Feasibility study concerning the actual implementation of a joint cross-border procurement procedure by public buyers from different Member States

Joint procurement refers to a situation in which two or more contracting authorities conduct a procurement procedure together. The key characteristic of this specific procedure is that only one tender is published on behalf of all participating contracting authorities. The notion of joint procurement does not automatically imply any cross-border element as such. Joint cross-border procurement refers to the particular procurement procedure which involves contracting authorities from different Member States conducting a common tender by bundling their demands and acting jointly in the award of the contract. There have already been some attempts to conduct JCBPP procedures in the European Union, despite the fact that until the implementation of Directive 2014/24/EU there were no explicit legal provisions to facilitate such forms of cooperation. Therefore contracting authorities faced both legal and practical difficulties, mostly due to conflicts between national public procurement rules and barriers preventing recourse to other Member States’ central purchasing body or the joint cross-border award of public contracts. Currently existing literature still offers only a few contributions describing the use and impact of JCBPP and the limited practical experience there is in conducting such procedures has not been presented in an aggregated form so far. This analysis is intended to help identify the best solutions for implementing JCBPP projects and offers concrete recommendations which should serve as a guideline for all interested stakeholders. The aim of the study is not to assess theoretical scenarios of JCBPP between contracting authorities in different Member States or to offer a legal analysis of factors that can influence the implementation of such projects. Its scope is to practically analyse projects that have been implemented in the past months or years and to highlight how they have been conducted, the obstacles or difficulties experienced by the participating contracting authorities and how they managed to overcome them. Centralised – and therefore “joint” – purchasing techniques are successfully used in most Member States and the idea of exploring a cross-border dimension is generating more and more interest as it facilitates cooperation between contracting authorities across Europe and at the same time enhances the benefits of the Internal Market by creating better business opportunities for economic operators. Thus, this feasibility study on the possible implementation of a JCBPP procedure consists of an analysis of relevant JCPPP projects, including a cost benefit analysis, and draws conclusions based on the main issues which need to be considered when conducting a JCBPP. The results of the feasibility study have allowed the drafting of recommendations for the implementation of JCBPP procedures. The feasibility study focuses on the legal, administrative and procedural aspects encountered in four selected JCBPP projects, taking into consideration country and sector-specific characteristics relevant to the implementation of such procedures

Presence of celiac disease epitopes in modern and old hexaploid wheat varieties: wheat breeding may have contributed to increased prevalence of celiac disease

Gluten proteins from wheat can induce celiac disease (CD) in genetically susceptible individuals. Specific gluten peptides can be presented by antigen presenting cells to gluten-sensitive T-cell lymphocytes leading to CD. During the last decades, a significant increase has been observed in the prevalence of CD. This may partly be attributed to an increase in awareness and to improved diagnostic techniques, but increased wheat and gluten consumption is also considered a major cause. To analyze whether wheat breeding contributed to the increase of the prevalence of CD, we have compared the genetic diversity of gluten proteins for the presence of two CD epitopes (Glia-α9 and Glia-α20) in 36 modern European wheat varieties and in 50 landraces representing the wheat varieties grown up to around a century ago. Glia-α9 is a major (immunodominant) epitope that is recognized by the majority of CD patients. The minor Glia-α20 was included as a technical reference. Overall, the presence of the Glia-α9 epitope was higher in the modern varieties, whereas the presence of the Glia-α20 epitope was lower, as compared to the landraces. This suggests that modern wheat breeding practices may have led to an increased exposure to CD epitopes. On the other hand, some modern varieties and landraces have been identified that have relatively low contents of both epitopes. Such selected lines may serve as a start to breed wheat for the introduction of ‘low CD toxic’ as a new breeding trait. Large-scale culture and consumption of such varieties would considerably aid in decreasing the prevalence of CD

A Universal Approach to Eliminate Antigenic Properties of Alpha-Gliadin Peptides in Celiac Disease

Celiac disease is caused by an uncontrolled immune response to gluten, a heterogeneous mixture of wheat storage proteins, including the α-gliadins. It has been shown that α-gliadins harbor several major epitopes involved in the disease pathogenesis. A major step towards elimination of gluten toxicity for celiac disease patients would thus be the elimination of such epitopes from α-gliadins. We have analyzed over 3,000 expressed α-gliadin sequences from 11 bread wheat cultivars to determine whether they encode for peptides potentially involved in celiac disease. All identified epitope variants were synthesized as peptides and tested for binding to the disease-associated HLA-DQ2 and HLA-DQ8 molecules and for recognition by patient-derived α-gliadin specific T cell clones. Several specific naturally occurring amino acid substitutions were identified for each of the α-gliadin derived peptides involved in celiac disease that eliminate the antigenic properties of the epitope variants. Finally, we provide proof of principle at the peptide level that through the systematic introduction of such naturally occurring variations α-gliadins genes can be generated that no longer encode antigenic peptides. This forms a crucial step in the development of strategies to modify gluten genes in wheat so that it becomes safe for celiac disease patients. It also provides the information to design and introduce safe gluten genes in other cereals, which would exhibit improved quality while remaining safe for consumption by celiac disease patients

Identification of Rothia Bacteria as Gluten-Degrading Natural Colonizers of the Upper Gastro-Intestinal Tract

Gluten proteins, prominent constituents of barley, wheat and rye, cause celiac disease in genetically predisposed subjects. Gluten is notoriously difficult to digest by mammalian proteolytic enzymes and the protease-resistant domains contain multiple immunogenic epitopes. The aim of this study was to identify novel sources of gluten-digesting microbial enzymes from the upper gastro-intestinal tract with the potential to neutralize gluten epitopes.Oral microorganisms with gluten-degrading capacity were obtained by a selective plating strategy using gluten agar. Microbial speciations were carried out by 16S rDNA gene sequencing. Enzyme activities were assessed using gliadin-derived enzymatic substrates, gliadins in solution, gliadin zymography, and 33-mer α-gliadin and 26-mer γ-gliadin immunogenic peptides. Fragments of the gliadin peptides were separated by RP-HPLC and structurally characterized by mass spectrometry. Strains with high activity towards gluten were typed as Rothia mucilaginosa and Rothia aeria. Gliadins (250 µg/ml) added to Rothia cell suspensions (OD(620) 1.2) were degraded by 50% after ∼30 min of incubation. Importantly, the 33-mer and 26-mer immunogenic peptides were also cleaved, primarily C-terminal to Xaa-Pro-Gln (XPQ) and Xaa-Pro-Tyr (XPY). The major gliadin-degrading enzymes produced by the Rothia strains were ∼70-75 kDa in size, and the enzyme expressed by Rothia aeria was active over a wide pH range (pH 3-10).While the human digestive enzyme system lacks the capacity to cleave immunogenic gluten, such activities are naturally present in the oral microbial enzyme repertoire. The identified bacteria may be exploited for physiologic degradation of harmful gluten peptides

Clinical practice: Coeliac disease

Coeliac disease (CD) is an immune-mediated systemic condition elicited by gluten and related prolamines in genetically predisposed individuals and characterised by gluten-induced symptoms and signs, specific antibodies, a specific human leukocyte antigen (HLA) type and enteropathy. The risk of coeliac disease is increased in first-degree relatives, certain syndromes including Down syndrome and autoimmune disorders. It is thought to occur in 1 in 100–200 individuals, but still only one in four cases is diagnosed. Small-bowel biopsy is no longer deemed necessary in a subgroup of patients, i.e. when all of the following are present: typical symptoms or signs, high titres of and transglutaminase antibodies, endomysial antibodies, and HLA-type DQ2 or DQ8. In all other cases, small-bowel biopsy remains mandatory for a correct diagnosis. Therapy consists of a strictly gluten-free diet. This should result in complete disappearance of symptoms and of serological markers. Adequate follow-up is considered essential. Conclusion: Although small-bowel biopsy may be omitted in a minority of patients, small-bowel biopsy is essential for a correct diagnosis of CD in all other cases. Diagnostic work-up should be completed before treatment with gluten-free diet instituted

Parallels between Pathogens and Gluten Peptides in Celiac Sprue

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell–mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights

Diagnostic value of hybrid FDG-PET/MR imaging of chronic osteomyelitis

Background Magnetic resonance imaging (MRI) and 2-[F-18]-fluoro-2-deoxy-d-glucose (F-18-FDG) Positron Emission Tomography, paired with Computed Tomography (PET/CT) are commonly used modalities in the complicated diagnostic work-up of osteomyelitis. PET/MRI is a relatively novel hybrid modality with suggested applications in bone infection imaging, based on expert opinion and previous qualitative research. F-18-FDG PET/MRI has the advantages of reduced radiation dose, more soft tissue information, and is deemed more valuable for surgical planning compared to F-18-FDG PET/CT. The goal of this study is to quantitatively assess the diagnostic value of hybrid F-18-FDG PET/MRI for chronic osteomyelitis. Methods A retrospective analysis was performed by a nuclear medicine physician and radiologist on 36 patients with F-18-FDG PET/MRI scans for suspected osteomyelitis. Sensitivity, specificity, and accuracy were determined with the clinical assessment by the orthopaedic surgeon (based on subsequent intraoperative microbiology or long-term follow-up) as the ground truth. Standardized uptake values (SUV) were measured and analysed by means of receiver operating characteristics (ROC). Results This first study to quantitatively report the diagnostic value of F-18-FDG PET/MRI yielded a sensitivity, specificity, and accuracy of 78%, 100%, and 86% respectively. Area under the ROC curve was .736, .755, and .769 for the SUVmax, target to background ratio, and SUVmax_ratio respectively. These results are in the same range and not statistically different compared to diagnostic value for F-18-FDG PET/CT imaging of osteomyelitis in literature. Conclusions Based on the aforementioned advantages of F-18-FDG PET/MRI and the diagnostic value reported here, the authors propose F-18-FDG PET/MRI as an alternative to F-18-FDG PET/CT in osteomyelitis diagnosis, if available

Diagnostic value of hybrid FDG-PET/MR imaging of chronic osteomyelitis

Background Magnetic resonance imaging (MRI) and 2-[F-18]-fluoro-2-deoxy-d-glucose (F-18-FDG) Positron Emission Tomography, paired with Computed Tomography (PET/CT) are commonly used modalities in the complicated diagnostic work-up of osteomyelitis. PET/MRI is a relatively novel hybrid modality with suggested applications in bone infection imaging, based on expert opinion and previous qualitative research. F-18-FDG PET/MRI has the advantages of reduced radiation dose, more soft tissue information, and is deemed more valuable for surgical planning compared to F-18-FDG PET/CT. The goal of this study is to quantitatively assess the diagnostic value of hybrid F-18-FDG PET/MRI for chronic osteomyelitis. Methods A retrospective analysis was performed by a nuclear medicine physician and radiologist on 36 patients with F-18-FDG PET/MRI scans for suspected osteomyelitis. Sensitivity, specificity, and accuracy were determined with the clinical assessment by the orthopaedic surgeon (based on subsequent intraoperative microbiology or long-term follow-up) as the ground truth. Standardized uptake values (SUV) were measured and analysed by means of receiver operating characteristics (ROC). Results This first study to quantitatively report the diagnostic value of F-18-FDG PET/MRI yielded a sensitivity, specificity, and accuracy of 78%, 100%, and 86% respectively. Area under the ROC curve was .736, .755, and .769 for the SUVmax, target to background ratio, and SUVmax_ratio respectively. These results are in the same range and not statistically different compared to diagnostic value for F-18-FDG PET/CT imaging of osteomyelitis in literature. Conclusions Based on the aforementioned advantages of F-18-FDG PET/MRI and the diagnostic value reported here, the authors propose F-18-FDG PET/MRI as an alternative to F-18-FDG PET/CT in osteomyelitis diagnosis, if available

Hybrid FDG-PET/MR imaging of chronic osteomyelitis: a prospective case series

BackgroundMagnetic resonance imaging (MRI) and 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography paired with computed tomography (PET/CT) are two commonly used imaging modalities in the complicated diagnostic workup of osteomyelitis. Diagnosis using these modalities relies on, respectively, anatomical (MRI) and metabolic (PET) signs. With hybrid PET/MRI being recently available, our goal is to qualitatively compare hybrid FDG PET/MRI to FDG PET/CT in the diagnosis and operative planning of chronic osteomyelitis.MethodsFive patients with suspected chronic osteomyelitis in an extremity underwent an F-18-FDG single-injection/dual-imaging protocol with hybrid PET/CT and hybrid PET/MR. Images and clinical features were evaluated using a standardized assessment method. Standardized uptake value (SUV) measurements were performed on all images. Concordant and discordant findings between PET/MRI and PET/CT were analysed.ResultsThe consensus diagnoses based on PET/MRI and PET/CT images were identical for all five patients. One discrepancy between PET/MRI and PET/CT was found in the assessment of the features in one patient. PET signal intensities and target-to-background ratios were on average highest for PET/MRI. On PET/MRI, the location of infection based on FDG uptake could clearly be correlated with certain soft tissue structures (oedema, fluid collection, or muscle), which is paramount for surgical planning.ConclusionsIn the presented cases, FDG PET/MRI led to the same diagnosis and provided at least the same diagnostic information as PET/CT. PET/MRI was able to provide additional soft-tissue information for the physician planning treatment. Because of this, we suggest that PET/MRI could be used for osteomyelitis diagnosis and treatment planning