor is obtained by solving the Laplace equation: ∇2ϕ = 0 while keeping ϕ = 0 V at the anodes and ϕ = −2000 V at the cathodes and keeping all in- and outgoing fluxes to 0. For the drift velocity of the charge carriers we have μe, μh are the mobilities for electrons and holes respectively. The probability for electrons and holes to get trapped while drifting towards the electrodes is expressed by their lifetimes, τe, τh. In μ and τ) is smaller for holes than for electrons, since holes are more affected by trapping. The density of electrons e,hG corresponds to the generation term which is equal to t′ the location and time of the impact of the gamma.An incoming gamma will create a cloud of charge carriers  in the semi-conductor material. The number of charge carriers is proportional to the energy of the gamma. When an electric bias potential weighting potentials to simplify the calculation of charge induction. The induced charge kQ on an electrode k by a single charge carrier q depends on the weighting potential kΨ at the start z0 and at the end point z1 of the charge carrier trajectory as: kQ = −q(Ψk(z1)−Ψk(z0)). The total induced charge is equal to the sum of the induced charges by all electrons and holes. The weighting potential Ψk for anode k can be obtained numerically by solving the Laplace equation: ∇2Ψk = 0, where Ψk is set to 1 V at anode k and 0 V at all other electrodes and all in- and outgoing fluxes are set to 0. In the case of planar electrodes , the weighting potential reduces to a straightforward linear function of the depth of interaction z and can be calculated analytically with ϕw = z/d. When a charge cloud is created far away from the anode, electrons will move towards the anode for a longer time and thus induce more charge than electrons created near the anode, whereas holes will induce relatively little charge. The opposite argument holds when the charge cloud is created near the cathode, in which most of the induced charge comes from the holes. In both cases the total sum of induced charge is 1, independent of the gamma impact point, as long as there is no trapping. Charge carriers can get trapped by atoms in the semi-conductor, so the charge carrier density is not constant and the total induced charge kQ will be smaller than the original charge Q0 created by the gamma impact. Because the probability to get trapped is bigger for holes than for electrons, the signal gets worse when the impact point is further away from the cathode. For planar electrodes, charge induction depends linearly on z, so we could use the Hecht equation [The measured signal from the detector comes from charge induction which is caused by the motion of the charge carriers and is proportional to the energy deposition of the original incoming gamma. Charge induction starts from the moment the charge carriers are created until they are all collected. A method to calculate charge induction was found independently by both Shockley  and Ramoequation  to calcu2, the spatial resolution of the detector will improve. In this case, where the pixel lateral size is small compared to the pixel thickness (2 mm), the small pixel effect will occur, where the dependence of the weighting potential on the depth of interaction is no longer linear  is defined by the induced charge ned from  and (2.2rettyman , 13.n and p from the continuity n+ and p+ which represent the CIE for electrons and holes respectively, when the adjoint generation term is defined as cG+ = μc∇ϕ ∇kΨ. By solving the adjoint equations, we inmediately obtain the CIE for electrons and holes for all possible gamma impact points in the detector as a function of time. The complete adjoint equations to be solved for electrons and holes are:Whereas ϕ.Solve the Laplace equation to obtain the electric field potential Ψk.Solve the Laplace equation to obtain the weighting field potential Solve the adjoint Unless otherwise stated, for all results a bias voltage of −2000 V was used and CdTe was characterized in COMSOL by the parameters from Once we have obtained the CIE as a function of all possible impact points and for all times, we can plot it versus time for particular impact points or versus distance for a particular time. ϕ. The difference is mainly noticeable near the anode, where the contribution is mainly due to holes which, with lower bias voltage, will move slower towards the cathode and hence have more chance to get trapped. However, for the final charge sharing, averaging over all impact points within the 1 × 1 × 2 mm3 pixel, the difference is negligible and even with a bias voltage of 500 V the value for the charge sharing is equal as for the case with 2000 V.3, we found 19.5% and 26% of charge sharing in a 3×3 pixel array with 122 keV and 511 keV gammas respectively, using a threshold of 15 keV. Similar values for the charge sharing were found for different bias voltages 500 V, 1000 V and 2000 V.For a CdTe pixel of size 1 × 1 × 2 mm


Work disability remains a considerable problem for many patients with rheumatoid arthritis (RA). Morning stiffness is a symptom of RA associated with early retirement from work and with impaired functional ability. We aimed to explore the patient’s perception of the impact of morning stiffness on the working life of patients with RA. A survey was conducted in 11 European countries. Patients of working age, with RA for ≥6 months and morning stiffness ≥3 mornings a week, were interviewed by telephone using a structured questionnaire. Responses were assessed in the total sample and in subgroups defined by severity and duration of morning stiffness and by country. A total of 1,061 respondents completed the survey, 534 were working, 224 were retired and the rest were, i.e. homemakers and unemployed. Among the 534 working respondents, RA-related morning stiffness affected work performance (47 %), resulted in late arrival at work (33 %) and required sick leave in the past month (15 %). Of the 224 retired respondents, 159 (71 %) stopped working earlier than their expected retirement age, with 64 % giving RA-related morning stiffness as a reason. There was a differential impact of increasing severity and increasing duration of morning stiffness on the various parameters studied. There were notable inter-country differences in the impact of RA-related morning stiffness on ability to work and on retirement. This large survey showed that from the patient’s perspective, morning stiffness reduces the ability to work in patients with RA and contributes to early retirement. The introduction of biological therapies may have had some positive effects on work participation in patients with rheumatoid arthritis (RA) –3, with Work disability in RA appears to be multifactorial . One facSome results favour the use of MS duration as an outcome measure  and someDifferent time frames , 26, metPrevious surveys of patients have demonstrated the impact that impaired morning function has on routine activities , 31, as We focussed on participants of working age who regularly experience morning stiffness. Because national registers of patients with varying durations or severities of morning stiffness do not exist, methods used to recruit participants varied by country, but mainly involved contacts provided by primary and secondary care physicians and patient associations or databases. Those with a diagnosis of RA for at least 6 months, who were aged between 18 years and the state retirement age for the country of residence, and usually experienced morning stiffness on at least 3 days a week were invited to complete the survey.After exploratory interviews with patients, a structured questionnaire was developed and translated into local languages for use in 11 European countries . The countries were selected to be from different parts of Europe and with varying health care systems. Trained interviewers conducted the survey by telephone, taking approximately 10 min to complete the questionnaire with each respondent.The questionnaire collected socio-demographic background information including age, sex and working status . Disease and morning stiffness characteristics were also collected: respondents recorded time since RA diagnosis , the typical severity of morning stiffness , the typical duration of morning stiffness before they are able to function normally (in hours and minutes) and the impact of RA-related morning stiffness on quality of life .A number of questions were asked to evaluate the impact, if any, of RA-related morning stiffness on working ability or household tasks. All participants were asked the level of agreement  that RA-related morning stiffness resulted in reduced ability to carry out tasks at work or home and also that morning stiffness limited the types of tasks at work or home they were able to carry out. Respondents who were working, wanted to work (i.e. unemployed) or studying were asked if RA-related morning stiffness had ever resulted in inability to work, need to reduce working hours, work flexible hours, work from home, change profession, slowed career progression or had none of these effects. Respondents who were currently working or attending a place of study were asked if RA-related morning stiffness adversely affected their work or study performance at any time in an average week, ever resulted in late arrival at work  or resulted in need for sick leave during the last month.The contribution, if any, of RA-related morning stiffness to withdrawal from the workforce was evaluated in questions to participants with working status given as retired or partially retired. These respondents were asked if they were not in full time paid work as a direct result of RA and if they took early retirement. Respondents who retired early were asked for factors that influenced their decision. Retired and partially retired respondents were also asked the level of agreement  that morning stiffness due to RA specifically lowered the age at which they retired and also that their career was shorter than they would have liked as a direct result of RA-related morning stiffness.The responses to questions were recorded for the total group and for subgroups defined by severity and by duration of morning stiffness. Typical severity of morning stiffness was categorised as mild (rating of 0–3), moderate (4–6) or severe (7–10). Typical duration before normal functioning due tomorning stiffness was categorised as <1, 1–2 or >2 h. Responses were also analysed by country of respondent.t tests. Linear regression models were fitted to test the effects of patient characteristics on duration and severity of morning stiffness, while having the effects of other characteristics simultaneously controlled.The response to questions recording the level of agreement to statements were dichotomised to agreement (score of 4 or 5) or no agreement (other scores). Statistical analyses of the data were based on chi-square tests and Fisher’s exact tests for proportions and Student’s p < 0.001).A total of 1,061 patients were interviewed, approximately 100 from each country included in the survey, with the exception of Norway (55 respondents). Demographic, disease and work status characteristics of the respondents are summarised in Table Rheumatoid arthritis-related morning stiffness reduced working ability, with the impact significantly increasing with severity and duration of morning stiffness Fig. . The proOnly 33 % of the 582 participants who worked or could be working reported no direct impact of RA-related morning stiffness on their work and career, ranging from 14 % in Norway to 55 % in Poland. Inability to work was reported by 29 % (ranging from 8 % in Spain to 48 % in Norway) and 28 % reported reducing the number of working hours because of RA-related morning stiffness (ranging from 12 % in Poland to 43 % in Norway). The impact appeared to increase with severity of the RA-related morning stiffness, though the relationship with duration of the symptom appeared less pronounced , most commonly because they are less able to perform daily tasks (57 %) and they take more time to do their work (57 %). Late arrival at work because of RA-related morning stiffness was reported by 33 % , most commonly because of taking longer to get ready (77 %), difficulties driving (19 %) and difficulties using public transport (16 %). A total of 15 % of respondents reported taking sick leave because of RA-related morning stiffness during the previous month . The impact of RA-related morning stiffness on work performance, late arrival at work and sick leave appeared to increase with severity, but not necessarily with duration of the symptom , but not with increasing severity .Rheumatoid arthritis-related morning stiffness influenced the decision to take early retirement from work. The majority (71 %) of the 224 retired/semi-retired respondents stopped working earlier than their expected retirement age (ranging from 48 % in Poland to 92 % in Germany). The proportion of respondents retiring early increased with increasing duration of morning stiffness  as the reason, with 26 % citing other health issues. RA-related morning stiffness lowered the retirement age for 56 % of retired respondents, and 52 % noted that their career was shorter than they would have liked because of RA-related morning stiffness.The results of this large pan-European survey highlight the adverse impact of morning stiffness on working life among patients with RA who experience this common symptom. The majority of working patients in this population reported that RA-related morning stiffness affected working ability. RA-related morning stiffness commonly resulted in reduced work performance, late arrival at work and sick leave from work. Among those no longer in paid employment, morning stiffness contributed to early retirement from work. Subgroup analysis suggests that severity and duration of morning stiffness have different effects on working lives of patients with RA. The negative influence of RA-related morning stiffness on overall performance was also demonstrated by the relationship between morning symptoms and quality of life.The survey found a direct impact of RA-related morning stiffness on working life in two-thirds of the patients included in the survey. This is similar to 74 % of respondents in paid employment in a previous survey reporting a significant impact of impaired morning function on their job . In anotThe findings of the survey suggest that RA-related morning stiffness, by adversely impacting performance when at work (presenteeism) and attendance at work (absenteeism), may contribute to the considerable societal costs of RA. Presenteeism has an economic cost that contributes to the cost of lost productivity arising from RA . The surThe analysis of subgroups defined by severity and duration of morning stiffness revealed subtle distinctions in the impact of RA-related morning stiffness on working life. With respect to current working life, there appeared to be a more pronounced association between severity of the symptom than duration. In contrast, early retirement in those no longer in work appeared to have a closer association with duration of morning stiffness than severity, though current symptoms may not reflect those at the time of retirement. There is likely to be some relationship between severity and duration of morning stiffness, as indicated by the increasing severity as duration increased and vice versa. A similar relationship has been noted previously in both a survey of patients and a database analysis , 31. BotOur findings corroborate earlier studies showing that apart from having an impact on work ability, morning stiffness seems to be related to overall quality of life , 31. DesA strength of this survey was the large size and the wide distribution of European countries involved. The numbers of patients per country were estimated to be sufficient for comparisons between countries. By asking the role of morning stiffness in perceived disadvantage in each aspect of working life , the attempt was to identify the independent role of morning stiffness and exclude possible confounding effects of other symptoms and other concomitant diseases. Findings for the impact of RA-related morning stiffness within subgroups of respondents defined by country showed marked differences. This variation may affect the impact of RA-related morning stiffness on productivity. The variation in RA-related burden of illness, quality of life and work disability between countries has been reviewed , 14. OurThe study has some limitations. In common with other patient surveys, interpretation of the descriptive findings may be affected by confounding factors. One potential confounder of interest is respondent age. However, the pattern of response across subgroups defined by age was different to that defined by severity and duration of morning stiffness, suggesting that the impact of morning stiffness may not be strongly dependent on age.Another limitation of the survey was the focus on a selected population of patients of working age who experienced regular morning stiffness. Given the specific interest in the impact of morning stiffness on working life, this was a pragmatic design decision. With the peak incidence for development of RA being 30–60 years of age  and the In conclusion, this large survey conducted in 11 European countries has shown that morning stiffness reduces ability to work and contributes to early retirement. Impairment appears to be affected by both severity and duration of morning stiffness. Morning stiffness seemed to be an important symptom of rheumatoid arthritis when considering the effects of the disease on various aspects of working life. Further studies on its independent role are needed.


In heart bypass surgery, pieces of artery or vein (“conduits”) taken from elsewhere in the patients’ body are used to bypass the blocked or narrowed coronary arteries and improve the blood supply to the heart. The “Hyperplasia and Atherogenesis in Bypass Vein Grafts Following Different Surgical Preparation Techniques” (HArVeST) trial, is a single-centre study investigating if new methods of taking and preparing the conduit can improve the outcome for patients.The study has a 2x2 factorial design: (a) the method of taking the vein (pedicle harvest (leg vein and surrounding fat) versus conventional harvest (surrounding fat stripped from vein)) and (b) method for checking the vein is not damaged (low versus high pressure test).The primary outcome is the patency of the vein graft(s) 12 months after surgery, i.e. thickness of the wall of the graft and size of the lumen, assessed using intravascular ultrasound (IVUS). Multiple measurements are taken as the IVUS machine moves along the graft. Baseline measurements are assessed from a histological analysis of vein harvested.Analyses of the co-primary outcomes, which are both continuous measures, are on-going. Mixed regression models with different correlation structures are being explored to account for correlation arising from: (a) multiple grafts and conduits from one patient, (b) grafts taken from the same conduit, and (c) the repeated measures nature of the IVUS measurements within a graft. Methodological considerations are multi-faceted; our aim is to make maximal use of the data within a hierarchical framework.This research is supported by a National Institute for Health Research (NIHR) Bristol Cardiovascular Biomedical Research Unit. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NIHR, NHS or the Department of Health.


To overcome the shortage of appropriate-sized whole liver grafts for children, technical variant liver transplantation has been practiced for decades. We perform a meta-analysis to compare the survival rates and incidence of surgical complications between pediatric whole liver transplantation and technical variant liver transplantation.To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. The primary outcomes measured were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. The outcomes were pooled using a fixed-effects model or random-effects model.p<0.05). There was no significant difference in five-year graft survival rate between the two groups . The incidence of portal vein thrombosis and biliary complications were significantly lower in the whole liver transplantation group . The incidence of hepatic artery thrombosis was comparable between the two groups .The one-year, three-year, five-year patient survival rates and one-year, three-year graft survival rates were significantly higher in whole liver transplantation than technical variant liver transplantation (OR = 1.62, 1.90, 1.65, 1.78, and 1.62, respectively, Pediatric whole liver transplantation is associated with better outcomes than technical variant liver transplantation. Continuing efforts should be made to minimize surgical complications to improve the outcomes of technical variant liver transplantation. By the 1980s, pediatric liver transplantation had become the standard treatment for infants or children suffering from life-threatening end-stage liver disease . More thNowadays, pediatric liver transplantation has become one of the most successful solid organ transplantations, with a five-year patient survival rate exceeding 70% –10, primBefore data collection, two liver transplantation groups were identified for comparison: WLT and TVLT. TVLT included three subgroups, namely RLT, SLT, and LLT. We also compared these individual subgroups to WLT.To identify relevant studies up to January 2014, we searched PubMed/Medline, Embase, and Cochrane library databases. In addition, reference lists were scanned to identify additional potentially relevant studies. The search strategy included the terms: pediatric or children or infant, liver transplantation, and technical variant grafts or reduced or split or living donor liver transplantation. We included trials with no language or year restrictions.This meta-analysis only included studies meeting the following criteria: (1) studies were conducted in pediatric patients; and (2) studies were aimed to compare patient and graft survival rates, and incidence of complications between WLT and TVLT. Studies were excluded when they met the following criteria: (1) studies reporting combined organ transplantation; and (2) case reports, conference abstracts, or journal editorials.For the trials included in our meta-analysis, we sought data for authors, journal and year of publication, number of patients, demographic information, patient and graft survival rates, and incidences of surgical complication. The primary outcomes of the current meta-analysis were patient and graft survival rates, and the secondary outcomes were the incidence of surgical complications. When the data were not shown in the article, we attempted to contact the authors to obtain original information. The data were extracted by two investigators (YW and YK) independently, and disagreements were resolved by intervention of a third author (ZG). The conduct and reporting were in accordance with the Quality of Reporting of Meta-Analyses statement.I2. We used an I2 value of 50% as the line that is between heterogeneity and homogeneity in our meta-analysis [p value of <0.05 indicates significant heterogeneity. When the result showed homogeneity, a fixed-effects model was used to estimate the pooled effect on outcomes. When results showed heterogeneity, we use a random-effects model.We used the statistical software Review Manager 5.1  to analyze the collected data. The primary outcomes and the secondary outcomes were analyzed as dichotomized variables, and their results were reported as pooled odds ratio (OR) with 95% confidence interval (CI). Cumulative meta-analyses of the primary and secondary outcomes between WLT and TVLT were also carried out, to assess the evolution of the outcomes in time. The heterogeneity of included trials was measured by heterogeneity index analysis . And a pGraphical funnel plots were generated so that we could make visual inspections for publication bias . The staWe screened 2273 citations, from which we identified 13 articles to assess patient/graft survival rate as well as incidence of surgical complications between WLT and TVLT. Details on the study selection process are presented in The 13 articles –31 were p < 0.05), with low heterogeneity     of one-year patient survival rates between the WLT and TVLT groups. The one-year patient survival rate was higher in recipients undergoing WLT versus TVLT  . Similar = 0.29) , as well = 0.24) .p < 0.05) . Similar results were documented between the WLT and RLT groups    . The het = 0.52) . However = 0.02) .p = 0.001; I2 = 37%, p = 0.15)    . The fiv = 0.13) , as well = 0.08) .p < 0.05; I2 = 30%, p = 0.17)    . Similar = 0.27) , as well = 0.19) .p = 0.04; I2 = 60%, p = 0.03)    . The thr = 0.21) . However= 0.006) .p = 0.10; I2 = 57%, p = 0.02)    , as well = 0.02) . However = 0.04) .p = 0.61; I2 = 69%, p = 0.002) (p < 0.05) (p < 0.05) . When we compared WLT and RLT, there were no significant differences in the incidence of the three complications  (p = 0.07) (p < 0.05) , portal venal thrombosis (PVT) and biliary complications (BC). The incidence of HAT was comparable between WLT and TVLT  . However < 0.05)  and BC ( < 0.05)  between  = 0.15) . The com = 0.07) , while P < 0.05)  Fig. TheWe conducted cumulative meta-analyses of patient survival rate, graft survival rate and complications between WLT and TVLT to evaluate any changes in the outcomes. A cumulative meta-analysis of one-year patient survival rate showed that since 2007 the statistically significant difference between the two groups appeared , while tp values of Begg’s test for one-year, three-year, five-year patient survival rates and one-year, three-year, five-year graft survival rate comparisons between WLT and TVLT were 1.00, 0.81, 0.76, 0.59, 1.00, and 0.54, respectively, meanwhile the Egger’s test showed p values of 0.49, 0.46, 0.96, 0.58, 0.52 and 0.60, respectively.The appearance of the funnel plot analysis was symmetrical , and theWe comprehensively reviewed the existing literature on comparison of survival rates and incidence of complications between pediatric WLT and TVLT. The one-year, three-year, and five-year patient survival rate, as well as one-year and three-year graft survival rate were significantly higher in the WLT group compared to the TVLT group. There was no significant difference in five-year graft survival rate between the two groups. When it comes to complications, the results suggested a lower incidence of PVT and BC in the WLT group. The incidence of HAT was comparable between the groups. In addition, our cumulative meta-analysis showed that the difference in one-year patient survival has been present since 2007 and the difference in one-year graft survival has been present since 1999. Collectively, these results show that WLT is associated with a better outcome when compared to TVLT.Pediatric and small-sized donor organs are a scarce resource, making it difficult to find adequate grafts for small-sized transplant candidates . Some ceImportantly, the comparisons between subgroups (RLT and SLT) of TVLT and WLT demonstrate that the survival difference mainly exists in the short-term outcomes. These results are in accordance with previous studies , 46. PriInterestingly, our cumulative meta-analyses show that the short-term (one-year) survival outcomes after transplantation presented a significant trend over years that the difference between WLT and TVLT is getting smaller and smaller chronologically. The three-year survival rates also showed a similar trend. Therefore, the outcome of TVLT is continuously improving and may eventually achieve similar outcomes to that of WLT in the near future. Notably, the cumulative meta-analysis of complications demonstrated that, since 2007, statistical differences in PVT and BC between WLT and TVLT appeared, favoring the WLT group. Although there is no statistically significant difference in HAT incidence between WLT and TVLT, transplantation surgeons should try their best to avoid the occurrence of HAT, since HAT is a common complication and among the major causes for graft loss . These rTo our knowledge, this meta-analysis is the first systematic study of all available data on the comparison between WLT and TVLT in pediatric patients. The 13 analyzed studies come from nine different countries. Therefore, the bias due to racial, diet, environmental, and etiological differences could be minimized. Overall, this study provides the most convincing results on the topic so far. However, undoubtedly, there are some limitations. First, there was no randomized study included, and all included studies were observational studies. Given the reality of organ allocation, surgeons rarely have the luxury of randomizing the graft type. Second, we did not compare the LLT to WLT because of lack of data. Although there were numerous published papers focusing on LLT, they usually made the comparison between living donors and deceased donors, rarely compared LLT to WLT. All these limitations provide room for future studies to provide more information for better choice of graft types.In conclusion, this study suggests that currently, the pediatric WLT procedure has better outcomes than TVLT procedures. The difference between WLT and TVLT mainly exists in the short-term outcomes. Physicians should weigh the risks and benefits of performing a timely TVLT or waiting for a better WLT. Importantly, continuing efforts should be made to minimize surgical complications to improve the outcomes of TVLT. Multicenter, prospective, match controlled studies may add more information to the findings of this study.S1 PRISMA Checklist(DOC)Click here for additional data file.S1 Fig(A) 1-year patient survival rate between WLT and RLT, (B) 1-year patient survival rate between WLT and SLT, (C) 3-year patient survival rate between WLT and RLT, (D) 3-year patient survival rate between WLT and SLT, (E) 5-year patient survival rate between WLT and RLT, and (F) 5-year patient survival rate between WLT and SLT.(TIF)Click here for additional data file.S2 Fig(A) 1-year graft survival rate between WLT and RLT, (B) 1-year graft survival rate between WLT and SLT, (C) 3-year graft survival rate between WLT and RLT, (D) 3-year graft survival rate between WLT and SLT, (E) 5-year graft survival rate between WLT and RLT, (F) 5-year graft survival rate between WLT and SLT.(TIF)Click here for additional data file.S3 FigThe incidence of hepatic artery thrombosis (HAT) (A), portal vein thrombosis (PVT) (B), and biliary complications (BC) (C) in WLT and RLT. The incidence of HAT (D), PVT (E), and BC (F) in WLT and SLT.(TIF)Click here for additional data file.S4 Fig(A) 3-year patient survival rate between WLT and TVLT, (B) 3-year graft survival rate between WLT and TVLT, (C) 5-year patient survival rate between WLT and TVLT, (D) 5-year graft survival rate between WLT and TVLT. PDF.(TIF)Click here for additional data file.S5 Fig(A) 1-year patient survival, (B) 3-year patient survival, and (C) 5-year patient survival between WLT and TVLT; (D) 1-year graft survival, (E) 3-year graft survival, and (F) 5-year graft survival between WLT and TVLT.(TIF)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.