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Defects that occur in software products are a universal occurrence. Software defect prediction is usually carried out to determine the performance, accuracy, precision and performance of the prediction model or method used in research, using various kinds of datasets. Software defect prediction is one of the Software Engineering studies that is of great concern to researchers. This research was conducted to determine the performance of tree-based classification algorithms including Decision Trees, Random Forests and Deep Forests without using feature selection and using firefly feature selection. And also know the tree-based classification algorithm with firefly feature selection which can provide better software defect prediction performance. The dataset used in this study is the ReLink dataset which consists of Apache, Safe and Zxing. Then the data is divided into testing data and training data with 10-fold cross validation. Then feature selection is performed using the Firefly Algorithm. Each ReLink dataset will be processed by each tree-based classification algorithm, namely Decision Tree, Random Forest and Deep Forest according to the results of the firefly feature selection. Performance evaluation uses the AUC value (Area under the ROC Curve). Research was conducted using google collab and the average AUC value generated by Firefly-Decision Tree is 0.66, the average AUC value generated by Firefly-Random Forest is 0.77, and the average AUC value generated by Firefly-Deep Forest is 0, 76. The results of this study indicate that the approach using the Firefly algorithm with Random Forest classification can work better in predicting software damage compared to other tree-based algorithms. In previous studies, tree-based classification with hyperparameter tuning on software defect prediction datasets obtained quite good results. In another study, the classification performance of SVM, Naïve Bayes and K-nearest neighbor with firefly feature selection resulted in improved performance. Therefore, this research was conducted to determine the performance of a tree-based algorithm using the firefly selection feature.

Business competition has given birth to a network marketing system or what is commonly referred to as Network Marketing. The utilization used in Network Marketing, or what we currently know as MLM (Multi-Level Marketing), uses a network system where interpersonal communication is required both between MLM members and communication between members, customers, and prospective consultants. The interpersonal communication of consultants determines MLM business. How do they apply persuasive communication to persuade consumers or other consultants to join their network? This research uses a case study method. The results illustrate three important things young mothers do when running an MLM business to build the household economy. First, a trustworthy communicator will build credibility. Second, I need to understand how to convey messages in the MLM trading system; third, I need to choose communication channels that follow the objectives.

Type II mucopolysaccharidoses is an X-linked autosomal recessive disease, causing glycosaminoglycan accumulation, leading to repeated surgeries. Airway substrate deposits present a challenge for anesthesiologists. This case series describes airway characteristics and management in pediatric Hunter syndrome. Seven pediatric Hunter syndrome cases undergoing general anesthesia were studied. Preanesthetic assessment revealed obstructive sleep apnea and potential airway difficulties, including limited mouth openings, macroglossia, tonsiloadenoid hypertrophy, and restricted neck mobility. Visualizing the larynx was challenging during surgery, with hypersecretions, narrowed hypopharynx, and thickened vocal cords. Anesthesia plans incorporated sleep non-apnea as the preferred option, considering muscle relaxants if ventilation could be achieved with jaw thrust. Airway management strategies included using laryngeal mask airway (LMA) for difficult mask ventilation, employing C-MAC video laryngoscopy and bougie for first-pass intubation in two cases, and performing fiberoptic bronchoscopy through LMA with bougie-assisted endotracheal intubation in one case. Experienced anesthesiologists should prepare thoroughly for airway management in pediatric Hunter syndrome patients.

Informasi mengenai seks masih dianggap negatif dan tabu oleh masyarakat Indonesia, salah satu faktor yang dapat mempengaruhi perilaku seksual adalah sumber informasi yang masyarakat dapatkan dari media sosial mengenai pendidikan seksual. Instagram @tabu.id hadir sebagai salah satu sumber informasi dan forum diskusi untuk remaja terkait hak-hak kesehatan seksual dan reproduksi, serta membahas isu-isu penting yang masih dianggap tabu untuk dibicarakan dan kerap kali membuat remaja masih kurang tepat dalam mengambil keputusan. Penelitian ini bertujuan pada seberapa besar pengaruh konten pesan “sex education” instagram @tabu.id terhadap kepuasan followers yang juga merupakan pengguna media sosial. Peneliti menggunakan teori uses and gratifications, teori ini menjelaskan bahwa masyarakat aktif dan mampu mempelajari atau mengevaluasi berbagai jenis media dengan melihat bagaimana pengguna dalam memilih media yang paling dapat dipercaya memenuhi kebutuhannya dan sejauh mana pengguna puas dengan apa yang disajikan media tersebut. Penelitian ini menggunakan pendekatan kuantitatif. Metode yang digunakan dalam penelitian ini adalah metode survei. Populasi dari penelitian ini adalah pengikut instagram @tabu.id dengan jumlah sampel yang didapatkan sebanyak 100 responden. Hasil penelitian menunjukkan adanya bahwa pengaruh konten pesan “sex education” instagram @tabu.id terhadap kepuasan followers adalah sebesar 52,7% dan sisanya dipengaruhi oleh faktor lain. Kesimpulan dari penelitian ini bahwa terdapat pengaruh yang kuat antara konten pesan Instagram terhadap kepuasan followers sebagai penggunaan media. Peneliti berharap penelitian selanjutnya dapat menggali lebih dalam terkait faktor-faktor lain yang mampu mempengaruhi audiens dalam mendapatkan kepuasan penggunaan media.

Youth participation in socio-political issues in this modern time is gradually rising, and the effects of it on nation-building are well observed, especially when it comes to change and progress. The main objectives of this study are to identify the instances where the students participate, to determine how students get involved, to understand the driving force of youth participating, to understand the experience/s of the students, and to determine possible causes why youth do not participate in national and local socio-political issues. Through the use of key informant interviews and focused group discussions, the researchers found that participants have engaged and participated in different socio-political issues on a national or local scale, such as civic engagement, volunteerism, policy-making, joining the labor sector, safeguarding and preserving national sovereignty, information drive to combat cultural discrimination and misinformation, and such. It was also discovered that a preference for social media and conventional methods were used by participants in their participation, depending on their target audience and the specific area where they would take part. Furthermore, it was unveiled that disinterest in youth, lack of encouragement coming from the community leaders, and lack of ways to empower youth due to lack of platforms are reasons youth do not participate in socio-political activities. Lastly, this study found that participants are eager to participate to obtain self-awareness and knowledge. And the support from the government and different institutions is needed in order to increase the awareness of the youth when it comes to socio-political issues.

The aim of the research was to study the effects of biological seed treatment utilization rhizobacteria on seed germination and seedling growth, furthermore to figure out the competence of rhizobacteria isolates to dissolve phosphate, produce acetic indol acid (IAA) and siderophore. 18 rhizobacteria isolates used in this research, each isolates was anlayze in vitro; IAA, phosphate and siderophore. Then carried out the in vitro test, the pepper seeds were inoculated with rhizobacteria isolates suspension then germinated. Seedlings were transpalated into a plastic pot filled with medium soil and compost (2:1). The germination was observed everyday until 14 days, the seedlings was observed at 4 and 6 weeks after transplating. Based on the study, all the rhizobacteria isolates produced IAA, 13 rhizobacteria isolates capable to dissolve phosphate and 12 rhizobacteria isolates produced siderophore. Seed treatment using RBNA 14, RBNA 13, RBKB 5, and RBSPA 14 adequate to increase the germination in seed viability and vigor also increase seedling growth

Human life today is closely related to the use of plastic. Plastics are used in a variety of activities and for various purposes. Besides the convenience and perceived benefits, excessive use of plastic can also harm the environment. It is a common problem because of the excessive and continuously increasing use of plastic and the need for public awareness of their responsibility towards waste. This study aims to determine the effect of the #WasteDownBeautyUp message on Instagram on the environmental awareness of Sociolla's Instagram followers using the Nowak and Warneryd campaign models. The method used in this research is quantitative. Researchers used the survey method to distribute questionnaires to 100 respondents, namely followers of the Instagram account @sociolla, with a purposive sampling technique. The results showed that the t-count value was 3.637 > t-table 1.984 and the sig value 0.000 < 0.05, which means that Ho is rejected and Ha is accepted. The results show the effect of the #WasteDownBeautyUp campaign message on Instagram on environmental awareness among followers of Sociolla's Instagram.

Mental health among young people needs attention; even more these days, the search for information related to mental health has risen sharply on social media. This study aims to evaluate the role of motives for media use and the use of Instagram @iamokay.id to fulfill the need for mental health information. The study used a survey method by distributing questionnaires to 100 respondents who were Instagram social media followers @iamokay.id. The theory underlying the research is the Theory of Uses and Gratification. This study uses a research model that places media use as a mediating variable of the relationship between motives and fulfilling information needs. In contrast, the previous literature placed media use as the independent variable. The findings show the direct influence of the motives for media use and the use of Instagram @iamokay.id on fulfilling the need for health information. In addition, using Instagram @iamokay.id mediates the relationship between the motives for media use and the fulfillment of mental health information needs. Instagram can be an alternative source of information for the general public to eliminate mental health among young people.

Black betel leaf from East Kalimantan contains various secondary metabolites such as alkaloid saponins, flavonoids, and tannins. A compound, piperenamide A, which has antimicrobial activity, is also found in black betel leaf. This study aims to identify and authenticate the compound piperenamide A found in black betel leaf extract in other types of betel plant using HPLC and FTIR-chemometrics. The extraction method used was maceration with 70% ethanol solvent. Determination of piperenamide A content in black betel leaf extract was via HPLC column C18, with a maximum wavelength of 259 nm and a mobile phase of water:acetonitrile at a flow rate of 1 mL/minute. From the results, piperenamide A was only found in black betel (Piper acre) and not in Piper betel and Piper crocatum. Piperenamide A levels obtained were 4.03, 6.84, 5.35, 13.85, and 2.15%, respectively, in the samples studied. The combination of FTIR spectra with chemometric methods such as PCA and PLS-DA was used to distinguish the three types of betel. Discriminant analysis can classify black betel (Piper acre), Piper betel, and Piper crocatum according to its type. These methods can be used for identification and authentication of black betel.

Rhizobacteria play a positive role as biocontrol agents as well as Plant Growth Promoting Rhizobacteria (PGPR) agents. The research objective was to obtain indigenous rhizobacteria isolates on cocoa plants that have the potential to inhibit the attack of P. palmivora fungal pathogens, and act as PGPR in vitro and in vivo. The results of the study concluded that isolates TRI 7/1, TRI 8/8, GM 7/9 and GM 7/10 had the highest ability to inhibit the growth of pathogen. The lowest disease severity (20%) was obtained in the seedlings treated using isolates TRI 7/1 and TRI 8/8. Rhizobacterial isolates GM 3/6, GM 5/6, GM 7/9 and GM 8/8 produce high amounts of IAA. Rhizobacteria isolates GM 5/6, GM 7/9 and GM 8/8 has very high peroxidase enzyme activity. High production of HCN compounds was obtained in rhizobacteria isolates TRI 3/3, TRI 4/10 and TRI GM 8/11. All rhizobacterial isolates gave an increase in the value of maximum growth potential, germination and vigor values for growth strength compared with the control. The rizobacteria treatments using isolates TRI 7/1, TRI 8/8, GM 7/9 and GM 7/10 were able to increase plant height, stem diameter and number of leaves at 30, 40, 50, 60, and 70 DAP compared to control treatment.

Abstract Background Endophytic bacteria are an association between bacteria and plant tissue that could play a role as a biocontrol agent. Main body Endophytic bacteria were isolated from several high root plants in Aceh, Indonesia. This study aimed to detect the chemical compounds of the potential endophytic bacteria as a biocontrol agent against Fusarium oxysporum f. sp. lycopersici (FOL). There were 198 endophytic bacterial isolates detected in roots of 9 higher plant. The hypersensitive reaction showed that 193 isolated endophytic bacteria were non-pathogenic. There were 13 isolated endophytic bacteria that worked to inhibit FOL between 50.0 and 89.2%; such endophytic bacteria were isolated from Solanum lycopersicum L., Psidium guajava L., Dendrocalamus asper (Schult with f.) Backer ex Heyne, Pinus merkusii L., Theobroma cacao L., and Albizia chinensis L. Molecular identification using 16S rRNA gene sequence confirmed that the endophytic bacteria were derived from species Pseudomonas aeruginosa, P. mosselii, Arthrobacter sp., Bacillus cereus, B. thuringiensis, and Serratia marcescens. P. aeruginosa that showed the highest inhibition was analyzed using GC-MS analysis. The analysis identified that antibiotics as Pyrrolo [1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl)- was produced by P. aeruginosa succeeded in suppressing FOL. Conclusion The study recommends the species P. aeruginosa, as effective endophytic bacteria for the control of FOL pathogen.

PHBS SOCIALIZATION USING COMMUNICATION MEDIA AMONG STUDENTS OF MADRASAH IBTIDAIYAH MATHLA'UL ANWAR OF CILAJIM, CIPENDEUY VILLAGE, LEBAK. One of Indonesian Government effort to increase community health status is through PHBS (Perilaku Hidup Bersih dan Sehat) campaign. RISKESDAS 2013 data showed only 34,2% of Household in Banten practicing PHBS. There are five campaign group target, one of them are school community. We choose student of madrasah ibtidaiyah Matla’ul Andwar Cilajim desa Cipendeuy as responden because from previous observation there were a lot of student that didn’t practice PHBS, in this case washing hands with soap. Method. Audio visual using video and sing with song that created by the team and practicing washing hands with soap. Conclucion. All of the first year students (30) practicing the song and washing hands with soap and end with test.

First-line treatment of centrally involved diabetic macular oedema (CI-DMO) is often with an anti-vascular endothelial growth factor (anti-VEGF) agent. Although this can provide efficacy in the majority of eyes, a sizeable proportion do not respond sufficiently and many continue to receive anti-VEGF therapy after it may be optimal. This imposes a treatment burden on both patients and clinicians and, most importantly of all, can be sight threatening. Changing treatment to an intravitreal corticosteroid implant at the appropriate time may help optimise patient outcomes and reduce injection frequency, thereby reducing treatment burden.Eight retina specialists convened to discuss how to ensure eyes with CI-DMO receiving intravitreal anti-VEGF therapy are evaluated for a potential change to intravitreal corticosteroid therapy at the most effective time in their treatment journey. They concluded that clear criteria on when to consider changing treatment would be helpful and so developed a consensus guideline covering key decision points such as when and how to assess response to anti-VEGF therapy, when to consider a change to corticosteroid therapy and when and how to assess the response to corticosteroid therapy.The guideline was developed before the COVID-19 pandemic but, with the additional challenges arising from this including even greater pressure on clinic capacity, it is more important than ever to reconsider current working practices and adopt changes to improve patient care while also easing pressure on clinic capacity, reducing hospital visits and maintaining patient safety. This publication therefore also includes suggestions for adapting the guidelines in the COVID-19 era.

Molleculler study was conducted to identify several species of Trichoderma isolate from several plant (Pine, Cacao, Gliceria, Nutmeg, Bamboo, Coffee, Potato). The growth of eight species Trichodermaafter pelleting formulation has been observed. Pellet Trichoderma harzianum have good ability to growth on PDA medium after 4 weeks storage. Base on their mycelium diameter growth on PDA, T. harzianum have selected as potential species on pellet formulation growth. Several dose of pellet formulation have been applied for controlling Phythopthora disease. The application of T. harzianum pellets in the form of a 2 g / 100 ml (S1) suspension effective in inhibiting the development of Phytophthora sp in cacao seedlings, when the higher concentrations of T. harzianum pellets applied to cacao seeds,the disease severity increase. Pellet Trichoderma could be use as biological control agent of cacao seedling in certain dosage.

Ficus variegata Blume is specific plant of east Kalimantan. Flavonoid compound of Ficus variegata Blume was isolated by vacuum liquid and column chromatography, with previously extracted by maceration method using n-hexane and methanol, and fractination using ethyl acetate solvent. Eluent used in isolation were n-hexane:ethyl acetate (8:2). The results of elucidation structure by using spectroscopy methods (GC-MS, NMR, and FTIR) was obtained 5-Hidroxy-2-(4-methoxy-phenyl)-8,8-dymethyl-8H-pyrano[2,3-f] chromen-4-one. This compound has an antibacterial and antioxidant activities.

This research has aims to describe and analyze society development participation in Namo Bintang Village, Pancur Batu District and to know how development in Namo Bintang Village to empower communities. This research belongs to qualitative research aiming to describe in detail and deeply about society participation in rural development. The instruments for collecting data are observation sheet and interview as the qualitative data and using the document. The village of Namo Bintang has an area of 495.2 hectares, The area of Namo Bintang is in the form of swamps and fields and abandoned cultivation. The livelihoods of the villagers of Namo Bintang are diverse. From the data of Namo Bintang Village, the majority of Namo Bintang's population work as farmers. The results showed that planning development process has not implemented well in Namo Bintang Village, Society participation in development planning in Namo Bintang Village was still low, the communities aren`t involved to conduct the priority of the activities which is able to their need. Therefore, it needs an accomplishment in participative development. The government should consider the suitability of the budgetary budget with Rural needs. The budgetary budget for the implementation of rural development should be given as a whole without having to be gradual so that the Implementing Team and the workers do not stop before the activity is completed, other than that need optimal socialization in the provision of information to the community in Namo Bintang Village so that they are more involved in the process, more so that the development planning can become the needs of the community. Keywords: Society Participation, Rural Development

Objectives: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still's disease with atypical lung disease. We sought to characterise features of patients with Still's disease with DRESS compared with drug-tolerant Still's controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort., Methods: In a case/control study, we collected a multicentre series of patients with Still's disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still's controls (n=65). We retrospectively analysed clinical data from all Still's subjects and typed 94/131 for HLA. European Still's-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still's cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still's-DRESS cases (n=64) compared with drug-tolerant Still's controls (n=30). KD subjects (n=19) were similarly studied., Results: Still's-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still's-DRESS (64%) versus drug-tolerant Still's (3%; p=1.2×10 -14 ). We found striking enrichment for HLA-DRB1*15 haplotypes in Still's-DRESS cases versus INCHARGE Still's controls (p=7.5×10 -13 ) and versus self-identified, ancestry-matched Still's controls (p=6.3×10 -10 ). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions., Conclusions: DRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted., Competing Interests: Competing interests: VES, GD, report personal fees from Novartis, SP reports fees from Novartis outside the current work, SC reports personal fees from Novartis and grants from AB2 Bio, EDM reports grants from Novartis and JAH reports grant from Genentech. Drug Hypersensitivity Consortium: SL, GSS, SS and MS report personal fees from Novartis, AAG reports grants and personal fees from Novartis and grants from NovImmune. INCHARGE Consortium: No conflicts of interest., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Preclinical studies have shown that persistent mixed chimerism is linked to acceptance of organ allografts without immunosuppressive (IS) drugs. Mixed chimerism refers to continued mixing of donor and recipient hematopoietic cells in recipient tissues after transplantation of donor cells. To determine whether persistent mixed chimerism and tolerance can be established in patients undergoing living donor kidney transplantation, we infused allograft recipients with donor T cells and hematopoietic progenitors after posttransplant lymphoid irradiation. In 24 of 29 fully human leukocyte antigen (HLA)-matched patients who had persistent mixed chimerism for at least 6 months, complete IS drug withdrawal was achieved without subsequent evidence of rejection for at least 2 years. In 10 of 22 HLA haplotype-matched patients with persistent mixed chimerism for at least 12 months, reduction of IS drugs to tacrolimus monotherapy was achieved. Withdrawal of tacrolimus during the second year resulted in loss of detectable chimerism and subsequent rejection episodes, unless tacrolimus therapy was reinstituted. Posttransplant immune reconstitution of naïve B cells and B cell precursors was more rapid than the reconstitution of naïve T cells and thymic T cell precursors. Robust chimerism was observed only among naïve T and B cells but not among memory T cells. No evidence of rejection was observed in all surveillance graft biopsies obtained from mixed chimeric patients withdrawn from IS drugs, and none developed graft-versus-host disease. In conclusion, persistent mixed chimerism established in fully HLA- or haplotype-matched patients allowed for complete or partial IS drug withdrawal without rejection., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: The association of HLA mismatching with kidney allograft survival has been well established. We examined whether amino acid (AA) mismatches (MMs) at the antigen recognition site of HLA molecules represent independent and incremental risk factors for kidney graft failure (GF) beyond those MMs assessed at the antigenic (2-digit) specificity., Methods: Data on 240 024 kidney transplants performed between 1987 and 2009 were obtained from the Scientific Registry of Transplant Recipients. We imputed HLA-A, -B, and -DRB1 alleles and corresponding AA polymorphisms from antigenic specificity through the application of statistical and population genetics inferences. GF risk was evaluated using Cox proportional-hazards regression models adjusted for covariates including patient and donor risk factors and HLA antigen MMs., Results: We show that estimated AA MMs at particular positions in the peptide-binding pockets of HLA-DRB1 molecule account for a significant incremental risk that was independent of the well-known association of HLA antigen MMs with graft survival. A statistically significant linear relationship between the estimated number of AA MMs and risk of GF was observed for HLA-DRB1 in deceased donor and living donor transplants. This relationship was strongest during the first 12 months after transplantation (hazard ratio, 1.30 per 15 DRB1 AA MM; P < 0.0001)., Conclusions: This study shows that independent of the well-known association of HLA antigen (2-digit specificity) MMs with kidney graft survival, estimated AA MMs at peptide-binding sites of the HLA-DRB1 molecule account for an important incremental risk of GF.

Over the past 2 decades, reduced-intensity conditioning allogeneic hematopoietic cell transplantation (RIC HCT) has increased substantially. Many patients do not have fully HLA-matched donors, and the impact of HLA mismatch on RIC HCT has not been examined in large cohorts. We analyzed 2588 recipients of 8/8 HLA-high resolution matched (n = 2025) or single-locus mismatched (n = 563) unrelated donor (URD) RIC HCT from 1999 to 2011. Overall survival (OS) was the primary outcome. Secondary endpoints included treatment-related mortality (TRM), relapse, disease-free survival (DFS), and acute/chronic graft-versus-host disease (GVHD). Adjusted 1- and 3-year OS was better in 8/8- versus 7/8-matched recipients (54.7% versus 48.8%, P = .01, and 37.4% versus 30.9%, P = .005, respectively). In multivariate models 7/8 URD RIC HCT recipients had more grades II to IV acute GVHD (RR = 1.29, P = .0034), higher TRM (RR = 1.52, P < .0001), and lower DFS (RR = 1.12, P = .0015) and OS (RR = 1.25, P = .0001), with no difference in relapse or chronic GVHD. In subgroup analysis, inferior transplant outcomes were noted regardless of the HLA allele mismatched. Previously reported permissive mismatches at HLA-C (C*03:03/C*03:04) and HLA-DP1 (based on T cell-epitope matching) were not associated with better outcomes. Although feasible, single-locus mismatch in RIC URD HCT is associated with inferior outcomes., (Copyright © 2015 American Society for Blood and Marrow Transplantation. All rights reserved.)

Loss of heterozygosity (LOH) has been shown to be associated with leukemia relapse after haploidentical transplantation. Whether such changes are an important cause of relapse after HLA-matched transplantation remains unclear. We retrospectively HLA-typed leukemic blasts for 71 patients with AML/myelodysplastic syndrome obtained from stored samples, and the results were compared with those obtained at diagnosis and/or before the transplant. No LOH or any other changes in HLA Ag were found in any of the samples tested post transplant as compared with pretransplant specimens. One patient had LOH in HLA class I Ag (HLA-A,-B and -C); however, these changes were present in the pretransplant sample indicating that they occurred before the transplant. We concluded that, in contrast with haploidentical transplantation, HLA loss does not have a major role as a mechanism of relapse after allogeneic transplantation with a closely HLA-matched donor.

The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducts large, multi-institutional clinical trials with the goal of improving the outcomes of hematopoietic cell transplantation (HCT) for patients with life-threatening disorders. Well-designed HCT trials benefit from standardized criteria for defining diagnoses, treatment plans, and graft source selection. In this perspective, we summarize evidence supporting criteria for the selection of related and unrelated adult volunteer progenitor cell donors or umbilical cord blood units. These standardized criteria for graft source selection have been adopted by the BMT CTN to enhance the interpretation of clinical findings within and among future clinical protocols., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

We studied the effect of allele-level matching at human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 in 1568 single umbilical cord blood (UCB) transplantations for hematologic malignancy. The primary end point was nonrelapse mortality (NRM). Only 7% of units were allele matched at HLA-A, -B, -C, and -DRB1; 15% were mismatched at 1, 26% at 2, 30% at 3, 16% at 4, and 5% at 5 alleles. In a subset, allele-level HLA match was assigned using imputation; concordance between HLA-match assignment and outcome correlation was confirmed between the actual and imputed HLA-match groups. Compared with HLA-matched units, neutrophil recovery was lower with mismatches at 3, 4, or 5, but not 1 or 2 alleles. NRM was higher with units mismatched at 1, 2, 3, 4, or 5 alleles compared with HLA-matched units. The observed effects are independent of cell dose and patient age. These data support allele-level HLA matching in the selection of single UCB units.

Seasoned conservation researchers often struggle to bridge the research-implementation gap and promote the translation of their work into meaningful conservation actions. Graduate students face the same problems and must contend with obstacles such as limited opportunities for relevant interdisciplinary training and a lack of institutional support for application of research results. However, students also have a crucial set of opportunities (e.g., access to academic resources outside their degree programs and opportunities to design research projects promoting collaboration with stakeholders) at their disposal to address these problems. On the basis of results of breakout discussions at a symposium on the human dimensions of the ocean, a review of the literature, and our own experiences, we devised recommendations on how graduate students can create resources within their academic institutions, institutionalize resources, and engage with stakeholders to promote real-world conservation outcomes. Within their academic institutions, graduate students should foster links to practitioners and promote knowledge and skill sharing among students. To institutionalize resources, students should cultivate student leaders and faculty sponsors, systematically document their program activities, and engage in strategic planning to promote the sustainability of their efforts. While conducting research, students should create connections to and engage actively with stakeholders in their relevant study areas and disseminate research results both to stakeholders and the broader public. Our recommendations can serve as a template for graduate students wishing to bridge the research-implementation gap, both during their current studies and in their future careers as conservation researchers and practitioners., (© 2013 Society for Conservation Biology.)

The human leucocyte antigen (HLA) system shows extensive variation in the number and function of loci and the number of alleles present at any one locus. Allele distribution has been analysed in many populations through the course of several decades, and the implementation of molecular typing has significantly increased the level of diversity revealing that many serotypes have multiple functional variants. While the degree of diversity in many populations is equivalent and may result from functional polymorphism(s) in peptide presentation, homogeneous and heterogeneous populations present contrasting numbers of alleles and lineages at the loci with high-density expression products. In spite of these differences, the homozygosity levels are comparable in almost all of them. The balanced distribution of HLA alleles is consistent with overdominant selection. The genetic distances between outbred populations correlate with their geographical locations; the formal genetic distance measurements are larger than expected between inbred populations in the same region. The latter present many unique alleles grouped in a few lineages consistent with limited founder polymorphism in which any novel allele may have been positively selected to enlarge the communal peptide-binding repertoire of a given population. On the other hand, it has been observed that some alleles are found in multiple populations with distinctive haplotypic associations suggesting that convergent evolution events may have taken place as well. It appears that the HLA system has been under strong selection, probably owing to its fundamental role in varying immune responses. Therefore, allelic diversity in HLA should be analysed in conjunction with other genetic markers to accurately track the migrations of modern humans.

An important paradigm in evolutionary genetics is that of a delicate balance between genetic variants that favorably boost host control of infection but which may unfavorably increase susceptibility to autoimmune disease. Here, we investigated whether patients with psoriasis, a common immune-mediated disease of the skin, are enriched for genetic variants that limit the ability of HIV-1 virus to replicate after infection. We analyzed the HLA class I and class II alleles of 1,727 Caucasian psoriasis cases and 3,581 controls and found that psoriasis patients are significantly more likely than controls to have gene variants that are protective against HIV-1 disease. This includes several HLA class I alleles associated with HIV-1 control; amino acid residues at HLA-B positions 67, 70, and 97 that mediate HIV-1 peptide binding; and the deletion polymorphism rs67384697 associated with high surface expression of HLA-C. We also found that the compound genotype KIR3DS1 plus HLA-B Bw4-80I, which respectively encode a natural killer cell activating receptor and its putative ligand, significantly increased psoriasis susceptibility. This compound genotype has also been associated with delay of progression to AIDS. Together, our results suggest that genetic variants that contribute to anti-viral immunity may predispose to the development of psoriasis., Competing Interests: The authors have declared that no competing interests exist.

In this issue of Blood, Cutler and colleagues present evidence that donor-specific anti-HLA antibodies are associated with graft failure in double umbilical cord blood transplantation (CBT).1 Engraftment of donor cells is the first important step in successful transplantation and, until recently, the causes of engraftment failure remained elusive.

Available evidence suggests a Polynesian origin of the Easter Island population. We recently found that some native Easter Islanders also carried some common American Indian (Amerindian) human leukocyte antigen (HLA) alleles, which probably were introduced before Europeans discovered the island in 1722. In this study, we report molecular genetic investigations of 21 other selected native Easter Islanders. Analysis of mitochondrial DNA and Y chromosome markers showed no traces of an Amerindian contribution. However, high-resolution genomic HLA typing showed that two individuals carried some other common Amerindian HLA alleles, different from those found in our previous investigations. The new data support our previous evidence of an Amerindian contribution to the gene pool on Easter Island.

Psoriasis is a complex inflammatory disease of the skin affecting 1-2% of the Caucasian population. Associations with alleles from the HLA class I region (now known as PSORS1), particularly HLA-Cw*0602, were described over 20 years ago. However, extensive linkage disequilibrium (LD) within this region has made it difficult to identify the true susceptibility allele from this region. A variety of genes and regions from a 238-kb interval extending from HLA-B to corneodesmosin (CDSN) have been proposed to harbor PSORS1. In order to identify the minimum block of LD in the MHC class I region associated with psoriasis we performed a comprehensive case/control and family-based association study on 242 Northern European psoriasis families and two separate European control populations. High resolution HLA typing of HLA-A, -B and -C alleles was performed, in addition to the genotyping of 18 polymorphic microsatellites and 36 SNPs from a 772-kb segment of the HLA class I region harboring the previously described interval. This corresponded on average to one SNP every 7 kb in the candidate 238 kb region. With all tests, the association was the strongest with single markers and haplotypes from a block of LD harboring HLA-C and SNP n.9. Logistic regression analyses indicated that association seen with candidate genes from the interval such as CDSN and HCR was entirely dependent on association with HLA-Cw*0602 and SNP n.9-G alleles. The previously reported association with CDSN and HCR was observed to be due to the existence of the associated alleles lying on the most commonly over-transmitted haplotype. Rare over-transmitted haplotypes also harbored HLA-Cw*12 alleles. HLA-Cw*12 family members are closely related to HLA Cw*0602, sharing identical sequences in their alpha-2 domains, peptide-binding pockets A, D and E and all 3' introns. The introduction of a potential binding site for the RUNX/AML family of transcription factors in intron 7, is also specific to these HLA-C alleles. These variants need to be investigated further for their role as PSORS1.

Understanding HLA-restricted adaptive host immunity to defined epitopes of malarial antigens may be required for the development of successful malaria vaccines. Fourteen epitopes of preerythrocytic malarial antigens known to mediate cytotoxic T-lymphocyte responses against target cells expressing HLA-A2-restricted epitopes were synthesized and pooled based on antigen: thrombospondin-related anonymous protein (TRAP), circumsporozoite protein (CSP), and export protein 1 (Exp-1) peptides. HLA-A2 supertype (*0201, *0202, *0205, *6802) peripheral blood mononuclear cells collected from 774 Malian children, aged 3 months to 14 years, with severe Plasmodium falciparum malaria matched to uncomplicated malaria or healthy controls were stimulated with the HLA-A2-restricted peptide pools. Significant gamma interferon production, determined by enzyme-linked immunospot assay to at least one of the three peptide pools, was observed in 24/58 (41%) of the severe malaria cases, 24/57 (42%) of the uncomplicated malaria cases, and 34/51 (67%) of the healthy controls. Significant lymphoproliferation to these peptides was observed in 12/44 (27%) of the severe malaria cases, 13/55 (24%) of the uncomplicated malaria cases, and 18/50 (36%) of the healthy controls. Responses to individual peptide pools were limited. These studies confirm the presence of adaptive cell-mediated immunity to preerythrocytic malaria antigens in volunteers from Mali and demonstrate that suballeles of the HLA-A2 supertype can effectively present antigenic epitopes. However, whether these immune responses to TRAP, CSP, and Exp-1 malarial proteins play a substantial role in protection remains a matter of controversy.

This report presents serologic equivalents of human leukocyte antigen (HLA)-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, and -DQB1 alleles. The dictionary is an update of the one published in 2001. The data summarize equivalents obtained by the World Health Organization (WHO) Nomenclature Committee for Factors of the HLA System, the International Cell Exchange (UCLA), the National Marrow Donor Program, recent publications, and individual laboratories. This latest update of the dictionary is enhanced by the inclusion of results from studies performed during the 13th International Histocompatibility Workshop and from neural network analyses. A summary of the data as recommended serologic equivalents is presented as expert assigned types. The tables include remarks for alleles, which are or may be expressed as antigens with serologic reaction patterns that differ from the well-established HLA specificities. The equivalents provided will be useful in guiding searches for unrelated hematopoietic stem cell donors in which patients and/or potential donors are typed by either serology or DNA-based methods. The serological-DNA equivalent dictionary will also aid in typing and matching procedures for organ transplant programs whose waiting lists of potential donors and recipients are comprised of mixtures of serologic and DNA-based typings. The tables with HLA equivalents and a questionnaire for submission of serologic reaction patterns for poorly identified allelic products will be made available through the World Marrow Donor Association Web page (www.worldmarrow.org).

From an unusually informative family of 8 with near identical parental haplotypes (a and c), which differed by a single nucleotide substitution, we identified a new HLA-A1 null variant. While serologic antigen typing initially showed a "blank" allele in maternal haplotype "c" and 2 male offspring, more sophisticated DNA molecular HLA typing subsequently revealed the presence of a novel HLA-A0101 allele. Sequence-based typing showed a point mutation consisting of a nucleotide substitution of a cytosine for a guanine at nucleotide 215 yielding an amino acid change of arginine to proline at codon 48 in exon 2 (R48P). The impact on the HLA and immunogenetics laboratory is the need to not assume that all blanks are homozygous, as well as the need for the availability of high-resolution DNA molecular typing to clarify new alleles and to detect HLA-A null variants.

Purpose: Durable responses to cytokine therapy occur in a small subset of patients with renal cell carcinoma. We determined if a common HLA genotype existed among these patients which might be associated with response and survival., Materials and Methods: The study population consisted of 80 patients with metastatic renal cell carcinoma who had received cytokine therapy. DNA obtained from these patients was used for high resolution typing of HLA A, B, C, DRB1, DQA1 and DQB1 alleles., Results: The class II alleles from patients with prolonged disease-free survival were predominantly composed of haplotype DRB1*0301/DQA1*0501/DQB1*0201 and DRB1*1501/DQA1*0102/DQB1*0602. The frequency of heterozygosity or homozygosity for these alleles was significantly greater in the good outcome group of patients than in those whose disease progressed during therapy. Heterozygosity or homozygosity at these loci was also associated with significant prolongation of survival., Conclusions: We conclude that heterozygosity or homozygosity for the class II haplotypes DRB1*0301/DQA1*0501/DQB1*0201 and DRB1*1501/DQA1*0102/DQB1*0602 is associated with durable response and survival in patients with metastatic renal cell carcinoma treated with cytokine therapy.

The A*0201, A *0202, A*0203, A*0206, and A*6802 binding capacity of single amino acid substitution analogs of known A2-supertype binding peptides and of large nonredundant peptide libraries was measured. The results were utilized to rigorously define the peptide binding specificities of these A2-supertype molecules. Although each molecule was noted to have unique preferences, large overlaps in specificity were found. The presence of L, I, V, M, A, T, and Q residues in position 2, and L, I, V, M, A, and T residues at the C-terminus of peptide ligands were tolerated by all molecules. Likewise, whereas examination of secondary influences on peptide binding revealed allele specific preferences, shared features could also be identified. These shared features were utilized to define an A2-supermotif and were noted to correlate with crossreactivity. Over 70% of the peptides that bound A *0201 with high affinity were found to bind at least two other A2-supertype molecules. Because the A2-supertype molecules studied herein cover the variants most common in different major ethnicities, these findings have important implications for epitope-based approaches to vaccination, immunotherapy, and the monitoring of immune responses.

Approximately 2% of the Caucasian population is affected by psoriasis (PS); a chronic inflammatory skin disease triggered by both genetic and environmental risk factors. In addition to a major contribution from the HLA class I region, PS susceptibility loci have been mapped to a number of regions including 1q21, 3q21, 4qter, 14q31-q32, 17q24-q25, 19p13.3 and 20p. Some of these overlap with loci implicated in other autoimmune/inflammatory diseases. Global gene expression studies are beginning to provide insights into the etiology of these and other complex diseases. We used Affymetrix oligonucleotide arrays comprising approximately 12 000 known genes to initiate a more comprehensive analysis of the transcriptional changes that occur in involved and uninvolved skin of 15 psoriatic patients versus six normal controls. Expression levels of the transcripts detected on the arrays were first used to determine the relationship of samples to each other using hierarchical clustering. This analysis clearly differentiated involved psoriatic skin from uninvolved and normal skin. Clusters of differentially expressed genes with similar expression patterns in the same samples were then identified. Six out of 32 clusters contained a total of 177 transcripts that were differentially expressed in involved psoriatic skin versus normal skin. These differences were independent of the gender, age, skin site and HLA class I status of the patient. Ten of the 177 genes were also differentially expressed in uninvolved skin, and several mapped to regions previously shown to harbor psoriasis susceptibility loci.

The association of HLA antigens with susceptibility for development of psoriasis vulgaris has been studied mostly using serologic methods. A number of different HLA class I antigens have been reported to be associated with predisposition to develop this disease. While Cw6 is the allele most commonly thought to confer risk for psoriasis, a number of HLA-B locus alleles have also been thought to be involved and, recently, in at least three studies, a specific amino acid in the HLA-C heavy chain has been implicated. With the recent development of molecular methods for typing for HLA class I alleles, it has become possible to re-examine this association by performing high resolution typing. In the present study we have investigated 38 psoriasis patients and 84 ethnically and geographically matched controls from North India. They were typed for HLA-B and HLA-C. The results showed the Cw*0602 was the main allele that was increased in this group of patients. The previously reported association with alanine-73 was not found to be significant. Cw*0602 was found in 71% of the patients. B*5701 and B*3701 were also increased but appeared to be secondary to linkage disequilibrium with Cw*0602.

In a previous study of B locus alleles by sequence-specific oligonucleotide probe (SSOP) hybridization, we observed 18 novel patterns in a panel of 360 individuals. Four of these novel patterns were caused by alleles of the human leukocyte antigen (HLA)-B15 group, and three were available for this study. These alleles were found in Oriental, Latin American, African American, and Caucasian individuals. In addition, we analyzed a Caucasian subject who was found by serology to have an unusual B15 specificity. We sequenced these four samples by performing amplification from genomic DNA using polymerase chain reaction primers designed to obtain HLA class I products that included exon 2 and exon 3 as well as the intervening intron. The amplified segments were cloned and identified by colony hybridization with nonradioactive SSOP. Nucleotide sequences were obtained using an automated DNA sequencer. The allele B*1530 differs from B*1501 by a substitution of Asp for Asn in position 114 and Ser for Tyr in codon 116. The new allele B*1531 differs from B*1502 at amino acids 94, 95, and 152. The variant B*1524 was found to have N-77, I-80, A-81, L-82, R-83. A similar motif exists in B locus alleles that have the supertypic specificity Bw4 and in B*1513, B*1516, B*1517, and B*1523; it is likely to have been generated by gene conversion. Finally, the novel allele B*1527 is similar to B*1501 except for the presence of Phe instead of Tyr at position 99. Because this change exists also in B*1506, it is possible that B*1506 was derived from B*1501 through B*1527. It is of interest that a similar substitution (Cys for Tyr at position 99) distinguishes A*0201 from A*0207 and is known to determine an epitope recognized by T cells. Thus, B*1527 may also carry a change that is functionally relevant in cell-mediated immunity.

In a study of 523 normal subjects of differing ethnic groups, including 189 South American Indians, we have described novel hybridization pattern corresponding to 22 potentially new HLA-B locus alleles. Three of these alleles were subtypes of B35. The locally, assigned alleles, B-3504v, B-3505v, and B-3508v have been sequenced and were officially designated as B*3512, B*3517, and B*3518, respectively. In addition, we determined the nucleotide sequence of another new variant, locally designated B-3509.2. B*3517, was found in 3 individuals (2 Hispanic, 1 Caucasian), it differs from B*3505 by 3 nucleotide substitutions that lead to changes in residues 94, 95, and 103. B*3517 differs from B*3501 in residues 97 and 103. B*3518 was found in 7 South American Indian individuals (6 of 124 Toba Indians, 1 of 18 Pilaga Indians). It differs from B*3509 by 2 silent nucleotide substitutions and by one nonsynonymous substitution in codon 156 (Arg-->Leu). B*3512 differs from B*3504 by 3 nucleotides, one of them leading to a substitution in residue 103 (Val-->Leu). B*3509 was observed in 3 individuals from the Wichi tribe. The nucleotide sequence of one of these was determined and was found to differ from B*35091 by two synonymous nucleotide substitutions. The distinguishing amino acid substitutions in residues 95, 97, and 156 contribute to the structure of specificity pockets F, C, and E, and D and E respectively, therefore, it is possible that some of the new alleles may have different peptide binding profiles. It has been shown that differences at residue 156 may elicit different allorecognition and mediate graft-versus-host disease and rejection in bone marrow transplantation. The mechanisms for the generation of these novel alleles may involve gene conversion events in which short exon-3 segments from the common Native American alleles B*4002 or B*4801 were inserted in HLA-B35 backbone structures. The novel allele B*3518 is closely related to B*35092 and to B*3508. Two alternative hypotheses for its generation can be suggested, the most plausible one would involve B*35092, the putative progenitor of B*3518, since both alleles are prevalent in the same Indian tribes.

Pemphigus vulgaris (PV) is a cutaneous autoimmune disease characterized by blister formation in the suprabasilar layers of skin and mucosae and anti-desmoglein-3 (Dsg3) autoantibodies bound to the surface of lesional keratinocytes and circulating in the serum of patients. This disease can be reproduced in neonatal mice by passive transfer of patients' IgG, indicating that humoral immunity plays an important role in the pathogenesis of PV. Currently, the role of T lymphocytes in the development of PV is not clear. Here, we report that three immunoreactive segments of the ectodomain of Dsg3 specifically induced proliferation of T cells from PV patients. We found that T lymphocytes from 13 out of 14 patients responded to at least one of three Dsg3 peptides. T cells from controls and other patient groups did not respond to these Dsg3 peptides. The major T cell population stimulated by these Dsg3 peptides was CD4 positive. Dsg3-specific T cell lines and clones were developed and were shown to express a CD4 positive memory T cell phenotype. Upon stimulation, these cell lines and clones secreted a Th2-like cytokine profile. The Dsg3 responses of these T cells were restricted to HLA-DR, and not -DQ and -DP, of the major histocompatibility complex. This information will help to elucidate the cellular immune abnormalities leading to production of pathogenic IgG autoantibodies in patients with PV.

A gene involved in psoriasis susceptibility was localized to the distal region of human chromosome 17q as a result of a genome-wide linkage analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. In the family which showed the strongest evidence for linkage, the recombination fraction between a psoriasis susceptibility locus and D17S784 was 0.04 with a maximum two-point lod score of 5.33. There was also evidence for genetic heterogeneity and although none of the linked families showed any association with HLA-Cw6, two unlinked families showed weak levels of association. This study demonstrates that in some families, psoriasis susceptibility is due to variation at a single major genetic locus other than the human lymphocyte antigen locus.

Host factors seem to play an important role in determining the immune response and the differential manifestations of lepromatous (LL) and tuberculoid (TT) leprosy. In order to investigate the role of immunogenetic factors in determining the form of leprosy, the HLA class II alleles of DRB1, DRB3, DRB5, DQA1, DQB1 and DPB1 were studied by a PCR oligotyping technique in 93 patients and 47 healthy controls. DRB1*1501 and DRB1*1502 (two of five tested subsets of the serologically defined DR2) accounted for 81.5% of the multibacillary patients (relative risk 16.3) and 60.7% of the TT patients (relative risk 5.7) compared to 21.3% in normal, ethnically- and geographically-matched controls. The much stronger association of DRB1*1501 with the multibacillary form than with the TT type of leprosy suggests a possible role in the differential immune response to M. leprae antigens. DQB1*0601 was found significantly more often than in controls throughout the leprosy spectrum, while DQA1*0103 was most frequent in the LL group and DQA1*0102 was selectively increased in the borderline lepromatous (BL) patients. On the other hand, DRB1*0701, DQB1*0201 and DQA1*0201 were decreased in the multibacillary leprosy patients (MLP) compared to TT patients and controls, and DQB1*0503 was selectively decreased in TT patients, suggesting that these HLA alleles might play a role in modulating the immune response that determines the form of leprosy that develops in each patient.