Fish communicate with water flow to enhance a school's social network.

Schooling fish rely on a social network created through signaling between its members to interact with their environment. Previous studies have established that vision is necessary for schooling and that flow sensing by the lateral-line system may aid in a school's cohesion. However, it remains unclear to what extent flow provides a channel of communication between schooling fish. Based on kinematic measurements of the speed and heading of schooling tetras (Petitella rhodostoma), we found that compromising the lateral line by chemical treatment reduced the mutual information between individuals by ∼13%. This relatively small reduction in pairwise communication propagated through schools of varying size to reduce the degree and connectivity of the social network by more than half. Treated schools additionally showed more than twice the spatial heterogeneity of fish with unaltered flow sensing. These effects were much more substantial than the changes that we measured in the nearest-neighbor distance, speed, and intermittency of individual fish by compromising flow sensing. Therefore, flow serves as a valuable supplement to visual communication in a manner that is revealed through a school's network properties.

Mixed methods evaluation of a specialty-specific system to promote physician engagement in safety and quality reporting in a large academic health system.

BACKGROUND: Incident reporting systems (IRS) can improve care quality and patient safety, yet their impact is limited by clinician engagement. Our objective was to assess barriers to reporting in a hospital-wide IRS and use data to inform ongoing improvement of a specialty-specific IRS embedded in the electronic health record targeting anaesthesiologists. METHODS: This quality improvement (QI) evaluation used mixed methods, including qualitative interviews, faculty surveys and user data from the specialty-specific IRS. We conducted 24 semi-structured interviews from January to May 2023 in a large academic health system in Northern California. Participants included adult and paediatric anaesthesiologists, operating room nurses, surgeons and QI operators, recruited through convenience and snowball sampling. We identified key themes and factors influencing engagement, which were classified using the Systems Engineering Initiative for Patient Safety framework. We surveyed hospital anaesthesiologists in January and May 2023, and characterised the quantity and type of reports submitted to the new system. RESULTS: Participants shared organisation and technology-related barriers to engagement in traditional system-wide IRSs, many of which the specialty-specific IRS addressed-specifically those related to technological access to the system. Barriers related to building psychological safety for those who report remain. Survey results showed that most barriers to reporting improved following the specialty-specific IRS launch, but limited time remained an ongoing barrier (25 respondents out of 44, 56.8%). A total of 964 reports with quality/safety concerns were submitted over the first 8 months of implementation; 47-76 unique anaesthesiologists engaged per month. The top safety quality categories of concern were equipment and technology (25.9%), clinical complications (25.3%) and communication and scheduling (19.9%). CONCLUSIONS: These findings suggest that a specialty-specific IRS can facilitate increased physician engagement in quality and safety reporting and complement existing system-wide IRSs.

APOE ε4 Allele Frequency Among Cognitively Healthy Members of an Ojibwe Tribal Nation.

Objectives: APOE ε4 frequency varies by geography and ancestry. We provide data regarding the frequency of this allele in the Ojibwe people, the fifth largest Indigenous people in the United States. Methods: Population study including 33 cognitively normal older individuals of an Ojibwe Tribal Nation (total population: 984; all with ≥25% Ojibwe ancestry). Results: APOE ε4 allele frequency was 19.7%, which is comparable with other cognitively normal American Indian, Alaskan Native, and non-Hispanic White populations of the United States and Europe, with the exception of a lower frequency among Choctaw Nation of Oklahoma participants with >50% American Indian ancestry. Discussion: While some global populations have very low APOE ε4 prevalence, this allele appears common among American Indian Tribal Nations included thus far in the United States. Because APOE ε4 is a cornerstone for novel diagnostics and therapeutics for Alzheimer disease (AD), future study is warranted to understand ancestry-dependent effects of APOE ε4 on AD risk and biology.

Maternal vaccination against COVID-19 and neonatal outcomes during Omicron: INTERCOVID-2022 study.

BACKGROUND: In early 2023, when Omicron was the variant of concern, we showed that vaccinating pregnant women decreased the risk for severe COVID-19-related complications and maternal morbidity and mortality. OBJECTIVE: This study aimed to analyze the impact of COVID-19 during pregnancy on newborns and the effects of maternal COVID-19 vaccination on neonatal outcomes when Omicron was the variant of concern. STUDY DESIGN: INTERCOVID-2022 was a large, prospective, observational study, conducted in 40 hospitals across 18 countries, from November 27, 2021 (the day after the World Health Organization declared Omicron the variant of concern) to June 30, 2022, to assess the effect of COVID-19 in pregnancy on maternal and neonatal outcomes and to assess vaccine effectiveness. Women diagnosed with laboratory-confirmed COVID-19 during pregnancy were compared with 2 nondiagnosed, unmatched women recruited concomitantly and consecutively during pregnancy or at delivery. Mother-newborn dyads were followed until hospital discharge. The primary outcomes were a neonatal positive test for COVID-19, severe neonatal morbidity index, severe perinatal morbidity and mortality index, preterm birth, neonatal death, referral to neonatal intensive care unit, and diseases during the neonatal period. Vaccine effectiveness was estimated with adjustment for maternal risk profile. RESULTS: We enrolled 4707 neonates born to 1577 (33.5%) mothers diagnosed with COVID-19 and 3130 (66.5%) nondiagnosed mothers. Among the diagnosed mothers, 642 (40.7%) were not vaccinated, 147 (9.3%) were partially vaccinated, 551 (34.9%) were completely vaccinated, and 237 (15.0%) also had a booster vaccine. Neonates of booster-vaccinated mothers had less than half (relative risk, 0.46; 95% confidence interval, 0.23-0.91) the risk of being diagnosed with COVID-19 when compared with those of unvaccinated mothers; they also had the lowest rates of preterm birth, medically indicated preterm birth, respiratory distress syndrome, and number of days in the neonatal intensive care unit. Newborns of unvaccinated mothers had double the risk for neonatal death (relative risk, 2.06; 95% confidence interval, 1.06-4.00) when compared with those of nondiagnosed mothers. Vaccination was not associated with any congenital malformations. Although all vaccines provided protection against neonatal test positivity, newborns of booster-vaccinated mothers had the highest vaccine effectiveness (64%; 95% confidence interval, 10%-86%). Vaccine effectiveness was not as high for messenger RNA vaccines only. Vaccine effectiveness against moderate or severe neonatal outcomes was much lower, namely 13% in the booster-vaccinated group (all vaccines) and 25% and 28% in the completely and booster-vaccinated groups, respectively (messenger RNA vaccines only). Vaccines were fairly effective in protecting neonates when given to pregnant women ≤100 days (14 weeks) before birth; thereafter, the risk increased and was much higher after 200 days (29 weeks). Finally, none of the neonatal practices studied, including skin-to-skin contact and direct breastfeeding, increased the risk for infecting newborns. CONCLUSION: When Omicron was the variant of concern, newborns of unvaccinated mothers had an increased risk for neonatal death. Neonates of vaccinated mothers had a decreased risk for preterm birth and adverse neonatal outcomes. Because the protective effect of COVID-19 vaccination decreases with time, to ensure that newborns are maximally protected against COVID-19, mothers should receive a vaccine or booster dose no more than 14 weeks before the expected date of delivery.

PTP1B phosphatase dampens iPSC-derived neutrophil motility and antimicrobial function.

Neutrophils are rapidly recruited to sites of infection and are critical for pathogen clearance. Therapeutic use of primary neutrophils has been limited, as they have a short lifespan and are not amenable to genetic manipulation. Human induced pluripotent stem cells (iPSCs) can provide a robust source of neutrophils for infusion and are genetically tractable. However, current work has indicated that dampened intracellular signaling limits iPSC-derived neutrophil (iNeutrophil) cellular activation and antimicrobial response. Here, we show that protein tyrosine phosphatase 1B (PTP1B) inhibits intracellular signaling and dampens iNeutrophil effector function. Deletion of the PTP1B phosphatase increased PI3K and ERK signaling and was associated with increased F-actin polymerization, cell migration, and phagocytosis. In contrast, other effector functions like NETosis and reactive oxygen species production were reduced. PTP1B-deficient neutrophils were more responsive to Aspergillus fumigatus and displayed rapid recruitment and control of hyphal growth. Accordingly, depletion of PTP1B increased production of inflammatory factors including the neutrophil chemokine interleukin-8. Taken together, these findings suggest that PTP1B limits iNeutrophil motility and antimicrobial function.

Neutrophil motility is regulated by both cell intrinsic and endothelial cell ARPC1B.

Neutrophil-directed motility is necessary for host defense, but its dysregulation can also cause collateral tissue damage. Actinopathies are monogenic disorders that affect the actin cytoskeleton and lead to immune dysregulation. Deficiency in ARPC1B, a component of the Arp2/3 complex, results in vascular neutrophilic inflammation; however, the mechanism remains unclear. Here, we generated human induced pluripotent stem cell (iPSC)-derived neutrophils (denoted iNeutrophils) that are deficient in ARPC1B and show impaired migration and a switch from forming pseudopodia to forming elongated filopodia. We show, using a blood vessel on a chip model, that primary human neutrophils have impaired movement across an endothelium deficient in APRC1B. We also show that the combined deficiency of ARPC1B in iNeutrophils and endothelium results in further reduction in neutrophil migration. Taken together, these results suggest that ARPC1B in endothelium is sufficient to drive neutrophil behavior. Furthermore, the findings provide support for using the iPSC system to understand human neutrophil biology and model disease in a genetically tractable system.