Main chain selective polymer degradation: controlled by the wavelength and assembly.

The advent of reversible deactivation radical polymerization (RDRP) revolutionized polymer chemistry and paved the way for accessing synthetic polymers with controlled sequences based on vinylic monomers. An inherent limitation of vinylic polymers stems from their all-carbon backbone, which limits both function and degradability. Herein, we report a synthetic strategy utilizing radical ring-opening polymerization (rROP) of complementary photoreactive cyclic monomers in combination with RDRP to embed photoresponsive functionality into desired blocks of polyvinyl polymers. Exploiting different absorbances of photoreactive cyclic monomers, it becomes possible to degrade blocks selectively by irradiation with either UVB or UVA light. Translating such primary structures of polymer sequences into higher order assemblies, the hydrophobicity of the photodegradable monomers allowed for the formation of micelles in water. Upon exposure to light, the nondegradable blocks detached yielding a significant reduction in the micelle hydrodynamic diameter. As a result of the self-assembled micellar environment, telechelic oligomers with photoreactive termini (e.g., coumarin or styrylpyrene) resulting from the photodegradation of polymers in water underwent intermolecular photocycloaddition to photopolymerize, which usually only occurs efficiently at longer wavelengths and a much higher concentration of photoresponsive groups. The reported main chain polymer degradation is thus controlled by the irradiation wavelength and the assembly of the polymers.

Interpolation-split: a data-centric deep learning approach with big interpolated data to boost airway segmentation performance.

The morphology and distribution of airway tree abnormalities enable diagnosis and disease characterisation across a variety of chronic respiratory conditions. In this regard, airway segmentation plays a critical role in the production of the outline of the entire airway tree to enable estimation of disease extent and severity. Furthermore, the segmentation of a complete airway tree is challenging as the intensity, scale/size and shape of airway segments and their walls change across generations. The existing classical techniques either provide an undersegmented or oversegmented airway tree, and manual intervention is required for optimal airway tree segmentation. The recent development of deep learning methods provides a fully automatic way of segmenting airway trees; however, these methods usually require high GPU memory usage and are difficult to implement in low computational resource environments. Therefore, in this study, we propose a data-centric deep learning technique with big interpolated data, Interpolation-Split, to boost the segmentation performance of the airway tree. The proposed technique utilises interpolation and image split to improve data usefulness and quality. Then, an ensemble learning strategy is implemented to aggregate the segmented airway segments at different scales. In terms of average segmentation performance (dice similarity coefficient, DSC), our method (A) achieves 90.55%, 89.52%, and 85.80%; (B) outperforms the baseline models by 2.89%, 3.86%, and 3.87% on average; and (C) produces maximum segmentation performance gain by 14.11%, 9.28%, and 12.70% for individual cases when (1) nnU-Net with instant normalisation and leaky ReLU; (2) nnU-Net with batch normalisation and ReLU; and (3) modified dilated U-Net are used respectively. Our proposed method outperformed the state-of-the-art airway segmentation approaches. Furthermore, our proposed technique has low RAM and GPU memory usage, and it is GPU memory-efficient and highly flexible, enabling it to be deployed on any 2D deep learning model.

Extremely high extinction ratio electro-optic modulator via frequency upconversion to visible wavelengths.

Intensity modulators are fundamental components for integrated photonics. From near-infrared (NIR) to visible spectral ranges, they find applications in optical communication and quantum technologies. In particular, they are required for the control and manipulation of atomic systems such as atomic clocks and quantum computers. Typical integrated electro-optic modulators operating at these wavelengths show high bandwidth and low-voltage operation, but their extinction ratios are moderate. Here we present an integrated thin-film lithium niobate electro-optic (EO) modulator operating in the C-band, which uses a subsequent periodically poled waveguide to convert the modulated signal from 1536 to 768 nm using the second-harmonic (SH) generation. We demonstrate that the upconverted signal retains the characteristics of the modulated input signal, reaching a measured high bandwidth of 35 GHz. Due to the nature of the nonlinear process, it exhibits, with respect to the fundamental signal, a doubled extinction ratio of 46 dB, which is the highest, to the best of our knowledge, recorded for near-infrared light on this platform.

Collapsed Star Copolymers Exhibiting Near Perfect Mimicry of the Therapeutic Protein "TRAIL".

Here we introduce amphiphilic star polymers as versatile protein mimics capable of approximating the activity of certain native proteins. Our study focuses on designing a synthetic polymer capable of replicating the biological activity of TRAIL, a promising anticancer protein that shows very poor circulation half-life. Successful protein mimicry requires precise control over the presentation of receptor-binding peptides from the periphery of the polymer scaffold while maintaining enough flexibility for protein-peptide binding. We show that this can be achieved by building hydrophobic blocks into the core of a star-shaped polymer, which drives unimolecular collapse in water. By screening a library of diblock copolymer stars, we were able to design structures with IC50's of ∼4 nM against a colon cancer cell line (COLO205), closely approximating the activity of the native TRAIL protein. This finding highlights the broad potential for simple synthetic polymers to mimic the biological activity of complex proteins.

Delineating excess comorbidities in idiopathic pulmonary fibrosis: an observational study.

BACKGROUND: Our study examined whether prevalent and incident comorbidities are increased in idiopathic pulmonary fibrosis (IPF) patients when compared to matched chronic obstructive pulmonary disease (COPD) patients and control subjects without IPF or COPD. METHODS: IPF and age, gender and smoking matched COPD patients, diagnosed between 01/01/1997 and 01/01/2019 were identified from the Clinical Practice Research Datalink GOLD database multiple registrations cohort at the first date an ICD-10 or read code mentioned IPF/COPD. A control cohort comprised age, gender and pack-year smoking matched subjects without IPF or COPD. Prevalent (prior to IPF/COPD diagnosis) and incident (after IPF/COPD diagnosis) comorbidities were examined. Group differences were estimated using a t-test. Mortality relationships were examined using multivariable Cox proportional hazards adjusted for patient age, gender and smoking status. RESULTS: Across 3055 IPF patients, 38% had 3 or more prevalent comorbidities versus 32% of COPD patients and 21% of matched control subjects. Survival time reduced as the number of comorbidities in an individual increased (p < 0.0001). In IPF, prevalent heart failure (Hazard ratio [HR] = 1.62, 95% Confidence Interval [CI]: 1.43-1.84, p < 0.001), chronic kidney disease (HR = 1.27, 95%CI: 1.10-1.47, p = 0.001), cerebrovascular disease (HR = 1.18, 95%CI: 1.02-1.35, p = 0.02), abdominal and peripheral vascular disease (HR = 1.29, 95%CI: 1.09-1.50, p = 0.003) independently associated with reduced survival. Key comorbidities showed increased incidence in IPF (versus COPD) 7-10 years prior to IPF diagnosis. INTERPRETATION: The mortality impact of excessive prevalent comorbidities in IPF versus COPD and smoking matched controls suggests that multiorgan mechanisms of injury need elucidation in patients that develop IPF.

Time-bin entanglement at telecom wavelengths from a hybrid photonic integrated circuit.

Mass-deployable implementations for quantum communication require compact, reliable, and low-cost hardware solutions for photon generation, control and analysis. We present a fiber-pigtailed hybrid photonic circuit comprising nonlinear waveguides for photon-pair generation and a polymer interposer reaching 68 dB of pump suppression and photon separation based on a polarizing beam splitter with > 25 dB polarization extinction ratio. The optical stability of the hybrid assembly enhances the quality of the entanglement, and the efficient background suppression and photon routing further reduce accidental coincidences. We thus achieve a 96 - 8 + 3 % concurrence and a 96 - 5 + 2 % fidelity to a Bell state. The generated telecom-wavelength, time-bin entangled photon pairs are ideally suited for distributing Bell pairs over fiber networks with low dispersion.

Relation between resting spleen volume and apnea-induced increases in hemoglobin mass.

Introduction: Indigenous populations renowned for apneic diving have comparatively large spleen volumes. It has been proposed that a larger spleen translates to heightened apnea-induced splenic contraction and elevations in circulating hemoglobin mass (Hbmass), which, in theory, improves O2 carrying and/or CO2/pH buffering capacities. However, the relation between resting spleen volume and apnea- induced increases in Hbmass is unknown. Therefore, we tested the hypothesis that resting spleen volume is positively related to apnea-induced increases in total Hbmass. Methods: Fourteen healthy adults (six women; 29 ± 5 years) completed a two-minute carbon monoxide rebreathe procedure to measure pre-apneas Hbmass and blood volume. Spleen length, width, and thickness were measured pre-and post-five maximal apneas via ultrasound. Spleen volume was calculated via the Pilström equation (test-retest CV:2 ± 2%). Hemoglobin concentration ([Hb]; g/dl) and hematocrit (%) were measured pre- and post-apneas via capillary blood samples. Post-apneas Hbmass was estimated as post-apnea [Hb] x pre-apnea blood volume. Data are presented as mean ± SD. Results: Spleen volume decreased from pre- (247 ± 95 mL) to post- (200 ± 82 mL, p<0.01) apneas. [Hb] (14.6 ± 1.2 vs. 14.9 ± 1.2 g/dL, p<0.01), hematocrit (44 ± 3 vs. 45 ± 3%, p=0.04), and Hbmass (1025 ± 322 vs. 1046 ± 339 g, p=0.03) increased from pre- to post-apneas. Pre-apneas spleen volume was unrelated to post-apneas increases in Hbmass (r=-0.02, p=0.47). O2 (+28 ± 31 mL, p<0.01) and CO2 (+31 ± 35 mL, p<0.01) carrying capacities increased post-apneas. Conclusion: Larger spleen volume is not associated with a greater rise in apneas-induced increases in Hbmass in non-apnea-trained healthy adults.

Acute moderate normobaric hypoxia does not modify circulating thyroid hormone concentrations induced by 1 h of head-out cold-water immersion.

This study tested the hypothesis that acute moderate normobaric hypoxia augments circulating thyroid hormone concentrations during and following 1 h of cold head-out water immersion (HOWI), compared with when cold HOWI is completed during normobaric normoxia. In a randomized crossover single-blind design, 12 healthy adults (27 ± 2 yr, 2 women) completed 1 h of cold (22.0 ± 0.1°C) HOWI breathing either normobaric normoxia ([Formula: see text] = 0.21) or normobaric hypoxia ([Formula: see text] = 0.14). Free and total thyroxine (T3) and triiodothyronine (T4), and thyroid-stimulating hormone (TSH) concentrations were measured in venous blood samples obtained before (baseline), during (15-, 30-, and 60 min), and 15 min following HOWI (post-), and were corrected for changes in plasma volume. Arterial oxyhemoglobin saturation and core (rectal) temperature were measured continuously. Arterial oxyhemoglobin saturation was lower during hypoxia (90 ± 3%) compared with normoxia (98 ± 1%, P < 0.001). Core temperature fell from baseline (normoxia: 37.2 ± 0.4°C, hypoxia: 37.2 ± 0.4°C) to post-cold HOWI (normoxia: 36.4 ± 0.5°C, hypoxia: 36.3 ± 0.5°C, P < 0.001) in both conditions but did not change differently between conditions (condition × time: P = 0.552). Circulating TSH, total T3, free T4, total T3, and free T4 concentrations demonstrated significant main effects of time (all P ≤ 0.024), but these changes did not differ between normoxic and hypoxic conditions (condition × time: all P ≥ 0.163). These data indicate that acute moderate normobaric hypoxia does not modify the circulating thyroid hormone response during 1 h of cold HOWI.NEW & NOTEWORTHY Acute head-out cold (22°C) water immersion (HOWI) decreased core temperature and increased thermogenesis. This thermogenic response was paralleled by the activation of the hypothalamic-pituitary-thyroid axis, as evidenced by changes in thyroid hormones. However, cold HOWI in combination with moderate normobaric hypoxia did not modify the thermogenic nor the circulating thyroid hormone response. This finding suggests that hypoxia-induced alterations in thyroid hormone concentrations are unlikely to acutely contribute to adaptations resulting from repeated cold-water exposures.

The neurodiversity concept was developed collectively: An overdue correction on the origins of neurodiversity theory.

LAY ABSTRACT: This letter discusses the origins of the concept and theory of neurodiversity. It is important to correctly attribute concept and theories to the people who developed them. For some time, the concept of neurodiversity has primarily been attributed to one person, Judy Singer. We consider the available evidence and show that the concept and theory in fact has multiple origins. We draw particular attention to recent archival findings that show the concept of 'neurological diversity' was being used years earlier than previously thought. 'Neurodiversity' means the same thing as 'neurological diversity' and does not change the theory in any way. We conclude that both the concept of neurological diversity or neurodiversity, and the body of theory surrounding it, should be understood as having been collectively developed by neurodivergent people.

Polarization Dynamics of Solid-State Quantum Emitters.

Quantum emitters in solid-state crystals have recently attracted a great deal of attention due to their simple applicability in optical quantum technologies. The polarization of single photons generated by quantum emitters is one of the key parameters that plays a crucial role in various applications, such as quantum computation, which uses the indistinguishability of photons. However, the degree of single-photon polarization is typically quantified using the time-averaged photoluminescence intensity of single emitters, which provides limited information about the dipole properties in solids. In this work, we use single defects in hexagonal boron nitride and nanodiamond as efficient room-temperature single-photon sources to reveal the origin and temporal evolution of the dipole orientation in solid-state quantum emitters. The angles of the excitation and emission dipoles relative to the crystal axes were determined experimentally and then calculated using density functional theory, which resulted in characteristic angles for every specific defect that can be used as an efficient tool for defect identification and understanding their atomic structure. Moreover, the temporal polarization dynamics revealed a strongly modified linear polarization visibility that depends on the excited-state decay time of the individual excitation. This effect can potentially be traced back to the excitation of excess charges in the local crystal environment. Understanding such hidden time-dependent mechanisms can further improve the performance of polarization-sensitive experiments, particularly that for quantum communication with single-photon emitters.

Programmable high-dimensional Hamiltonian in a photonic waveguide array.

Waveguide lattices offer a compact and stable platform for a range of applications, including quantum walks, condensed matter system simulation, and classical and quantum information processing. However, to date, waveguide lattice devices have been static and designed for specific applications. We present a programmable waveguide array in which the Hamiltonian terms can be individually electro-optically tuned to implement various Hamiltonian continuous-time evolutions on a single device. We used a single array with 11 waveguides in lithium niobate, controlled via 22 electrodes, to perform a range of experiments that realized the Su-Schriffer-Heeger model, the Aubrey-Andre model, and Anderson localization, which is equivalent to over 2500 static devices. Our architecture's micron-scale local electric fields overcome the cross-talk limitations of thermo-optic phase shifters in other platforms such as silicon, silicon-nitride, and silica. Electro-optic control allows for ultra-fast and more precise reconfigurability with lower power consumption, and with quantum input states, our platform can enable the study of multiple condensed matter quantum dynamics with a single device.

Mortality surrogates in combined pulmonary fibrosis and emphysema.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) with coexistent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may associate with reduced forced vital capacity (FVC) declines compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts. METHODS: Visual emphysema presence (>0% emphysema) scored on computed tomography identified CPFE patients (CPFE/non-CPFE: derivation cohort n=317/n=183, replication cohort n=358/n=152), who were subgrouped using 10% or 15% visual emphysema thresholds, and an unsupervised machine-learning model considering emphysema and interstitial lung disease extents. Baseline characteristics, 1-year relative FVC and diffusing capacity of the lung for carbon monoxide (D LCO) decline (linear mixed-effects models), and their associations with mortality (multivariable Cox regression models) were compared across non-CPFE and CPFE subgroups. RESULTS: In both IPF cohorts, CPFE patients with ≥10% emphysema had a greater smoking history and lower baseline D LCO compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with ≥10% emphysema, 1-year D LCO decline showed stronger mortality associations than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials and in subjects subgrouped by ≥15% emphysema and using unsupervised machine learning. Importantly, the unsupervised machine-learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines ≥5% and ≥10% showed strong mortality associations. CONCLUSION: When assessing disease progression in IPF, D LCO decline should be considered in patients with ≥10% emphysema and a ≥5% 1-year relative FVC decline threshold considered in non-CPFE IPF patients.

Attitudes towards genetic testing: The role of genetic literacy, motivated cognition, and socio-demographic characteristics.

Understanding reasons for why people choose to have or not to have a genetic test is essential given the ever-increasing use of genetic technologies in everyday life. The present study explored the multiple drivers of people's attitudes towards genetic testing. Using the International Genetic Literacy and Attitudes Survey (iGLAS), we collected data on: (1) willingness to undergo testing; (2) genetic literacy; (3) motivated cognition; and (4) demographic and cultural characteristics. The 37 variables were explored in the largest to-date sample of 4311 participants from diverse demographic and cultural backgrounds. The results showed that 82% of participants were willing to undergo genetic testing for improved treatment; and over 73%-for research. The 35 predictor variables together explained only a small proportion of variance: 7%-in the willingness to test for Treatment; and 6%-for Research. The strongest predictors of willingness to undergo genetic testing were genetic knowledge and deterministic beliefs. Concerns about data misuse and about finding out unwanted health-related information were weakly negatively associated with willingness to undergo genetic testing. We also found some differences in factors linked to attitudes towards genetic testing across the countries included in this study. Our study demonstrates that decision-making regarding genetic testing is influenced by a large number of potentially interacting factors. Further research into these factors may help consumers to make decisions regarding genetic testing that are right for their specific circumstances.

BINOL as a Chiral Solvating Agent for Sulfiniminoboronic Acids.

1H NMR spectroscopic studies using BINOL as a chiral solvating agent (CSA) for a scalemic sulfiniminoboronic acid (SIBA) have revealed concentration- and enantiopurity-dependent variations in the chemical shifts of diagnostic imine protons used to determine enantiopurity levels. 11B/15N NMR spectroscopic studies and X-ray structural investigations revealed that unlike other iminoboronate species, BINOL-SIBA assemblies do not contain N-B coordination bonds, with 1H NMR NOESY experiments indicating that intermolecular H-bonding networks between BINOL and the SIBA analyte are responsible for these variations. These effects can lead to diastereomeric signal overlap at certain er values that could potentially lead to enantiopurity/configuration misassignments. Consequently, it is recommended that hydrogen-bonding-CSA-based 1H NMR protocols should be repeated using both CSA enantiomers to ensure that any concentration- and/or er-dependent variations in diagnostic chemical shifts are accounted for when determining the enantiopurity of a scalemic analyte.

Peptide-Conjugated Micelles Make Effective Mimics of the TRAIL Protein for Driving Apoptosis in Colon Cancer.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) drives apoptosis selectively in cancer cells by clustering death receptors (DR4 and DR5). While it has excellent in vitro selectivity and toxicity, the TRAIL protein has a very low circulation half-life in vivo, which has hampered clinical development. Here, we developed core-cross-linked micelles that present multiple copies of a TRAIL-mimicking peptide at its surface. These micelles successfully induce apoptosis in a colon cancer cell line (COLO205) via DR4/5 clustering. Micelles with a peptide density of 15% (roughly 1 peptide/45 nm2) displayed the strongest activity with an IC50 value of 0.8 µM (relative to peptide), demonstrating that the precise spatial arrangement of ligands imparted by a protein such as a TRAIL may not be necessary for DR4/5/signaling and that a statistical network of monomeric ligands may suffice. As micelles have long circulation half-lives, we propose that this could provide a potential alternative drug to TRAIL and stimulate the use of micelles in other membrane receptor clustering networks.

Comparative efficacy of various hypoxic training paradigms on maximal oxygen consumption: A systematic review and network meta-analysis.

Background: Enhancement in maximal oxygen consumption (VO2max) induced by hypoxic training is important for both athletes and non-athletes. However, the lack of comparison of multiple paradigms and the exploration of related modulating factors leads to the inability to recommend the optimal regimen in different situations. This study aimed to investigate the efficacy of seven common hypoxic training paradigms on VO2max and associated moderators. Methods: Electronic (i.e., five databases) and manual searches were performed, and 42 studies involving 1246 healthy adults were included. Pairwise meta-analyses were conducted to compare different hypoxic training paradigms and hypoxic training and control conditions. The Bayesian network meta-analysis model was applied to calculate the standardised mean differences (SMDs) of pre-post VO2max alteration among hypoxic training paradigms in overall, athlete, and non-athlete populations, while meta-regression analyses were employed to explore the relationships between covariates and SMDs. Results: All seven hypoxic training paradigms were effective to varying degrees, with SMDs ranging from 1.45 to 7.10. Intermittent hypoxia interval training (IHIT) had the highest probability of being the most efficient hypoxic training paradigm in the overall population and athlete subgroup (42%, 44%), whereas intermittent hypoxic training (IHT) was the most promising hypoxic training paradigm among non-athletes (66%). Meta-regression analysis revealed that saturation hours (coefficient, 0.004; P = 0.038; 95% CI [0.0002, 0.0085]) accounted for variations of VO2max improvement induced by IHT. Conclusion: Efficient hypoxic training paradigms for VO2max gains differed between athletes and non-athletes, with IHIT ranking best for athletes and IHT for non-athletes. The practicability of saturation hours is confirmed with respect to dose-response issues in the future hypoxic training and associated scientific research. Registration: This study was registered in the PROSPERO international prospective register of systematic reviews (CRD42022333548).

Establishing a common metric for physical function: Linking SARC-F and PROMIS® physical function.

INTRODUCTION: Aligned with the increasing need for standardized assessment of physical function in older individuals with cancer and other conditions, several patient-reported outcome measures (PROMs) have been developed and published. The aim of this study is to link the Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falls questionnaire (SARC-F), and the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Physical Function Short Form 8c (PROMIS PF 8c), and make their scores convertible, in order to expand the use of both instruments in research and inform clinicians and researchers about the interchangeability of critical cut-off scores. MATERIALS AND METHODS: The sample included 300 participants recruited from an online panel. Participants were included if they had received a cancer diagnosis from a clinician and reported receiving anti-cancer treatment. We conducted five linking procedures and selected an optimal one to generate the crosswalk table between the two measures. RESULTS: The linked T scores of all five methods showed acceptably small mean differences from the observed T scores, and the standard deviation (SD), and root-mean-squared deviation (RMSD) of the differences were generally similar across all methods. After comparing across all statistics, the Stocking-Lord approach was considered as the optimal approach to compute the crosswalk table for converting SARC-F raw scores to PROMIS PF 8c scores. The crosswalk table shows that the SARC-F cut-off value of 4 between healthy versus symptomatic with a corresponding score of 37 fell in the range of moderate physical function limitation from 30 to 39 on the PROMI PF 8c T score metric. DISCUSSION: The linkage in this study has potential for improving clinical and research activities for people with cancer and perhaps others with a similar range of physical function. It facilitates the interpretability in scores of both measures on a common metric anchored on general population for further group-level analysis. Researchers can use this crosswalk to harmonize data collected from either instrument without requiring all cohorts to administer the same instrument for a prospective data collection or retrospective data analysis purpose or for a cross-study effectiveness study.

Automated airway quantification associates with mortality in idiopathic pulmonary fibrosis.

OBJECTIVES: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF). METHODS: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT. RESULTS: No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66-0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22-2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco. CONCLUSIONS: AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value. CLINICAL RELEVANCE STATEMENT: Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree. KEY POINTS: • AirQuant generates measures of intersegmental tapering and segmental tortuosity. • Automated airway quantification associates with mortality in IPF independent of established measures of disease severity. • Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF.

Sustainable Syntheses of Paracetamol and Ibuprofen from Biorenewable ß-pinene.

Scalable processes have been developed to convert ß-pinene into 4-isopropenylcyclohexanone, which is then used as a feedstock for the divergent synthesis of sustainable versions of the common painkillers, paracetamol and ibuprofen. Both synthetic routes use Pd0 catalysed reactions to aromatize the cyclohexenyl rings of key intermediates to produce the benzenoid ring systems of both drugs. The potential of using bioderived 4-hydroxyacetophenone as a drop-in feedstock replacement to produce sustainable aromatic products is also discussed within a terpene biorefinery context.