Designing channel incentives to overcome reseller rejection

As more and more products are distributed through independent channel resellers, suppliers find it increasingly difficult to craft highly motivational incentive packages. Instead, many suppliers' product lines are neglected by resellers in deference to more compatible incentive offers. This paper studies the many aspects of incentive rejection and incentive compatibility and prescribes a four-step, theory-based process to help suppliers craft attractive incentive programs. The process involves identifying resellers' performance needs, recognizing how each need suggests a different basis for incentive rejection, and designing an incentive package such that the incentives support specific reseller needs. Also, unique channel conditions are considered.

Impact of band rejection in multichannel broadband subcarrier multiplexing

This paper explores experimentally the impairments in performance that are generated when multiple single-sideband (SSB) subcarrier multiplexing (SCM) signals are closely allocated in frequency to establish a spectrally efficient wavelength division multiplexing (WDM) link. The performance of cost-effective SSB WDM/ SCM implementations, without optical filters in the transmitter, presents a strong dependency on the imperfect sideband suppression ratio that can be directly achieved with the electro-optical modulator. A direct detected broadband multichannel SCM link composed of a state-of-the-art optical IQ modulator and five quadrature phase-shift keyed (QPSK) subcarriers per optical channel is presented, showing that a suppression ratio of 20 dB obtained directly with the modulator produced a penalty of 2 dB in overall performance, due to interference between adjacent optical channels.

Low gravity rotational culture and the integration of immunomodulatory stem cells reduce human islet allo-reactivity

Modification of human islets prior to transplantation may improve long-term clinical outcome in terms of diabetes management, by supporting graft function and reducing the potential for allo-rejection. Intragraft incorporation of stem cells secreting beta (β)-cell trophic and immunomodulatory factors represents a credible approach, but requires suitable culture methods to facilitate islet alteration without compromising integrity. This study employed a three-dimensional rotational cell culture system (RCCS) to achieve modification, preserve function, and ultimately influence immune cell responsiveness to human islets. Islets underwent intentional dispersal and rotational culture-assisted aggregation with amniotic epithelial cells (AEC) exhibiting intrinsic immunomodulatory potential. Reassembled islet constructs were assessed for functional integrity, and their ability to induce an allo-response in discrete T-cell subsets determined using mixed islet:lymphocyte reaction assays. RCCS supported the formation of islet:AEC aggregates with improved insulin secretory capacity compared to unmodified islets. Further, the allo-response of peripheral blood mononuclear cell (PBMC) and purified CD4+ and CD8+ T-cell subsets to AEC-bearing grafts was significantly (p < 0.05) attenuated. Rotational culture enables pre-transplant islet modification involving their integration with immunomodulatory stem cells capable of subduing the allo-reactivity of T cells relevant to islet rejection. The approach may play a role in achieving acute and long-term graft survival in islet transplantation.

Changes at the BCLA

As we welcome 2014 we say goodbye to 2013 and I must start with an apology to authors who have submitted papers to CLAE and seen a delay in either the review process or the hard copy publication of their proofed article. The delays were caused by a major hike in the number of submissions to the journal in 2012 that increased further in 2013. In the 12 months leading to the end of October 2011 we had 94 new paper submissions, and for the same period to the end of 2012 the journal had 116 new papers. In 2012 we were awarded an impact factor for the first time and following that the next 12 month period to the end of October 2013 saw a massive increase in submissions with 171 new manuscripts being submitted. This is nearly twice as many papers as 2 years ago and 3 times as many as when I took over as Editor-in-Chief. In addition to this the UK academics will know that 2014 is a REF year (Research Excellence Framework) where universities are judged on their research and one of the major components of this measure remains to be published papers so there is a push to publishing before the REF deadline for counting. The rejection rate at CLAE has gone up too and currently is around 50% (more than double the rejection rate when I took over as Editor-in-Chief). At CLAE the number of pages that we publish each year has remained the same since 2007. When compiling issue 1 for 2014 I chose the papers to be included from the papers that were proofed and ready to go and there were around 200 proofed pages ready, which is enough to fill 3½ issues! At present Elsevier and the BCLA are preparing to increase the number the pages published per issue so that we can clear some of this backlog and remain up to date with the papers published in CLAE. I should add that on line publishing of papers is still available and there may have been review delays but there are no publishing online so authors can still get an epub on line final version of their paper with a DOI (digital object identifier) number enabling the paper to be cited. There are two awards that were made in 2013 that I would like to make special mention of. One was for my good friend Jan Bergmanson, who was awarded an honorary life fellowship of the College of Optometrists. Jan has served on the editorial board of CLAE for many years and in 2013 also celebrated 30 years of his annual ‘Texan Corneal and contact lens meeting’. The other award I wish to mention is Judith Morris, who was the BCLA Gold Medal Award winner in 2013. Judith has had many roles in her career and worked at Moorfields Eye Hospital, the Institute of Optometry and currently at City University. She has been the Europe Middle East and Africa President of IACLE (International Association of Contact Lens Educators) for many years and I think I am correct in saying that Judith is the only person who was President of both the BCLA (1983) and a few years later she was the President College of Optometrists (1989). Judith was also instrumental in introducing Vivien Freeman to the BCLA as they had been friends and Judith suggested that Vivien apply for an administrative job at the BCLA. Fast forward 29 years and in December 2013 Vivien stepped down as Secretary General of the BCLA. I would like to offer my own personal thanks to Vivien for her support of CLAE and of me over the years. The BCLA will not be the same and I wish you well in your future plans. But 2014 brings in a new position to the BCLA – Cheryl Donnelly has been given the new role of Chief Executive Officer. Cheryl was President of the BCLA in 2000 and has previously served on council. I look forward to working with Cheryl and envisage a bright future for the BCLA and CLAE. In this issue we have some great papers including some from authors who have not published with CLAE before. There is a nice paper on contact lens compliance in Nepal which brings home some familiar messages from an emerging market. A paper on how corneal curvature is affected by the use of hydrogel lenses is useful when advising patients how long they should leave their contact lenses out for to avoid seeing changes in refraction or curvature. This is useful information when refracting these patients or pre-laser surgery. There is a useful paper offering tips on fitting bitoric gas permeable lenses post corneal graft and a paper detailing surgery to implant piggyback multifocal intraocular lenses. One fact that I noted from the selection of papers in the current issue is where they were from. In this issue none of the corresponding authors are from the United Kingdom. There are two papers each from the United States, Spain and Iran, and one each from the Netherlands, Ireland, Republic of Korea, Australia and Hong Kong. This is an obvious reflection of the widening interest in CLAE and the BCLA and indicates the new research groups emerging in the field.

Estudo da resposta Th17 no transplante renal alogênico: contribuição do eixo quimiotático CCR6/CCL20 e dos polimorfismos gênicos em IL17A e IL17RA

Kidney transplantation is the best treatment for patients who have lost kidney function. Renal transplant patients require accurate immunosuppressive drugs to prevent rejection. In this process T helper cells of the immune system perform key role in the immune response to the graft, and recently the Th17 cells has been investigated by production of IL-17 potent proinflammatory cytokine whose role in the rejection has also been described. Increased of Th17 cell expression has an important association with the development of rejection in renal microenvironment, however the likely mechanism is not well understood. This study aimed to evaluate the Th17 response from the influence of the chemotactic axis CCR6/CCL20 and genetic variants in IL-17 and IL-17RA. We conducted a case-control study involving 148 patients transplanted at the University Hospital Onofre Lopes/UFRN in which assessed by immunohistochemistry protein expression of IL-17 and chemokines CCR6/CCL20 and by PCR-RFLP genetic variants in IL17A and IL17RA. Our results showed no influence of genetic polymorphisms on the outcome of the graft or the protein expression of IL-17. In renal graft microenvironment found several sources producing IL-17: tubular epithelial cells, glomerular cells, neutrophils and cell interstitial infiltration, in turn the expression of chemotactic axis CCR6/CCL20 was restricted to the tubular epithelium cells. There was a slight positive linear correlation between the presence of IL-17 and expression of chemotactic axis CCR6/CCL20 in the microenvironment of renal graft. Therefore, we believe that, combined with our results, further studies with increased "n" sample and greater control over the variables involved in obtaining the renal specimen, can determine more clearly the influence of chemotactic axis CCR6 / CCL20 and polymorphisms in cytokines related to Th17 profile on the control of this cell subtype response in rejection processes to renal allograft.

Nonlethal, Attenuated, Transfusion-Associated Graft-Versus-Host Disease in an Immunocompromised Child: Case Report and Review of the Literature

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of transfusion of nonirradiated blood components. It usually affects children in high-risk groups, including those who have primary immunodeficiencies (PIDs). It usually presents with skin, hepatic, digestive, and hematologic involvement and is normally fatal.

Heart Transplantation in Patients Older than 65 Years: Worthwhile or Wastage of Organs?

BACKGROUND: Patients older than 65 years have traditionally not been considered candidates for heart transplantation. However, recent studies have shown similar survival. We evaluated immediate and medium-term results in patients older than 65 years compared with younger patients. METHODS: From November 2003 to December 2013, 258 patients underwent transplantation. Children and patients with other organ transplantations were excluded from this study. Recipients were divided into two groups: 45 patients (18%) aged 65 years and older (Group A) and 203 patients (81%) younger than 65 years (Group B). RESULTS: Patients differed in age (67.0 ± 2.2 vs. 51.5 ± 9.7 years), but gender (male 77.8 vs. 77.3%; p = 0.949) was similar. Patients in Group A had more cardiovascular risk factors and ischemic cardiomyopathy (60 vs. 33.5%; p < 0.001). Donors to Group A were older (38.5 ± 11.3 vs. 34.0 ± 11.0 years; p = 0.014). Hospital mortality was 0 vs. 5.9% (p = 0.095) and 1- and 5-year survival were 88.8 ± 4.7 versus 86.8 ± 2.4% and 81.5 ± 5.9 versus 77.2 ± 3.2%, respectively. Mean follow-up was 3.8 ± 2.7 versus 4.5 ± 3.1 years. Incidence of cellular/humoral rejection was similar, but incidence of cardiac allograft vasculopathy was higher (15.6 vs. 7.4%; p = 0.081). Incidence of diabetes de novo was similar (p = 0.632), but older patients had more serious infections in the 1st year (p = 0.018). CONCLUSION: Heart transplantation in selected older patients can be performed with survival similar to younger patients, hence should not be restricted arbitrarily. Incidence of infections, graft vascular disease, and malignancies can be reduced with a more personalized approach to immunosuppression. Allocation of donors to these patients does not appear to reduce the possibility of transplanting younger patients.

Continuous acquisition of MHC:peptide complexes by recipient cells contributes to the generation of anti-graft CD8+T cell immunity

Understanding the evolution of the direct and indirect pathways of allorecognition following tissue transplantation is essential in the design of tolerance-promoting protocols. On the basis that donor bone marrow-derived antigen presenting cells are eliminated within days of transplantation, it has been argued that the indirect response represents the major threat to long term transplant survival, and is consequently the key target for regulation. However, the detection of MHC transfer between cells, and particularly the capture of MHC:peptide complexes by dendritic cells, led us to propose a third, semi-direct, pathway of MHC allorecognition. Persistence of this pathway would lead to sustained activation of direct pathway T cells, arguably persisting for the life of the transplant. In this study, we focused on the contribution of acquired MHC class I, on recipient DCs, during the life span of a skin graft. We observed that MHC class I acquisition by recipient DCs occurs for at least one month following transplantation and may be the main source of alloantigen that drives CD8+ cytotoxic T cell responses. In addition, acquired MHC class I-peptide complexes stimulate T cell responses in vivo further emphasizing the need to regulate both pathways to induce indefinite survival of the graft.

What Is Direct Allorecognition?

Direct allorecognition is the process by which donor-derived major histocompatibility complex (MHC)-peptide complexes, typically presented by donor-derived ‘passenger’ dendritic cells, are recognised directly by recipient T cells. In this review, we discuss the two principle theories which have been proposed to explain why individuals possess a high-precursor frequency of T cells with direct allospecificity and how self-restricted T cells recognise allogeneic MHCpeptide complexes. These theories, both of which are supported by functional and structural data, suggest that T cells recognising allogeneic MHC-peptide complexes focus either on the allopeptides bound to the allo-MHC molecules or the allo-MHC molecules themselves. We discuss how direct alloimmune responses may be sustained long term, the consequences of this for graft outcome and highlight novel strategies which are currently being investigated as a potential means of reducing rejection mediated through this pathway.

Prosthetic carotid bypass graft for in-stent restenosis performed for post-endarterectomy recurrent stenosis: technical details

Aim. Carotid artery stenting (CAS) is the treatment of choice for recurrent stenosis after carotid endarterectomy (CEA). However a significative incidence of in-stent restenosis could be occurred. Despite classical CEA leads to good results, in selective cases bypass graft may be the best treatment of in-stent restenosis. Case reports. We describe two cases of carotid bypass graft performed to treat a recurrent in-stent stenosis after CAS for post-CEA restenosis. No death and cardiac complication occurred and no cranial nerves impairment was detected. Conclusion. Prosthetic bypass graft is safe and effective in treatment of in-stent recurrent restenosis after CEA restenosis.