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

Clinical supervision is a relationship-based education, considered crucial in providing clinicians with emotional support, skill development and improving client outcomes. Culturally responsive supervision assumes that culture permeates clinical practice and supervision. Culturally responsive supervisors promote the development of cultural competence in supervision, through modelling, reflective discussion and responsivity. Research has demonstrated that greater perceived cultural responsivity in supervision may result in greater satisfaction for supervisees, particularly those from racially or ethnically minoritised (REM) backgrounds. The current study explores supervisee perceptions of culturally responsive supervision and supervisory relationships between different supervisory dyads, comprising supervisees from REM and White backgrounds. This was a cross-sectional design incorporating a between-groups comparison. Trainee and qualified clinical psychologists, counselling psychologists and CBT therapists (n = 222) completed an online survey. Perceptions of cultural responsivity and the supervisory relationship were explored. Participants provided information about their supervisor’s race and ethnicity and their own, and were organised into four supervisory dyads. Participants from REM backgrounds in dyads with White supervisors perceived their supervision as significantly less culturally responsive, with significantly lower quality supervisory relationships. Greater perceived cultural responsivity in supervision significantly predicted better supervisory relationships (regardless of participant cultural background). Findings suggest that culturally responsive supervisory practices may play an important role in developing cultural competence and strengthening the supervisory relationship, particularly in cross-cultural supervisory dyads. Findings present important clinical and theoretical implications.

Ethofumesate is a broad-spectrum, soil-applied herbicide used to control broadleaf and grass weeds in sugarbeet crops. Ethofumesate is commonly applied preemergence at rates ranging from 1.25 to 4.2 kg ai ha−1, or applied postemergence (POST), up to 0.38 kg ai ha−1. The Generic Crop Science company has developed a new Ethofumesate 4SC label that has increased ethofumesate POST rates up to 4.48 kg ha−1 in sugarbeet with more than two true leaves per plant. Field and greenhouse experiments were conducted in 2018 and 2019 to evaluate sugarbeet tolerance and herbicide efficacy. Field tolerance experiments indicated sugarbeet stature from ethofumesate applied POST at 0.28, 0.56, and 1.12 kg ha−1 was the same as that of the nontreated control, but ethofumesate at 2.24 kg ha−1 reduced sugarbeet stature, although that rate did not affect yield components. Ethofumesate applied POST at 4.48 kg ha−1 reduced sugarbeet stature and affected sugarbeet yield components. Ethofumesate applied alone POST provided weed control of up to 85%, 76%, and 84% on common lambsquarters, redroot pigweed, and waterhemp, respectively, in field efficacy experiments. Mixing ethofumesate at 1.12 kg ha−1 with glyphosate does not provide a second effective herbicide for POST control of common lambsquarters or redroot pigweed, but it does provide residual control of these weeds when at least one-half inch of penetrating rainfall occurs, following application. In greenhouse experiments, ethofumesate alone or ethofumesate plus glyphosate applied to common lambsquarters, redroot pigweed, or waterhemp at heights of less than 2.5 cm provided the best combination of burndown and soil residual control compared with weeds that were 2.5 to 5 cm tall. Ethofumesate applied POST at 1.12 kg ha−1 plus glyphosate provided the best combination of tolerance and efficacy, especially on waterhemp.

Concerns over compromised companion rabbit (Oryctolagus cuniculus domesticus) welfare are widespread. The welfare problems have been linked to the perception of rabbits as low investment ‘children’s pets.’ To test this hypothesis and investigate the current conditions for rabbits, data were gathered from two surveys in 2021: a nationally representative survey of Danish companion animal owners (Survey I) and a detailed social media-based survey of Danish rabbit owners (Survey II). Using logistic regression, three owner-related variables (whether a child/adult was responsible for care of the rabbit, owner-opinion on rabbits’ suitability as ‘starter pets’ and willingness-to-pay [WTP] for veterinary treatment) were employed to investigate the effect of rabbit status on owner-provision of selected husbandry conditions. The 76 (Survey I) and 4,335 (Survey II) responses suggested that most rabbits are acquired for children and are solitarily housed, and that many are kept in cages of an unsuitable size and not checked daily. Owners who perceived rabbits as ‘starter pets’ and with lower WTP were more likely to house rabbits in restricted space and to not provide continuous gnawing opportunities, ad libitum hay or routine healthcare. A child fulfilling the role of the rabbit’s main caretaker was also associated with inadequate housing type and fewer gnawing opportunities. Thus, many rabbits live in unsuitable conditions, and owners who perceive rabbits as low investment ‘children’s pets’ are more likely to not provide recommended resources. Changing owners’ perceptions of rabbits and promoting suitable husbandry through official education programmes and minimum requirements is important if there are to be improvements made to rabbit welfare.

Healthcare generates vast quantities of ‘routinely collected’ data that is recognised as a valuable substrate to drive improvement. Realising this benefit however, requires the sequential distillation of new knowledge before analytical findings are used to inform real-world change. This dichotomy requires the combination of techniques from data science (to derive meaningful knowledge) and improvement (to deliver change). Recognising this transdisciplinary need and the complexity of modern healthcare, we developed an improvement project to incorporate a ‘systems approach’ into the analysis of pseudonymised perioperative data for the purpose of redesigning the systems that deliver surgical care to older patients. This required the development of novel mixed-methods workflows combining tools used to realise a systems approach in practice and to support meaningful analysis, and to translate these findings towards ‘better’ care systems. This paper recounts the incorporation of these tools into ‘dataintensive improvement’ and reflects on the relevance of design thinking to improve the conduct of the necessary data science to achieve our ultimate aim, using data to improve services for older surgical patients.

Cystic echinococcosis (CE) is endemic in humans and domestic animals in eastern Africa. All the species of the Echinococcus granulosus sensu lato complex have been reported in this region except for E. equinus, possibly due to the small number of studies involving equids. This study reports the frequency of different Echinococcus species in donkeys from eastern Africa. A total of 5961 donkeys were examined during meat inspection in 3 slaughterhouses in Kenya. Identification of Echinococcus spp. was achieved through polymerase chain reaction-restriction fragment-length polymorphism and sequencing of the mitochondrial nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 gene. The prevalence of CE was 5.7% (337/5961). The 263 genotyped cysts belonged to E. equinus (n = 163), E. granulosus sensu stricto (n = 70), E. canadensis (G6/7) (n = 26) and E. ortleppi (n = 4). One donkey harboured a metacestode of Spirometra theileri. All E. equinus cases, except 2, originated from southern Ethiopia, whereas the other species were more evenly distributed across the study area. Most of the cysts belonging to E. equinus were fertile (111/163), while those of the other species were non-fertile. This is the first report of Echinococcus spp. in donkeys from sub-Saharan Africa and the first confirmation of E. equinus in East Africa. The frequent fertility of E. equinus cysts in donkeys affirms their suitability as intermediate hosts of this species, while low frequency and cyst fertility suggest a marginal role of donkeys in the transmission of E. granulosus s. s., E. canadensis (G6/7) and E. ortleppi.

We deal with a challenging scheduling problem on parallel machines with sequence-dependent setup times and release dates from a real-world application of semiconductor work-shop production. There, jobs can only be processed by dedicated machines, thus few machines can determine the makespan almost regardless of how jobs are scheduled on the remaining ones. This causes problems when machines fail and jobs need to be rescheduled. Instead of optimising only the makespan, we put the individual machine spans in non-ascending order and lexicographically minimise the resulting tuples. This achieves that all machines complete as early as possible and increases the robustness of the schedule. We study the application of answer-set programming (ASP) to solve this problem. While ASP eases modelling, the combination of timing constraints and the considered objective function challenges current solving technology. The former issue is addressed by using an extension of ASP by difference logic. For the latter, we devise different algorithms that use multi-shot solving. To tackle industrial-sized instances, we study different approximations and heuristics. Our experimental results show that ASP is indeed a promising knowledge representation and reasoning (KRR) paradigm for this problem and is competitive with state-of-the-art constraint programming (CP) and Mixed-Integer Programming (MIP) solvers.

We investigate decision-making in the Judge-Advisor-System where one person, the “judge”, wants to estimate the number of a certain entity and is given advice by another person. The question is how to combine the judge’s initial estimate and that of the advisor in order to get the optimal expected outcome. A previous approach compared two frequently applied strategies, taking the average or choosing the better estimate. In most situations, averaging produced the better estimates. However, this approach neglected a third strategy that judges frequently use, namely a weighted mean of the judges’ initial estimate and the advice. We compare the performance of averaging and choosing to weighting in a theoretical analysis. If the judge can, without error, detect ability differences between judge and advisor, a straight-forward calculation shows that weighting outperforms both of these strategies. More interestingly, after introducing errors in the perception of the ability differences, we show that such imperfect weighting may or may not be the optimal strategy. The relative performance of imperfect weighting compared to averaging or choosing depends on the size of the actual ability differences as well as the magnitude of the error. However, for a sizeable range of ability differences and errors, weighting is preferable to averaging and more so to choosing. Our analysis expands previous research by showing that weighting, even when imperfect, is an appropriate advice taking strategy and under which circumstances judges benefit most from applying it.

Indicators are important sources of information about problems across many policy areas. However, despite a growing number of indicators across most policy areas, such as health care, business promotion, or environmental protection, we still know little about if, how, and when such indicators affect the policy agenda. This article develops a theoretical answer to these questions and examines the implications using a new large-n dataset with 220,000 parliamentary questions asked by government and opposition MPs in Australia, Belgium, Denmark, Germany, France, Italy, and Spain. The data contain information on political attention to 17 problems, such as unemployment, C02 emission, and crime from 1960 to 2015. Across this wealth of data, the article demonstrates that politicians respond to the severity and development of problem indicators over time and in comparison to other countries. Results also show that politicians respond much more when problem indicators develop negatively than when they develop positively.

Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with significant side effects. With the transition of PCa from a foudroyant course to a chronic disease, managing these side effects has become increasingly important. There is growing evidence that nutritional changes and physical activity are beneficial in these patients. Here we examine the impact of written patient information on the physical activity and dietary habits of PCa patients receiving ADT and behaviour changes between baseline and 1 year, in the open-label, non-interventional LEAN study. In total, 959 patients with advanced hormone-sensitive PCa requiring ADT with the Leuprorelin Sandoz® implant were included from January 2014 to July 2015 and followed for ≥ 12 months. At the start of the study, urologists received a questionnaire concerning the written information provided to patients regarding their disease, patient advocacy groups, diet and physical activity. Patients received a questionnaire on their dietary habits and physical activity at the start and end of the study. Urologists from 147 study centres and 540 patients responded to the questionnaires. While 69 % of these patients received disease-specific information, only 30 % and 17 % received information regarding nutrition and physical activity, respectively. The majority of urologists estimate that their patients rarely or never follow guidance on nutrition or physical activity, yet > 90 % of patients indicate they would make use of this information, if provided. Few patients showed behavioural changes between baseline and 1 year without evident differences between patients that received information and those that did not.

James Wilkie's The Mexican Revolution: Federal Expenditure and Social Change Since 1910 is an industrious attempt to get beneath the conventional wisdom about the changes wrought by the Mexican Revolution. The author's careful compilation of budgetary data should sharply challenge the longstanding and widespread assumptions that: (a) useful historical material from Latin America does not exist in statistical form, and (b) even if it did exist, the mystical qualities of Latin culture defy all efforts at measurement. Wilkie has shown that—with luck, perseverence, and imagination—data can be found. One hopes that his example will encourage other students of the area to seek out similar data and reap further intellectual benefits from quantitative analysis: hypothesis-testing, measurement of trends, and rigorous comparison.

Thirty years after the discovery of an Early Neolithic timber hall at Balbridie in Scotland was reported in Antiquity, new analysis of the site's archaeobotanical assemblage, featuring 20 000 cereal grains preserved when the building burnt down in the early fourth millennium BC, provides new insights into early farming practices. The results of stable isotope analyses of cereals from Balbridie, alongside archaeobotanical and stable isotope results from three other sites, indicate that while cereals were successfully cultivated in well-established plots without manuring at Balbridie, a variety of manuring strategies was implemented at the other sites. These differences reinforce the picture of variability in cultivation practices across Neolithic North-west Europe.

Regional and local studies suggest that the Tufted Puffin Fratercula cirrhata in North America is declining in portions of its range. However, whether the overall population is declining, or its range is contracting with little change to the overall population size, is unknown. To examine population trends throughout its North American range, we assembled 11 datasets that spanned 115 years (1905–2019) and included at-sea density and encounter estimates and at-colony burrow and bird counts. We assessed trends for the California Current, Gulf of Alaska, and Bering Sea/Aleutian Islands large marine ecosystems (LME). We found: (1) nearly uniform and long-term declines of Puffins breeding in the California Current ecosystem, with most ecosystem colonies surveyed, (2) declining trends at two large colonies and in one at-sea dataset in the Gulf of Alaska LME, with the fourth smaller colony exhibiting no significant trend, and (3) positive trends at four out of five colonies in the Bering Sea/Aleutian Islands ecosystem complex, with no detectable trend at the fifth very large colony. The general pattern of Tufted Puffin declines across the California Current and Gulf of Alaska LMEs may be attributable to a variety of factors, but additional study is needed to evaluate the relative influence of potential population drivers both independently and synergistically. Potential mechanisms driving population increases in the Bering Sea/Aleutian Islands ecosystem include reduced depredation and bycatch, intrinsic population growth, and immigration. We found strong evidence for declines in two of the three LMEs evaluated representing approximately three quarters of the species’ North American range. This region of decline includes the Gulf of Alaska LME, which contains a significant portion of the species’ estimated total North American population. Despite data limitations, our analysis coupled with more focused and local studies indicates that the Tufted Puffin is a species of conservation concern.