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 dynamics of the Greenland Ice Sheet are affected by surface meltwater reaching the base of the ice, altering ice contact with the bedrock. Lack of understanding of this evolution hampers the ability to predict the effects of increasing temperatures on the Greenland Ice Sheet mass balance. Here we present a unique high-resolution study of ice velocity response to surface melting based on data from a COSMO-SkyMed satellite campaign over Upernavik Isstrøm (Northwest Greenland) for two months around the end of the 2014 melt season. We show that the velocity variations, due to both short-term (days) and seasonal variations in surface melt rates, are increasing in relative strength farther from the glacier terminus. Furthermore, we observe how ice dynamic response to frontal retreat, reaching several kilometres inland, can obscure the meltwater-induced velocity change close to the terminus. Future studies should consider the flow velocity dependence on the distance to the terminus, and local geometry, to distinguish subglacial hydrologic system changes from frontal processes and local basal conditions.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the “Lifespan and Life Course Research: integrating strategies” “Un-Meeting” to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

Temperature is one of the most important factors affecting soil organisms, including the infective stages of parasites and entomopathogenic nematodes, which are important biological control agents. We investigated the response of 2 species of entomopathogenic nematodes to different storage regimes: cold (9°C), culture temperature (20°C) and temperature swapped from 9 to 20°C. For Steinernema carpocapsae, cold storage had profound effects on chemotaxis, stress tolerance and protein expression that were retained in temperature-swapped individuals. These effects included reversal of chemotactic response for 3 (prenol, methyl salicylate and hexanol) of the 4 chemicals tested, and enhanced tolerance to freezing (−10°C) and desiccation (75% RH). Label-free quantitative proteomics showed that cold storage induced widespread changes in S. carpocapsae, including an increase in heat-shock proteins and late embryogenesis abundant proteins. For Heterorhabditis megidis, cold storage had a less dramatic effect on chemotaxis (as previously shown for proteomic expression) and changes were not maintained on return to 20°C. Thus, cold temperature exposure has significant effects on entomopathogenic nematodes, but the nature of the change depends on the species. Steinernema carpocapsae, in particular, displays significant plasticity, and its behaviour and stress tolerance may be manipulated by brief exposure to low temperatures, with implications for its use as a biological control agent.

Over the past 20 years, collaboration has become an essential aspect of archaeological practice in North America. In paying increased attention to the voices of descendant and local communities, archaeologists have become aware of the persistent injustices these often marginalized groups face. Building on growing calls for a responsive and engaged cultural heritage praxis, this forum article brings together a group of Native and non-Native scholars working at the nexus of history, ethnography, archaeology, and law in order to grapple with the role of archaeology in advancing social justice. Contributors to this article touch on a diverse range of critical issues facing Indigenous communities in the United States, including heritage law, decolonization, foodways, community-based participatory research, and pedagogy. Uniting these commentaries is a shared emphasis on research practices that promote Indigenous sovereignty and self-determination. In drawing these case studies together, we articulate a sovereignty-based model of social justice that facilitates Indigenous control over cultural heritage in ways that address their contemporary needs and goals.

Diamondback moth, Plutella xylostella (Linnaeus) (Lepidoptera: Plutellidae), a globally important pest of Brassicaceae crops, migrates into all provinces of Canada annually. Life tables were used to determine the mortality levels contributed by the parasitoid complexes associated with diamondback moth in British Columbia, Ontario, Prince Edward Island, and insular Newfoundland. Overall, diamondback moth populations showed high generational mortality (> 90%) in all provinces, although parasitism levels were generally low. The net reproductive rate of increase in diamondback moth was less than 1.0 (populations declined) in both years in British Columbia and in each of two years in Newfoundland and Ontario, but it was greater than 1.0 in all three years in Prince Edward Island. Lower parasitism levels were found in Prince Edward Island (3.0–6.3%) compared with other provinces (8.4–17.6%, except one year in British Columbia). Diadegma insulare was the main larval parasitoid found; it was present in all provinces. Microplitis plutellae was present in all provinces except British Columbia. Oomyzus sokolowskii was found in British Columbia and Ontario. The parasitoid community documented from sentinel sampling was less diverse than that found through destructive sampling. Hypotheses are provided to explain the presence of major parasitoids. Increasing larval parasitism would have the largest effect on diamondback moth population growth in Canada.

Less is known about the relationship between conduct disorder (CD), callous–unemotional (CU) traits, and positive and negative parenting in youth compared to early childhood. We combined traditional univariate analyses with a novel machine learning classifier (Angle-based Generalized Matrix Learning Vector Quantization) to classify youth (N = 756; 9–18 years) into typically developing (TD) or CD groups with or without elevated CU traits (CD/HCU, CD/LCU, respectively) using youth- and parent-reports of parenting behavior. At the group level, both CD/HCU and CD/LCU were associated with high negative and low positive parenting relative to TD. However, only positive parenting differed between the CD/HCU and CD/LCU groups. In classification analyses, performance was best when distinguishing CD/HCU from TD groups and poorest when distinguishing CD/HCU from CD/LCU groups. Positive and negative parenting were both relevant when distinguishing CD/HCU from TD, negative parenting was most relevant when distinguishing between CD/LCU and TD, and positive parenting was most relevant when distinguishing CD/HCU from CD/LCU groups. These findings suggest that while positive parenting distinguishes between CD/HCU and CD/LCU, negative parenting is associated with both CD subtypes. These results highlight the importance of considering multiple parenting behaviors in CD with varying levels of CU traits in late childhood/adolescence.

In response to the rapid spread of novel coronavirus disease 2019 (COVID-19), health-care systems should establish procedures for early recognition and management of suspected or confirmed cases. We describe the various steps taken for the development, implementation, and dissemination of the interdisciplinary COVID-19 protocol at Jackson Health System (JHS), a complex tertiary academic health system in Miami, Florida. Recognizing the dynamic nature of COVID-19, the protocol addresses the potential investigational treatment options and considerations for special populations. The protocol also includes infection prevention and control measures and routine care for suspected or proven COVID-19 patients.

Tuberculosis (TB) increasingly appears in a multidrug-resistant form (MDR-TB) in Europe, too. Treatment remains difficult due to various side effects of the multi-drug-regimens. Ciprofloxacin is widely used as one of the few TB-second-line drugs. We report on the course of a ciprofloxacin-induced acute psychosis in a patient with MDR(isoniazid, streptomycin)-TB which resolved after cessation of ciprofloxacin treatment and introduction of a novel oxazolidone. Careful treatment considerations particularly in patients with additional predisposing factors to neuropsychiatric symptoms are recommended in the potentially dangerous MDR-TB, thus creating an enormous therapeutic challenge.

We describe elongate, wet, subglacial bedforms in the shear margins of the NE Greenland Ice Stream and place some constraints on their formation. Lateral shear margin moraines have been observed across the previously glaciated landscape, but little is known about the ice-flow conditions necessary to form these bedforms. Here we describe in situ sediment bedforms under the NE Greenland Ice Stream shear margins that are observed in active-source seismic and ground-penetrating radar surveys. We find bedforms in the shear margins that are ~500 m wide, ~50 m tall, and elongated nearly parallel to ice-flow, including what we believe to be the first subglacial observation of a shear margin moraine. Acoustic impedance analysis of the bedforms shows that they are composed of unconsolidated, deformable, water-saturated till. We use these geophysical observations to place constraints on the possible formation mechanism of these subglacial features.

Graphene oxide (GO)/MnO2 nanocomposites were synthesized by adding KMnO4 in a solution of water and ethanol (3:1), containing 10 mg of GO. Brown precipitates were obtained after a continuous stirring for 1 hr. The precipitates were then washed with deionized water (DI) water and dried to obtain the MnO2-GO nanocomposites. Pure MnO2 was also synthesized using the same method without GO for the comparison. X-ray diffraction pattern confirm δ-MnO2 type of MnO2 with birnessite type MnO2 structure. The TEM images show the average diameter of MnO2 nanorods as 15 nm. Electrochemical characterizations were carried out in an aqueous solution of 3M KOH. Charge-discharge studies were carried out between 1A/g to 20 A/g current range. The MnO2-GO nanocomposites showed improved electrochemical performances. The capacitance of MnO2 and MnO2-GO electrodes was found to be as 300 F/g, and 350 F/g, respectively at a current of 0.5 A/g.