Protocolized reduction of non-resuscitation fluids versus usual care in septic shock patients (REDUSE): a randomized multicentre feasibility trial.

BACKGROUND/PURPOSE: Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care. METHODS: Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion. RESULTS: Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960-8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804-12,401) in the control group (n = 48); corresponding to a Hodges-Lehmann median difference of 3560 ml [95% confidence interval 1614-5302]; p < 0.001). Outcome data on all-cause mortality, days alive and free of mechanical ventilation and acute kidney injury or ischemic events in the ICU within 90 days of inclusion were recorded in 98/98 (100%), 95/98 (98%) and 95/98 (98%) of participants respectively. Cognition and health-related quality of life at six months were recorded in 39/52 (75%) and 41/52 (79%) of surviving participants, respectively. Ninety out of 134 patients (67%) of eligible patients were randomized, and 15/98 (15%) of the participants experienced at least one protocol violation. CONCLUSION: Protocolized reduction of non-resuscitation fluids in patients with septic shock resulted in a large decrease in fluid administration compared with usual care. A trial using this design to test if reducing non-resuscitation fluids improves outcomes is feasible. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05249088, 18 February 2022. https://clinicaltrials.gov/ct2/show/NCT05249088.

Role of gestational age at time of placental laser surgery in outcomes of twin-to-twin transfusion syndrome.

OBJECTIVE: There are conflicting data on whether fetoscopic laser photocoagulation of placental anastomoses (FLP) for treating twin-to-twin transfusion syndrome (TTTS) is associated with lower rates of overall survival. The objective of this study is to characterize survival and other associated morbidity after FLP across gestational ages of FLP. METHODS: This is a secondary analysis of prospectively collected data on patients with monochorionic-diamniotic twins that had FLP for TTTS at two centers between 2011 and 2022. Patients were divided into gestational age epochs for FLP before 18 wks, 18 0/7 - 19 6/7 wks, 20 0/7 - 21 6/7 wks, 22 0/7 - 23 6/7 wks, 24 0/7 - 25 6/7 wks and after 26 wks. Demographic characteristics, sonographic characteristics of TTTS and operative characteristics were compared across the gestational age epochs. Outcomes including overall survival, preterm delivery, preterm prelabor rupture of membranes (PPROM), intrauterine fetal demise (IUFD) and neonatal demise (NND) were also compared across gestational age epochs. Multivariate analysis was performed by fitting logistic regression models for these outcomes. Kaplan-Mejer curves were constructed to compare the interval from PPROM to delivery for each gestational age epoch. RESULTS: There were 768 patients that met inclusion criteria. The dual survival rate was 61.3% for FLP performed prior to 18 weeks compared to 78.0% - 86.7% across later gestational age epochs. This appears to be related to increased rates of donor IUFD following FLP performed before, versus after 18 weeks (28.0% vs. 9.3% - 14.1%). Rates of recipient IUFD/NND and donor NND were similar regardless of gestational age of FLP. Rates of PPROM were higher for earlier FLP, ranging from 45.6% for FLP before 18 weeks to 11.9% for FLP at 24 - 26 weeks gestational age. However, the gestational age of delivery was similar across gestational age epochs with a median of 31.7 weeks. In multivariate analysis, donor loss was independently associated with FLP before 18 weeks after adjusting for selective fetal growth restriction, Quintero stage and other covariates. PPROM and PTD were also associated with FLP before 18 weeks after adjusting for cervical length, placental location, trocar size, laser energy and amnioinfusion. CONCLUSION: FLP performed at earlier gestational ages is associated with lower overall survival, which is driven by higher risk of donor IUFD, as opposed to differences in PPROM or PTD. Counseling regarding survival should account for gestational age of presentation. This article is protected by copyright. All rights reserved.

Leveraging ecological momentary assessment to understand variability in food parenting practices within a low-income racially/ethnically diverse sample of parents of preschoolers.

Children's eating behaviors are shaped significantly by their home food environment, including exposure to food parenting practices. The current study leveraged ecological momentary assessment (EMA) to describe how food parenting practices used to feed preschoolers (n = 116) differed across contextual factors around eating, including type of eating occasion (i.e., meals vs. snacks), day of the week (i.e., weekend vs. weekday), who initiated the meal (parent vs. child), emotional climate of the eating occasion. Parent perceptions of how well the eating occasion went, including how well the child ate and whether the food parenting practices worked as intended were also explored. Parent use of specific food parenting practices, situated within four higher-order domains (i.e., structure, autonomy support, coercive control, indulgent), was found to differ by type of eating occasion; parents engaged in a higher proportion of structure practices at meals than at snacks. Use of specific food parenting practices differed by mealtime emotional climate; parent use of structure and autonomy support was associated with eating occasions described as relaxed, enjoyable, neutral, and fun. Finally, parent perception of how well the child ate differed by use of specific food parenting practices; during eating occasions when parent's felt their child ate "not enough", they used less autonomy support and more coercive control compared to eating occasions where the child ate "enough and a good balance." Leveraging EMA allowed for increased understanding of the variability in food parenting practices and contextual factors. Findings may be utilized to inform the development of larger-scale studies seeking to understand why parents choose specific approaches to feeding their children, as well as the impact of various approaches to child feeding on child health outcomes.

Parents of preschoolers use multiple strategies to feed their children: Findings from an observational video pilot study.

The current study leveraged observational data collection methods to fill gaps in our understanding of parent approach to feeding as well as child responses to various parental approaches. Specifically, the study aimed to: 1) characterize the broad range of food parenting practices used by parents of preschoolers during shared mealtimes at home, including differences by child gender, and 2) describe child responses to specific parent feeding practices. Forty parent-child dyads participated by recording two in-home shared meals. Meals were coded using a behavioral coding scheme that coded the occurrence of 11 distinct food parenting practices (e.g. indirect and direct commands, praise, bribes) and eight child responses (e.g., eat, refuse, cry/whine) to food parenting practices. Results revealed that parents engaged in a broad range of food parenting practices at meals. On average, parents in our sample used 10.51 (SD 7.83; Range 0-30) total food parenting practices per mealtime with a mean use of 3.38 (SD 1.67; Range 0-8) unique food parenting practices per mealtime. Use of indirect and direct commands to eat were most common; direct and indirect commands were used by 97.5% (n = 39) and 87.5% (n = 35) of parents at meals, respectively. No statistically significant differences were observed by child gender. No one specific feeding practice consistently yielded compliance or refusal to eat from the child, instead child responses were often mixed (e.g., compliance followed by refusal and/or refusal followed by compliance). However, use of praise to prompt eating was the practice that most often resulted in child compliance; 80.8% of children complied following parent's use of praise as a prompt to eat. Findings deepen our understanding of the types and frequency of food parenting practices used by parents of preschoolers during meals eaten at home and illuminate child responses to specific food parenting practices.

Broad responses and attitudes to having music in surgery (the BRAHMS study) - a South African perspective.

BACKGROUND: Music is played in operating theatres (OTs) throughout the world, though controversy around its use exists. While some clinicians may find background music favourable to the theatre mood and a way to augment surgical performance, there is concern raised over its distracting and noise-creating properties. METHODS: In this prospective observational study, between August and December 2021, 110 surgeons and registrars in South Africa responded to a survey investigating the way they use music, and their perceptions and attitudes towards its effect on the OT environment. RESULTS: In this cohort, 66% were male, 29% were consultants and the most common age range was 30-39 years old. Eighty per cent of respondents reported that music was played at least "sometimes", with 74% reporting that they enjoyed it. Easy Listening was the most played and preferred genre followed by Top 40/Billboard hits. Overwhelmingly, respondents reported that background music in the OT improved temperament, focus, mood, and performance, though over a quarter felt it worsened communication. Thirty-one per cent of respondents reported that the choice of music depended on the type of operation, and 70% would turn music down or off during crises. Those who enjoyed music in their spare time were significantly more likely to enjoy music in the OT and perceive it positively. CONCLUSION: This study provides a window into the surgeons' use of and attitudes to intraoperative music in South Africa. While overall, music is viewed positively by this cohort, some concerns remain regarding communication and distractedness. Further interventional and qualitative studies would be useful.

Prevalence of early postpartum depression and associated risk factors among selected women in southern Malawi: a nested observational study.

BACKGROUND: The birth of a child should be a time of celebration. However, for many women, childbirth represents a time of great vulnerability to becoming mentally unwell, a neglected maternal morbidity. This study aimed to determine the prevalence of early postpartum depression (PPD) and its associated risk factors among women giving birth at health facilities in southern Malawi. Identifying women vulnerable to PPD will help clinicians provide appropriately targeted interventions before discharge from the maternity ward. METHOD: We conducted a nested cross-sectional study. Women were screened for early PPD using a locally validated Edinburgh Postpartum Depression Scale (EPDS) as they were discharged from the maternity ward. The prevalence of moderate or severe (EPDS ≥ 6) and severe (EPDS ≥ 9) PPD was determined, including 95% confidence intervals (CI). Data on maternal age, education and marital status, income source, religion, gravidity, and HIV status, among others, were collected during the second trimester of pregnancy, and obstetric and infant characteristics during childbirth were examined as potential risk factors for early PPD using univariable and multivariable logistic regression analyses. RESULTS: Data contributed by 636 women were analysed. Of these women, 9.6% (95% CI; 7.4-12.1%) had moderate to severe early PPD using an EPDS cut-off of ≥ 6, and 3.3% (95% CI; 2.1-5.0%) had severe early PPD using an EPDS cut-off of ≥ 9. Multivariable analyses indicated that maternal anaemia at birth (aOR; 2.65, CI; 1.49-4.71, p-value; 0.001) was associated with increased risk for moderate and/or severe early PPD, while live birth outcome (aOR; 0.15, 95% CI; 0.04-0.54, p-value; 0.004), being single compared to divorced/widowed (aOR; 0.09, 95% CI; 0.02-0.55, p-value; 0.009), and lower education level (aOR; 0.36, 95% CI; 0.20-0.65, p-value; 0.001) were associated with decreased risk. Being HIV positive (aOR; 2.88, 95% CI; 1.08-7.67, p-value; 0.035) was associated with severe PPD only. CONCLUSION: The prevalence of early PPD was slightly lower in our selected sample compared to previous reports in Malawi and was associated with maternal anaemia at birth, non-live birth, being divorced/widowed and HIV-positive status. Therefore, health workers should screen for depressive symptoms in women who are at increased risk as they are discharged from the maternity ward for early identification and treatment.

Maternal responsiveness and toddler body mass index z-score: Prospective analysis of maternal and child mealtime interactions.

Responsive feeding, where parents are guided by children's hunger and satiation cues and provide appropriate structure and support for eating, is believed to promote healthier weight status. However, few studies have assessed prospective associations between observed parental feeding and toddler growth. We characterized toddler growth from 18 to 36 months and, in a subset of families, examined whether observed maternal responsiveness to toddler satiation cues and encouraging prompts to eat at 18 and 24 months were associated with toddler body mass index z-score (BMIz) from 18 to 36 months. Participants included 163 toddlers and their mothers with overweight/obesity who had participated in a lifestyle intervention during pregnancy. Anthropometrics were measured at 18, 24, and 36 months. In a subsample, mealtime interactions were recorded in families' homes at 18 (n = 77) and 24 (n = 75) months. On average, toddler BMIz remained stable from 18 to 36 months with 31.3% (n = 51) categorized with a healthy weight, 56.4% (n = 92) with at risk for overweight and 12.3% (n = 20) with overweight. Fewer maternal prompts to eat at 18 months was associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p = .002). Higher child weight status at 12 months was also associated with both higher probability of having at risk for overweight/overweight (p < .05), and higher child 36-month BMIz (p < .001). Neither 24-month maternal prompts nor 18 or 24 month responsiveness to satiation cues were associated with toddler BMIz. In this diverse sample, weight status was relatively stable from 18 to 36 months. Maternal prompts to eat measured earlier in toddlerhood and prior child weight status were associated with toddler BMIz.

Modeling Global Carbon Costs of Plant Nitrogen and Phosphorus Acquisition.

Most Earth system models (ESMs) do not explicitly represent the carbon (C) costs of plant nutrient acquisition, which leads to uncertainty in predictions of the current and future constraints to the land C sink. We integrate a plant productivity-optimizing nitrogen (N) and phosphorus (P) acquisition model (fixation & uptake of nutrients, FUN) into the energy exascale Earth system (E3SM) land model (ELM). Global plant N and P uptake are dynamically simulated by ELM-FUN based on the C costs of nutrient acquisition from mycorrhizae, direct root uptake, retranslocation from senescing leaves, and biological N fixation. We benchmarked ELM-FUN with three classes of products: ILAMB, a remotely sensed nutrient limitation product, and CMIP6 models; we found significant improvements in C cycle variables, although the lack of more observed nutrient data prevents a comprehensive level of benchmarking. Overall, we found N and P co-limitation for 80% of land area, with the remaining 20% being either predominantly N or P limited. Globally, the new model predicts that plants invested 4.1 Pg C yr-1 to acquire 841.8 Tg N yr-1 and 48.1 Tg P yr-1 (1994-2005), leading to significant downregulation of global net primary production (NPP). Global NPP is reduced by 20% with C costs of N and 50% with C costs of NP. Modeled and observed nutrient limitation agreement increases when N and P are considered together (r 2 from 0.73 to 0.83).

Understanding the differences in wear testing method standards for total knee replacement.

Preclinical evaluation of the wear of total knee replacements (TKR) is usually undertaken using International Standards Organization (ISO) test methods. Two international standards for the preclinical wear simulation of TKRs have been developed; using either force or displacement control. In addition, based on previously published measured kinematics of healthy subjects, a gait cycle (displacement control) was also developed at the University of Leeds, which pre-dates the ISO displacement control standard. Furthermore, different test methods have adopted different approaches to defining the centres of rotation and polarity (direction of application) of motions. However, the effects of using these different control regimes and input conditions on the kinematics, contact mechanics, and wear of any one TKR have not been fully investigated previously. The current study investigated the kinematics, contact mechanics, and wear performance of a TKR when running under ISO force and displacement control test methods as well as the Leeds gait cycle inputs using experimental and computational simulation methods, with the aim of understanding the mechanical and tribological outcomes predicted by the different test method standard conditions. Three ISO wear testing standards were investigated using a mid-size Sigma curved TKR (DePuy, UK), with moderately cross-linked UHMWPE curved inserts; ISO-14243-3-2004, ISO-14243-3-2014 and ISO-14243-1-2009. In addition, the Leeds displacement control gait cycle was also investigated. According to the computational simulation predictions, reversing the anterior-posterior (AP) displacement and tibial rotation polarities in the displacement control ISO-2014 standard compared to the ISO-2004 standard resulted in high stress, of more than 65 MPa, at the posterior edge of the inserts with more than 10% increase in wear rate for this TKR design. Although Leeds gait input kinematics produced femoral rollback, it did not result in high stress edge loading on the posterior lip of the insert. This was attributed to different test input kinematics and different centres of rotation of the femoral component adopted in the displacement control standard ISO-2014 and Leeds gait test methods. The predicted AP displacement and tibial rotation from the force control ISO-2009 had different polarities and magnitudes to the corresponding displacement control profiles. In addition, the predicted wear rate, from the computational model, under the force control ISO-2009 standard was more than double that predicted under displacement control ISO standards due to the increased AP displacement and tibial rotation motions predicted under the force control standard. These major differences, in the mechanics and wear, between different test methods imply that each standard must therefore be used with its own predicate control results from a device with proven clinical history and results across different standards should never be compared, as the choice of test method standard may well be dependent on the design solution for the knee. Clinically, the kinematics in the population are extremely variable, which results in highly variable wear rates. While a standard method is necessary, on its own it is not adequate and needs to be supported by tests under a portfolio of representative conditions with different kinematic conditions, different soft tissue constraints, as well as with different alignments, so that the variability and range of wear rates expected clinically might be determined. This study enables further progress towards the definition of such a portfolio of representative conditions, by deepening the understanding of the relationships between currently used input conditions and the resulting mechanical and wear outputs.

A Post Hoc Exploratory Analysis: Induced Abortion Complications Mistaken for Miscarriage in the Emergency Room are a Risk Factor for Hospitalization.

Introduction: Previous research indicates that an increasing number of women who go to an emergency room for complications following an induced abortion are treated for a miscarriage, meaning their abortion is miscoded or concealed. Objective: To determine if the failure to identify a prior induced abortion during an ER visit is a risk factor for higher rates of subsequent hospitalization. Methods: Post hoc analysis of hospital admissions following an induced abortion and ER visit within 30 days: 4273 following surgical abortion and 408 following chemical abortion; abortion not miscoded versus miscoded or concealed at prior ER visit. Results: Chemical abortion patients whose abortions are misclassified as miscarriages during an ER visit subsequently experience on average 3.2 hospital admissions within 30 days. 86% of the patients ultimately have surgical removal of retained products of conception (RPOC). Chemical abortions are more likely than surgical abortions (OR 1.80, CL 1.38-2.35) to result in an RPOC admission, and chemical abortions concealed are more likely to result (OR 2.18, CL 1.65-2.88) in a subsequent RPOC admission than abortions without miscoding. Surgical abortions miscoded/concealed are similarly twice as likely to result in hospital admission than those without miscoding. Conclusion: Patient concealment and/or physician failure to identify a prior abortion during an ER visit is a significant risk factor for a subsequent hospital admission. Patients and ER personnel should be made aware of this risk.

A descriptive assessment of a broad range of food-related parenting practices in a diverse cohort of parents of preschoolers using the novel Real-Time Parent Feeding Practices Survey.

BACKGROUND: Much of the research to-date on food parenting has evaluated typical use of various parent feeding practices via questionnaire. The Real-Time Parent Feeding Practices Measurement survey was developed for use within an Ecological Momentary Assessment (EMA) protocol to capture momentary use of parent feeding practices in real-time. METHODS: This manuscript describes the development of the EMA-based Real-Time Parent Feeding Practices survey and highlights initial descriptive data on the real-time use of 22 individual parent feeding practices (e.g., pressure-to-eat, guided choices, etc.) as reported via EMA by parents of preschool-aged children (n = 116) over a 10-day data collection time period. A total of 3382 eating occasions were reported, with an average of 29.2 reported eating occasions per participant. RESULTS: Results revealed that most participants used a variety of food-related parenting practices day-to-day that span four higher-order domains: structure, autonomy support, coercive control and indulgence. Supportive feeding practices, defined as those from the structure and autonomy support domains, were reported most frequently, with one or more structure behavior (e.g., specific mealtime rules/routines) was used at 88.9% of reported eating occasions and one or more autonomy support behavior (e.g., involvement of the child in meal preparation) was used at 87.3% of eating occasions. While unsupportive feeding practices, defined as practices from within the coercive control (e.g., pressure-to-eat) and indulgent (e.g., anticipatory catering) feeding domains, were reported less frequently, one or more behaviors from each of these domains were still reported at over 25% of all eating occasions. CONCLUSIONS: Results of the current study take a next step towards deepening our understanding of the use of a broad range of food-related parenting practices in real-time. Findings revealed that the vast majority of practices used by parents fall within the structure and autonomy support domains. However, most parents did not exclusively use supportive or unsupportive practices, rather they used a combination of food-related parenting practices across all domains. Future research should continue to explore a broad range of food-related parenting practices and seek to understand how parent approaches to feeding are associated with long-term child outcomes, including dietary intake, food preferences, and eating patterns.

COVID-19 pandemic shifts in food-related parenting practices within an ethnically/racially and socioeconomically diverse sample of families of preschool-aged children.

This study aimed to evaluate the influence of the COVID-19 pandemic on food parenting practices used by parents of young children. Ecological Momentary Assessment (EMA) was used to evaluate parents' use of coercive, indulgent, structured, and autonomy supportive food parenting practices before and during the COVID-19 pandemic among a diverse racial/ethnic sample (n = 72) of parents of preschool-aged children. The impact of parent and child mood/behavior on use of specific food parenting practices was also evaluated during both time periods. Results revealed that most parents of preschoolers use a variety of food parenting practices, including coercive control, indulgence, structure, and autonomy support practices. The use of structured and autonomy supportive practices, however, decreased during the COVID-19 pandemic. Further, the types of practices used by parents were contextually associated with the mood of the parent as well as child mood. Parent negative mood during COVID-19 was associated with higher levels of coercive control and indulgence and lower levels of structure, whereas child positive child mood was associated with greater use of autonomy supportive practices. These findings suggest that effects of the COVID-19 pandemic on family dynamics around feeding young children include shifts away from theoretically supportive approaches to parenting and highlight the roles of parent and child mood/behavior as potentially important momentary influences on food parenting during this time. Public health practitioners and clinicians working with parents of young children during COVID-19, and in years to come, should consider the potential impact of parental mood and stress, as well as child mood and behaviors. Additional research is needed to better understand how to best help parents maintain supportive feeding practices in the face of challenging situations.

Interventions to prevent preterm delivery in women with short cervix before fetoscopic laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: Preoperative short cervical length (CL) remains a major risk factor for preterm birth after laser surgery for twin-twin transfusion syndrome (TTTS), but the optimal intervention to prolong pregnancy remains elusive. The objective of this study was to compare secondary methods for the prevention of preterm birth in twin pregnancies with TTTS undergoing fetoscopic laser photocoagulation (FLP), in the setting of a short cervix at the time of FLP, in five North American Fetal Treatment Network (NAFTNet) centers. METHODS: This was a secondary analysis of data collected prospectively at five NAFTNet centers, conducted from January 2013 to March 2020. Inclusion criteria were a monochorionic diamniotic twin pregnancy complicated by TTTS, undergoing FLP, with preoperative CL < 30 mm. Management options for a short cervix included expectant management, vaginal progesterone, pessary (Arabin, incontinence or Bioteque cup), cervical cerclage or a combination of two or more treatments. Patients were not included if the intervention was initiated solely on the basis of having a twin gestation rather than at the diagnosis of a short cervix. Demographics, ultrasound characteristics, operative data and outcomes were compared. The primary outcome was FLP-to-delivery interval. Propensity-score matching was performed, with each treatment group matched (1:1) to the expectant-management group for CL, in order to estimate the effect of each treatment on the FLP-to-delivery interval. RESULTS: A total of 255 women with a twin pregnancy complicated by TTTS and a short cervix undergoing FLP were included in the study. Of these, 151 (59%) were managed expectantly, 32 (13%) had vaginal progesterone only, 21 (8%) had pessary only, 21 (8%) had cervical cerclage only and 30 (12%) had a combination of treatments. A greater proportion of patients in the combined-treatment group had had a prior preterm birth compared with those in the expectant-management group (33% vs 9%; P = 0.01). Mean preoperative CL was shorter in the pessary, cervical-cerclage and combined-treatment groups (14-16 mm) than in the expectant-management and vaginal-progesterone groups (22 mm for both) (P < 0.001). There was no significant difference in FLP-to-delivery interval between the groups, nor in gestational age at delivery or the rate of live birth or neonatal survival. Vaginal progesterone was associated with a decrease in the risk of delivery before 28 weeks' gestation compared with cervical cerclage and combined treatment (P = 0.03). Using propensity-score matching for CL, cervical cerclage was associated with a reduction in FLP-to-delivery interval of 13 days, as compared with expectant management. CONCLUSIONS: A large proportion of pregnancies with TTTS and a short maternal cervix undergoing FLP were managed expectantly for a short cervix, establishing a high (62%) risk of delivery before 32 weeks in this condition. No treatment that significantly improved outcome was identified; however, there were significant differences in potential confounders and there were also likely to be unmeasured confounders. Cervical cerclage should not be offered as a secondary prevention for preterm birth in twin pregnancies with TTTS and a short cervix undergoing FLP. A large randomized controlled trial is urgently needed to determine the effects of treatments for the prevention of preterm birth in these pregnancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Multilaboratory Comparison of Omadacycline MIC Test Strip to Broth Microdilution MIC against Gram-Negative, Gram-Positive, and Fastidious Bacteria.

The performance of the Liofilchem omadacycline MIC Test Strip (MTS) was evaluated in a multisite study. Three testing sites collected/tested clinical isolates and one site tested challenge isolates that totaled 175 S. aureus, 70 S. lugdunensis, 121 E. faecalis, 100 E. faecium, 578 Enterobacterales, 142 Haemophilus spp., 181 S. pneumoniae, 45 S. anginosus group, 35 S. pyogenes,and 20 S. agalactiae. MIC testing was performed by CLSI broth microdilution (BMD) and MTS. Fastidious isolates testing included BMD and MTS testing with both CLSI and EUCAST Mueller-Hinton Fastidious (MH-F). In addition, each site performed reproducibility for nonfastidious and fastidious isolates and QC by MTS and BMD. All BMD and MTS results for the QC strains were within expected ranges, with exception of one MTS HTM result for H. influenzae ATCC 49247. Among reproducibility isolates, omadacycline MTS results were within one dilution of the modal MIC for 95.2% of nonfastidious Gram-positive, 100% of Gram-negative, 99.3% and 98.5% of fastidious isolates tested on CLSI and EUCAST media, respectively. MTS results for all study isolates were within one doubling dilution of the CLSI BMD MIC for 98.9% of S. aureus, 100% of S. lugdunensis, 98.3% of E. faecalis, 100% of E. faecium, and 99.6% of Enterobacterales. Essential agreement rates for CLSI and EUCAST MH-F agar compared to CLSI BMD were 98.2% and 98.2%, for H. influenzae, 91.1% and 73.6%, for S. pneumoniae and 100% and 85-91.7% for other streptococcus species, respectively. Based on CLSI media, all categorical errors were minor errors and categorical agreement rates were >90% with exception of C. freundii, S. lugdunensis, E. faecalis, S. anginosus and S. constellatus.

Conceptualizing a New System of Care in Hawai'i for Native Hawaiians and Substance Use.

Native Hawaiians of all age groups tend to show a higher prevalence of substance use than other ethnic groups in the state. Research shows that this inequitable health status results from several complex and interconnected social determinants of health, including historical trauma, discrimination, and lifestyle changes. Before European contact, Native Hawaiians understood that balanced nutrition, physical activity, social relationships, and spirituality were fundamental to maintaining optimal health. Western influences triggered an imbalance in Native Hawaiian society, shifting the paradigm of Native Hawaiian family systems. Historical and cultural trauma affect multiple generations and are linked to Native Hawaiian health disparities. Cultural trauma is defined as "the loss of identity and meaning that negatively affects group consciousness. It marks and changes them in fundamental and irreversible ways, often resulting in the loss of language, lifestyles, and values." The remedy for cultural trauma is cultural reclamation. Historical trauma is defined as psychosocial trauma experienced by Indigenous groups as a result of colonization, war, genocide, or cultural, social, and political subjugation. These historical and cultural aspects have impacted and reached across generations of Native Hawaiians. The outcomes of these traumas are reflected in higher rates of health disparities, including mental health and addiction, which have affected the social determinants of health. Current access to treatment and recovery is limited for Native Hawaiian residents with substance use problems. This article will look at a system of care that would reduce silos and incorporate cultural aspects to improve outcomes for Native Hawaiians receiving services. This article will also introduce an 'aina- (land-) based model for creating healthy, thriving Native Hawaiian individuals, 'ohana (family), communities, and care systems.

Multiscale Assessment of Agricultural Consumptive Water Use in California's Central Valley.

Spatial estimates of crop evapotranspiration with high accuracy from the field to watershed scale have become increasingly important for water management, particularly over irrigated agriculture in semiarid regions. Here, we provide a comprehensive assessment on patterns of annual agricultural water use over California's Central Valley, using 30-m daily evapotranspiration estimates based on Landsat satellite data. A semiempirical Priestley-Taylor approach was locally optimized and cross-validated with available field measurements for major crops including alfalfa, almond, citrus, corn, pasture, and rice. The evapotranspiration estimates explained >70% variance in daily measurements from independent sites with an RMSE of 0.88 mm day-1. When aggregated over the Valley, we estimated an average evapotranspiration of 820 ± 290 mm yr-1 in 2014. Agricultural water use varied significantly across and within crop types, with a coefficient of variation ranging from 8% for Rice (1,110 ± 85 mm yr-1) to 59% for Pistachio (592 ± 352 mm yr-1). Total water uses in 2016 increased by 9.6%, as compared to 2014, mostly because of land-use conversion from fallow/idle land to cropland. Analysis across 134 Groundwater Sustainability Agencies (GSAs) further showed a large variation of agricultural evapotranspiration among and within GSAs, especially for tree crops, e.g., almond evapotranspiration ranging from 339 ± 80 mm yr-1 in Tracy to 1,240 ± 136 mm yr-1 in Tri-County Water Authority. Continuous monitoring and assessment of the dynamics and spatial heterogeneity of agricultural evapotranspiration provide data-driven guidance for more effective land use and water planning across scales.

Considerations for the Nonclinical Safety Evaluation of Antibody-Drug Conjugates.

The targeted delivery of drugs by means of linking them to antibodies (Abs) to form antibody-drug conjugates (ADCs) has become an important approach in oncology and could potentially be used in other therapeutic areas. Targeted therapy is aimed at improving clinical efficacy while minimizing adverse reactions. The nonclinical safety assessment of ADCs presents several unique challenges involving the need to examine a complex molecule, each component of which can contribute to the effects observed, in appropriate animal models. Some considerations for the nonclinical safety evaluation of ADCs based on a literature review of ADCs in clinical development (currently or previously) are discussed.

A trade-off between plant and soil carbon storage under elevated CO2.

Terrestrial ecosystems remove about 30 per cent of the carbon dioxide (CO2) emitted by human activities each year1, yet the persistence of this carbon sink depends partly on how plant biomass and soil organic carbon (SOC) stocks respond to future increases in atmospheric CO2 (refs. 2,3). Although plant biomass often increases in elevated CO2 (eCO2) experiments4-6, SOC has been observed to increase, remain unchanged or even decline7. The mechanisms that drive this variation across experiments remain poorly understood, creating uncertainty in climate projections8,9. Here we synthesized data from 108 eCO2 experiments and found that the effect of eCO2 on SOC stocks is best explained by a negative relationship with plant biomass: when plant biomass is strongly stimulated by eCO2, SOC storage declines; conversely, when biomass is weakly stimulated, SOC storage increases. This trade-off appears to be related to plant nutrient acquisition, in which plants increase their biomass by mining the soil for nutrients, which decreases SOC storage. We found that, overall, SOC stocks increase with eCO2 in grasslands (8 ± 2 per cent) but not in forests (0 ± 2 per cent), even though plant biomass in grasslands increase less (9 ± 3 per cent) than in forests (23 ± 2 per cent). Ecosystem models do not reproduce this trade-off, which implies that projections of SOC may need to be revised.