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BackgroundInflammatory muscle diseases are systemic inflammatory disorders that affect not only muscles but also skin, joints, lungs, and heart. Dermatomyositis (DM) and polymyositis (PM) are characterized by the production of antibodies. Measurement of these antibodies is useful for diagnosis, classification of disease type, evaluation of disease activity, prognosis prediction, and determination of therapeutic strategy. However, the sensitivity and specificity vary depending on the measurement method, and some autoantibodies can only be measured in limited laboratories.ObjectivesWe developed a novel comprehensive assay kit for myositis-associated antibodies with the aim of developing a rapid and simple detection method for myositis-specific or related autoantibodies. we used a proteome-wide antibody screening and quantification with wet protein arrays consisting of proteins synthesized from proteome-wide human cDNA library (HuPEX). We examined whether this assay kit is clinically useful compared to enzyme-linked immunosolbent assay (ELISA).MethodsSera from 47 patients diagnosed or suspected of inflammatory muscle disease were used to measure myositis-specific autoantibodies (anti-ARS, anti-MDA5, anti-TIF1-γ, anti-Mi-2, and anti-SRP, antibodies) and myositis-related autoantibodies (anti-U1RNP, anti-Ku, and anti-PM-Scl, anti-mitochondria antibodies) were measured using a proteome-wide antibody screening and quantification with wet protein arrays consisting of proteins synthesized from proteome-wide human cDNA library (HuPEX) and compared with the results of ELISA, which is commercially available and immunoprecipitation with some autoantibodies（anti-OJ, anti-Zo antibodies).Autoantibodies that were undetectable by the ELISA and positive only on the array were subjected to immunoprecipitation. In immunoprecipitation, primary antibody added to a solution containing an antigen to form an antigen-antibody complex in the solution. Next, a secondary antibody immobilized on the beads is added to adsorb the antigen-antibody complex to the beads. Finally, the antigen was eluted from the beads using SDS and analyzed using SDS-PAGE.ResultsIn the 47 cases, the clinical diagnosis was DM in 26 cases, PM in 20 cases, and inclusion body myositis in 1 case. In the ELISA commercially available, 20 cases of anti-ARS antibody (17 cases of DM, 3 cases of PM), 5 cases of anti-MDA5 antibody (Amyopathic DM), 1 case of anti-TIF1-γ antibody (DM), 2 cases of Mi-2 antibody (1 case of DM, 1 case of PM), 2 cases of anti-RNP antibody (PM), and 2 cases of anti-mitochondria antibody (PM).Compared with the results measured by the ELISA commercially available, eighteen of the 20 cases were positive for anti-ARS antibodies using the proteome-wide antibody screening system and all other autoantibodies were 100% concordant.In addition, 1 case of DM in which autoantibodies could not be detected by the ELISA was positive for anti-OJ antibody by the proteome-wide antibody screening system. Of the 6 PM cases whose autoantibodies could not be detected by the ELISA, 1 was anti-HMGCR antibody-positive and 1 was anti-Zo antibody-positive, consistent with the clinical diagnosis. Furthermore, among the 4 PM cases who were positive only for anti-SS-A antibody by ELISA, 2 were anti-SRP antibody positive, 1 was anti-Ku antibody positive, and 1 was anti-Ki antibody positive by the proteome-wide antibody screening system. Those samples that could be detected by the array were also confirmed to be positive by immunoprecipitation.ConclusionCollectively, proteome-wide screening of antibodies using the in vitro proteome can reveal the myositis-associated antibodies of patients and may provide novel clinical biomarkers.References[1]Mimori T, Autoantibodies in idiopathic inflammatory myopathy:an update on clinical and pathophysiological significance. Curr Opin Rheumatol, 2007. 19: p. 523-529[2]Fukuda E, et al. Identification and characterization of the antigen recognized by the germ cell mAb TRA98 using a human comprehensive wet protein array. Genes Cells, 2021. 26(3): p.180-189.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Summary We estimated the number of hip fracture patients in 2012 in Japan and investigated the trends in incidence during a 25-year period from 1987 to 2012. Despite the increasing number of patients, the incidence of hip fracture in both men and women aged 70–79 years showed the possibility of decline. Introduction The objectives of this study were to estimate the number of hip fracture patients in 2012, to investigate the trends in incidence during a 25-year period from 1987 to 2012, and to determine the regional differences in Japan. Methods Data were collected through a nationwide survey based on hospitals by a mail-in survey. Hip fracture incidences by sex and age and standardized incidence ratios by region were calculated. Results The estimated numbers of new hip fracture patients in 2012 were 175,700 in total (95 % CI 170,300–181,100), 37,600 (36,600–38,600) for men and 138,100 (134,300–141,900) for women. The incidence rates in both men and women aged 70–79 years were the lowest in the 20-year period from 1992 to 2012. The incidence was higher in western areas of Japan than that in eastern areas in both men and women; however, the difference in the incidence of hip fracture between western and eastern areas is becoming smaller. Conclusions Despite the increasing number of new patients, the incidence of hip fracture in both men and women aged 70–79 years showed the possibility of decline. The exact reasons for this are unknown, but various drugs for improving bone mineral density or preventing hip fracture might have influenced the results. A decrease in the differences in nutrient intake levels might explain some of the change in regional differences in Japan.

Refinement of intermetallic compounds (IMCs) through enhancing heterogeneous nucleation during casting process is an important approach to improve the properties of aluminium alloys, which greatly increases the economy value of recycled Al-alloys. However, heterogeneous nucleation of IMCs is inherently more difficult than that of a pure metal or a solid solution. It requires not only creation of a crystal structure but also the positioning of 2 or more different types of atoms in the lattice with specific composition close to that of the nucleated IMCs. Previous understanding on heterogeneous nucleation is based on structural templating, usually considering the small lattice misfit at the interface between the nucleating solid and substrate. In this work, we proposed a hypothesis and demonstrated that composition templating plays a critical role in heterogeneous nucleation of IMCs. The experimental results revealed that segregation of Fe atoms on the AlB 2 surface, i.e., the Fe modified AlB 2 particle, provides the required composition templating and hence enhances heterogeneous nucleation of α-Al 15 (Fe, Mn) 3 Si 2 , resulting in a significant refinement of the α-Al 15 (Fe, Mn) 3 Si 2 particles in an Al-5 Mg-2Si-1.0Mn-1.2Fe alloy.

Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease characterized by lymphocyte infiltration in salivary and lacrimal glands. pSS affects primarily middle-aged and elderly patients, although younger age groups may also be involved. However, differences of etiology and pathogenesis between early-onset pSS (EOpSS) and late-onset pSS (LOpSS) are unknown. Recently, standardized outcome tools for measuring disease-specific activity and patients' reported symptoms have been formulated by the European League Against Rheumatism (EULAR) SS study group: the EULAR SS Disease Activity Index (ESSDAI) for systemic features of pSS [1]. Also, as the new imaging techniques, salivary gland ultrasonography (SGUS) proved valuable for assessing salivary gland involvement in SS and seemed to exhibit good diagnostic properties. In addition, previous studies have demonstrated usefulness of SGUS for the prognostic stratification of patients with pSS [2], [3], [4]. The aim of this study was to examine the differences of etiology and pathogenesis between EOpSS and LOpSS using ESSDAI and SGUS. Fifty-six pSS patients who fulfilled the American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) classification criteria for SS were studied. Based on the disease onset age, all pSS patients were divided into two groups as those with the onset age of 40 years old or younger (EOpSS: n=26) and those with the onset age of older than 65 years old (LOpSS: n=30). The clinical findings were evaluated ESSDAI and OMERACT SGUS score at the first visit to our hospital. The ESSDAI (0–123) proposes the evaluation of 12 domains or organ systems (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system, muscular, hematological and biology). All patients were examined SGUS by a single investigator who was blinded to device (TUS-A300; Canon Medical Systems, Tokyo, Japan) with a linear transducer (7.5-10MHz). The OMERACT SGUS score was used for graded changes in the parenchymal homogeneity of salivary glands: grade 0, normal-appearing salivary gland parenchyma; grade 1, minimal change: mild inhomogeneity without hypo/anechoic areas; grade 2, moderate change: moderate inhomogeneity with focal hypo/anechoic areas; grade 3, severe change: diffuse inhomogeneity with hypo/anechoic areas occupying the entire gland surface [5]. The proportions of positive sera of RF, anti-SS-A and anti-SS-B antibodies were not different in the two groups, but the disease activities were higher in the EOpSS than in the LOpSS patients by measuring ESSDAI (7.30 vs 4.23, p=0.008), especially in constitutional domain (1.50 vs 0.60, p=0.03), articular domain (1.54 vs 0.40, p=0.0002) and biological domain (1.35 vs 0.90, p=0.04). No difference in salivary secretion was found between two groups (EOpSS: 8.02 vs LOpSS: 6.31 mL/10min.), but the OMERACT SGUS score was higher in LOpSS than in EOpSS patients (2.00 vs 2.70, p=0.0002). Although serological findings were not different, EOpSS patients had higher disease activity but less severe salivary gland degeneration than that in LOpSS patients, suggesting the pathogenesis of these two groups was different. [1]Seror R, et al. Ann Rheum Dis. 2010 Jun;69(6):1103-9. [2]Arthritis Care Res (Hoboken). 2014 Jul;66(7):1102-7. [3]Hammenfors DS, et al. Clin Exp Rheumatol. 2015 Jan-Feb;33(1):56-62. [4]Milic V, et al. PLoS One. 2019 Dec 31;14(12): e0226498. [5]Jousse-Joulin S, et al. Ann Rheum Dis. 2019 Jul;78(7):967-973. None declared

The reflectance spectra of the most abundant meteorites, ordinary chondrites, are different from those of the abundant S-type (mnemonic for siliceous) asteroids. This discrepancy has been thought to be due to space weathering, which is an alteration of the surfaces of airless bodies exposed to the space environment. Here we report evidence of space weathering on particles returned from the S-type asteroid 25143 Itokawa by the Hayabusa spacecraft. Surface modification was found in 5 out of 10 particles, which varies depending on mineral species. Sulfur-bearing Fe-rich nanoparticles exist in a thin (5 to 15 nanometers) surface layer on olivine, low-Ca pyroxene, and plagioclase, which is suggestive of vapor deposition. Sulfur-free Fe-rich nanoparticles exist deeper inside (<60 nanometers) ferromagnesian silicates. Their texture suggests formation by metamictization and in situ reduction of Fe2+.

Background:Rheumatoid arthritis (RA) is a chronic inflammatory joint disease that eventually leads to the destruction of cartilage and bone[1]. A type I interferon (INF-I) signature (ISG) is detectable in the peripheral blood of RA patients and may be present in the preclinical phase of the disease[2]. INF-Is have been implicated in the pathogenesis of RA. JAK inhibitors (Jakinibs) block the activation of the IFN pathway by inhibiting JAKs, resulting in a very promising therapeutic strategy for adults suffering from autoimmune, inflammatory and haematological diseases such as RA. We have shown that serum Mac-2BPGi (M2BP) levels are significantly elevated in patients with rheumatic diseases associated with type 1 interferonopathies, including rheumatoid arthritis, compared to healthy controls[3]. At present, the significance of M2BP in RA is unclear.Objectives:The aim of this study is to evaluate the utility of serum M2BP levels in patients with RA.Methods:This was a retrospective cross-sectional study. A total of 135 eligible RA patients were included in this study in our department’s database from January to April 2020, excluding patients with neither RA disease activity nor laboratory data including M2BP. Serum levels of M2BP were measured using the HISCLÒ M2BP glycosylation isomer assay kit. Clinical remission was defined as a Simplified Disease Activity Index (SDAI) ≤ 3.3. Serum M2BP levels were categorised into tertiles (LOW, MID and HIGH).Results:The median age of patients was 67.0 (IQR: 57.0-73.0) years, and the median disease duration was 13.0 (9.0-6.5) years. The median SDAI was 2.02 (1.16-5.11) and the median Disease Activity Score 28-C-reactive protein (DAS28-CRP) was 1.61 (1.26-2.12). Of the 135 patients, 85 were in clinical remission (REM). There were no significant differences between the REM and non-REM groups in the proportion of methotrexate (MTX) use, biologics and JAK inhibitors use, but prednisolone (PSL) use and csDMARDs other than MTX were significantly higher in the non-REM group. Median serum M2BP levels were 0.85 cut-off index (C.O.I.) (0.63-1.18). M2BP was significantly correlated with SDAI and DAS28-CRP (r=0.230 and r=0.238, respectively). Serum M2BP tended to be lower in the SDAI remission group compared to the non-remission group (0.79 vs. 0.93); serum M2BP levels were significantly lower in the DAS28-CRP remission group compared to the non-remission group (0.80 vs. 1.07, p<0.02). The proportion of SDAI remission tended to decrease with increasing serum M2BP, whereas the proportion of DAS28-CRP remission significantly decreased with increasing serum M2BP. Multiple regression analysis of serum M2BP identified age and SDAI as independent factors. In this multiple regression analysis, treatment with biologics and JAKinib, excluding abatacept (ABT), tended to reduce M2BP compared to csDMARDs alone. The use of MTX and PSL also tended to reduce it. And treatment with JAKinibs tended to reduce M2BP more than the other treatments.Conclusion:The study showed that serum M2BP levels correlate with disease activity in rheumatoid arthritis as an independent factor. Previous studies have reported that serum M2BP correlates with type 1 interferon signalling in RA, and this study found a trend for JAKinibs treatment to reduce M2BP more than other treatments. Therefore, it has been suggested that serum M2BP may be a marker not only for the assessment of disease activity, but also for treatment selection and response in RA.REFERENCES:[1] Drossaers-Bakker KW, de BM, van ZD, et al. Arthritis Rheum 1999;42:1854–60.[2] Lubbers, J. et al. Ann. Rheum. Dis. 72, 776–780 (2013).[3] Yoshikawa T, Azuma K, Furukawa T, Tamura M, Hashimoto T, Morimoto M, et al. Ann Rheum Dis. 2021;80(Suppl 1):1181.1-1181.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Janus kinase inhibitors (JAKi) represent a novel class of oral targeted disease-modifying drugs, heralding a recent revolution in the therapeutic landscape for rheumatoid arthritis (RA) and other immune-mediated conditions. These inhibitors, which can complement or even replace conventional and biological drugs, operate through a distinctive mechanism involving intracellular disruption of the JAK-STAT pathway—a pivotal player in the immune response. The Hill coefficient (H) serves to describe the sigmoidicity of a drug’s concentration-response curve. When H > 2.0, a “time-dependent” effect is observed, where the critical factor is not the peak drug concentration but the crossing of a threshold beneath which the effect becomes negligible. The prolonged serum concentration above this threshold correlates with a more pronounced effect. Conversely, when H < 2.0, a “concentration-dependent” effect emerges, with the peak concentration holding significance [1]. In the report by Chimalakonda A et al [2], the H for the inhibitory effect of JAK1/3 in tofacitinib, baricitinib, and upadacitinib ranged from 1.0-1.3. For JAK1 inhibition in filgotinib (FIL), the H was nearly 2 [3]. Intriguingly, in a phase II study, FIL at 100 mg BID demonstrated a tendency to be more effective than FIL at 200 mg QD after 12 weeks of treatment [4]. However, the time-dependency of FIL’s effect on rheumatoid arthritis remains unclear.Objectives:The objective of this investigation is to assess whether the impact of FIL on rheumatoid arthritis exhibits time-dependent characteristics.Methods:This constituted a retrospective, observational study involving 25 patients diagnosed with rheumatoid arthritis (RA) who met the 2010 American College of Rheumatology (ACR)/EULAR classification criteria. These patients were prescribed FIL and underwent a minimum 12-week follow-up at our hospital from November 2020 to October 2023. The efficacy of FIL was assessed based on the EULAR response at 12-week treatment, with concurrent measurement of the change in DAS28-CRP. Patients were categorized into three groups based on renal function and FIL dosage: FIL 200 mg group [FIL200], FIL 100 mg with chronic kidney disease (CKD) (eGFR < 60 ml/min/1.73m2) [FIL100CKD], and FIL 100 mg without CKD [FIL100].Results:The median age of the patients was 69.0 years (IQR: 61.0-76.0), and the median disease duration was 156 months (102-180). The median DAS28-CRP was 3.60 (3.16-4.49). Comparing the FIL100CKD group to the FIL200 group, the former exhibited a higher median age (80.0 vs. 73.0 year, P<0.05). However, other patient backgrounds showed no statistically significant differences. No significant variations were observed in the number of concomitant MTX, other csDMARDs, or prednisolone among the three groups. But, there was a tendency towards fewer patients being biologics- and JAKi-naive in the FIL200 group (FIL100 group; 60.0%, FIL100CKD group; 66.7% and FIL200 group; 14.3%, respectively). In terms of treatment outcomes, the EULAR response and ΔDAS28-CRP at 12 weeks tended to be higher in the FIL100, FIL100CKD, and FIL200 groups, in that sequential order (Figure 1).Conclusion:FIL exhibits a Hill coefficient close to 2, implying a time-dependent pharmacodynamic effect rather than concentration dependence. In cases with eGFR <60, the time above IC5 for JAK1 is extended (FIL100; approximately 6 hours, FIL100CKD; approximately 8 hours, FIL200; approximately 9.5 hours) [5,6]. Clinical data derived from the current study imply that the efficacy of FIL is time-dependent. Further studies are needed to confirm this.REFERENCES:[1] Czock D, Keller F. J Pharmacokinet Phar. 2007;34(6):727–51.[2] Chimalakonda A, et al. Dermatology Ther. 2021;11(5):1763–76.[3] Namour F, et al. Clin Pharmacokinet. 2015;54(8):859–74.[4] Westhovens R, et al. Ann Rheum Dis. 2017;76(6):998.[5] Namour F, et al. Brit J Clin Ph REFERENCES armaco. 2018;84(12):2779–89.[6] Veeravalli V, et al. Drug Safety. 2020;1–15.12W EULAR responseAcknowledgements:NIL.Disclosure of Interests:None declared.

Background:Based on the idea that therapeutic approach for oral dryness in patients with Sjögren’s syndrome (SS) should be driven by salivary glandular function, rather than the patient’s subjective feelings, the EULAR recommendations for the management of Sjögren’s syndrome with topical and systemic therapies recommend that salivary glandular function be evaluated by measuring whole salivary flows before starting therapeutic interventions and that different therapeutic approaches be provided depending on the measured salivary flow rates. Although the recommendations do not indicate a preferred therapeutic approach for SS patients with unstimulated whole salivary flows (UWSF) ≥0.1 mL/min, in clinical practice, SS patients with preserved salivary flow rates often complain of oral dryness.Objectives:To evaluate the oral health-related quality of life (OHRQoL) in SS patients with UWSF ≥0.1 ml/min.Methods:Forty-five SS patients (35 with primary SS; 43 women and 2 men; mean age, 62.4 years; mean disease duration, 6.6 years) and 23 non-SS individuals (control; 18 women and 5 men; mean age, 56.1 years) participated in this study. All SS patients met the 1999 revised Japanese Ministry of Health criteria for diagnosis of SS. Individuals with factors that can affect saliva secretion, intraoral lesion formation, or OHRQoL were excluded. The UWSF of SS patients were measured by the spitting method (mL/15 min). OHRQoL was quantitatively assessed using the Japanese version of the short-form Oral Health Impact Profile (OHIP-14; maximum possible score, 56 points), a self-administered questionnaire, at an average of 7.2 months after the UWSF measurement in SS patients and as needed in non-SS individuals. Since the assessment of dryness symptoms by ESSPRI includes more than just oral dryness, it was not used for the OHRQoL assessment in this study.Results:In SS patients, the mean UWSF was 1.1 mL/15 min; 34 (75.6%) had a UWSF <0.1 mL/min, and 11 (24.4%) had ≥0.1 mL/min. Their mean OHIP-14 score was 15.9. There was no significant difference in the percentage of patients who perceived oral dryness between the UWSF <0.1 ml/min and ≥0.1 ml/min groups (97.1% vs 81.8%, p=0.143). The OHIP-14 score also did not differ significantly between the two groups (16.6 vs 13.6, p=0.227). The OHIP-14 score of even the UWSF ≥0.1 mL/min group was significantly higher than that of the non-SS group (13.6 vs. 7.1, p=0.029). Among the OHIP-14 questions, the UWSF ≥0.1 mL/min group scored significantly higher than the non-SS group for “self-conscious,” “diet unsatisfactory,” “difficult to relax,” and “felt life less satisfying.” In addition, the UWSF ≥0.1 mL/min group tended to score higher for “trouble pronouncing words,” “uncomfortable to eat foods,” “been embarrassed,” “irritable with other people,” and “unable to function.”Conclusion:This study revealed that SS patients – even with UWSF ≥0.1 mL/min – had lower OHRQoL. Because of the wide normal range of salivary flow rates and high interindividual variability, it is considered difficult to determine whether an individual’s salivary flow rate is abnormal. Signs of oral dryness are said to appear when the salivary flow rate decreases by 40–50%. Therefore, it is more important whether there is a change in salivary flow rate over time than whether an individual has a high or low salivary flow rate. Even if the salivary flow rate is preserved in a single measurement, the possibility of having oral dryness due to a decrease in the salivary flow rate from the normal value for that patient should be considered.REFERENCES:[1] Ramos-Casals M, et al. Ann Rheum Dis 2020;79:3-18.Acknowledgements:NIL.Disclosure of Interests:Naoto Azuma: None declared, Maki Iwatani: None declared, Yuichi Yokoyama: None declared, Naoaki Hashimoto: None declared, Masao Tamura: None declared, Teppei Hashimoto: None declared, Mai Morimoto: None declared, Aki Nishioka: None declared, Masayasu Kitano: None declared, Shinichiro Tsunoda: None declared, Hajime Sano: None declared, Kiyoshi Matsui KM has received scholarship grant from Chugai Pharmaceutical Co., Ltd. and Asahi Kasei Pharma Corporation.

Wisdom is the hallmark of social judgment, but how people across cultures recognize wisdom remains unclear—distinct philosophical traditions suggest different views of wisdom’s cardinal features. We explore perception of wise minds across 16 socio-economically and culturally diverse convenience samples from 12 countries. Participants assessed wisdom exemplars, non-exemplars, and themselves on 19 socio-cognitive characteristics, subsequently rating targets’ wisdom, knowledge, and understanding. Analyses reveal two positively related dimensions—Reflective Orientation and Socio-Emotional Awareness. These dimensions are consistent across the studied cultural regions and interact when informing wisdom ratings: wisest targets—as perceived by participants—score high on both dimensions, whereas the least wise are not reflective but moderately socio-emotional. Additionally, individuals view themselves as less reflective but more socio-emotionally aware than most wisdom exemplars. Our findings expand folk psychology and social judgment research beyond the Global North, showing how individuals perceive desirable cognitive and socio-emotional qualities, and contribute to an understanding of mind perception. The authors examine wisdom perception in convenience samples from twelve countries. They observe two latent dimensions that guide participant’s evaluation of wisdom-related characteristics in others and the self—reflective orientation and socio-emotional awareness, which were consistent across the studied cultural regions.

Background Expansion of genomic resources for the Pacific white shrimp ( Litopenaeus vannamei ), such as the construction of dense genetic linkage maps, is crucial for the application of genomic tools in order to improve economically relevant traits. Sexual dimorphism exists in Pacific white shrimp, and the mapping of the sex-determination region in this species may help in future reproductive applications. We have constructed male, female, and sex-averaged high-density genetic maps using a 50 K single-nucleotide polymorphism (SNP) array, followed by a genome-wide association study (GWAS) to identify genomic regions associated with sex in white shrimp. Results The genetic map yielded 15,256 SNPs assigned to 44 linkage groups (LG). The lengths of the male, female, and sex-averaged maps were 5,741.36, 5,461.20 and 5,525.26 cM, respectively. LG18 was found to be the largest for both sexes, whereas LG44 was the shortest for males and LG31 for females. A sex-determining region was found in LG31 with 21 statistically significant SNPs. The most important SNP was previously identified as a sex-linked marker and was able to identify 99% of the males and 88% of the females. Although other significant markers had a lower ability to determine sex, putative genes were intercepted or close to them. The oplophorus-luciferin 2-monooxygenase , serine/arginine repetitive matrix protein and spermine oxidase genes were identified as candidates with possible participation in important processes of sexual differentiation in shrimp. Conclusions Our results provide novel genomic resources for shrimp, including a high-density linkage map and new insights into the sex-determining region in L. vannamei , which may be usefulfor future genetics and reproduction applications.