Implementing an Interprofessional Early Childhood Screening Program at the St. Paul City School

Early childhood screening (ECS) is required with 30 days of starting kindergarten in the state of Minnesota. However, due to lack of access and barriers to access many current kindergartners have not been screened within the deadline. Low SES and minority students face barriers to access such as transportation and caregiver trust. This project was designed to create an ECS program at the St. Paul City School to address the barriers to screens that the students and families faced. Having the ECS program on-site at the school is more convenient for families and allows them to stay in the environment they are comfortable in. The model for this ECS program was to create a partnership between St. Paul City School and St. Catherine University. Occupational therapy and prelicensure nursing students will be completing screens under the supervision of St. Catherine faculty. In the process of this project a GHR Grant was submitted and approved to fund the purchase of tools and equipment needed for the ECS program. Training materials were also created to train the students who will be completing the screens. As a result of this project a mutually beneficial relationship between St. Catherine University and the St. Paul City School was established. St. Paul City School will be reimbursed by the Minnesota Department of Education for each screen they complete and St. Catherine University students will gain valuable experience and knowledge by completing screens. Creating onsite ECS programs can be a viable way to address barriers to access that low SES and minority families face. Occupational therapists can be valuable members on an ECS team. By assessing needs communities and organizations can work together to solve complex problems in a mutually beneficial manner

Protist predation can favour cooperation within bacterial species

Here, we studied how protist predation affects cooperation in the opportunistic pathogen bacterium Pseudomonas aeruginosa, which uses quorum sensing (QS) cell-to-cell signalling to regulate the production of public goods. By competing wild-type bacteria with QS mutants (cheats), we show that a functioning QS system confers an elevated resistance to predation. Surprisingly, cheats were unable to exploit this resistance in the presence of cooperators, which suggests that resistance does not appear to result from activation of QS-regulated public goods. Instead, elevated resistance of wild-type bacteria was related to the ability to form more predation-resistant biofilms. This could be explained by the expression of QS-regulated resistance traits in densely populated biofilms and floating cell aggregations, or alternatively, by a pleiotropic cost of cheating where less resistant cheats are selectively removed from biofilms. These results show that trophic interactions among species can maintain cooperation within species, and have further implications for P. aeruginosa virulence in environmental reservoirs by potentially enriching the cooperative and highly infective strains with functional QS system

Bacterial community profiles and Vibrio parahaemolyticus abundance in individual oysters and their association with estuarine ecology

Oysters naturally harbor the human gastric pathogen Vibrio parahaemolyticus, but the nature of this association is unknown. Because microbial interactions could influence the accumulation of V. parahaemolyticus in oysters, we investigated the composition of the microbiome in water and oysters at two ecologically unique sites in the Great Bay Estuary, New Hampshire using 16s rRNA profiling. We then evaluated correlations between bacteria inhabiting the oyster with V. parahaemolyticus abundance quantified using a most probable number (MPN) analysis. Even though oysters filter-feed, their microbiomes were not a direct snapshot of the bacterial community in overlaying water, suggesting they selectively accumulate some bacterial phyla. The microbiome of individual oysters harvested more centrally in the bay were relatively more similar to each other and had fewer unique phylotypes, but overall more taxonomic and metabolic diversity, than the microbiomes from tributary-harvested oysters that were individually more variable with lower taxonomic and metabolic diversity. Oysters harvested from the same location varied in V. parahaemolyticus abundance, with the highest abundance oysters collected from one location. This study, which to our knowledge is the first of its kind to evaluate associations of V. parahaemolyticus abundance with members of individual oyster microbiomes, implies that sufficient sampling and depth of sequencing may reveal microbiome members that could impact V. parahaemolyticus abundance

Conformal Risk Control

We extend conformal prediction to control the expected value of any monotone loss function. The algorithm generalizes split conformal prediction together with its coverage guarantee. Like conformal prediction, the conformal risk control procedure is tight up to an $\mathcal{O}(1/n)$ factor. Worked examples from computer vision and natural language processing demonstrate the usage of our algorithm to bound the false negative rate, graph distance, and token-level F1-score.Comment: Code available at https://github.com/aangelopoulos/conformal-ris

The Biomechanical Aspects of Pedestrian Protection

In this paper a biomechanical basis for pedestrian protection is presented based on reviews of epidemiological and biomechanical studies conducted over the last three decades. Epidemiological studies reveal the nature and cause of pedestrian crashes and injuries sustained in the field. The various factors that influence pedestrian crashes and fatalities such as pedestrian demographics, time and location of crash, type of vehicles involved and their design characteristics, impact speeds, and nature and severity of injuries sustained are covered in the epidemiology section. The biomechanical studies identify the injury mechanisms and the biomechanical tolerances. Several biomechanical studies that attempt to identify the injury mechanisms and quantify the tolerances are critically reviewed in this paper, and the existing gaps in literature are identified. Further, the three primary injury mechanisms for pedestrian lower extremity injuries are highlighted, and an injury mechanism for depressed tibial fracture is hypothesized. The effect of exterior vehicle parameters such as bumper height, bumper stiffness, hood length, hood stiffness, bumper lead angle on the nature and severity of injuries sustained are also discussed. The biomechanical injury criteria and tolerance values in a proposed draft ECE pedestrian regulation are also presented. Finally conclusions are drawn based on the epidemiological and biomechanical studies, which lead to a proposal for future work

Durable Responses With Mosunetuzumab in Relapsed/Refractory Indolent and Aggressive B-Cell Non-Hodgkin Lymphomas: Extended Follow-Up of a Phase I/II Study

Mosunetuzumab; B-cell non-Hodgkin lymphomas; RelapsedMosunetuzumab; Limfomes no Hodgkin de cèl·lules B; RecaigudaMosunetuzumab; Linfomas no Hodgkin de células B; RecaídaClinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Mosunetuzumab is a CD20xCD3 T-cell–engaging bispecific antibody administered as an off-the-shelf, fixed-duration treatment in an outpatient setting. We report an updated analysis of the durability of response, by investigator assessment, after an overall median follow-up of 3.5 years in patients with relapsed/refractory indolent or aggressive B-cell non-Hodgkin lymphoma (iNHL/aNHL) from the dose-escalation stage of a phase I/II study of mosunetuzumab (ClinicalTrials.gov identifier: NCT02500407). Across dose levels, 65.7% of patients with iNHL and 36.4% with aNHL achieved a complete or partial response to mosunetuzumab. Median duration of response (DoR) in patients with iNHL for all responders was 23.2 months (95% CI, 13.8 to not estimable [NE]), but was not reached in complete responders (95% CI, 21.0 to NE). After a median time on study of 38.9 months, no relapses were observed beyond 26 months in complete responders. In patients with aNHL, median DoR for all responders was 7.8 months (95% CI, 4.6 to 22.8). Among 12 complete responders who progressed postmosunetuzumab treatment and were retreated with mosunetuzumab, 83.3% had an objective response and 58.3% achieved a second complete response. Our study reports the longest follow-up using bispecific antibodies in patients with B-cell non-Hodgkin lymphoma and demonstrates that mosunetuzumab can mediate durable remissions with time-limited treatment.Supported by Genentech, Inc

Analysis of a large spatiotemporal groundwater quality dataset, Ontario 2010–2017: Informing human health risk assessment and testing guidance for private drinking water wells

Approximately 1.5 million individuals in Ontario are supplied by private water wells (private groundwater supplies). Unlike municipal supplies, private well water quality remains unregulated, with owners responsible for testing, treating, and maintaining their own water supplies. The primary goal of this study was to assess the effect of repeat sampling of private well water in Ontario and investigate the efficacy of geographically- and/or temporally specific testing recommendations and health risk assessments. The current study combines the Well Water Information System Dataset and the Well Water Testing Dataset from 2010 to 2017, inclusive. These two large existing province-wide datasets collated over an eight-year period were merged using an integrated spatial fuzzy logic and (next)- nearest neighbour approach. Provincial sampling data from 239,244 wells (702,861 samples) were analyzed for Escherichia coli to study the relationship between sampling frequency and Escherichia coli detection. Dataset variables were delineated based on hydrogeological setting (e.g. aquifer type, overburden depth, well depth, bedrock type) and seasonality to provide an in-depth understanding of Escherichia coli detection in private well water. Findings reveal differences between detection rates in consolidated and unconsolidated aquifers (p = 0.0191), and across seasons (p \u3c 0.0001). The variability associated with Escherichia coli detection rates was explored by estimating sentinel sampling rates for private wells sampled three times, twelve times and twenty-four times per year. As sample size increases on an annual basis, so too does detection rate, highlighting the need to address current testing frequency guidelines. Future health risk assessments for private well water should consider the impact of spatial and temporal factors on the susceptibility of this drinking water source, leading to an increasingly accurate depiction of private well water contamination and the estimated effects on human health

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study

Mosunetuzumab; B-cell lymphomasMosunetuzumab; Limfomes de cèl·lules bMosunetuzumab; Linfomas de células bPURPOSE Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). METHODS This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 (group B), for eight or 17 cycles on the basis of tumor response. RESULTS Two hundred thirty patients were enrolled. Doses up to 2.8 mg and 60 mg were assessed in groups A and B, respectively; maximum tolerated dose was not exceeded. In group B (n = 197), common adverse events (≥ 20% of patients) were neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Cytokine release syndrome was mostly low-grade (grade ≥ 3: 1.0%) and mainly confined to cycle 1. Across the doses investigated (group B), best overall response rates were 34.9% and 66.2% in patients with aggressive and indolent B-NHL, respectively, and complete response rates were 19.4% and 48.5%. Among patients with a complete response, the median duration of response was 22.8 months (95% CI, 7.6 to not estimable) and 20.4 (95% CI, 16 to not estimable) in patients with aggressive and indolent B-NHL, respectively. CONCLUSION Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in R/R B-NHL. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study