Bullous Pemphigoid

Bullous pemphigoid (BP) is a chronic, acquired, autoimmune bullous disease characterized by subepidermal bullae. It is usually seen in the elderly but, rarely, may also be seen in children. Autoantibodies against hemidesmosomal proteins BP230 (BPAG1) and BP180 (BPAG2 or type XVII collagen) are blamed for the pathogenesis. Clinically, it is characterized by large, tense blisters. Blisters can occur on normal skin or erythematous base with a predilection of flexural aspects of the limbs, abdomen, groin and axillae. Mucous membrane involvement is seen in about 10–35% of the patients. For treatment, general maintenance of BP patients is the first step. Systemic steroids are the common treatment agents. But localized disease can be treated successfully with topical corticosteroids. The common immunosuppressive agents are azathioprine, mycophenolate mofetil, methotrexate, chlorambucil and less often cyclophosphamide. In a minority of resistant cases, intravenous immunoglobulins, plasma exchange, anti-CD20 immunotherapy (rituximab), leflunomide, chlorambucil and methotrexate may be effective

Effects of lead user method on product development performance and a case study

Etkili ve güçlü ürün geliştirme, müşteri ihtiyaçlarının doğru olarak analiz edilmesine bağlıdır.  Müşteriyi ürün geliştirme proseslerine dâhil eden firmalar, pazarda büyük bir rekabet avantajı elde edeceklerdir. Yeni ürün geliştirme proseslerine müşterinin daha sık dâhil edilmesi, yeni ürünlerin pazara çıkma hızı üzerinde olumlu etkiye sahiptir. Bu bağlamda, pazarların en önemli müşterileri olarak görülen lider kullanıcılar da yeni ürün kavramları ve dizaynları elde etme çalışmalarında, müşteri ihtiyaçlarını analiz etmede önemli ihtiyaç ve çözüm bilgisi sağlarlar. Müşteri ihtiyaçlarının artmasından ve hızlı değişiklik göstermesinden dolayı kilit müşterilerin ürün geliştirme proseslerine dahil edilmesi özellikle otomotiv sektöründe oldukça önemlidir. Bu çalışmada, yeni ürün fikirlerinin üretilmesi prosesine müşterinin dâhil edilmesi, lider kullanıcı kavramı ve metodu ele alınmıştır.  Lider kullanıcı metodunun temel uygulama adımları ve bu metodun kullanılmasındaki kritik başarı faktörlerine yer verilmiş ve ürün geliştirme performansı açıklanmıştır. Bu çalışma kapsamında, lider kullanıcıların ürün geliştirme prosesine dahil edilmesinin ürün geliştirme performansı üzerindeki etkilerini incelemek amacıyla otomotiv yan sanayinde faaliyet gösteren 51 firmayı kapsayan bir anket çalışması yapılmıştır. Elde edilen veriler SPSS 11.0 istatistik programı kullanılarak değerlendirilmiştir. Değerlendirme kapsamında; faktör analizi, güvenilirlik analizi, korelasyon ve regresyon analizi yapılmıştır. İstatistiksel analiz bulguları incelendiğinde, ürün geliştirme performansı ile lider kullanıcıların ürün geliştirme prosesinde yer alması değişkeni arasında anlamlı ve pozitif yönde bir ilişkinin olduğu tespit edilmiştir.  Anahtar Kelimeler: Lider kullanıcı metodu, ürün geliştirme performansı, faktör analizi, güvenilirlik analizi, korelasyon analizi, regresyon analizi.As a result of increasing competitive pressures together with continuously increasing costumers needs, decreasing production costs and product development times urge companies to adept a systematic product development process. As the product are designed and produced for the costumers, costumer views are vital for the design and it dictates a close collaboration with the costumers. In order to meet their increasing customers’ needs, today many companies are seeking the ways to reflect their costumers’ voices and requirements into their products and services. A product development process based on rapid, non-problematical and costumer voices will provide companies a market success through developed products and services. An effective new product development process depends on the definition of uneasy customer problems. In today’s competitive environment, companies are utilising different methods to define costumers’ needs and to develop products accordingly. Nowadays companies are incorporating the lead users having the abilities to see the general future trends of the market and getting important solutions to these future market needs. In this way, the companies both define the changing costumer needs and getting important competitive advantages by entering their products to the market in shorter times. In this study, firstly the importance of the inclusion of the costumers to the creation of new product development process is outlined, the lead user concept is defined, and the lead user method is explained and the importance of this method in product development studies is underlined. Secondly, the main application steps of the lead user method, namely definition of definition of lead users and lead user characteristics, creation of product concept with lead users and lead users’ product concept test are outlined in detail. Finally, the success factors in the application of this method are examined and the product development performance scales are explained. In the application stage of the work, a theoretical model explaining the effect of inclusion of the lead users into product development process was developed. As a result of continuously improvement of automotive technology and increase in customers’ expectations, the automotive sub-industry has to develop new product and improve the performance of the product they develop. Automotive sub-industry is one of the high value added industries in sustainable, social and economical development of a society and from this perspective it is highly important for Turkey. In this respect, a market survey with a questionnaire in automotive sub-industry was conducted in order to define the effects of lead users considered in the product development process performance independent variable on product development performance dependent variable in the theoretical model. According to the State Statistical Institute (DİE) and Small and Medium Industry Development Organisation (KOSGEB) criterion, 51 out of 210 small and medium sized companies active in automotive sub industry in and around Istanbul and Gebze were responded positively to our questionnaire. 27 of these responded companies were contacted with face-to-face method and 27 of the remaining companies were responded via e-mail.  The characteristics of these companies participated in the study are detailed in presented tables.  The information gathered from the field survey was analyses with SPSS 11.0 statistical analysis software. In the statistical analysis, it is determined that the dependent and independent variables in the factor analysis are ascertained in the related factors, the scales developed in the reliability analysis are rather reliable. The analysis also revealed that in the correlation analysis there is a meaningful and positive relationship between dependent and independent variables and with the help of simple linear regression analysis it was determined the variable of the inclusion of the lead users in the product development process affects the product development process in high meaningful level and positive manner. Under the light of the current study, the effects of the inclusion of the lead users in the product development process are interpreted from automotive sub-industries perspective. The comments made on this sectoral basis could be considered as a guideline for other companies and the researches. Keywords: Lead user method, product development performance, factor analysis, reliability analysis, correlation analysis, regression analysis

CD4(+) T cells of myasthenia gravis patients are characterized by ıncreased IL-21, IL-4, and IL-17A productions and higher presence of PD-1 and ICOS

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies predominantly against the acetylcholine receptor (AChR). Specific T cell subsets are required for long-term antibody responses, and cytokines secreted mainly from CD4(+) T cells regulate B cell antibody production. The aim of this study was to assess the differences in the cytokine expressions of CD4(+) T cells in MG patients with AChR antibodies (AChR-MG) and the effect of immunosuppressive (IS) therapy on cytokine activity and to test these findings also in MG patients without detectable antibodies (SN-MG). Clinically diagnosed AChR-MG and SN-MG patients were included. The AChR-MG patients were grouped as IS-positive and -negative and compared with age- and sex-matched healthy controls. Peripheral blood mononuclear cells were used for ex vivo intracellular cytokine production, and subsets of CD4(+) T cells and circulating follicular helper T (cTfh) cells were detected phenotypically by the expression of the chemokine and the costimulatory receptors. Thymocytes obtained from patients who had thymectomy were also analyzed. IL-21, IL-4, IL-10, and IL-17A productions in CD4(+) T cells were increased in AChR-MG compared to those in healthy controls. IS treatment enhanced IL-10 and reduced IFN-gamma production in AChR-MG patients compared to those in IS-negative patients. Increased IL-21 and IL-4 productions were also demonstrated in SN-MG patients. Among CD4(+) T cells, Th17 cells were increased in both disease subgroups. Treatment induced higher proportions of Th2 cells in AChR-MG patients. Both CXCR5(+) and CXCR5(-) CD4(+) T cells expressed higher programmed cell death protein 1 (PD-1) and inducible costimulatory (ICOS) in AChR-MG and SN-MG groups, mostly irrespective of the treatment. Based on chemokine receptors on CXCR5(+)PD-1(+) in CD4(+) T (cTfh) cells, in AChR-MG patients without treatment, the proportions of Tfh17 cells were higher than those in the treated group, whereas the Tfh1 cells were decreased compared with those in the controls. The relevance of CXCR5 and PD-1 in the pathogenesis of AChR-MG was also suggested by the increased presence of these molecules on mature CD4 single-positive thymocytes from the thymic samples. The study provides further evidence for the importance of IL-21, IL-17A, IL-4, and IL-10 in AChR-MG. Disease-related CD4(+)T cells are identified mainly as PD-1(+) or ICOS+ with or without CXCR5, resembling cTfh cells in the circulation or probably in the thymus. AChR-MG and SN-MG seem to have some similar characteristics. IS treatment has distinctive effects on cytokine expression.Istanbul Universit

Tedarikçi Değerlendirme Sürecinde Yapay Sinir Ağlarının Kullanımı ve Sektörel Bir Uygulama

Bu çalışmada, Seramik Sektöründe faaliyet gösteren tedarikçi firmaların, eş zamanlı mühendislik metodunu kullanım etkinliğine göre değerlendirilmesi sürecinde kullanmak üzere; üç katmanlı, ileri beslemeli, geriye yayılımlı bir Yapay Sinir Ağı modeli geliştirilerek, bu modelin, tedarikçi değerlendirme sürecinde kullanılabilirliği araştırılmıştır. Çalışma kapsamında oluşturulan araştırma modelinin bağımsız değişkenleri ağın giriş değişkenleri olarak, bağımlı değişkeni ise çıkış değişkeni olarak kullanılmıştır. Bu değişkenlerin değerleri faktör analizi yardımı ile belirlenmiştir. Analizde kullanılacak veri setinin temini için, ağın giriş ve çıkış değişkenlerini açıklayan otuz dört soruluk bir anket formu hazırlanarak, ilgili sektörde faaliyet gösteren 52 firmayı kapsayan anket çalışması gerçekleştirilmiştir. Ağın daha doğru sonuçlar vermesi için, analiz sonuçlarına göre faktör yükü 0.6'nın altında değere sahip sorular elenmiştir. Elenen soruların değerlendirme dışı bırakılması ile, 8 giriş değişkenini açıklayan 22 soruya verilen cevaplar ağın giriş değerlerinin belirlenmesinde, çıkış değişkenini açıklayan 3 soruya verilen cevaplar ağın çıkış değerinin belirlenmesinde kullanılmıştır. Ağın giriş ve çıkış değerlerine ilişkin veri seti, k-fold yöntemi ile 4 eşit gruba ayrılarak dört farklı alternatif ağ yapısı oluşturulmuştur. Sonuç olarak, en düşük hatayı veren ağın test simülasyonu sonucunda elde edilen tahmini firma puanları ile gerçek firma puanları birbirine çok yakın çıktığı için, geliştirilen Yapay Sinir Ağı modelinin, tedarikçi değerlendirme sürecinde kullanılabileceği sonucuna varılmıştır

Using an Artificial Neural Network Approach for Supplier Evaluation Process and a Sectoral Application

In this study, a-three layered feed-forward backpropagation Artificial Neural Network (ANN) model is developed for the supplier firms in ceramic sector on the bases of user effectiveness for using concurrent engineering method. The developed model is also questioned for its usability in the supplier evaluation process. The network's independent variables of the developed model are considered as input variables of the network and dependent variables are used as output variables. The values of these variables are determined with factor analysis. For obtaining the date set to be used in the analysis, a questionnaire form with 34 questions explaining the network's input and output variables are prepared and sent out to 52 firms active in related sector. For obtaining more accurate results from the network, the questions having factor load below 0,6 are eliminated from the analysis. With the elimination of the questions from the analysis, the answers given for 22 questions explaining 8 input variables are used for the evaluation the network's inputs, the answers given for 3 questions explaining output variables are used for the evaluation the network's outputs. The data set of the network's are divided into four equal groups with k-fold method in order to get four different alternative network structures. As a conclusion, the forecasted firm scores giving the minimum error from the network test simulation and real firm scores are found to be very close to each other, thus, it is concluded that the developed artificial neural network model can be used effectively in the supplier evaluation process