People who inject drugs are at risk of acute bacterial and fungal injecting-related infections. There is evidence that incidence of hospitalizations for injecting-related infections are increasing in several countries, but little is known at an individual level. We aimed to examine injecting-related infections in a linked longitudinal cohort of people who inject drugs in Melbourne, Australia. A retrospective descriptive analysis was conducted to estimate the prevalence and incidence of injecting-related infections using administrative emergency department and hospital separation datasets linked to the SuperMIX cohort, from 2008 to 2018. Over the study period, 33% (95%CI: 31–36%) of participants presented to emergency department with any injecting-related infections and 27% (95%CI: 25–30%) were admitted to hospital. Of 1,044 emergency department presentations and 740 hospital separations, skin and soft tissue infections were most common, 88% and 76%, respectively. From 2008 to 2018, there was a substantial increase in emergency department presentations and hospital separations with any injecting-related infections, 48 to 135 per 1,000 person-years, and 18 to 102 per 1,000 person-years, respectively. The results emphasize that injecting-related infections are increasing, and that new models of care are needed to help prevent and facilitate early detection of superficial infection to avoid potentially life-threatening severe infections.

Background: Antibiotics alone are often insufficient to treat recurrent C. difficile infection (rCDI) because they have no activity against C. difficile spores that germinate within a disrupted microbiome. SER-109, an investigational, oral, microbiome therapeutic comprised of purified Firmicutes spores, was designed to reduce rCDI through microbiome repair. We report an integrated efficacy analysis through week 24 for SER-109 from phase 3 studies, ECOSPOR III and ECOSPOR IV. Methods: ECOSPOR III was a randomized, placebo-controlled phase 3 trial conducted at 56 US or Canadian sites that included 182 participants with ≥2 CDI recurrences, confirmed via toxin EIA testing. Participants were stratified by age (<65 years or ≥65 years) and antibiotic regimen (vancomycin, fidaxomicin) and were randomized 1:1 to placebo or SER-109 groups. ECOSPOR IV was an open-label, single-arm study conducted at 72 US or Canadian sites including 263 participants with rCDI enrolled in 2 cohorts: (1) rollover participants from ECOSPOR III who experienced on-study recurrence diagnosed by toxin EIA (n = 29) and (2) participants with ≥1 CDI recurrence (diagnosed by PCR or toxin EIA), inclusive of the current episode (n = 234). In both studies, the investigational product was administered orally as 4 capsules over 3 consecutive days following symptom resolution after standard-of-care antibiotics. The primary efficacy end point was rCDI (recurrent toxin-positive diarrhea requiring treatment) through week 8. Other end points included CDI recurrence rates and safety through 24 weeks. Results: These 349 participants received at least 1 dose of SER-109 in ECOSPOR III or ECOSPOR IV (mean age 64.2; 68.8% female). Overall, 77 participants (22.1%) enrolled with their first CDI recurrence. Four participants received blinded SER-109 in ECOSPOR III followed by a second dose of open-label SER-109 in ECOSPOR IV. Overall, the proportion of participants who received any dose of SER-109 with rCDI at week 8 was 9.5% (33 of 349; 95% CI, 6.6 %–13.0%), and the CDI recurrence rate remained low through 24 weeks (15.2%, 53 of 349; 95% CI, 11.6%–19.4%), corresponding to sustained clinical response rates of 90.5% (95% CI, 87.0%–93.4%) and 84.8% (95% CI, 80.6%–88.4%), respectively (Fig. 1). Most rollover participants (25 of 29, 86.2%) were from the placebo arm; 13.8% had rCDI by week 8. Conclusions: In this integrated analysis, the rates of rCDI were low and durable in participants who received the investigational microbiome therapeutic SER-109, with sustained clinical response rates of 90.5% and 84.8% at weeks 8 and 24, respectively. These data further support the potential benefit of microbiome repair with SER-109 following antibiotics for rCDI to prevent recurrence in high-risk patients.

Financial support: This study was funded by Seres Therapeutics.

Disclosure: None

The next generation of high-power lasers enables repetition of experiments at orders of magnitude higher frequency than what was possible using the prior generation. Facilities requiring human intervention between laser repetitions need to adapt in order to keep pace with the new laser technology. A distributed networked control system can enable laboratory-wide automation and feedback control loops. These higher-repetition-rate experiments will create enormous quantities of data. A consistent approach to managing data can increase data accessibility, reduce repetitive data-software development and mitigate poorly organized metadata. An opportunity arises to share knowledge of improvements to control and data infrastructure currently being undertaken. We compare platforms and approaches to state-of-the-art control systems and data management at high-power laser facilities, and we illustrate these topics with case studies from our community.

White kidney bean extract (WKBE) is a nutraceutical often advocated as an anti-obesity agent. The main proposed mechanism for these effects is alpha-amylase inhibition, thereby slowing carbohydrate digestion and absorption. Thus, it is possible that WKBE could impact the gut microbiota and modulate gut health. We investigated the effects of supplementing 20 healthy adults with WKBE for 1 week in a randomised, placebo-controlled crossover trial on the composition of the gut microbiota, gastrointestinal (GI) inflammation (faecal calprotectin), GI symptoms, and stool habits. We conducted in vitro experiments and used a gut model system to explore potential inhibition of alpha-amylase. We gained qualitative insight into participant experiences of using WKBE via focus groups. WKBE supplementation decreased the relative abundance of Bacteroidetes and increased that of Firmicutes, however, there were no significant differences in post-intervention gut microbiota measurements between the WKBE and control. There were no significant effects on GI inflammation or symptoms related to constipation, or stool consistency or frequency. Our in vitro and gut model system analyses showed no effects of WKBE on alpha-amylase activity. Our findings suggest that WKBE may modulate the gut microbiota in healthy adults, however, the underlying mechanism is unlikely due to active site inhibition of alpha-amylase.

This work presents a $\textsf{Python}$ EMD package named AdvEMDpy that is both more flexible and generalises existing empirical mode decomposition (EMD) packages in $\textsf{Python}$, $\textsf{R}$, and $\textsf{MATLAB}$. It is aimed specifically for use by the insurance and financial risk communities, for applications such as return modelling, claims modelling, and life insurance applications with a particular focus on mortality modelling. AdvEMDpy both expands upon the EMD options and methods available, and improves their statistical robustness and efficiency, providing a robust, usable, and reliable toolbox. Unlike many EMD packages, AdvEMDpy allows customisation by the user, to ensure that a broader class of linear, non-linear, and non-stationary time series analyses can be performed. The intrinsic mode functions (IMFs) extracted using EMD contain complex multi-frequency structures which warrant maximum algorithmic customisation for effective analysis. A major contribution of this package is the intensive treatment of the EMD edge effect which is the most ubiquitous problem in EMD and time series analysis. Various EMD techniques, of varying intricacy from numerous works, have been developed, refined, and, for the first time, compiled in AdvEMDpy. In addition to the EMD edge effect, numerous pre-processing, post-processing, detrended fluctuation analysis (localised trend estimation) techniques, stopping criteria, spline methods, discrete-time Hilbert transforms (DTHT), knot point optimisations, and other algorithmic variations have been incorporated and presented to the users of AdvEMDpy. This paper and the supplementary materials provide several real-world actuarial applications of this package for the user’s benefit.

U.S. equity exchanges have experienced a dramatic increase in competition from new entrants, resulting in the fragmentation of trading across venues. While market quality has generally improved over this period, we show most of the improvements have accrued to the largest stocks. We then show this bifurcation in market quality is related to the fragmentation of trading. Theoretically, more exchange competition should reduce trading costs, yet it may also increase adverse selection for liquidity providers, leading to higher spreads. We document evidence of both effects (fragmentation improves market quality for large stocks while small stocks experience relatively worse quality).

Minimising the effects of restraint and human interaction on the endocrine physiology of animals is essential for collection of accurate physiological measurements. Our objective was to compare stress-induced cortisol (CORT) and noradrenalin (NorA) responses in automated vs manual blood sampling in pigs. A total of 16 pigs (30 kg) were assigned to either: (i) automated blood sampling via an indwelling catheter using a novel-penning system called PigTurn® which detects the pig's rotational movement and responds by counter-rotating, allowing free movement while preventing catheter twisting; (ii) automated sampling while exposed to visual and auditory responses of manually sampled pigs; or (iii) manual sampling by jugular venipuncture while pigs were restrained in dorsal recumbency. During sampling of (i), personnel were not permitted in the room; samplings of (ii) and (iii) were performed simultaneously in the same room. Blood samples were collected every 20 min for 120 min and measured for CORT (ng ml−1) using mass spectrometry and NorA (pg ml−1) using High Performance Liquid Chromatography (HPLC). Effects of treatment and time were computed with mixed models adjusted by Tukey post hoc. CORT and NorA concentrations were lowest in group (i) followed by group (ii), which were not different. However, CORT and NorA levels in manually sampled animals (iii) were highest compared to automated methods (i) and (ii). Plasma concentrations across time were not different for CORT, but NorA concentration at time 0 min was higher than at 120 min. The presence of visual and auditory stimuli evoked by manual sampled animals did not affect non-handled pigs’ responses. Restraint and manual sampling of pigs can be extremely stressful while the automated blood sampling of freely moving pigs, housed in the PigTurn® was significantly less stressful for the animals.

We present evidence from a pre-registered experiment indicating that a philosophical argument – a type of rational appeal – can persuade people to make charitable donations. The rational appeal we used follows Singer’s “shallow pond” argument (1972), while incorporating an evolutionary debunking argument (Paxton, Ungar and Greene, 2012) against favoring nearby victims over distant ones. The effectiveness of this rational appeal did not differ significantly from that of a well-tested emotional appeal involving an image of a single child in need (Small, Loewenstein and Slovic, 2007). This is a surprising result, given evidence that emotions are the primary drivers of moral action, a view that has been very influential in the work of development organizations. We found no support for our hypothesis that combining our rational and emotional appeals would have a stronger effect than either appeal in isolation. However, our finding that both kinds of appeal can increase charitable donations is cause for optimism, especially concerning the potential efficacy of well-designed rational appeals. We consider the significance of these findings for moral psychology, ethics, and the work of organizations aiming to alleviate severe poverty.

Shock tubes are a crucial source of experimental data for the aerothermodynamic modelling of atmospheric entry vehicles. Notably, many chemical-kinetic and radiative models are validated directly against optical measurements from these facilities. Typically, the incident shock speed at the location of the experimental measurement is taken to be representative of the test slug; however, the shock velocity can vary substantially upstream of this location. These variations have been long posited as a source of disagreement with computational predictions, although a definitive link has proved elusive. This work describes a series of experiments which aim to isolate and confirm the importance of the shock deceleration effect. This is achieved by generating different shock trajectories and comparing the post-shock trends in atomic oxygen emission and electron density. These trends are shown to be directly linked to the upstream shock speed variations using a recently developed numerical tool (LASTA). The close agreement of the comparisons confirms the importance of shock speed variation for shock tube experiments; these findings have direct and potentially critical relevance for all such studies, both past and present.

The mammalian respiratory system or lung is a tree-like branching structure, and the main site of gas exchange with the external environment. Structurally, the lung is broadly classified into the proximal (or conducting) airways and the distal alveolar region, where the gas exchange occurs. In parallel with the respiratory tree, the pulmonary vasculature starts with large pulmonary arteries that subdivide rapidly ending in capillaries adjacent to alveolar structures to enable gas exchange. The NOTCH signalling pathway plays an important role in lung development, differentiation and regeneration post-injury. Signalling via the NOTCH pathway is mediated through activation of four NOTCH receptors (NOTCH1-4), with each receptor capable of regulating unique biological processes. Dysregulation of the NOTCH pathway has been associated with development and pathophysiology of multiple adult acute and chronic lung diseases. This includes accumulating evidence that alteration of NOTCH3 signalling plays an important role in the development and pathogenesis of chronic obstructive pulmonary disease, lung cancer, asthma, idiopathic pulmonary fibrosis and pulmonary arterial hypertension. Herein, we provide a comprehensive summary of the role of NOTCH3 signalling in regulating repair/regeneration of the adult lung, its association with development of lung disease and potential therapeutic strategies to target its signalling activity.

Phylogenetic analyses can be used to resolve taxonomic uncertainties and reconstruct a species’ evolutionary history. This can be combined with ecological data to predict missing life history traits which are important for creation of conservation management strategies. We investigated the evolutionary and life history of the ‘Critically Endangered’ Grenada Dove Leptotila wellsi by estimating its phylogenetic placement and using this new phylogeny to test the accuracy of phylogenetic comparative methods for estimating both documented and unknown life history traits. We extracted DNA from two Grenada Dove samples and obtained sequences from three mitochondrial markers: Cytochrome oxidase I (COI), NADH dehydrogenase 2 (ND2) and Cytochrome b (Cyt b); and one nuclear marker: β-Fibrinogen intron 7 (β-FIB). We present the first genetic data obtained for the Grenada Dove. Our data identify the Grey-Chested Dove Leptotila cassinii as the species which shares both a most recent common ancestor, with an estimated divergence of approximately 2.53 million years ago, and the smallest genetic distance (P = 0.0303) with the Grenada Dove. Life history trait values for the Grenada Dove predicted from our analyses using phylogenetic imputation are: clutch size = 2 (± 0.09) eggs; clutches per year = 1.4 (± 0.81); incubation time = 14.2 (± 0.75) days; hatching weight = 3.8 g (± 1.05) and single imputation: fledging age (genus median) = 15.5 days, longevity (genus median) = 8.6 years. This study contributes novel information regarding evolutionary history and life history characteristics to inform long-term conservation actions for a ‘Critically Endangered’ species.