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Full‐service sex workers (FSSWs) are at heightened risk of contracting HIV due to facing multi‐level challenges to sexual health. This study investigated factors associated with willingness to use Pre‐Exposure Prophylaxis (PrEP)—a daily HIV preventative medication, among FSSWs. Using social–ecological theory, an online survey was developed with initial guidance from a local sex worker advocacy organization to assess barriers and facilitators to PrEP uptake willingness. The survey was disseminated with the assistance of local and national sex work advocacy organizations. In our sample of FSSWs (n = 83), two barriers and two facilitators initially were associated with PrEP uptake. However, in adopting a more conservative analysis, only anticipating stigmatizing disapproval from others for using PrEP and providing others with PrEP knowledge maintained statistical significance. These two variables collectively explained nearly 30% of the variance in PrEP uptake willingness. Implications for both future research and clinical work with FSSWs are discussed. [ABSTRACT FROM AUTHOR]

To achieve the sustainable development goals and a transition to the circular economy, we need to tackle the problem of single‐use packaging. As reusable packaging options are increasingly available, both from a technical and business perspective, most studies focus on its technical and value chain aspects while largely ignoring customer perspectives. In this paper, we present results from survey data, evaluating customer preferences on reusable food packaging of 40 food product categories, controlling for shopping preferences, personal characteristics and environmental orientation. Our results inform business strategies on market entry for a wide array of food products. Support for reusable food packaging can be mainly found among younger and environmentally conscious customers, which can be identified as first‐mover customer segments. Awareness of the waste problem and the environmental impact of packaging, most specifically on the issue of 'overpackaging' food, are shown to be positively related to interest in reusable food packaging. Promising food product markets to introduce reusable packaging are eggs, dry food products and bread‐based products. Reversely, interest in reusable food packaging is low for frozen food products, even among environmentally conscious customers. We formulate recommendations for product managers, designers and policymakers, stressing the importance of social learning by showcasing successful implementations of reusable packaging in classical grocery store outlets. [ABSTRACT FROM AUTHOR]

Background and Purpose: The voltage‐gated sodium channel isoform NaV1.7 is a high‐interest target for the development of non‐opioid analgesics due to its preferential expression in pain‐sensing neurons. NaV1.7 is also expressed in autonomic neurons, yet its contribution to involuntary visceral reflexes has received limited attention. The small molecule inhibitor ST‐2560 was advanced into pain behaviour and cardiovascular models to understand the pharmacodynamic effects of selective inhibition of NaV1.7. Experimental Approach: Potency of ST‐2560 at NaV1.7 and off‐target ion channels was evaluated by whole‐cell patch‐clamp electrophysiology. Effects on nocifensive reflexes were assessed in non‐human primate (NHP) behavioural models, employing the chemical capsaicin and mechanical stimuli. Cardiovascular parameters were monitored continuously in freely‐moving, telemetered NHPs following administration of vehicle and ST‐2560. Key Results: ST‐2560 is a potent inhibitor (IC50 = 39 nM) of NaV1.7 in primates with ≥1000‐fold selectivity over other isoforms of the human NaV1.x family. Following systemic administration, ST‐2560 (0.1–0.3 mg·kg−1, s.c.) suppressed noxious mechanical‐ and chemical‐evoked reflexes at free plasma concentrations threefold to fivefold above NaV1.7 IC50. ST‐2560 (0.1–1.0 mg·kg−1, s.c.) also produced changes in haemodynamic parameters, most notably a 10‐ to 20‐mmHg reduction in systolic and diastolic arterial blood pressure, at similar exposures. Conclusions and Implications: Acute pharmacological inhibition of NaV1.7 is antinociceptive, but also has the potential to impact the cardiovascular system. Further work is merited to understand the role of NaV1.7 in autonomic ganglia involved in the control of heart rate and blood pressure, and the effect of selective NaV1.7 inhibition on cardiovascular function. [ABSTRACT FROM AUTHOR]

When manipulating objects, humans begin adjusting their grip force to friction within 100 ms of contact. During motor adaptation, subjects become aware of the slipperiness of touched surfaces. Previously, we have demonstrated that humans cannot perceive frictional differences when surfaces are brought in contact with an immobilised finger, but can do so when there is submillimeter lateral displacement or subjects actively make the contact movement. Similarly, in, we investigated how humans perceive friction in the absence of intentional exploratory sliding or rubbing movements, to mimic object manipulation interactions. We used a two‐alternative forced‐choice paradigm in which subjects had to reach and touch one surface followed by another, and then indicate which felt more slippery. Subjects correctly identified the more slippery surface in 87 ± 8% of cases (mean ± SD; n = 12). Biomechanical analysis of finger pad skin displacement patterns revealed the presence of tiny (<1 mm) localised slips, known to be sufficient to perceive frictional differences. We tested whether these skin movements arise as a result of natural hand reaching kinematics. The task was repeated with the introduction of a hand support, eliminating the hand reaching movement and minimising fingertip movement deviations from a straight path. As a result, our subjects' performance significantly declined (66 ± 12% correct, mean ± SD; n = 12), suggesting that unrestricted reaching movement kinematics and factors such as physiological tremor, play a crucial role in enhancing or enabling friction perception upon initial contact. Key points: More slippery objects require a stronger grip to prevent them from slipping out of hands.Grip force adjustments to friction driven by tactile sensory signals are largely automatic and do not necessitate cognitive involvement; nevertheless, some associated awareness of grip surface slipperiness under such sensory conditions is present and helps to select a safe and appropriate movement plan.When gripping an object, tactile receptors provide frictional information without intentional rubbing or sliding fingers over the surface. However, we have discovered that submillimeter range lateral displacement might be required to enhance or enable friction sensing.The present study provides evidence that such small lateral movements causing localised partial slips arise and are an inherent part of natural reaching movement kinematics. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the status of patient education among highly myopic individuals focusing on the presence, sources, content, timing of the education and impact on patients. Methods: Self‐reported data were collected through an online 13‐item questionnaire consisting of open and multiple‐choice questions. The questionnaire was sent to 250 highly myopic members of a patient organization in the Netherlands, of whom 128 (51%) responded. Results: At least one acute event had occurred in 66% (84/128) of participants at the time of the questionnaire. Among all participants, 25% (32/128) had not received patient education regarding alarm symptoms for any of these events. Among those who had been informed, the ophthalmologist was the most frequent (57%, 73/128) source of information. Participants who visited the ophthalmologist annually were more frequently informed than participants without annual visits (53%, 26/49 versus 26%, 9/35, p = 0.002). Those not informed were more likely to have a more than 3 days patient delay (92%, 12/13). Doctors delay was also present; 26% (22/84) of the participants with alarm symptoms had to wait 2 or more days before the first appointment. Long‐term consequences of myopia had been discussed with 102 participants (80%, 102/128), again with the ophthalmologist as the most frequent source (59%, 76/128). Perspectives: Many myopic individuals have not been educated about their increased risk of acute events, which can result in patient delay and serious consequences with respect to visual prognosis. These findings underscore the critical importance of integrating patient education across the entire ophthalmic care chain for myopia. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM), a complex heterogeneous metabolic disorder characterized by a defect in the function of insulin, is on the rapid rise globally. Sustained hyperglycemia which is a major sign of DM is linked to the generation of reactive oxygen species which promotes adverse complications of the disorder. Traditional herbal treatment of DM is a common practice in Africa and other tropical parts of the world. Vernonia amygdalina (VA), one of the highly researched species in the Asteraceae family, has proven to possess potent antidiabetic properties. Several phytochemicals identified in multiple extracts from VA are purported to be responsible for the antidiabetic potential of the plant. In this review, we discuss the therapeutic potential of VA in diabetes and its associated complications. We appraise the current evidence and further suggest potential areas that could be effectively exploited in future VA research on diabetes. [ABSTRACT FROM AUTHOR]

Consistent with the minority stress perspective, lesbian/gay, bisexual, and transgender (LGBT) individuals on average report worse health than heterosexual individuals in several domains, for example, general health, mental health, physical health, and healthcare access. Intersectionality‐based research shows that LGBT people of color (POC) are, on average, at even greater risk for adverse health outcomes. Discrimination and social cohesion may be two mechanisms underlying these between‐ and within‐group disparities, given that both constructs are frequently reported within marginalized populations, and that both broadly relate to health. This study used data from the Chicago Department of Public Health to examine broad health differences between White LGBT and LGBT POC, and to test specific models in which social cohesion mediated links between discrimination and health. LGBT POC reported experiencing worse general health, lower access to health care, more experiences of discrimination, and lower feelings of social cohesion than did White LGBT individuals. No mediation effects emerged; however, there was a direct effect of experiencing discrimination on mental health distress. Discrimination exposure inversely related to the feelings of social cohesion. [ABSTRACT FROM AUTHOR]

Purpose: To understand and compare perspectives of patients and professionals on current ophthalmologic care for high myopia, and to identify challenges and future opportunities. Methods: Self‐reported data were collected through two online questionnaires. Patient perspective was obtained from highly myopic members of a patient organisation based in the Netherlands using a 17‐item questionnaire consisting of open and multiple‐choice questions regarding personal experience with myopia care. The ophthalmologist perspective was obtained from practising Dutch ophthalmologists with a 12‐item questionnaire of multiple‐choice questions on work‐related demographics, myopia care in daily practice and need for improvement. The response rate for patients was 27% (n = 136/500) and for ophthalmologists, 24% (n = 169/716). Results: Patients were highly concerned about personal progressive loss of vision (69%) and feared their psychological well‐being (82%) in case this would happen. The quality of performance of care provided by ophthalmologists was rated as excellent or satisfactory by 64% of the patients. These ratings for multidisciplinary care and insurance reimbursement were as low as 28% and 18% respectively. The mean concern among ophthalmologists about the rise in high myopia was 6.9 (SEM 0.1) on a 10‐point scale. Sixty‐nine per cent of the ophthalmologists reported that asymptomatic myopic patients should not be examined regularly at outpatient clinics. Ophthalmologists urged the development of clinical guidelines (74%), but did report (95%) that they informed patients about risk factors and complications. This contrasted with the view of patients, of whom 42% were discontent with information provided by ophthalmologists. Conclusions: These questionnaires demonstrated that the current clinical care delivered to highly myopic patients is in need of improvement. The expected higher demand for myopia care in the near future requires preferred practice patterns, professionals specifically trained to manage myopic pathology, accurate and comprehensive information exchange and collaboration of in‐ and out‐of‐hospital professionals across the full eye care chain. [ABSTRACT FROM AUTHOR]

This is the protocol for a Campbell systematic review. The review will address the following research questions: What is the evidence on the effects of adult mentoring programmes in reducing anti‐social, violent and offending behaviour in children aged under 18 years? Are these effects sustained after the end of mentoring? Which aspects/features of adult mentoring programmes promote the reduction of anti‐social, violent and criminal behaviour in children aged under 18 years? What are the hindering factors/barriers that affect the successful implementation of adult mentoring programmes in children aged under 18 years? What are the supporting factors/facilitators that contribute to the successful implementation of adult mentoring programmes in children aged under 18 years? What is the evidence on programme costs and incremental cost effectiveness? (The incremental (or marginal cost) is the cost of providing the intervention over and above the cost of usual services). [ABSTRACT FROM AUTHOR]

The hypoxia‐inducible factors (HIF)‐1α and HIF‐2α are central regulators of transcriptional programmes in settings such as development and tumour expansion. HIF‐2α moonlights as a cap‐dependent translation factor. We provide new insights into how the interferon‐stimulated gene 15 (ISG15), a ubiquitin‐like modifier, and the HIFs regulate one another in hypoxia and interferon‐induced cells. We show that upon ISGylation induction and HIF‐α stabilization, both HIFs promote protein ISGylates through transcriptional and/or post‐transcriptional pathways. We show the first evidence of HIF‐2α modification by ISG15. ISGylation induces system‐level alterations to the HIF transcriptional programme and increases the cytoplasmic/nuclear fraction and translation activity of HIF‐2α. This work identifies ISG15 as a regulator of hypoxic mRNA translation, which has implications for immune processes and disease progression. [ABSTRACT FROM AUTHOR]

The stabilizing properties of mineral–organic carbon (OC) interactions have been studied in many soil environments (temperate soils, podzol lateritic soils, and paddy soils). Recently, interest in their role in permafrost regions is increasing as permafrost was identified as a hotspot of change. In thawing ice‐rich permafrost regions, such as the Yedoma domain, 327–466 Gt of frozen OC is buried in deep sediments. Interactions between minerals and OC are important because OC is located very near the mineral matrix. Mineral surfaces and elements could mitigate recent and future greenhouse gas emissions through physical and/or physicochemical protection of OC. The dynamic changes in redox and pH conditions associated with thermokarst lake formation and drainage trigger metal‐oxide dissolution and precipitation, likely influencing OC stabilization and microbial mineralization. However, the influence of thermokarst processes on mineral–OC interactions remains poorly constrained. In this study, we aim to characterize Fe, Mn, Al, and Ca minerals and their potential protective role for OC. Total and selective extractions were used to assess the crystalline and amorphous oxides or complexed metal pools as well as the organic acids found within these pools. We analyzed four sediment cores from an ice‐rich permafrost area in Central Yakutia, which were drilled (i) in undisturbed Yedoma uplands, (ii) beneath a recent lake formed within Yedoma deposits, (iii) in a drained thermokarst lake basin, and (iv) beneath a mature thermokarst lake from the early Holocene period. We find a decrease in the amount of reactive Fe, Mn, Al, and Ca in the deposits on lake formation (promoting reduction reactions), and this was largely balanced by an increase in the amount of reactive metals in the deposits on lake drainage (promoting oxidation reactions). We demonstrate an increase in the metal to C molar ratio on thermokarst process, which may indicate an increase in metal–C bindings and could provide a higher protective role against microbial mineralization of organic matter. Finally, we find that an increase in mineral–OC interactions corresponded to a decrease in CO2 and CH4 gas emissions on thermokarst process. Mineral–OC interactions could mitigate greenhouse gas production from permafrost thaw as soon as lake drainage occurs. [ABSTRACT FROM AUTHOR]

Real‐time hybrid testing involves the separation of a system into an experimental component and a numerically simulated substructure which are coupled and run together. The coupling between substructures is achieved using actuators and force sensors which comprise the transfer system. Close synchronization is required between substructures for reliable hybrid testing. However, actuator lag may cause tracking errors and instability in hybrid tests. Existing lag compensation schemes require identification of the coupled dynamics of the transfer system and experimental component and can be sensitive to changes in these components. Passivity control is a technique intended to maintain stability without the need for system identification or assumptions about the actuators or test specimens. Yet, the tuning of existing passivity controllers is sensitive to both the system being tested and the amplitude and frequency range excited. This paper presents a new, normalized passivity controller which behaves well across a much broader range of operating conditions once tuned for a single‐test scenario. The proposed approach uses a virtual damping element on the numerical substructure to dissipate spurious power injected by the actuator into the system, based on the ratio of net power output to mean power throughput. The scheme has been shown to result in identical performance for a linear hybrid test with a range of step excitations from 0.5 mm up to 500 mm. The proposed method can be used to improve test stability and fidelity in isolation or alongside other compensation schemes to further improve performance. [ABSTRACT FROM AUTHOR]

ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1623 endometriosis‐associated ovarian carcinomas, including 1078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas, through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour‐infiltrating lymphocytes (CD8+ TILs), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOCs and 25% of ENOCs. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p = 0.012) and was associated with MMRd (p < 0.001) and the presence of CD8+ TILs (p = 0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOCs we also observed an association with ARID1A loss‐of‐function mutation as a result of small indels (p = 0.035, versus single nucleotide variants). In ENOC, the association with ARID1A loss, CD8+ TILs, and age appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss‐of‐function mutations in endometriosis‐associated ovarian cancers and brings clarity to the prognostic significance. © 2021 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Liquid biopsy in ovarian cancer: recent advances on circulating tumor cells and circulating tumor DNA. 173 Demidov VN, Lipatenkova J, Vikhareva O, Van Holsbeke C, Timmerman D, Valentin L. Imaging of gynecological disease (2): clinical and ultrasound characteristics of Sertoli cell tumors, Sertoli-Leydig cell tumors and Leydig cell tumors. I The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of ovarian tumors, including imaging techniques, biomarkers and prediction models i . This multiclass prediction model is the first risk model to differentiate between benign and malignant tumors, whilst also offering subclassification of any malignancy into borderline tumors, Stage-I and Stage-II-IV primary cancers and secondary metastatic tumors. Positron emission tomography-computed tomography Positron emission tomography-computed tomography (PET-CT) may be useful in differentiating malignant from borderline or benign ovarian tumors, with the limitation that its diagnostic performance can be impacted negatively by certain tumor histological subtypes, due to the lower fluorodeoxyglucose uptake in clear-cell and mucinous invasive subtypes147-152. [Extracted from the article]

The indication for staging lymphadenectomy in patients with ovarian cancer (both early- and late-stage disease) has been a major topic of debate in the last decades. Because the Lymphadenectomy in Ovarian Neoplasms (LION) study has recently demonstrated that systematic lymphadenectomy is not beneficial to patients with advanced ovarian cancer, the discussion has become more complex for patients with early-stage ovarian cancer. Further factors, such as differences in the lymph node metastasis rates of different histologic subtypes, which were not known in the past, need to be taken into account. This review is focused on the available evidence concerning lymphadenectomy in patients with newly diagnosed ovarian cancer. [ABSTRACT FROM AUTHOR]

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Background and objective: MicroRNA (miRNA) are transcriptional regulators implicated in pulmonary sarcoidosis and packaged in extracellular vesicles (EV) during cellular communication. We characterized EV and investigated miRNA expression in bronchoalveolar lavage (BAL) fluid from sarcoidosis patients. Methods: EV were characterized for size(s) using dynamic light scattering and transmission electron microscopy (TEM) analysis and protein markers by immunoblotting. Twelve extracellular and 5 cellular miRNA were investigated in BAL from 16 chest X‐ray stage‐I (CXR‐I) and 17 CXR stage‐II (CXR‐II) sarcoidosis patients. Associations between miRNA and disease characteristics (extrapulmonary involvement, pulmonary function and BAL cell profile) were statistically analysed. Results: BAL from sarcoidosis patients contained exosomes and microvesicles (MV) as EV. In these EV, expression of miR‐146a (P = 0.007), miR‐150 (P = 0.003) and BAL cellular miR‐21 (P = 0.01) was increased in CXR‐II compared with CXR‐I. Other detected EV (miR‐21 and miR‐26a) and cellular (miR‐31, miR‐129‐3p, miR‐146a and miR‐452) miRNA were not differentially expressed. The investigated miRNA did not reflect extrapulmonary involvement, but EV miR‐146a and miR‐150 were negatively correlated with pulmonary function (miR‐146a with vital capacity (VC; Spearman's correlation coefficient (rs), P = −0.657, 0.007), percent predicted forced expiratory volume in 1 s (FEV1; −0.662, 0.006) and FEV1/forced vital capacity (FVC) ratio (−0.649, 0.008); miR‐150 correlated negatively with VC (−0.584, 0.019) and FEV1/FVC ratio (−0.746, 0.001) in CXR‐II cases). Conclusion: Our data provide evidence that exosomes and microvesicles as extracellular vesicles are present in the bronchoalveolar space of sarcoidosis patients and they differentially express EV miRNA (miR‐146a and miR‐150), the expression of which correlates negatively with pulmonary function indices. The significance of these findings for disease pathophysiology and clinical course require further investigation. Extracellular vesicles (EV: exosomes and microvesicles) in sarcoidosis bronchoalveolar lavage samples contained more EV miR‐146a, miR‐150 in chest X‐ray stage‐II (CXR‐II) than in CXR stage‐I (CXR‐I); levels were negatively correlated to lung function indices. This study is the first to document bronchoalveolar vesicles containing differentially expressed extracellular microRNA (miRNA) in pulmonary sarcoidosis. [ABSTRACT FROM AUTHOR]

Aims: Bedaquiline is an important novel drug for treatment of multidrug‐resistant tuberculosis, but no paediatric formulation is yet available. This work aimed to explore the possibility of using the existing tablet formulation in children by evaluating the relative bioavailability, short‐term safety, acceptability and palatability of suspended bedaquiline tablets compared to whole tablets. Methods: A randomized, open‐label, two‐period cross‐over study was conducted in 24 healthy adult volunteers. Rich pharmacokinetic sampling over 48 h was conducted at two occasions 14 days apart in each participant after administration of 400 mg bedaquiline (whole or suspended in water). The pharmacokinetic data were analysed with nonlinear mixed‐effects modelling. A questionnaire was used to assess palatability and acceptability. Results: There was no statistically significant difference in the bioavailability of the suspended bedaquiline tables compared to whole. The nonparametric 95% confidence interval of the relative bioavailability of suspended bedaquiline tablets was 94–108% of that of whole bedaquiline tablets; hence, the predefined bioequivalence criteria were fulfilled. There were no Grade 3 or 4 or serious treatment emergent adverse events recorded in the study and no apparent differences between whole tablets and suspension regarding taste, texture or smell. Conclusions: The bioavailability of bedaquiline tablets suspended in water was the same as for tablets swallowed whole and the suspension was well tolerated. This suggests that the currently available bedaquiline formulation could be used to treat multidrug‐resistant tuberculosis in children, to bridge the gap between when paediatric dosing regimens have been established and when a paediatric dispersible formulation is routinely available. [ABSTRACT FROM AUTHOR]

Abstract: A general and operationally convenient method for intermolecular amination of C(sp3)−H bonds is described. This technology allows for efficient functionalization of complex molecules, including numerous pharmaceutical targets. The combination of pivalonitrile as a solvent, Al2O3 as an additive, and phenyl sulfamate as a nitrogen source affords differential reaction performance and substrate scope. Mechanistic data strongly implicate a pathway for catalyst decomposition that initiates with solvent oxidation, thus providing rationale for the marked influence of pivalonitrile on this reaction process. [ABSTRACT FROM AUTHOR]

A general and operationally convenient method for intermolecular amination of C(sp3)-Hbonds is described. This technology allows for efficient functionalization of complex molecules, including numerous pharmaceutical targets. The combination of pivalonitrile as a solvent, Al2O3 as an additive, and phenyl sulfamate as a nitrogen source affords differential reaction performance and substrate scope. Mechanistic data strongly implicate a pathway for catalyst decomposition that initiates with solvent oxidation, thus providing rationale for the marked influence of pivalonitrile on this reaction process. [ABSTRACT FROM AUTHOR]

This paper presents a detailed case study on the effective upcycling of a post‐industrial plastic waste stream to a renewed compound, fit for re‐use in a new application. The material investigated was a PET‐contaminated recycled PP, destined for a high‐impact, medium‐stiffness application. After two research trials and one large‐scale industrial trial, an upcycling formulation was determined to bring the recyclate to the required level of the new application, thus closing this specific material loop within the case company. The used methodology adheres to the Design from Recycling principle, in which industrially available (mechanically) recycled polymer materials are matched to potential new products. The design strategy starts from either the properties of an available recycled polymer (and then defines the product) or from the functional boundary conditions of the product (and then selects the material and/or an optional material upcycling step). The Design from Recycling principles can elegantly be combined with those of Design for Recycling, within the framework of a Circular Economy. POLYM. ENG. SCI., 58:528–534, 2018. © 2017 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

The prognosis of gastric and oesophageal adenocarcinoma remains generally poor. However, mounting evidence suggests a positive role of human epidermal growth factor receptor-2 (HER-2) expression in the prognosis of patients with these cancers. In this work, the patterns of HER-2 protein expression were determined in patients with gastric or oesophageal adenocarcinoma. Retrospectively, we reviewed records of gastric and oesophageal biopsies received from 2008 to 2012 and their corresponding archived formalin-fixed paraffin-embedded tissue blocks selected for immunohistochemical analysis. The prevalence of gastric and oesophageal adenocarcinomas and their association with HER-2 protein overexpression were evaluated. Gastric adenocarcinoma made up 18.79% of the gastric biopsies reviewed, and majority of these cancers occurred in males. Regarding the tumour type, HER-2 overexpression was common in the intestinal subtype compared to the diffuse type. Although squamous cell carcinoma was observed to be the commonest (31%) tumour type in the oesophagus compared to adenocarcinoma (8.79%), HER-2 was overexpressed in 42.9% of oesophageal adenocarcinomas, like gastric adenocarcinoma (41.4%). There is a high prevalence of gastric and oesophageal adenocarcinoma, with significant overexpression of HER-2 in these tumours, a window of hope for the management of patients with these cancers. [ABSTRACT FROM AUTHOR]

Background: It was this study's objective to evaluate the echocardiographic characteristics and flow patterns in abdominal arteries of Fontan patients before the onset of protein‐losing enteropathy (PLE) or plastic bronchitis (PB). Design: In this retrospective cohort investigation, we examined 170 Fontan patients from 32 different centers who had undergone echocardiographic and Doppler ultrasound examinations between June 2006 and May 2013. Follow‐up questionnaires were completed by 105 patients a median of 5.3 (1.5–8.5) years later to evaluate whether one of the complications had occurred since the examinations. Results: A total of 91 patients never developed PLE or PB (“non‐PLE/PB”); they were compared to 14 affected patients. Eight of the 14 patients had already been diagnosed with “present PLE/PB” when examined. Six “future PLE/PB” patients developed those complications later on and were identified on follow‐up. The “future PLE/PB” patients presented significantly slower diastolic flow velocities in the celiac artery (0.1 (0.1–0.5) m/s vs 0.3 (0.1–1.0) m/s (P = .04) and in the superior mesenteric artery (0.0 (0.0–0.2) m/s vs 0.2 (0.0–0.6) m/s, P = .02) than the “non‐PLE/PB” group. Median resistance indices in the celiac artery were significantly higher (0.9 (0.8–0.9) m/s vs 0.8 (0.6–0.9) m/s, (P = .01)) even before the onset of PLE or PB. Conclusion: An elevated flow resistance in the celiac artery may prevail in Fontan patients before the clinical manifestation of PLE or PB. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinomas (NPC) are endemic in Far East Asia and commonly harbour Epstein-Barr virus (EBV) which is known to serve as a key oncogenic promoter. Human papillomavirus (HPV) is known to contribute to the pathogenesis of NPC. However, in Ghana these two viruses have not been linked to NPC prevalence. This study was designed to determine the HPV genotypes and EBV involved in NPC tissue biopsies. A retrospective study design involving 72 formalin-fixed paraffin-embedded tissue (FFPET) samples of NPC from 2006 to 2012 were retrieved from the Department of Pathology, University of Ghana School of Biomedical and Allied Health Sciences. Sections were taken for histological analysis and for DNA lysate preparation. The DNA lysates were subjected to polymerase chain reaction (PCR) analysis to determine the presence of HPV genotypes and EBV. HPV specific primers were used to type for fourteen HPV genotypes (HPV-16, 18, 6/11, 31, 33, 35, 44, 42, 43, 45, 56, 52, 58, and 59). Out of the 72 NPC biopsies analyzed by PCR, EBV DNA was present in 18 (25%) cases and HPV DNA in 14 (19.23%). High risk HPV (HR-HPV) genotypes 18 and 31 were associated with the NPC. There were 3 (4.2%) cases of coinfection by both viruses. The EBV DNA present in the undifferentiated variant of the NPC and the histopathology of the NPC in Ghana is similar to the type described in endemic areas. [ABSTRACT FROM AUTHOR]

Objectives: The association between HLA class II alleles and susceptibility to sarcoidosis is well documented. Further, the HLA-DRB1 15 and DQB1 0602 haplotype has been considered as a marker for both chronic and severe disease. Splenomegaly has been proposed as a marker for severity and activity in sarcoidosis, although its functional mechanism is unknown. In other diseases, HLA class II alleles can be markers for splenomegaly. We therefore set out to test the hypothesis that the primary DRB1 15-DQB1 0602 link in sarcoidosis would be to splenomegaly. Design and Subjects: We performed abdominal ultrasonography to evaluate the prevalence and extent of splenomegaly and genotyped for HLA-DRB1 and DQB1 using allele or allele group specific primers in polymerase-chain-reaction on 138 Japanese sarcoidosis patients as case comparison study. Furthermore, we explored their relationship with other clinically important indices, e.g. chest radiograph stage, serum angiotensin-converting enzyme (ACE) concentration and duration of disease. Results: Splenomegaly was detected in 37 (26.8%) sarcoidosis patients. DQB1 0602 showed associations with splenomegaly (P < 0.0001) and longer disease duration (P = 0.007). In addition, higher chest radiograph staging was associated with both DQB1 0602 (P = 0.02) and splenomegaly (P = 0.003). The presence of splenomegaly was associated with higher serum ACE concentration (P < 0.0001). Conclusion: We conclude that in the Japanese population the primary association of HLA class II DQB1 0602 is with splenomegaly. This allele is also a marker for chronicity and lung disease severity. On the other hand, the presence of splenomegaly is a marker for severity and activity. Further studies are needed to explore the relationship between splenomegaly and sarcoidosis in other ethnic groups and its association with HLA-DQB1 0602. [ABSTRACT FROM AUTHOR]

Objective To investigate novel systemic sclerosis (SSc) autoantibodies in autoantibody-negative patients and establish clinical associations. Methods Serum samples and clinical data for 548 patients with SSc were collected. Routine serologic techniques were used to test the serum samples for known SSc autoantibodies, and samples with negative results were further investigated by radiolabeled-protein immunoprecipitation assay. Sera that immunoprecipitated a novel 30-kd band were analyzed by indirect immunofluorescence and immunoprecipitation, using depleted cell extracts to establish a common reactivity. Mass spectrometry was performed to identify the novel autoantigen, and the results were confirmed using commercial antibodies. Sera from 426 patients with other forms of connective tissue disease, 103 with rheumatoid arthritis, 114 with idiopathic interstitial lung disease (ILD), and 150 healthy subjects were serotyped as controls. Results A novel autoantigen with a molecular weight of ∼30 kd was recognized by 7 sera from patients with SSc, 6 of whom had ILD, and by no controls. Six of the patients had diffuse cutaneous involvement, and 4 had overlap features with other autoimmune diseases. Immunodepletion experiments indicated that all samples targeted the same autoantigen, and mass spectrometry identified the novel autoantigen as eukaryotic initiation factor 2B (eIF2B). Conclusion We report the identification of a novel autoantibody (anti-eIF2B) in a small number of patients with SSc (∼1%); this autoantibody is closely associated with diffuse cutaneous manifestations and the presence of ILD. [ABSTRACT FROM AUTHOR]

The young leaves of Vernonia amygdalina are often utilized as vegetable and for medicinal purpose compared to the old leaves. This study was designed to evaluate and compare the antidiabetic effects between ethanolic leaf extracts of old and young V. amygdalina on streptozotocin (STZ) induced diabetic rat for four weeks. Preliminary screening of both young and old ethanolic extracts revealed the presence of the same phytochemicals except flavonoids which was only present in the old V. amygdalina. Difference in antioxidant power between the young and old leaf extracts was statistically significant (p<0.05). Both leaf extracts produced a significant (p<0.05) antihyperglycaemic effect. Also results from treated rats revealed increasing effect in some haematological parameters. Similarly, the higher dose (300 mg/kg) of both extracts significantly (p<0.05) reduced serum ALT, AST, and ALP levels as compared to the diabetic control rats. Results also showed significant (p<0.05) decrease in LDL-C and VLDL-C in the extract-treated rats with a corresponding increase in HDL-C, as compared to the diabetic control rats. Moreover histopathological analysis revealed ameliorative effect of pathological insults induced by the STZ in the pancreas, liver, and spleen, most significantly the regeneration of the beta cells of the islets of Langerhans in treated rats. [ABSTRACT FROM AUTHOR]

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Aims The recent recognition that ovarian carcinoma is composed of five distinct disease entities has served to increase the value of accurate histotyping. Reliable identification of histotypes is essential for the success of studies testing novel therapies, as well as for biomarker discovery research. The aim of this study was to examine the utility of a nine-marker immunohistochemical ( IHC) panel, designated the Calculator for Ovarian Subtype Prediction ( COSP), to reliably reproduce the consensus diagnosis of two expert gynaecological pathologists. Methods and results A total of 423 cases from the AGO- OVAR11 trial were evaluated using the COSP IHC panel, and compared to original diagnoses from >100 local contributing pathologists and independent expert gynaecopathology review. The overall concordance between COSP and expert review was 89%; in cases where a local pathologist's diagnosis was confirmed by COSP, the expert gynaecopathologist also agreed in 97.5% of cases. Conclusions The incorporation of COSP into a high-throughput diagnostic review algorithm will decrease the need for expert review by identifying a small number of difficult cases that truly require expert review. This modification will serve to increase the efficiency of the diagnostic review process, which will probably serve to reduce operational costs and expedite translational studies on ovarian carcinoma. [ABSTRACT FROM AUTHOR]

C ‐ H ‐ Insertion: Eine Methode für die intermolekulare Aminierung von C ‐ H ‐ Bindungen wird beschrieben, die limitierende Substratmengen und eine bequeme, Phenol ‐ abgeleitete Stickstoffquelle einsetzt. Selektivitäts ‐ und mechanistische Studien ergeben, dass die sterische Wechselwirkung zwischen dem Substrat und dem aktiven Oxidans entscheidend für die Produktselektivität ist. [ABSTRACT FROM AUTHOR]

Most principal-agent literature of nonprofit organizations has focused on the relationship between board members and managers. However, in addition to the role as an agent of the board, the manager also performs a role as principal with respect to the nonprofit employees. By using a discrete choice experiment, we identify the objectives of managers and employees in nonprofit organizations and assess the presence of agency problems in this relationship. Our sample consists of 76 headmasters, 161 teachers, and 39 administrative employees in 74 secondary nonprofit schools in Belgium. We find that the six objectives set out in the experiment play an important role for both headmasters and subordinate staff. However, the results also indicate that some of these objectives are significantly more important for the headmasters. In sum, our results suggest that agency theory and stewardship theory are not necessarily in conflict with each other but can be combined into a more general governance framework for nonprofit organizations. Consequently, we argue that incentive structures that incorporate different types of objectives can facilitate the recruitment and retention of employees in nonprofit organizations. [ABSTRACT FROM AUTHOR]

Pirfenidone has been shown in three recently published trials to slow down the progression of the devastating interstitial lung disease, idiopathic pulmonary fibrosis ( IPF). The precise mechanisms that initiate and perpetuate the histopathological process leading to lung fibrosis in IPF are still uncertain, but increased concentrations of reactive oxidative species and fibrogenetic factors have been observed in the pulmonary tissue of patients. Although the exact mechanisms of its action are unknown, pirfenidone is a small molecule with antifibrotic and some hydroxyl scavenger properties that has recently been approved in Europe and elsewhere for the treatment of IPF. Along with the new ATS/ ERS/ JRS/ ALAT 2011 statement for ' Evidence Based Guidelines for Diagnosis and Management', there is now a more profound basis for offering IPF patients an evidence-based evaluation and treatment. This review summarizes the background to the recommended use of pirfenidone for the treatment of IPF. Please cite this paper as: Hilberg O, Simonsen U, du Bois R and Bendstrup E. Pirfenidone: significant treatment effects in idiopathic pulmonary fibrosis. Clin Respir J 2012; 6: 131-143. [ABSTRACT FROM AUTHOR]

Volumetric computed cone beam tomography offers a number of significant advantages over conventional intraoral and extraoral panoramic radiography, as well as computed tomography. To date, periodontal diagnosis has relied heavily on the assessment of both intraoral radiographs and extraoral panoramic radiographs. With emerging technology in radiology there has been considerable interest in the role that volumetric cone beam computed tomography might play in periodontal diagnostics. This narrative reviews the current evidence and considers whether there is a role for volumetric cone beam computed tomography in periodontics. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Seretide (GlaxoSmithKline, UK) is a combination inhaler which contains both fluticasone (FP) and salmeterol (SM). • A generic fluticasone/salmeterol (FP/SM) combination inhaler (Neolab, UK) has recently been developed. • Determination of therapeutic equivalence is essential in the development of generic products. WHAT THIS STUDY ADDS • This paper determines that in vitro fine particle dose may not predict pharmacokinetic and systemic pharmacodynamic outcomes. • This paper shows that the generic and reference products were equivalent in terms of FP, but not SM pharmacokinetics. • No significant differences were found between generic and reference products in terms of either adrenal suppression or hypokalaemia. AIM To compare a test version of HFA fluticasone/salmeterol (FP/SM) combination inhaler (Neolab, UK) with the reference product Seretide (GlaxoSmithKline, UK). METHODS An in vitro Anderson cascade impactor was used to compare the fine particle dose (<4.7 µm). Two separate randomized cross-over studies were performed to compare the systemic bioavailability of test vs. reference (T vs. R) formulations of FP/SM 250/25 µg pMDI in healthy volunteers. In study 1 blood pharmacokinetic analysis using oral charcoal block was performed over 24 h following a single dose of four puffs via pMDI alone. In study 2 systemic bioactivity was measured following single doses of four and eight puffs via a spacer device: serum potassium (K+) to reflect SM, and overnight urinary cortisol : creatinine (OUCC) for FP. An early pharmacokinetic profile was also assessed over 120 min. RESULTS The in vitro fine particle dose was similar for test vs. reference pMDI alone and via spacer. The results of both studies were consistent: No significant differences between formulations were seen in terms of FP kinetics. Analysis of SM kinetics revealed superiority of the test product. No significant dose–response or difference in T : R ratio was noted for OUCC. Fall in K+ revealed a significant dose–response with a non-significant T : R ratio. CONCLUSIONS The in vitro fine particle dose may not predict pharmacokinetic and systemic pharmacodynamic outcomes. Single dosing studies with fluticasone/salmeterol 250/25 µg via pMDI or with spacer showed pharmacokinetic equivalence with FP, but not SM. No significant difference between formulations was seen with either adrenal suppression or hypokalaemia. [ABSTRACT FROM AUTHOR]

Lung complications may occur as a result of hepatic disease from any cause and represent a highly heterogeneous group of conditions. Early recognition of such complications may be challenging but is crucial both in forming a meaningful differential diagnosis and in avoiding severe sequelae and irreversible damage. Although a number of different pathogenetic mechanisms are likely to be involved, chronic liver dysfunction may cause pulmonary manifestations because of alterations in the production or clearance of circulating cytokines and other mediators. This is likely to be the case in hepatopulmonary syndrome, portopulmonary hypertension and primary biliary cirrhosis, although their pathogenesis remains largely speculative. Moreover, the severity of lung manifestations may or may not correspond to that of liver impairment, making disease outcome often unpredictable. Congenital and inflammatory disorders, however, may primarily affect both the liver and lung. Apart from specific diseases, a number of medications can also result in pulmonary and hepatic toxic effects. This is particularly important with cytokine therapy – used to treat viral hepatitis, among other diseases – because treatment consists of drug discontinuation, which, in turn, may cause reactivation or progression of the underlying disease that the drug was used for. This review summarizes salient diagnostic and therapeutic aspects of these often misdiagnosed conditions and highlights, based on the most recent literature, the need for early referral of such patients to centres with specific expertise in the field. In fact, a multidisciplinary approach involving pulmonologists, hepatologists and, in particularly severe cases, transplant surgeons has been already proven successful. [ABSTRACT FROM AUTHOR]

Detecting agency problems is an important task when assessing the effectiveness of a nonprofit organization's governance. A first step is to examine the objectives of principals and agents and determine whether there is a systematic difference between them. Using a discrete choice experiment, we identify the objectives of board chairpersons (principals) and headmasters (agents) of Flemish nonprofit schools. We find systematic differences between the two groups. Of the seven possible objectives set out in the experiment, six are relevant for both headmasters and board chairpersons. For four of these, the preferences of both groups differ significantly. Whereas ideological values play an important role for both the board and the headmaster, they are significantly more important for the board. Both parties dislike having a large number of pupils, and the disutility is larger for the board. With respect to job satisfaction and pupil satisfaction, we find the opposite: while the board is prepared to give up pupil and job satisfaction in favor of the other objectives, these two objectives score very high on the priority list of the headmasters. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the feasibility and diagnostic validity of the sentinel lymph node technique in detecting inguinal lymph node metastases in patients with invasive squamous cancer of the vulva. Design: Retrospective analysis of the in-house tumor registry. Setting: Dr. Horst Schmidt Klinik, a tertiary gynecologic oncology unit in Wiesbaden, Germany, June 2000-May 2008. Population: All consecutive operated patients with primary envisaged diagnosis were included. Methods: The sentinel node identification technique was performed and patients were informed accordingly. Patients who consented and were found eligible underwent preoperative lymphscintigraphy on the day before surgery. Main Outcome Measures: Sentinel node detection in specimen from sentinel lymph node biopsy and from full lymphadenectomy (LNE); sentinel lymph node biopsy as a sole surgical groin procedure in patients with histological negative sentinel node; benefit with respect to side effects for sentinel lymph node biopsy compared to full LNE; complication rates; and recurrences of vulvar cancer. Results: In all, 46 of 59 patients with vulvar malignancy underwent inguinofemoral LNE, sentinel lymph node biopsy (SLB) of the groin followed by LNE, or SLB alone. Most patients had been diagnosed in the early stages of the disease. Since no false positive or false negative results were recorded, the sensitivity, specificity, positive predictive value and negative predictive value of the sentinel lymph node were 100%. However, in 6%, a sentinel lymph node could not be detected intraoperatively indicating a feasibility of 94%. Conclusion: The implementation of sentinel lymph node technique for groin staging in squamous cell vulvar cancer seems to provide a feasible and safe technique in tertiary gynecologic oncology. [ABSTRACT FROM AUTHOR]

This symposium presented recent progress of the pathogenesis and treatment of colorectal cancer (CRC). Field cancerization by modified stem cells may be the earliest changes associated with CRC. CD34+-immature myeloid cells are deeply involved in CRC invasion. Inflammatory mediators stimulate cancer progression. We must strive for a better understanding of the molecular mechanisms responsible for this connection. Serial analysis of gene expression data analysis has identified novel biomarkers for cancer detection and possible prognosis. Better endoscopic techniques are suitable for early detection and resection of colonic lesions. Chemoprevention of CRC using sulindac and aberrant crypt foci as a clinical endpoint have shown glutathione S-transferase π as a possible new target. A new drug delivery system using nanoparticles is being developed with SN-38, a biologically active metabolite of irinotecan. Survival of Japanese male patients with CRC is the best in the world due to lymph node dissection and surveillance. The use of laparoscopic surgery has increased, especially for advanced cancer. A treatment trial by the Sanin Study Group suggests that modified 5-fluorouracil and leucovorin with oxaliplatin treatment could be carried out in elderly patients. A great deal of information for understanding carcinogenesis and treatment has provided us with novel strategies for the management and prevention of CRC. ( Cancer Sci 2009; 100: 978–981) [ABSTRACT FROM AUTHOR]

The article cites a study assessing the bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) preponderance in patients with breast cancer. A retrospective study was carried on and a structured interviews were conducted to all patients. Results from the study show that 5.3% of the observed patients show prevalence of BP-ONJ.

Flemish non-profit schools have no legally imposed composition rules with respect to their board of directors. Hence, large variation exists in their size and composition. We argue that these differences in board composition can result in different policies followed by the board. To empirically test this hypothesis we question the board's chairpersons of Flemish non-profit schools about the objectives set forward by the board. Ordered probit regressions on the importance attached to different educational objectives provide support for our hypothesis and thus alert policy makers to account for the linkages between objectives and board characteristics when formulating legislation with respect to school board composition. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF), a severe lung disease with unknown aetiology, is thought to have an important genetic component. Single nucleotide polymorphism, C5507G, of the complement receptor 1 ( CR1) gene, which affects the number of CR1 molecules on erythrocytes, has been associated with susceptibility to IPF in a single European population. To replicate this finding, 53 Czech IPF patients with 203 Czech healthy control subjects and 70 English IPF patients with 149 English controls were investigated. In both populations, there were no significant differences in distribution of CR1 C5507G variants between IPF patients and their appropriate control groups. In conclusion, the association of the CR1 C5507G polymorphism with susceptibility to IPF was not reproducible in Czech and English populations. [ABSTRACT FROM AUTHOR]

Aim. Sarcoidosis is a heterogeneous disorder with a strong genetic influence. Genetic factors are also thought to influence disease severity and outcome. We sought to determine whether polymorphisms within CCR2 gene predispose to Löfgren’s syndrome – a clinically and genetically distinct sarcoidosis phenotype – and, importantly, whether this association is independent of the known association with the HLA-DRB1*0301 allele. Methods. We investigated 5 CCR2 variants and HLA-DRB1*0301 by sequence-specific primer (SSP) polymerase chain reaction (PCR) in 176 Spanish (76 Löfgren’s syndrome, 100 controls) and 387 Swedish subjects (126 Löfgren’s syndrome, 77 non-Löfgren sarcoidosis, 184 controls). Results. One of the deduced haplotypes ( CCR2 haplotype 2) was associated with Löfgren’s syndrome in both Spanish (OR: 2.03, uncorrected P = 0.02; permuted P = 0.041 vs. controls) and Swedish patients (OR: 3.02, uncorrected P = 0.0007; permuted P = 0.0027 vs. non-Löfgren sarcoidosis; OR: 2.46, uncorrected P = 0.0005; permuted P = 0.0031 vs. controls). HLA-DRB1*0301 allele frequency was also increased in Spanish (OR: 3.52, P = 0.0004 vs. controls) and Swedish patients with Löfgren’s syndrome (OR: 10.98, P < 0.0001 vs. non-Löfgren sarcoidosis, OR: 7.71, P < 0.0001 vs. controls). Finally, multivariate analysis revealed that the CCR2 association was independent of HLA-DRB1*0301 in both Spanish ( P = 0.02 vs. controls) and Swedish cohorts ( P = 0.002 vs. non-Löfgren sarcoidosis, P = 0.001 vs. controls). Conclusions. This study confirms that CCR2 haplotype 2 and HLA-DRB1*0301 are independent genetic risk factors for Löfgren’s syndrome. [ABSTRACT FROM AUTHOR]

Apoptosis may perpetuate some forms of inflammation. Of the apoptotic pathway proteins, Fas is particularly overexpressed in sarcoidosis. We hypothesized that Fas promoter single nucleotide polymorphisms (SNPs) contribute to the development and severity of sarcoidosis. Associations of known Fas promoter SNPs (−670, −690 and −1377) and deduced haplotypes with sarcoidosis and sarcoidosis severity were evaluated using matched case–control ( n = 656 pairs) and case–comparison ( n = 656) studies, respectively, using conditional logistic regression. Hardy–Weinberg equilibrium was confirmed for all three polymorphisms in African-Americans (AA), and for the −670 and −1377 in whites. Genotype and allele frequencies were significantly different between whites and AA. Race-stratified analysis revealed that a common haplotype, −1377G/−690T/−670G, was associated with sarcoidosis [odds ratio (OR) = 1.78, P = 0.05] only in AA. The haplotype −1377G/−690C/−670A was negatively associated with sarcoidosis (OR = 0.39, P = 0.03) only in AA. In conclusion, the consistency of these findings suggests that Fas promoter genetic variants may be related to sarcoidosis disease risk in AA. [ABSTRACT FROM AUTHOR]