Predictors of Loss to Follow Up and Mortality Among Children ?12 Years Receiving Anti Retroviral Therapy During the First Year at a Referral Hospital in Bali

Background and purpose: Many HIV-infected children in Bali have started antiretroviral therapy (ART), but loss to follow up (LTFU) is a continuing concern, and the issue of childhood adherence is more complex compared to adults.Methods: This was a retrospective study among cohort of 138 HIV+ children on ART in Sanglah General Hospital, Denpasar, Bali from January 2010 to December 2015. Kaplan-Meier analysis was used to describe incidence and median time to LTFU/mortality and Cox Proportional Hazard Model was used to identify predictors. Variables which were analysed were socio-demographic characteristics, birth history, care giver and clinical condition of the children.Results: Mean age when starting ARV therapy was 3.21 years. About 25% experienced LTFU/death by 9.1 month resulting in an incidence rate of 3.28 per 100 child month. The higher the WHO stage, the higher the risk for LTFU/mortality along with low body weight (AHR=0.90; 95%CI: 0.82-0.99).Conclusion: Clinical characteristics were found as predictors for LTFU/mortality among children on ART

Concomitant therapy with Cineole (Eucalyptole) reduces exacerbations in COPD: A placebo-controlled double-blind trial

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3D Surface Measurement for Medical Application—Technical Comparison of Two Established Industrial Surface Scanning Systems

In 3D mapping of flexible surfaces (e.g. human faces) measurement errors due to movement or positioning occur. Aggravated by equipment- or researcher-caused mistakes considerable deviations can result. Therefore first the appliances' precision handling and reliability in clinical environment must be established. Aim of this study was to investigate accuracy and precision of two contact-free 3D measurement systems (white light vs. laser). Standard specimens of known diameter for sphere deviation, touch deviation and plane deviation were tested. Both systems are appropriate for medical application acquiring solid data (<mm). The more complex white-light system shows better accuracy at 0.2s measuring time. The laser system is superior concerning robustness, while accuracy is poorer and input time (1.5-2.5s) longer. Due to the clinical demand the white-light system is superior in a laboratory environment, while the laser system is easier to handle under non-laboratory condition

Reperfusion after Fibrinolytic Therapy (RAFT) : an open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention

Background The safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI. Objectives We conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI. Methods Between 2010–2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score. Results The trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52–7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83–14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin. Conclusions Whether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022)

Following the Nonthermal Phase Transition in Niobium Dioxide by Time-Resolved Harmonic Spectroscopy

Photoinduced phase transitions in correlated materials promise diverse applications from ultrafast switches to optoelectronics. Resolving those transitions and possible metastable phases temporally are key enablers for these applications, but challenge existing experimental approaches. Extreme nonlinear optics can help probe phase changes, as higher-order nonlinearities have higher sensitivity and temporal resolution to band structure and lattice deformations. Here the ultrafast transition from the semiconducting to the metallic phases in polycrystalline thin-film NbO2 is investigated by time-resolved harmonic spectroscopy. The emission strength of all harmonic orders shows a steplike suppression when the excitation fluence exceeds a threshold (∼11-12 mJ/cm2), below the fluence required for the thermal transition - a signature of the nonthermal emergence of a metallic phase within 100 ± 20 fs. This observation is backed by full ab initio simulations as well as a 1D chain model of high-harmonic generation from both phases. Our results demonstrate femtosecond harmonic probing of phase transitions and nonthermal dynamics in solids.</p

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Biological Parts for Kluyveromyces marxianus Synthetic Biology

Kluyveromyces marxianus is a non-conventional yeast whose physiology and metabolism lends itself to diverse biotechnological applications. While the wild-type yeast is already in use for producing fragrances and fermented products, the lack of standardised tools for its genetic and metabolic engineering prevent it from being used as a next-generation cell factory for bio-based chemicals. In this paper, we bring together and characterise a set of native K. marxianus parts for the expression of multiple genes for metabolic engineering and synthetic biology. All parts are cloned and stored according to the MoClo/Yeast Tool Kit standard for quick sharing and rapid construction. Using available genomic and transcriptomic data, we have selected promoters and terminators to fine-tune constitutive and inducible gene expression. The collection includes a number of known centromeres and autonomously replication sequences (ARS). We also provide a number of chromosomal integration sites selected for efficiency or visible phenotypes for rapid screening. Finally, we provide a single-plasmid CRISPR/Cas9 platform for genome engineering and facilitated gene targeting, and rationally create auxotrophic strains to expand the common range of selection markers available to K. marxianus. The curated and characterised tools we have provided in this kit will serve as a base to efficiently build next-generation cell factories from this alternative yeast. Plasmids containing all parts are available at Addgene for public distribution

Significant improvement in freshwater invertebrate biodiversity in all types of English rivers over the past 30 years

There remains a persistent concern that freshwater biodiversity is in decline and being threatened by pollution. As the UK, and particularly England, is a densely populated nation with rivers of modest dilution capacity, this location is very suitable to examine how freshwater biodiversity has responded to human pressures over the past 30 years. A long-term dataset of 223,325 freshwater macroinvertebrate records from 1989 to 2018 for England was retrieved and examined. A sub-set of approximately 200 sites per English Region (1515 sites in total with 62,514 samples), with the longest and most consistent records were matched with predicted wastewater exposure, upstream land cover and terrain characteristics (latitude, altitude, slope gradient and flow discharge). To understand changes in macroinvertebrate diversity and sensitivity with respect to these parameters, the biotic indices of (i) overall family richness, (ii) Ephemeroptera, Plecoptera, Trichoptera (EPT) family richness, and (iii) the Biological Monitoring Working Party (BMWP) scores of NTAXA (number of scoring taxa) and (iv) ASPT (average score per taxon) were selected. A review of how close the BMWP scores come to those expected at minimally impacted reference sites was included. For all latitudes, altitudes, channel slope, river size, wastewater exposure levels, and differing proportions of upstream woodland, seminatural, arable and urban land cover, all diversity or sensitivity indices examined improved over this period, although this improvement has slowed in some cases post 2003. Mean overall family richness has increased from 15 to 25 family groups, a 66 % improvement. The improvement in mean EPT family richness (3 to 10 families, >300 % improvement), which are considered to be particularly sensitive to pollution, implies macroinvertebrate diversity has benefited from a national improvement in critical components of water quality