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Chronic obstructive pulmonary disease – diagnosis and classification of severity

Chronic obstructive pulmonary disease (COPD) is a common, progressive and preventable  non-communicable respiratory disorder. It is often confused with asthma and poorly understood by many lay people. The primary cause of COPD is tobacco smoking, but in the South African (SA) context, biomass fuel exposure/household pollution, tuberculosis, HIV and mining exposure are additional  important causes. There is a very high prevalence of COPD in SA and it is the third leading cause of  mortality globally. The diagnosis of COPD is based predominantly on symptoms, i.e. progressive  shortness of breath and cough in a patient with risk factors – usually smoking. Lung function testing is required to formally make the diagnosis, which places a significant hurdle in correctly identifying COPD in SA, given the limited access to spirometry in many areas. Spirometry is also required to grade the  severity of lung function obstruction. Severity assessment, which is used to plan a management strategy (predominantly bronchodilators with inhaled steroids in severe cases), combines symptoms, lung  function and exacerbations. Based on these 3 factors, a patient can be categorised into 1 of 4 groups and appropriate management instituted. Additional comorbidities, particularly cardiovascular and mental  illness, should also be evaluated. Early identification of COPD, with further avoidance of an aetiological cause such as smoking, is key in preventing disease progression. Appropriate therapy, comprising  non-pharmacological and pharmacological interventions and based on a comprehensive severity assessment, should result in symptom improvement and reduced risk for exacerbation

Demonstration of an ultra-short polarization converter in InGaAsP/InP membrane

An ultra-short (<10 µm length) polarization converter is demonstrated in an indium phosphide based membrane. Measurements show very high polarization conversion efficiency (97 %) with low excess losses (~ 1 dB)

Information-Derived Mechanistic Hypotheses for Structural Cardiotoxicity

Adverse events resulting from drug therapy can be a cause of drug withdrawal, reduced and or restricted clinical use, as well as a major economic burden for society. To increase the safety of new drugs, there is a need to better understand the mechanisms causing the adverse events. One way to derive new mechanistic hypotheses is by linking data on drug adverse events with the drugs’ biological targets. In this study, we have used data mining techniques and mutual information statistical approaches to find associations between reported adverse events collected from the FDA Adverse Event Reporting System and assay outcomes from ToxCast, with the aim to generate mechanistic hypotheses related to structural cardiotoxicity (morphological damage to cardiomyocytes and/or loss of viability). Our workflow identified 22 adverse event-assay outcome associations. From these associations, 10 implicated targets could be substantiated with evidence from previous studies reported in the literature. For two of the identified targets, we also describe a more detailed mechanism, forming putative adverse outcome pathways associated with structural cardiotoxicity. Our study also highlights the difficulties deriving these type of associations from the very limited amount of data available

A massive, quiescent galaxy at redshift of z=3.717

In the early Universe finding massive galaxies that have stopped forming stars present an observational challenge as their rest-frame ultraviolet emission is negligible and they can only be reliably identified by extremely deep near-infrared surveys. These have revealed the presence of massive, quiescent early-type galaxies appearing in the universe as early as z$\sim$2, an epoch 3 Gyr after the Big Bang. Their age and formation processes have now been explained by an improved generation of galaxy formation models where they form rapidly at z$\sim$3-4, consistent with the typical masses and ages derived from their observations. Deeper surveys have now reported evidence for populations of massive, quiescent galaxies at even higher redshifts and earlier times, however the evidence for their existence, and redshift, has relied entirely on coarsely sampled photometry. These early massive, quiescent galaxies are not predicted by the latest generation of theoretical models. Here, we report the spectroscopic confirmation of one of these galaxies at redshift z=3.717 with a stellar mass of 1.7$\times$10$^{11}$ M$_\odot$ whose absorption line spectrum shows no current star-formation and which has a derived age of nearly half the age of the Universe at this redshift. The observations demonstrates that the galaxy must have quickly formed the majority of its stars within the first billion years of cosmic history in an extreme and short starburst. This ancestral event is similar to those starting to be found by sub-mm wavelength surveys pointing to a possible connection between these two populations. Early formation of such massive systems is likely to require significant revisions to our picture of early galaxy assembly.Comment: 6 pages, 7 figures. This is the final preprint corresponding closely to the published version. Uploaded 6 months after publication in accordance with Nature polic

InP-based membrane photodetectors for optical interconnects to Si

We present the design, fabrication and a characterization of an InP-based membrane photodetector on an SOI wafer containing a Si-wiring photonic circuit. Waveguide losses in the Si-wiring circuit are below 5 dB/cm. Measured detector responsivity is 0.45 A/W. The photonic device fabrication is compatible with wafer scale processing steps, guaranteeing compatibility towards future generation electronic IC processing

Protein disulfide isomerases as CSF biomarkers for the neuronal response to tau pathology

Introduction: Cerebrospinal fluid (CSF) biomarkers for specific cellular disease processes are lacking for tauopathies. In this translational study we aimed to identify CSF biomarkers reflecting early tau pathology-associated unfolded protein response (UPR) activation. Methods: We employed mass spectrometry proteomics and targeted immunoanalysis in a combination of biomarker discovery in primary mouse neurons in vitro and validation in patient CSF from two independent large multicentre cohorts (EMIF-AD MBD, n = 310; PRIDE, n = 771). Results: First, we identify members of the protein disulfide isomerase (PDI) family in the neuronal UPR-activated secretome and validate secretion upon tau aggregation in vitro. Next, we demonstrate that PDIA1 and PDIA3 levels correlate with total- and phosphorylated-tau levels in CSF. PDIA1 levels are increased in CSF from AD patients compared to controls and patients with tau-unrelated frontotemporal and Lewy body dementia (LBD). Highlights: Neuronal unfolded protein response (UPR) activation induces the secretion of protein disulfide isomerases (PDIs) in vitro. PDIA1 is secreted upon tau aggregation in neurons in vitro. PDIA1 and PDIA3 levels correlate with total and phosphorylated tau levels in CSF. PDIA1 levels are increased in CSF from Alzheimer's disease (AD) patients compared to controls. PDIA1 levels are not increased in CSF from tau-unrelated frontotemporal dementia (FTD) and Lewy body dementia (LBD) patients