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Item does not contain fulltext, OBJECTIVES: Free thyroxine (FT4) in serum is routinely measured in clinical practice to diagnose and monitor thyroid disease. Due to its concentration in picomolar range and the delicate equilibrium of free and protein-bound T4, accurate measurement is challenging. As a consequence, large inter-method differences in FT4 results exists. Optimal method design and standardization of the FT4 measurement is therefore necessary. The IFCC Working Group for Standardization of Thyroid Function Tests proposed a reference system with a conventional reference measurement procedure (cRMP) for FT4 in serum. In this study, we describe our FT4 candidate cRMP and its validation in clinical samples. METHODS: This candidate cRMP is based on equilibrium dialysis (ED) combined with determination of T4 with an isotope-dilution liquid chromatography tandem mass-spectrometry (ID-LC-MS/MS) procedure and was developed according to the endorsed conventions. Its accuracy, reliability, and comparability was investigated using human sera. RESULTS: It was shown that the candidate cRMP adhered to the conventions and its accuracy, precision, and robustness were adequate in serum of healthy volunteers. CONCLUSIONS: Our candidate cRMP measures FT4 accurately and performs well in serum matrix.

Contains fulltext : 214790.pdf (Publisher’s version ) (Closed access), The aim of the current study was to compare levels of oxytocin, cortisol, and testosterone in adolescents with either autism spectrum disorder (ASD), or oppositional defiant disorder (ODD)/conduct disorder (CD), and in typically developing individuals (TDI), and relate hormone levels to severity and subtype of aggression and callous-unemotional (CU) traits. Saliva concentrations of oxytocin, cortisol, and testosterone were assessed in 114 male participants (N = 49 ASD, N = 37 ODD/CD, N = 28 TDI,) aged 12-19 years (M = 15.4 years, SD = 1.9). The ASD and the ODD/CD groups had significantly lower levels of oxytocin than the TDI group, and the ODD/CD group had significantly higher levels of testosterone than the ASD group. There were no group effects on cortisol levels. Group differences remained for oxytocin after correcting for the influence of CU traits, but were not significant after controlling for aggression. Results for testosterone became non-significant after correction for either CU traits or aggression. Across groups, higher levels of CU traits were related to higher levels of cortisol and testosterone, however, proactive and reactive aggression were unrelated to all three hormonal levels. The current findings show that, regardless of cognitive ability or comorbid disorders, the diagnostic groups (ASD, ODD/CD) differ from each other by their hormonal levels, with the ASD group characterized by relative low level of oxytocin, and the ODD/CD group by a relative low level of oxytocin and high level of testosterone. These group effects were partly driven by differences in CU traits between the groups.

Contains fulltext : 220468.pdf (Publisher’s version ) (Open Access), OBJECTIVE: The plasminogen activator system (PAS) and vascular endothelial growth factor (VEGF) are important in the carcinogenesis and play a key role in cancer invasion and mediating metastasis of carcinomas. The aim of the study was to evaluate the correlation of serum levels of VEGF and components of the PAS with clinicopathological risk factors and outcome in patients with endometrial cancer (EC). METHODS: Preoperative blood was collected from 173 patients treated for EC between 1999 and 2009. Serum concentrations of VEGF, urokinase plasminogen activator (uPA) tissue plasminogen activator (tPA), plasminogen activator inhibitor type-1 (PAI-1) and -2 (PAI-2) were assessed by enzyme-linked immunosorbent assays (ELISA). RESULTS: Serum levels of VEGF and components of the PAS were significantly associated with stage of the disease, tumor histology, tumor grade, myometrial invasion (MI), presence of lymphovascular space invasion (LVSI) and lymph node metastases (LNM). Preoperative serum levels of PAI-1 and -2 and tPA were higher in patients who experienced a recurrence than in patients who remained disease free (p < 0.01). PAI-1 and -2 and tPA were significantly independent prognostic factors for DFS with a HR of 3.85 (95% CI 1.84-8.07), 3.90 (95% CI 1.75-8.66) and 2.53 (95% CI 1.16-5.55), respectively. PAI-1 and tPA turned out to be independent prognostic factors for OS, with a HR of 2.09 (95% CI 1.08-4.05) and 2.16 (95% CI 1.06-4.44), respectively. CONCLUSION: Serum levels of VEGF and components of the PAS at primary diagnosis were associated with well-known clinicopathological risk factors such as; FIGO stage, tumor histology, tumor grade, MI, LVSI and LNM. High concentrations of PAI-1 and-2 and tPA are independent factors for poor prognosis in patients with endometrial cancer.

BACKGROUND: In the generalised epidemics of sub-Saharan Africa (SSA), human immunodeficiency virus (HIV) prevalence shows patterns of clustered micro-epidemics. We mapped and characterised these high-prevalence areas for young adults (15-29 years of age), as a proxy for areas with high levels of transmission, for 7 countries in Eastern and Southern Africa: Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS AND FINDINGS: We used geolocated survey data from the most recent United States Agency for International Development (USAID) demographic and health surveys (DHSs) and AIDS indicator surveys (AISs) (collected between 2008-2009 and 2015-2016), which included about 113,000 adults-of which there were about 53,000 young adults (27,000 women, 28,000 men)-from over 3,500 sample locations. First, ordinary kriging was applied to predict HIV prevalence at unmeasured locations. Second, we explored to what extent behavioural, socioeconomic, and environmental factors explain HIV prevalence at the individual- and sample-location level, by developing a series of multilevel multivariable logistic regression models and geospatially visualising unexplained model heterogeneity. National-level HIV prevalence for young adults ranged from 2.2% in Tanzania to 7.7% in Mozambique. However, at the subnational level, we found areas with prevalence among young adults as high as 11% or 15% alternating with areas with prevalence between 0% and 2%, suggesting the existence of areas with high levels of transmission Overall, 15.6% of heterogeneity could be explained by an interplay of known behavioural, socioeconomic, and environmental factors. Maps of the interpolated random effect estimates show that environmental variables, representing indicators of economic activity, were most powerful in explaining high-prevalence areas. Main study limitations were the inability to infer causality due to the cross-sectional nature of the surveys and the likely under-sampling of key p

Diagnostic imaging often outperforms the surgeon's ability to identify small structures during therapeutic procedures. Smart soft tissue markers that translate the sensitivity of diagnostic imaging into optimal therapeutic intervention are therefore highly warranted. This paper presents a unique adaptable liquid soft tissue marker system based on functionalized carbohydrates (Carbo-gel). The liquid state of these markers allows for high-precision placement under image guidance using thin needles. Based on step-by-step modifications, the image features and mechanical properties of markers can be optimized to bridge diagnostic imaging and specific therapeutic interventions. The performance of Carbo-gel is demonstrated for markers that (i) have radiographic, magnetic resonance, and ultrasound visibility; (ii) are palpable and visible; and (iii) are localizable by near-infrared fluorescence and radio guidance. The study demonstrates encouraging proof of concept for the liquid marker system as a well-tolerated multimodal imaging marker that can improve image-guided radiotherapy and surgical interventions, including robotic surgery.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is well established and the most effective treatment for advanced Parkinson's disease (PD). However, little is known of the long-term effects. Objectives: The aim of this study was to examine the long-term effects of STN-DBS in PD and evaluate the effect of reprogramming after more than 8 years of treatment. Methods: A total of 82 patients underwent surgery in Copenhagen between 2001 and 2008. Before surgery and at 8 to 15 years follow-up, the patients were rated with the Unified Parkinson's Disease Rating Scale (UPDRS) with and without stimulation and medicine. Furthermore, at long-term follow-up, the patients were offered a systemic reprogramming of the stimulation settings. Data from patients' medical records were collected. The mean (range) age at surgery was 60 (42–78) years, and the duration of disease was 13 (5–25) years. A total of 30 patients completed the long-term follow-up. Results: The mean reduction of the motor UPDRS by medication before surgery was 52%. The improvement of motor UPDRS with stimulation alone compared with motor UPDRS with neither stimulation nor medication was 61% at 1 year and 39% at 8 to 15 years after surgery (before reprogramming). Compared with before surgery, medication was reduced by 55% after 1 year and 44% after 8 to 15 years. After reprogramming, most patients improved. Conclusions: STN-DBS remains effective in the long run, with a sustained reduction of medication in the 30 of 82 patients available for long-term follow-up. Reprogramming is effective even in the late stages of PD and after many years of treatment.

Ashodaya Samithi, an organization run by and for female, male, and transgender sex workers in Mysore, India, has worked since 2004 to prevent sexually transmitted infection (STI)/human immunodeficiency virus (HIV) transmission and improve HIV cascade outcomes. We reviewed published and programmatic data, including measures of coverage, uptake, utilization and retention, and relate STI/HIV outcomes to evolving phases of community mobilization. Early interventions designed “for” sex workers mapped areas of sex work and reached half the sex workers in Mysore with condoms and STI services. By late 2005, when Ashodaya Samithi registered as a community-based organization, interventions were implemented “with” sex workers as active partners. Microplanning was introduced to enable peer educators to better organize and monitor their outreach work to reach full coverage. By 2008, programs were run “by” sex workers, with active community decision making. Program data show complete coverage of community outreach and greater than 90% clinic attendance for quarterly checkups by 2010. Reported condom use with last occasional client increased from 65% to 90%. Surveys documented halving of HIV and syphilis prevalence between 2004 and 2009, while gonorrhoea declined by 80%. Between 2005 and 2013, clinic checkups tripled, whereas the number of STIs requiring treatment declined by 99%. New HIV infections also declined, and Ashodaya achieved strong cascade outcomes for HIV testing, antiretroviral treatment linkage, and retention. Program performance dropped markedly during several periods of interrupted funding, then rebounded when restored. Ashodaya appear to have achieved rapid STI/HIV control with community-led approaches including microplanning. Available data support near elimination of curable STIs and optimal cascade outcomes.

Contains fulltext : 205071.pdf (publisher's version ) (Open Access)

Basement membrane transmigration during embryonal development, tissue homeostasis and tumor invasion relies on invadosomes, a collective term for invadopodia and podosomes. An adequate structural framework for this process is still missing. Here, we reveal the modular actin nano-architecture that enables podosome protrusion and mechanosensing. The podosome protrusive core contains a central branched actin module encased by a linear actin module, each harboring specific actin interactors and actin isoforms. From the core, two actin modules radiate: ventral filaments bound by vinculin and connected to the plasma membrane and dorsal interpodosomal filaments crosslinked by myosin IIA. On stiff substrates, the actin modules mediate long-range substrate exploration, associated with degradative behavior. On compliant substrates, the vinculin-bound ventral actin filaments shorten, resulting in short-range connectivity and a focally protrusive, non-degradative state. Our findings redefine podosome nanoscale architecture and reveal a paradigm for how actin modularity drives invadosome mechanosensing in cells that breach tissue boundaries.

Introduction: UNAIDS’ goal of ending AIDS by 2030 is unreachable without better targeting of testing, prevention and care. Female sex workers (FSW) in Zimbabwe are at high risk of HIV acquisition and transmission. Here, we report on collated programme and research data from Zimbabwe's national sex work programme. We also assess the potential for wider population impact of FSW programmes by modelling the impact on HIV incidence of eliminating transmission through FSW (i.e. calcu

Peer education with micro-planning has been integral to scaling up key population (KP) HIV/STI programmes in Kenya since 2013. Micro-planning reinforces community cohesion within peer networks and standardizes programme inputs, processes and targets for outreach, including peer educator (PE) workloads. We assessed programme performance for outreach-in relation to the mean number of KPs for which one PE is responsible (KP:PE ratio)-and effects on HIV/STI service utilisation. Quarterly programmatic monitoring data were analysed from October 2013 to September 2016 from implementing partners working with female sex workers (FSWs) and men who have sex with men (MSM) across the country. All implementing partners are expected to follow national guidelines and receive micro-planning training for PEs with support from a Technical Support Unit for KP programmes. We examined correlations between KP:PE ratios and regular outreach contacts, condom distribution, risk reduction counselling, STI screening, HIV testing and violence reporting by KPs. Kenya conducted population size estimates (PSEs) of KPs in 2012. From 2013 to 2016, KP programmes were scaled up to reach 85% of FSWs (PSE 133,675) and 90% of MSM (PSE 18,460). Overall, mean KP:PE ratios decreased from 147 to 91 for FSWs, and from 79 to 58 for MSM. Lower KP:PE ratios, up to 90:1 for FSW and 60:1 for MSM, were significantly associated with more regular outreach contacts (p<0.001), as well as more frequent risk reduction counselling (p<0.001), STI screening (p<0.001) and HIV testing (p<0.001). Condom distribution and reporting of violence by KPs did not differ significantly between the two groups over all time periods. Micro-planning with adequate KP:PE ratios is an effective approach to scaling up HIV prevention programmes among KPs, resulting in high levels of programme uptake and service utilisation.

The undesired oxidation of SO2 was studied experimentally at elevated pressures of up to 4.5 bar across two commercial vanadium-based (1.2 and 3 wt% V2O5) selective catalytic reduction (SCR) catalysts. This pressure range is of interest for preturbine SCR reactor configuration for NOx reduction on ships. The residence time in the catalyst was kept constant, independent on pressure, by adjusting the total flow rate. The conversion of SO2 was of the order 0.2–3% at temperatures of 300–400 °C and was independent of the pressure. Based on the measured conversion of SO2, the kinetics were fitted using an nth order rate expression. The reaction order of SO2 was found close to 1, and the reaction order of SO3 was found close to 0, also at increased pressures of up to 4.5 bar. The rate of SO2 oxidation was clearly promoted by the presence of 1000 ppm NOx at elevated pressure; however, at atmospheric pressure, the effect was within experimental uncertainty. The promoting effect is explained by a catalyzed redox reaction between SO2 and NO2, and since more NO2 is formed at elevated pressure, a higher degree of promotion by NOx is observed at elevated pressures.