Quantitative Analysis of the Efficiency of Clonal Deletion in the Thymus

One of the major mechanisms for establishing self-tolerance is the clonal deletion of self-reactive T cells during their development in the thymus. Using a TCR transgenic mouse model, we have established a quantitative ex vivo assay for examining the sensitivity and specificity of negative selection. Thymic organ cultures established from mice of varying MHC haplotypes were incubated with antigen, and the efficiency of clonal deletion assessed. We show here that clonal deletion of CD4+8+ thymocytes is sensitive to both the gene dosage and the allelic variation of MHC class II molecules expressed on thymic antigen-presenting cells. We also find that when epithelial cells in the thymic cortex are the only antigen-presenting cells expressing the appropriate MHC class II molecules, negative selection of CD4+8+ cells is as efficient as when antigen is presented on all thymic antigen-presenting cells. These studies demonstrate that the induction of self-tolerance via clonal deletion in the thymus is a function not only of antigen concentration, but also of MHC class II cell-surface density. In addition, together with the reports of others, these results confirm that cortical epithelial cells can mediate negative selection, and demonstrate that they do so in the intact thymic microenvironment

First Danish Single-Institution Experience with Radical Prostatectomy: Biochemical Outcome in 1200 Consecutive Patients

Radical retropubic prostatectomy (RRP) as intended curative therapy for patients with clinically localized prostate cancer (PC) was initiated in 1995 in Denmark. This paper reports single-institution results from the first 1200 consecutive patients operated during a 15-year period. Median age at surgery was 63 years. Median PSA was 9 ng/mL. Palpable tumors (≤cT2) were present in 48% of patients. Gleason score at biopsy was ≤7 for 85% of patients. In sixty-five percent of patients, histopathology revealed localized PCa after RRP. Positive surgical margins were found in 39.2% of the cases. Biochemical recurrence (BR) occurred for 214 (18%) of patients. The estimated biochemical recurrence free survival (BRFS) was 71.7% and 63.2% after 5 and 10 years, respectively. When patients were stratified according to the D'Amico criteria, BRFS after 10 years was 75.3%, 59.7%, and 39.3% for low-, medium- and high-risk patients, respectively. In univariate analysis, clinical stage, PSA at diagnosis and type of surgery were significant predictors of BR. In multivariate analysis, Gleason score > 7, PSA > 10, and higher clinical stage were significant predictors of BR. Early Danish results in a population not subjected to screening demonstrate BRFS rates comparable with earlier reports from the prescreening era

Number-related Brain Potentials Are Differentially Affected by Mapping Novel Symbols on Small versus Large Quantities in a Number Learning Task

The nature of the mapping process that imbues number symbols with their numerical meaning-known as the "symbolgrounding process"-remains poorly understood and the topic of much debate. The aim of this study was to enhance insight into how the nonsymbolic-symbolic number mapping process and its neurocognitive correlates might differ between small (1-4; subitizing range) and larger (6-9) numerical ranges. Hereto, 22 young adults performed a learning task in which novel symbols acquired numerical meaning by mapping them onto nonsymbolic magnitudes presented as dot arrays (range 1-9). Learning-dependent changes in accuracy and RT provided evidence for successful novel symbol quantity mapping in the subitizing (1-4) range only. Corroborating these behavioral results, the number processing related P2p component was only modulated by the learning/mapping of symbols representing small numbers 1-4. The symbolic N1 amplitude increased with learning independent of symbolic numerical range but dependent on the set size of the preceding dot array; it only occurred when mapping on one to four item dot arrays that allow for quick retrieval of a numeric value, on the basis of which, with learning, one could predict the upcoming symbol causing perceptual expectancy violation when observing a different symbol. These combined results suggest that exact nonsymbolic-symbolic mapping is only successful for small quantities 1-4 from which one can readily extract cardinality. Furthermore, we suggest that the P2p reflects the processing stage of first access to or retrieval of numeric codes and might in future studies be used as a neural correlate of nonsymbolic-symbolic mapping/symbol learning

Analisis Unit Cost Pelayanan Rawat Inap Postpartum Di Rumah Sakit Umum Dewi Sartika Dengan Menggunakan Metode Activity Based Costing (ABC) System

Iklim kompetitif tidak hanya terjadi pada Perusahaan yang berorientasi profit, namun juga berdampak padaperusahaan yang berorientasi nonprofit, salah satunya adalah rumah sakit. Rumah sakit yang berada di SulawesiTenggara pada tahun 2014 berjumlah 36, sedangkan kota Kendari memiliki 13 rumah sakit dan harus melayani347.496 penduduk. Hal ini menjadikan persaingan bisnis rumah sakit baik umum maupun swasta kini semakinketat. Salah satu solusi untuk memenangkan persaingan adalah dengan cara menentukan tarif yang lebih rendahdan kualitas atau jasa yang lebih tinggi dari pada pesaing. Solusi tersebut tentunya menjadikan biaya operasionalrumah sakit akan semakin besar sehingga sistem akuntansi manajemen di rumah sakit harus efektif dan efisiensehingga menghasilkan informasi yang akurat dalam pengambilan keputusan. Rumah sakit cenderung masihmenggunakan system akuntansi tradisional yang memiliki distorsi biaya. Penelitian ini menganalisis perhitungantarif rawat inap pelayanan postpartum di RSU Dewi Sartika menggunakan metode activity based costing system.Penelitian ini menggunakan metode deskriptif komparatif dengan pendekatan kuantitatif, data yang digunakanadalah seluruh data keuangan pada Oktober 2015-September 2016 dan aktivitas yang diobservasi yaitu ruangperawatan kelas VIP, kelas I, kelas II, kelas III dan bangsal. Hasil perhitungan menunjukkan hasil yang berbeda daritarif yang diterapkan. Tarif kelas VIP, kelas I dan kelas III lebih rendah dari tarif rumah sakit sedangkan tarif kelas IIdan bangsal lebih tinggi

Mining for nonribosomal peptide synthetase and polyketide synthase genes revealed a high level of diversity in the sphagnum bog metagenome

Sphagnum bog ecosystems are one of the oldest vegetation forms harbouring a specific microbial community, which is known to produce an exceptionally wide variety of bioactive substances. Although the Sphagnum metagenome indicate a rich secondary metabolism, the genes are not yet explored. To analyse non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) the diversity of NRPS and PKS genes in Sphagnum-associated metagenome was investigated by in silico data mining and sequence-based screening (PCR-amplification of 9500 fosmid clones). The in silico Illumina-based metagenomic approach resulted in the identification of 279 NRPS, 346 PKS, as well as 40 PKS-NRPS hybrid gene sequences. Occurrence of NRPS sequences was strongly dominated by the phyla Protebacteria, especially by the genus Burkholderia, while PKS sequences were mainly affiliated to Actinobacteria. Thirteen novel NRPS-related sequences were identified by PCR-amplification screening, displaying amino acid sequence identities of 48 to 91% to annotated sequences of the phyla Proteobacteria, Actinobacteria and Cyanobacteria. Some of the identified metagenomic clones showed closest similarity to peptide synthases from Burkholderia or Lysobacter, which are emerging bacterial sources of yet undescribed bioactive metabolites. This study highlights the role of the extreme natural ecosystems as a promising source for detection of secondary compounds and enzymes, serving as a source for biotechnological applications

Stock Identification Methods Working Group (SIMWG)

The Stock Identification Methods Working Group (SIMWG) reviews new methods for the defi-nition and investigation of stock structure and provides advice to other ICES expert groups on how to interpret patterns of population structure. The identification of the spatial boundaries of exploited stocks is a fundamental requirement before any stock assessment or modelling can be contemplated, and therefore lies at the heart of resource management. SIMWG continues to provide annual updates on recent applications of stock identification methods to species assessed by ICES and on advances in stock identification methods. Based on the wide expertise of SIMWG members, the group provides reviews of recent literature on genetics, growth marks in calcified structures, life history parameters, morphometrics/ me-ristics, tagging, otolith shape, otolith chemistry, parasites and interdisciplinary approaches. A key activity of SIMWG is to address requests by ICES working groups for technical advice on issues of stock identity. In 2020, the working group reviewed the outcome of the Workshop on Stock Identification of North Sea Cod (WKNSCodID). SIMWG contributes to the general understanding of the biological features of the north Atlantic ecosystem through its work to describe fish population structure. Additionally, SIMWG’s annual reviews on advances in stock identification methods keeps ICES members abreast of best prac-tices in this field of study. SIMWG expert reviews on questions of stock structure for particular ICES species are directly relevant to the appropriate definition of stock and contribute to the accuracy of stock assessment and effectiveness of management actions. We see an important role for SIMWG in the future as ICES copes with the shifting distributions of fishery resources and questions regarding the appropriate definition of fish stocks. Understanding stock structure is a fundamental requirement before any assessment or modelling on a stock can be contemplated and SIMWG will continue to work with ICES expert groups to address pressing stock identifica-tion issues

The PRS Rainbow Classification for Assessing Postbariatric Contour Deformities

Background: There is a need for a reliable classification system to grade contour deformities and to inform reimbursement of body contouring surgery after massive weight loss. We developed the PRS Rainbow Classification, which uses select photographs to provide standardized references for evaluating patient photographs, to classify contour deformities in postbariatric patients. To assess the reliability of the PRS Rainbow Classification to classify contour deformities in massive weight loss patients. Methods: Ten independent experienced plastic surgeons, 7 experienced medical advisors of the healthcare insurance company, and 10 laypersons evaluated 50 photographs per anatomical region (arms, breast, abdomen, and medial thighs). Each participant rated the patient photographs on a scale of 1-3 in an online survey. The inter-observer and the intra-observer reliabilities were determined using intra-class correlation coefficients (ICCs). The ICC analyses were performed for each anatomical region. Results: Inter-observer reliability was moderate to good in the body regions "arms," "abdomen," "medial thighs," with mean ICC values of 0.678 [95% confidence interval (CI), 0.591-0.768], 0.685 (95% CI, 0.599-0.773), and 0.658 (95% CI, 0.569-0.751), respectively. Inter-observer reliability was comparable within the 3 different professional groups. Intra-observer reliability (test-retest reliability) was moderate to good, with a mean overall ICC value of 0.723 (95% CI, 0.572-0.874) for all groups and all 4 body regions. Conclusions: The moderate to good reliability found in this study validates the use of the PRS Rainbow Classification as a reproducible and reliable classification system to assess contour deformities after massive weight loss. It holds promise as a key part of instruments to classify body contour deformities and to assess reimbursement of body contouring surgery

TB STIGMA – MEASUREMENT GUIDANCE

TB is the most deadly infectious disease in the world, and stigma continues to play a significant role in worsening the epidemic. Stigma and discrimination not only stop people from seeking care but also make it more difficult for those on treatment to continue, both of which make the disease more difficult to treat in the long-term and mean those infected are more likely to transmit the disease to those around them. TB Stigma – Measurement Guidance is a manual to help generate enough information about stigma issues to design and monitor and evaluate efforts to reduce TB stigma. It can help in planning TB stigma baseline measurements and monitoring trends to capture the outcomes of TB stigma reduction efforts. This manual is designed for health workers, professional or management staff, people who advocate for those with TB, and all who need to understand and respond to TB stigma

Not the Root of the Problem-Hair Cortisol and Cortisone Do Not Mediate the Effect of Child Maltreatment on Body Mass Index.

BACKGROUND: Experiencing maltreatment during childhood exerts substantial stress on the child and increases the risk for overweight and obesity later in life. The current study tests whether hair cortisol-a measure of chronic stress-and its metabolite cortisone mediate the relation between abuse and neglect on the one hand, and body mass index (BMI) on the other. METHOD: The sample consisted of 249 participants aged 8 to 87 years (M = 36.13, SD = 19.33). We collected data on child abuse and neglect using questionnaires, measured cortisol and cortisone concentrations in hair, and BMI. In a structural model, the effects of abuse and neglect on hair cortisol, hair cortisone, and BMI were tested, as well as the covariance between hair cortisol and BMI, and hair cortisone and BMI. RESULTS: Within the sample, 23% were overweight but not obese and 14% were obese. Higher levels of experienced abuse were related to higher cortisone concentrations in hair (β = 0.24, p < .001) and higher BMI (β = 0.17, p =.04). Neglect was not related to hair cortisol, hair cortisone, or BMI. Hair cortisol and cortisone did not mediate the association between maltreatment, and BMI. Sensitivity analyses demonstrate the same pattern of results in a subsample of adult participants currently not living with their parents. However, in younger participants who were still living with their parents, the associations between abuse and cortisone (β = 0.14, p =.35) and abuse and BMI (β = 0.02, p =.92) were no longer significant. CONCLUSION: These findings confirm that experiencing abuse is related to higher BMI but suggest that hair cortisol and cortisone are not the mechanism underlying the association between child maltreatment and BMI. This is the first study to show abuse may be associated to elevated concentrations of hair cortisone-evidence of long-term alterations in chronic stress levels. Future research may benefit from exploring the effects of maltreatment on weight gain in longitudinal designs, including measures of other potential mediators such as eating as a coping mechanism, and more direct indicators of metabolic health

Not the Root of the Problem—Hair Cortisol and Cortisone Do Not Mediate the Effect of Child Maltreatment on Body Mass Index

Background: Experiencing maltreatment during childhood exerts substantial stress on the child and increases the risk for overweight and obesity later in life. The current study tests whether hair cortisol—a measure of chronic stress—and its metabolite cortisone mediate the relation between abuse and neglect on the one hand, and body mass index (BMI) on the other. Method: The sample consisted of 249 participants aged 8 to 87 years (M = 36.13, SD = 19.33). We collected data on child abuse and neglect using questionnaires, measured cortisol and cortisone concentrations in hair, and BMI. In a structural model, the effects of abuse and neglect on hair cortisol, hair cortisone, and BMI were tested, as well as the covariance between hair cortisol and BMI, and hair cortisone and BMI. Results: Within the sample, 23% were overweight but not obese and 14% were obese. Higher levels of experienced abuse were related to higher cortisone concentrations in hair (β = 0.24, p <.001) and higher B