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Circadian rhythms are endogenous biological cycles that regulate physiology and behavior for optimal adaptive function and survival; they are synchronized to precisely 24 hours by daily light exposure. Disruption of the daily light-dark (LD) cycle by exposure to artificial light at night (ALAN) dysregulates core clock genes and biological function. Exposure to ALAN has been associated with increased health risks in humans, and elderly individuals are at elevated risk for poor outcome from disease and often experience elevated exposure to ALAN due to increased care requirements. The role of disrupted circadian rhythms in healthy, aged animals remains unspecified; thus, we hypothesized that disrupted circadian rhythms via chronic exposure to dim ALAN (dLAN) impair immune response and survival in aged mice. Twenty-month-old C57BL/6 male and female mice were exposed to 24 weeks of LD conditions or dLAN (5 lux); then, cell-mediated immune response was assessed using a delayed-type hypersensitivity test. Aged female mice exposed to dLAN displayed dysregulated hypersensitivity and inflammation as a measure of cell-mediated immune response and decreased lifespan compared to females housed in dark nights. Nighttime lighting did not affect cell-mediated immune response or lifespan in males but dysregulated body mass and increased adrenal mass after immune challenge after chronic exposure to dLAN. Together, these data indicate that chronic exposure to dLAN affects lifespan in aged females and suggest that females are more susceptible to the detrimental consequences of disrupted circadian rhythms.

Glucose control in patients after total pancreatectomy is problematic because of the complete absence of α- and β-cells, leading to impaired quality of life. A novel, bihormonal artificial pancreas (BIHAP), using both insulin and glucagon, may improve glucose control, but studies in this setting are lacking.To assess the efficacy and safety of the BIHAP in patients after total pancreatectomy.This randomized crossover clinical trial compared the fully closed-loop BIHAP with current diabetes care (ie, insulin pump or pen therapy) in 12 adult outpatients after total pancreatectomy. Patients were recruited between August 21 and November 16, 2020. This first-in-patient study began with a feasibility phase in 2 patients. Subsequently, 12 patients were randomly assigned to 7-day treatment with the BIHAP (preceded by a 5-day training period) followed by 7-day treatment with current diabetes care, or the same treatments in reverse order. Statistical analysis was by Wilcoxon signed rank and Mann-Whitney U tests, with significance set at a 2-sided P.05.The primary outcome was the percentage of time spent in euglycemia (70-180 mg/dL [3.9-10 mmol/L]) as assessed by continuous glucose monitoring.In total, 12 patients (7 men and 3 women; median [IQR] age, 62.5 [43.1-74.0] years) were randomly assigned, of whom 3 did not complete the BIHAP phase and 1 was replaced. The time spent in euglycemia was significantly higher during treatment with the BIHAP (median, 78.30%; IQR, 71.05%-82.61%) than current diabetes care (median, 57.38%; IQR, 52.38%-81.35%; P = .03). In addition, the time spent in hypoglycemia (70 mg/dL [3.9 mmol/L]) was lower with the BIHAP (median, 0.00% [IQR, 0.00%-0.07%] vs 1.61% [IQR, 0.80%-3.81%]; P = .004). No serious adverse events occurred.Patients using the BIHAP after total pancreatectomy experienced an increased percentage of time in euglycemia and a reduced percentage of time in hypoglycemia compared with current diabetes care, without apparent safety risks. Larger randomized trials, including longer periods of treatment and an assessment of quality of life, should confirm these findings.trialregister.nl Identifier: NL8871.

The primary objective of this study was to determine whether the level of concentrate allowance in an automated milking system (AMS) affects the feed intake, eating behavior, milking activity, and performance of lactating dairy cows. The secondary objective of this study was to describe how the response to concentrate allocation, specifically in feeding and milking behavior, varies with cow personality traits. Fifteen Holstein cows were used in a crossover design with two 28-d periods, each including 14 d of adaptation and 14 d of data collection. The cows were housed in a freestall pen with free-traffic access to the AMS. Treatments consisted of a basal partial mixed ration (PMR) common to both treatment groups, with a concentrate allowance (on dry matter basis) of (1) 3.0 kg/d in the AMS (L-AMS) or (2) 6.0 kg/d in the AMS (H-AMS). Between the 2 treatment periods, each cow was assessed for personality traits using a combined arena test consisting of exposure to a novel environment, novel object, and novel human. Principal component analysis of behaviors observed during the novel environment and object tests revealed 3 factors (interpreted as active, social, and alert-curious) that together explained 76% of the variance, whereas principal component analysis of the novel human test revealed 2 factors (interpreted as active-vocal and fearful of novel humans) that together explained 77% of the variance. When on the H-AMS treatment, PMR dry matter intake (DMI) was less (24.5 vs. 26.0 kg/d) and AMS concentrate delivery was greater (5.9 vs. 3.1 kg/d), as per design. Consequently, total DMI was greater on the H-AMS treatment (30.4 vs. 29.1 kg/d). When on the H-AMS treatment, cows who were more alert-curious consumed more PMR, whereas cows who were more fearful of the novel human were less likely to receive the maximum amount of AMS concentrate available, limiting their total DMI and increasing the day-to-day variability of that intake. Although this was a preliminary study, these data suggest an association between dairy cow personality traits and how cows respond to increased AMS concentrate allowance.

Milk production may be reduced before dry-off to decrease the risk of cows developing intramammary infections during the dry period. Such reductions in milk may be possible in automated milking systems (AMS) where milking frequency and feed allocation at the AMS can be controlled at the cow level. This study investigated the effect of dry-off management of cows milked in AMS on milk yield, milking behavior, and somatic cell count (SCC). Using a 2 × 2 factorial arrangement of treatments, applied from d 14 to 1 before dry-off, 445 cows from 5 commercial dairy farms in Quebec, Canada, were assigned within farm to either (1) reduced feed [RF; allowed a maximum of 0.75 kg/d of AMS pellet for the first week (14 to 8 d before dry-off) of treatment, and 0.50 kg/d for the second week (7 to 1 d before dry-off) of treatment], or (2) nonreduced feed (NF; allowed up to 2 kg/d of AMS pellet), and either (1) reduced milking (RM; reduced to 2 milkings/d or as many times as required to yield 17 kg/milking), or (2) nonreduced milking (NM; allowed up to 6 AMS milkings/d) and no maximum production. Feed and milking behavior data, as well as milk yield and SCC were collected from the AMS software. The RF cows had lower AMS feed delivered during the treatment period, as per the experimental design. Across the treatment period, the NF-NM cows had the highest milking frequency (2.7 times/d), followed by the RF-NM cows (2.4 times/d), and then both of the RM groups (1.8 times/d), which did not differ from each other. All cows, except the NF-NM cows, were gradually milked less frequently as dry-off approached. Across the entire 2-wk treatment period before dry-off, cows with RM allowance experienced a higher reduction in milk yield compared with the cows with no milking allowance restrictions (-4.8 vs. -3.6 kg). Similarly, cows with a RF allocation tended to have a higher reduction in milk yield than cows with NF (-4.6 vs. -3.7 kg). As result, those cows with both reduced milking permissions and feed allocation at the AMS experienced the greatest drop in milk production before dry-off. There were no differences between treatments for milking frequency or yield in the next lactation. Somatic cell score (calculated from SCC) was not different between treatments in the 2-wk or day before dry-off, nor in the first month after calving. Overall, these data suggest that reducing both milking frequency and feed quantity in the AMS is the most efficient method to decrease milk yield before dry-off, without negatively influencing milking frequency or yield in the next lactation, as well as without affecting milk quality.

Bed bugs (Cimex lectularius) have proliferated globally and have become one of the most challenging pests to control indoors. They are nocturnal and use multiple sensory cues to detect and orient towards their human hosts. After feeding, usually on a sleeping human, they return to a shelter on or around the sleeping surface, but not directly on the host. We hypothesized that although human skin odors attract hungry bed bugs, human skin compounds may also prevent arrestment on hosts. We used arrestment assays to test human skin swabs, extracts from human skin swabs, and pure compounds identified from human skin swabs. When given a choice, bed bugs preferred to arrest on substrates not previously conditioned by humans. These responses were consistent among laboratory-reared and apartment-collected bed bugs. The compounds responsible for this behavior were found to be extractable in hexane, and bed bugs responded to such extracts in a dose-dependent manner. Bioassay-guided fractionation paired with thin-layer chromatography, GC–MS, and LC–MS analyses suggested that triglycerides (TAGs), common compounds found on human skin, were preventing arrestment on shelters. Bed bugs universally avoided sheltering in TAG-treated shelters, which was independent of the number of carbons or the number of double bonds in the TAG. These results provide strong evidence that the complex of human skin compounds serve as multifunctional semiochemicals for bed bugs, with some odorants attracting host-seeking stages, and others (TAGs and possibly other compounds) preventing bed bug arrestment. Host chemistry, environmental conditions and the physiological state of bed bugs likely influence the dual nature behavioral responses of bed bugs to human skin compounds.

Item does not contain fulltext OBJECTIVES: We developed an epidemiological algorithm to classify types of diabetes mellitus (DM) in chronic pancreatitis (CP), and applied it to a nationwide prospective longitudinal cohort of CP patients. METHODS: Patients with definite CP (M-ANNHEIM criteria) were classified as having DM types 1, 2, or 3c, or no DM using an algorithm based on epidemiological characteristics: DM onset in relation to age, CP onset, exocrine insufficiency. Variables associated with development of DM were identified. RESULTS: Of 1130 included patients with CP between 2011 and 2018, 368 patients (33%) had DM at inclusion. Among patients with DM, 11 were classified as having type 1 (3%), 159 as type 2 (43%), and 191 as type 3c (52%). Patients with DM type 3c had longer duration of CP, more severe pain and lower physical quality of life. During longitudinal follow-up of median 47 months, 120 (20%) patients developed DM, of which 99 patients were classified as type 3c. This was independently associated with pancreatic endoscopy and surgery. CONCLUSIONS: The described algorithm based on epidemiological characteristics can help to classify types of DM in patients with CP. Diabetes mellitus type 3c is associated with longer duration of CP and more severe CP sequelae.

Background An estimated 1.8 billion children live in countries where COVID-19 disrupted violence prevention and response. It is important to understand how government policies to contain COVID-19 impacted children’s ability to seek help, especially in contexts where there was limited formal help-seeking prior to the pandemic. We aimed to quantify how the national lockdown in Zimbabwe affected helpline calls for violence against children, estimated the number of calls that would have been received had the lockdown not occurred and described characteristics of types of calls and callers before and after the national lockdown. Methods We used an interrupted time series design to analyse the proportion of violence related calls (17,913 calls out of 57,050) to Childline Zimbabwe’s national child helpline between 2017 to 2021. We applied autoregressive integrated moving average regression (ARIMA) models to test possible changes in call trends before and after the March 2020 lockdown and forecasted how many calls would have been received in the absence of lockdown. In addition, we examined call characteristics before and after lockdown descriptively. Results The proportion of violence related calls decreased in the 90 days after the lockdown and subsequently returned to pre-COVID-19 levels. We estimate that 10.3% (95% confidence interval [CI] 6.0–14.6%) more violence related calls would have occurred in this period had there not been a lockdown. Violence was increasingly reported as occurring in children’s households, with fewer reports from children and formal child protection actors. Conclusions Lockdowns dramatically change everyday life and strain populations, which is unlikely to reduce violence prevalence but may reduce help-seeking. The three months after COVID-19 lockdowns may be key time periods when help-seeking for violence decreases drastically. Policy makers should ensure that in-person and remote services support help-seeking. Interventions and campaigns may additionally want to target adult female family members in encouraging reporting of suspected violence cases when they occur within households and are perpetuated by other family members. We suggest a composite approach of scaling-up remote reporting mechanisms that are accessible and geographically well-distributed, establishing non-traditional sites for help seeking within communities and continuing limited in-person home visitation for known cases of violence.

Background Patellar instability among adolescents has an incidence of 29 to 43 per 100,000 per year. Trochlear dysplasia has been found in up to 85% of those with recurrent patellar instability. The prevalence of trochlear dysplasia in the general population has not yet been defined. The purpose of the present study was to determine the prevalence of trochlear dysplasia as defined by ultrasound in a skeletally mature population and to characterize associations of trochlear dysplasia with a history of patellofemoral instability or pain. Methods Skeletally mature adolescents and parents of patients (≤50 years of age) who had presented to orthopaedic clinics were prospectively enrolled from 2019 to 2020. Those presenting with knee pain, open physes, prior intra-articular fracture, total knee arthroplasty, and syndromic ligamentous laxity or neuromuscular disease were excluded. Information regarding a history of anterior knee pain, patellar instability, and/or surgery was obtained, and an abbreviated Anterior Knee Pain Scale (AKPS) was collected. An AKPS score of ≥4 was considered positive. Bilateral ultrasound of the knee was performed, and the osseous sulcus angle of the trochlea and the trochlear depth were measured. Basic descriptive statistics are reported. Results One hundred and two patients (203 knees) were studied. The mean sulcus angle was 144.1° ± 6.8°, and the mean trochlear depth was 5.5 ± 1.4 mm. High-grade trochlear dysplasia was defined as the 95th percentile and above, which was shown to be a sulcus angle of ≥154° or a trochlear depth of ≤3 mm for female patients and ≤4 mm for male patients. The prevalence of high-grade trochlear dysplasia was 5.4% based on the sulcus angle and 9.9% based on trochlear depth. Knees with high-grade trochlear dysplasia based on the sulcus angle were 11 times more likely to have had previous patellar instability (p = 0.013). Conclusions The prevalence of high-grade trochlear dysplasia in the general population is approximately 10%, and there may be an association with patellar instability. The use of ultrasound to diagnose trochlear dysplasia may prove to be a rapid and useful tool for guiding patient education and treatment decisions. Level of evidence Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Study objective Intramuscular medications are commonly used to treat agitation in the emergency department (ED). The purpose of this study is to compare intramuscular droperidol and olanzapine for treating agitation. Methods This was a prospective observational study of ED patients receiving intramuscular droperidol or olanzapine for acute agitation. The treating physician determined the medication and dose; however, over time drug shortages made either olanzapine (July to September 2019) or droperidol (November 2019 to March 2020) unavailable, creating a natural experiment. The primary outcome was time to adequate sedation, assessed by the Altered Mental Status Scale (AMSS), defined as time to AMSS score less than or equal to 0. Results We analyzed 1,257 patients (median age 42 years; 73% men); 538 received droperidol (median dose 5 mg) and 719 received olanzapine (median dose 10 mg). The majority of patients (1,086; 86%) had agitation owing to alcohol intoxication. Time to adequate sedation was 16 minutes (interquartile range 10 to 30 minutes) for droperidol and 17.5 minutes (interquartile range 10 to 30 minutes) for olanzapine (absolute difference –0.7 minutes; 95% confidence interval –2.1 to 0.5 minutes). Adjusted Cox proportional hazard model analysis revealed no difference between groups in time to sedation (hazard ratio for adequate sedation for droperidol compared with olanzapine 1.12; 95% confidence interval 1.00 to 1.25). Patients receiving olanzapine were more likely to receive additional medications for sedation (droperidol 17%; olanzapine 24%; absolute difference –8% [95% confidence interval –12% to –3%]). We observed no difference between drugs regarding adverse effects except for extrapyramidal adverse effects, which were more common with droperidol (n=6; 1%) than olanzapine (n=1; 0.1%). Conclusion We found no difference in time to adequate sedation between intramuscular droperidol and olanzapine.

Type 2 diabetes (T2D) risk is lower in females than males. It has been reported that females have greater pancreatic 𝛽-cell function than males, which may at least in part contribute to the T2D risk in females. 𝛽-cell function is influenced by exercise training; however, previous trials comparing 𝛽-cell function between the sexes have not included participants matched for training status. Furthermore, the acute effects of different modes of exercise on 𝛽-cell function, and whether sex inherently influences these effects, are largely unexamined. Males and females (12/sex) completed a 120-min oral glucose tolerance test (OGTT) at rest (CON) and following acute bouts of high-intensity interval exercise (HIIE), moderate intensity continuous (MIC) exercise, and low-load high-repetition (LLHR) resistance exercise to assess whether sex inherently influences baseline and/or post-exercise pancreatic function in the absence of pathology. We found no sex differences in basal pancreatic 𝛽-cell function. Females had greater basal insulin clearance following MIC exercise compared to males (p = 0.01) and males tended to have a higher potentiation ratio following HIIE (p = 0.07). Females also had lower glucose sensitivity following MIC exercise compared to HIIE (p = 0.007) and LLHR (p = 0.003). Insulin clearance during the OGTT was greater following HIIE as compared with CON and MIC exercise (p = 0.02). 2-H oral glucose insulin sensitivity was greater following LLHR compared to CON (p = 0.01). Acute bouts of different modes of exercise do not differentially influence 𝛽-cell function but do influence insulin clearance and insulin sensitivity. Therefore, sex and exercise mode interact to differentially influence insulin clearance and glucose sensitivity.

The objective of this study was to assess the effects of feeding negative dietary cation-anion difference (DCAD) dry cow diets on postpartum health. Cows from 4 commercial dairy farms in Ontario, Canada, were enrolled in a pen-level controlled trial from November 2017 to April 2019. Close-up pens (1 per farm), with cows 3 wk before expected calving, were randomly assigned to a negative DCAD [TRT; −108 mEq/kg of dry matter (DM); target urine pH 6.0–6.5] or a control diet (CON; +105 mEq/kg of DM with a placebo supplement). Each pen was fed TRT or CON for 3 mo (1 period) then switched to the other treatment for the next period, with 4 periods per farm. Urine pH was measured weekly until calving, and body condition score (BCS) was measured at enrollment and at 5 wk postpartum. Data from 15 experimental units [8 TRT and 7 CON, with 1,086 (TRT: n = 681; CON: n = 405) observational units (cows)] that received the assigned diet for >1 wk were included. The incidence of milk fever (MF), retained placenta (RP), metritis, hyperketonemia (blood β-hydroxybutyrate >1.2 mmol/L, measured weekly in wk 1 and 2), clinical mastitis within 30 DIM (MAST), displaced abomasum (DA) within 30 d in milk (DIM), purulent vaginal discharge (PVD, assessed once at wk 5), and number of disease events (≥1 or ≥2) were analyzed with logistic regression models with treatment, parity, BCS, and their interactions, accounting for pen-level randomization and clustering of animals within farm with random effects, giving 10 degrees of freedom to test treatment effects. Multiparous cows fed TRT had greater blood calcium between 1 and 4 DIM than multiparous cows fed CON, and the prevalence of subclinical hypocalcemia (total Ca ≤2.14 mmol/L) was lesser when fed TRT compared with CON (d 1: 73 ± 6% vs. 93 ± 4%; d 2: 65 ± 7% vs. 90 ± 5%), with no differences between treatments detected in primiparous cows. We detected interactions of treatment and BCS at enrollment for MF in multiparous cows and of treatment and parity for ≥2 disease events. Overconditioned (BCS ≥3.75) multiparous cows had reduced incidence of MF when fed TRT (TRT: 2 ± 1%, vs. CON: 13 ± 8%). We detected no treatment effects on RP, metritis, hyperketonemia, or PVD incidence. Cows fed TRT had lesser incidence of DA (1.7 ± 0.7% vs. 3.6 ± 1.6%) and tended to have lesser incidence of MAST compared with CON (1.8% ± 0.6% vs. 4.4 ± 1.4%). No treatment effect was detected on ≥1 disease events (TRT: 38 ± 7%, vs. CON: 42 ± 8%); however, multiparous cows on TRT were less likely to have ≥2 disease events than cows on CON (14 ± 4% vs. 23 ± 6%). Under commercial herd conditions, feeding prepartum diets with negative DCAD improved several measures of postpartum health.

Our objective was to assess the effects of feeding negative dietary cation-anion difference (DCAD) prepartum diets on milk production, reproductive performance, and culling. Cows from 4 commercial farms in Ontario, Canada were enrolled in a pen-level controlled trial from November 2017 to April 2019. Close-up pens (1 per farm) with cows 3 wk before calving were randomly assigned to a negative DCAD (TRT; -108 mEq/kg of dry matter; target urine pH 6.0-6.5) or a control diet (CON; +105 mEq/kg of dry matter with a placebo supplement). Each pen was fed TRT or CON for 3 mo (1 period), and then switched to the other treatment for the next period (4 periods per farm). Data from 15 experimental units (8 pen treatments in TRT and 7 in CON), with a total of 1,086 observational units (cows), were included. The effect of treatment on milk yield at the first 3 milk recording tests of lactation was assessed with linear regression models accounting for repeated measures. The risk of pregnancy at first artificial insemination and culling by 30, 60, and 305 d in milk (DIM) were analyzed with logistic regression models, and effects on time to first AI, pregnancy, and culling were assessed with Cox proportional hazards models. All models included treatment, parity, and their interactions, accounting for pen-level randomization and clustering of animals within farm with random effects, giving 10 degrees of freedom for treatment effects. Multiparous cows fed TRT produced more milk at the first (42.0 vs. 38.8 ± 1.2 kg/d) and second (44.2 vs. 41.7 ± 1.3 kg/d) milk tests. However, multiparous cows fed TRT tended to have 0.2 percentage units less milk fat content at these tests. Although multiparous cows fed TRT tended to have greater energy-corrected milk at the first test (least squares means ± standard error: TRT = 46.1 ± 0.9 vs. CON = 43.8 ± 1 kg/d), there were no differences observed in energy-corrected milk at the second or third tests. In primiparous cows, there was no effect of treatment on milk production. Multiparous cows fed TRT had greater pregnancy to first insemination (TRT = 42 ± 3 vs. CON = 32 ± 4%) and tended to have shorter time to pregnancy [hazard ratio (HR) = 1.20; 95% CI: 0.96-1.49]. In primiparous cows fed TRT, time to pregnancy was increased (HR = 0.76; 95% CI: 0.59-0.99). Culling by 30 DIM tended to be less in TRT (3.3 ± 1.1%) than CON (5.5 ± 1.8%). No effect of treatment on culling by 305 DIM was detected in primiparous cows, but in multiparous cows, the TRT diets decreased the odds of culling (21.3 ± 1.9 vs. 31.7 ± 2.8%) and daily risk of culling to 305 DIM (HR = 0.64; 95% CI: 0.46 to 0.89). Under commercial herd conditions, prepartum negative DCAD diets improved milk production and reproductive performance, and reduced culling risk in multiparous cows. In primiparous cows, TRT diets had no effect on milk yield or culling, but increased the time to pregnancy. Our results suggest that negative DCAD diets should be targeted to multiparous cows.

Exercise elicits direct benefits to insulin sensitivity but may also indirectly improve glucose uptake by hemodynamic conditioning of the vasculature. The purpose of this study was to examine the modifying effect of 3 different types of exercise on the vascular response to an oral glucose challenge. Twenty healthy adults (9 women, 11 men; aged 23 ± 3 years) completed a standard oral glucose tolerance test (OGTT) at rest, as well as 1.5 hours after moderate continuous cycling exercise (30 min; 65% peak oxygen consumption), high-intensity interval cycling exercise (10 × 1 min at 90% peak heart rate), and lower-load higher-repetition resistance exercise (25–35 repetitions/set, 3 sets). Brachial and superficial femoral artery blood flow, conductance, and oscillatory shear index were measured throughout the OGTT. Regardless of rested state or exercise preconditioning, the OGTT induced reductions in brachial artery blood flow and conductance (p < 0.001), and transient increases in brachial and superficial femoral artery oscillatory shear index and retrograde blood flow (p < 0.01). Continuous cycling and resistance exercise were followed with a small degree of protection against prolonged periods of oscillatory flow. Our findings imply transient peripheral vasoconstriction and decreased limb blood flow during a standard OGTT, for which prior exercise was unable to prevent in healthy adults. Novelty: We investigated the impact of continuous, interval, and resistance exercise on the hemodynamic response to an OGTT. Our findings suggest decreased upper-limb blood flow during an OGTT is not prevented by prior exercise in healthy adults.

Study objective Some contend that patients with acute alcohol or illicit substance intoxication should be treated in outpatient detoxification centers rather than in the ED. However, these patients often have underlying acute medical needs. We sought to determine the frequency of medical interventions required by ED patients with alcohol or illicit substance intoxication. Methods This was a prospective observational study of consecutive ED patients presenting to an urban tertiary care ED with altered mental status due to alcohol or illicit substance use. We performed data collection for patients deemed to be low-risk for complications, as defined by receiving care in an intoxication observation unit. Trained staff observed and recorded all medical interventions, including medications administered, diagnostic testing, procedures performed, and airway interventions. The incidence of agitation was recorded using the Altered Mental Status Scale (AMSS, ordinal scale from −4 to +4, where +4 is most agitated). The data analysis is descriptive. Results This analysis included 2685 encounters (1645 unique patients; median age 39; 73% male) from January to May 2019. Average breath alcohol concentration was 0.20 g/dL (range 0.00–0.47). There were 89% encounters with alcohol intoxication, and in 17% encounters the patient was suspected or known to have drug intoxication (either alone or in conjunction with alcohol use). On arrival to the ED, 372 (14%) had agitation (AMSS +1 or higher) and 32 (1%) were profoundly agitated (AMSS +4). In total, 1526 (56%) received at least one intervention that could not be provided by a local detoxification or sobering facility. Of the study population, 955 (36%) received a sedating medication, 903 (34%) required physical restraints for patients or staff safety, 575 (21%) underwent imaging studies, 318 (12%) underwent laboratory testing, 367 (13%) received another intervention (IV access, EKG, splinting, wound care, etc). Additionally, 111 (4%) patients received an airway intervention (19 intubation, 23 nasal airway, 85 supplemental oxygen) and 275 (10%) required repositioning to protect the airway. There were 168 (6%) patients admitted to the hospital. Conclusion In this population of relatively low-risk ED patients with drug and alcohol intoxication, a substantial proportion of patients received medical interventions.

The objective of this study was to develop and validate equations for estimating growth of dairy heifers using measures of withers height, body weight (BW), and age. Measures of BW and withers height of 207 Holstein heifers raised in a tropical climate were taken from birth to calving, totaling to 2,047 observations. To be included in the database, the heifer had to have at least 4 measures recorded. After that, 4 models were built and evaluated as follows: (1) a linear model of BW as function of age (BW~A), (2) a linear model of the BW-to-height ratio as function of age (BW:H~A), (3) a quadratic model, adjusted for a defined plateau, to describe height as function of age (H~A), and (4) an exponential growth model of BW as function of height (BW~H). A cross-validation procedure was performed to evaluate accuracy and precision of the models. The linear relationship of BW~A and BW:H~A were estimated, respectively, by the equations: BW = 42.65 + 0.62 × A and BW:H = 0.70 + 0.0041 × A, where BW is in kilograms, BW:H = BW-to-height ratio (kg/cm), and A = age (d). Using the quadratic plateau for the model H~A, a critical “x” value of ~806 d and a height plateau of 138.6 cm were identified. Therefore, the following equations for estimating the height of animals younger and older than 806 d, respectively, were developed: H = 78.15 + 0.150 × A – 0.00009 × A2 and H = 78.15 + 0.150 × cvx – 0.00009 × cvx2, where H = height (cm) and cvx = 806 (critical “x” value; given in days). Additionally, the exponential model of W~H was estimated by the following equation: BW = 4.25 × exp(0.034 × H), where BW is in kilograms and H = height (cm). A cross validation demonstrated that all equations had very high accuracy and precision. Overall, these models demonstrated that BW and BW-to-height ratio increase linearly as a function of age, while BW follows an exponential growth pattern as a function of height. Additionally, the H~A model predicted that heifers achieve a maximum height of 138.6 cm at 806 d of age.

Reproductive fitness and survival are enhanced by adaptive behaviors that are modulated by internal physiological states and external social contexts. The common bed bug, Cimex lectularius, is an obligate hematophagous ectoparasite that requires host blood for growth, development, and reproduction. We investigated how mating, starvation and social interactions affect host-seeking, blood feeding, oviposition, and survival of female bed bugs. The percentage of females that fed and the amount of blood they ingested were greater in mated females (90–100%) than in unmated females (48–60%). Mating state also modulated the female’s orientation towards human skin odor in an olfactometer; more mated (69%) than unmated (23%) females responded to human odors. The response rate of unmated females (60%) to skin odor increased with longer starvation period, while the opposite pattern was observed in mated females (20%). Although fecundity after a single blood meal was unaffected by long or short residence and interaction with males, females subjected to frequent copulation attempts had lower survivorship and lifespan than females housed with males for only 24 h. Taken together, these results indicate that by adaptively and coordinately expressing behaviors based on the internal physiological state, females maximize their survival and reproductive fitness.

The common bed bug (Cimex lectularius L.) is a hematophagous pest species that lives in close proximity to humans. Following a blood meal, bed bugs deposit fecal material indoors. The feces contain a variety of compounds, including histamine, which serves as a component of their aggregation pheromone. Histamine is a pivotal mammalian immune modulator, and recently it was shown to be present in high concentrations in household dust from homes infested with bed bugs. To better understand the dynamics of histamine excretion, we analyzed bed bug fecal material from different life stages and populations, along with fecal material collected at different post-feeding times and from bed bugs fed on different diets. Our analysis showed significant variation in histamine excretion among life stages, with mated females excreting the most histamine and first instar nymphs excreting the least histamine. However, when histamine excretion was normalized for blood consumption, males were found to excrete more histamine than the other life stages. There was no difference in histamine excretion among laboratory and recently home-collected bed bug populations. Further, we found histamine excretion continued for at least 14 d post-feeding, with the highest amount of histamine excreted 3–4 d after a bloodmeal. Overall, this work demonstrates that bed bugs excrete histamine across all feeding life stages, populations, and at various times after feeding, and that histamine excretion is directly related to blood feeding. These results will be used to better understand the health risks associated with histamine excretion and potential mitigation strategies of environmental histamine.

The path to childhood asthma is thought to initiate in utero and be further promoted by postnatal exposures. However, the underlying mechanisms remain underexplored. We hypothesized that prenatal maternal immune dysfunction associated with increased childhood asthma risk (revealed by low IFN-γ:IL-13 secretion during the third trimester of pregnancy) alters neonatal immune training through epigenetic mechanisms and promotes early-life airway colonization by asthmagenic microbiota.We examined epigenetic, immunologic, and microbial features potentially related to maternal prenatal immunity (IFN-γ:IL-13 ratio) and childhood asthma in a birth cohort of mother-child dyads sampled pre-, peri-, and postnatally (N = 155). Epigenome-wide DNA methylation and cytokine production were assessed in cord blood mononuclear cells (CBMC) by array profiling and ELISA, respectively. Nasopharyngeal microbiome composition was characterized at age 2-36 months by 16S rRNA sequencing.Maternal prenatal immune status related to methylome profiles in neonates born to non-asthmatic mothers. A module of differentially methylated CpG sites enriched for microbe-responsive elements was associated with childhood asthma. In vitro responsiveness to microbial products was impaired in CBMCs from neonates born to mothers with the lowest IFN-γ:IL-13 ratio, suggesting defective neonatal innate immunity in those who developed asthma during childhood. These infants exhibited a distinct pattern of upper airway microbiota development characterized by early-life colonization by Haemophilus that transitioned to a Moraxella-dominated microbiota by age 36 months.Maternal prenatal immune status shapes asthma development in her child by altering the epigenome and trained innate immunity at birth, and is associated with pathologic upper airway microbial colonization in early life.

BACKGROUND Periacetabular osteotomy (PAO) increases acetabular coverage of the femoral head and medializes the hip's center, restoring normal joint biomechanics. Past studies have reported data regarding the degree of medialization achieved by PAO, but measurement of medialization has never been validated through a comparison of imaging modalities or measurement techniques. The ilioischial line appears to be altered by PAO and may be better visualized at the level of the inferior one-third of the femoral head, thus, an alternative method of measuring medialization that begins at the inferior one-third of the femoral head may be beneficial. QUESTIONS/PURPOSES (1) What is the true amount and variability of medialization of the hip's center that is achieved with PAO? (2) Which radiographic factors (such as lateral center-edge angle [LCEA] and acetabular inclination [AI]) correlate with the degree of medialization achieved? (3) Does measurement of medialization on plain radiographs at the center of the femoral head (traditional method) or inferior one-third of the femoral head (alternative method) better correlate with true medialization? (4) Are intraoperative fluoroscopy images different than postoperative radiographs for measuring hip medialization? METHODS We performed a retrospective study using a previously established cohort of patients who underwent low-dose CT after PAO. Inclusion criteria for this study included PAO as indicated for symptomatic acetabular dysplasia, preoperative CT scan, and follow-up between 9 months and 5 years. A total of 333 patients who underwent PAO from February 2009 to July 2018 met these criteria. Additionally, only patients who were between 16 and 50 years old at the time of surgery were included. Exclusion criteria included prior ipsilateral surgery, femoroacetabular impingement (FAI), pregnancy, neuromuscular disorder, Perthes-like deformity, inadequate preoperative CT, and inability to participate. Thirty-nine hips in 39 patients were included in the final study group; 87% (34 of 39) were in female patients and 13% (5 of 39 hips) were in male patients. The median (range) age at the time of surgery was 27 years (16 to 49). Low-dose CT images were obtained preoperatively and at the time of enrollment postoperatively; we also obtained preoperative and postoperative radiographs and intraoperative fluoroscopic images. The LCEA and AI were assessed on plain radiographs. Hip medialization was assessed on all imaging modalities by an independent, blinded assessor. On plain radiographs, the traditional and alternative methods of measuring hip medialization were used. Subgroups of good and fair radiographs, which were determined by the amount of pelvic rotation that was visible, were used for subgroup analyses. To answer our first question, medialization of all hips was assessed via measurements made on three-dimensional (3-D) CT hip reconstruction models. For our second question, Pearson correlation coefficients, one-way ANOVA, and the Student t-test were calculated to assess the correlation between radiographic parameters (such as LCEA and AI) and the amount of medialization achieved. For our third question, statistical analyses were performed that included a linear regression analysis to determine the correlation between the two radiographic methods of measuring medialization and the true medialization on CT using Pearson correlation coefficients, as well as 95% confidence intervals and standard error of the estimate. For our fourth question, Pearson correlation coefficients were calculated to determine whether using intraoperative fluoroscopy to make medialization measurements differs from measurements made on radiographs. RESULTS The true amount of medialization of the hip center achieved by PAO in our study as assessed by reference-standard CT measurements was 4 ± 3 mm; 46% (18 of 39 hips) were medialized 0 to 5 mm, 36% (14 hips) were medialized 5 to 10 mm, and 5% (2 hips) were medialized greater than 10 mm. Thirteen percent (5 hips) were lateralized (medialized < 0 mm). There were small differences in medialization between LCEA subgroups (6 ± 3 mm for an LCEA of ≤ 15°, 4 ± 4 mm for an LCEA between 15° and 20°, and 2 ± 3 mm for an LCEA of 20° to 25° [p = 0.04]). Hips with AI ≥ 15° (6 ± 3 mm) achieved greater amounts of medialization than did hips with AI of < 15° (2 ± 3 mm; p < 0.001). Measurement of medialization on plain radiographs at the center of the femoral head (traditional method) had a weaker correlation than using the inferior one-third of the femoral head (alternative method) when compared with CT scan measurements, which were used as the reference standard. The traditional method was not correlated across all radiographs or only good radiographs (r = 0.16 [95% CI -0.17 to 0.45]; p = 0.34 and r = 0.26 [95% CI -0.06 to 0.53]; p = 0.30), whereas the alternative method had strong and very strong correlations when assessed across all radiographs and only good radiographs, respectively (r = 0.71 [95% CI 0.51 to 0.84]; p < 0.001 and r = 0.80 [95% CI 0.64 to 0.89]; p < 0.001). Measurements of hip medialization made on intraoperative fluoroscopic images were not found to be different than measurements made on postoperative radiographs (r = 0.85; p < 0.001 across all hips and r = 0.90; p < 0.001 across only good radiographs). CONCLUSION Using measurements made on preoperative and postoperative CT, the current study demonstrates a mean true medialization achieved by PAO of 4 mm but with substantial variability. The traditional method of measuring medialization at the center of the femoral head may not be accurate; the alternate method of measuring medialization at the lower one-third of the femoral head is a superior way of assessing the hip center's location. We suggest transitioning to using this alternative method to obtain the best clinical and research data, with the realization that both methods using plain radiography appear to underestimate the true amount of medialization achieved with PAO. Lastly, this study provides evidence that the hip center's location and medialization can be accurately assessed intraoperatively using fluoroscopy. LEVEL OF EVIDENCE Level III, diagnostic study.

Background In patients requiring emergency rapid sequence intubation (RSI), 100% oxygen is often delivered for preoxygenation to replace alveolar nitrogen with oxygen. Sometimes, however, preoxygenation devices are prematurely removed from the patient prior to the onset of apnea, which can lead to rapid loss of preoxygenation. Objective We sought to determine the elapsed time, on average, between removing the oxygen source and the loss of preoxygenation among non–critically ill patients in the emergency department (ED). Methods We conducted a prospective, crossover study of non–critically ill patients in the ED. Each patient received two identical preoxygenation trials for 4 min using a non–rebreather mask with oxygen flow at flush rate and a nasal cannula with oxygen flow at 10 L/min. After each preoxygenation trial, patients underwent two trials in random order while continuing spontaneous breathing: 1) removal of both oxygen sources and 2) removal of non–rebreather mask with nasal cannula left in place. We defined loss of preoxygenation as an end-tidal oxygen (exhaled oxygen percentage; EtO2) value Results We enrolled 42 patients, median age was 43 years (interquartile range [IQR] 30 to 54 years) and 72% were male. Median time to loss of preoxygenation was 20 s (IQR 17–25 s, 4.5 breaths) when all oxygen devices were removed, and 39 s (IQR 21–56 s, 8 breaths) when the nasal cannula was left in place. Conclusions In this population of non–critically ill ED patients, most had loss of preoxygenation after 5 breaths if all oxygen devices were removed, and after 8 breaths if a nasal cannula was left in place. These data suggest that during ED RSI, preoxygenation devices should be left in place until the patient is completely apneic.

Breast cancer survivors receiving chemotherapy often report increased anxiety and depression. However, the mechanism underlying chemotherapy-induced changes in affect remains unknown. We hypothesized that chemotherapy increases cytokine production, in turn altering exploratory and depressive-like behavior. To test this hypothesis, female Balb/C mice received two injections, separated by two weeks, of vehicle (0.9% saline) or a chemotherapeutic cocktail [9 mg/kg doxorubicin (A) and 90 mg/kg cyclophosphamide (C)]. Peripheral and central cytokine concentrations were increased one and seven days, respectively, after AC. Because of the beneficial effects of social enrichment on several diseases with inflammatory components, we examined whether social enrichment could attenuate the increase in peripheral and central cytokine production following chemotherapy administration. Socially isolated mice receiving AC therapy demonstrated increased depressive-like and exploratory behaviors with a concurrent increase in hippocampal IL-6. Whereas, group housing attenuated AC-induced IL-6 and depressive-like behavior. Next, we sought to determine whether central oxytocin may contribute to the protective effects of social housing after AC administration. Intracerebroventricular administration of oxytocin to socially isolated mice recapitulated the protective effects of social enrichment; specifically, oxytocin ameliorated the AC-induced effects on IL-6 and depressive-like behavior. Furthermore, administration of an oxytocin antagonist to group housed mice recapitulated the responses of socially isolated mice; specifically, AC increased depressive-like behavior and central IL-6. These data suggest a possible neuroprotective role for oxytocin following chemotherapy, via modulation of IL-6. This study adds to the growing literature detailing the negative behavioral effects of chemotherapy and provides further evidence that social enrichment may be beneficial to health.

Psychological stressors have been implicated in the progression of various tumor types. We investigated a role for stress in tumor immune cell chemotaxis in the B16F10 mouse model of malignant melanoma. We exposed female mice to 6-hour periods of restraint stress (RST) for 7 days, then implanted B16F10 malignant melanoma tumor cells and continued the RST paradigm for 14 additional days. We determined serum corticosterone and liver catecholamine concentrations in these mice. To evaluate the tumor microenvironment, we performed IHC and examined cytokine expression profiles using ELISA-based analysis of tumor homogenates. We found that tumors in mice subjected to RST grew significantly slower, had reduced tumor C-C motif ligand 2 (CCL2), and contained fewer F4/80-positive macrophages than tumors from unstressed mice. We observed a concomitant increase in norepinephrine among the RST mice. An in vitro assay confirmed that norepinephrine downregulates CCL2 production in both mouse and human macrophages, and that pretreatment with the pan-β-adrenergic receptor inhibitor nadolol rescues this activity. Furthermore, RST had no effect on tumor growth in transgenic CCL2-deficient mice. This study suggests that stress reduces malignant melanoma by reducing recruitment of tumor-promoting macrophages by CCL2.

Disbudding is a common procedure practiced in the dairy industry and is known to cause pain when performed without pain control. Dairy producers who disbud calves with caustic paste are less likely to provide pain control than those using cautery. Little research has been conducted on pain control for caustic paste disbudding and no studies have specifically examined calves under 9 d of age. The objective of this study was to evaluate the efficacy of local anesthesia and nonsteroidal anti-inflammatory drug analgesia on indicators of pain and inflammation in dairy calves disbudded using caustic paste. One hundred forty Holstein heifer calves 1 to 9 d of age were enrolled in 28 blocks and randomly allocated to 1 of 5 treatments: sham control (SH); positive control (POS); lidocaine cornual nerve block (LC); meloxicam (MEL); and lidocaine cornual nerve block plus meloxicam (LCM). We measured outcomes including serum cortisol and haptoglobin, pressure sensitivity, and lying behavior. Data were analyzed using mixed linear regression models with treatment as a fixed effect, baseline values as a covariate, and trial block as a random effect. Compared with the POS group, the LCM group had reduced serum cortisol at 15, 30, 45, and 60 min post-disbudding; cortisol values were not different between LC, LCM, and SH calves at these time points. At 60, 90, 120, and 180 min post-disbudding, LCM calves had reduced cortisol compared with LC calves, whereas, values did not differ between LCM and SH calves at these time points. At 3 to 4 d post-disbudding, the LCM group tended to have reduced haptoglobin, but no differences were found between groups at 180 min and 7 d post-disbudding. At 60, 90, and 120 min post-disbudding, LC and LCM treated calves had decreased pressure sensitivity compared with other groups. No differences were seen in pressure sensitivity between groups at 180 min, 3 to 4 or 7 d post-disbudding. No differences in lying behavior were found between treatment groups on any of the 7 d following disbudding. These findings demonstrate that the combination of a local anesthetic with a nonsteroidal anti-inflammatory drug is beneficial for reducing indicators of pain and inflammation in young calves disbudded with caustic paste.

The objective of this study was to determine how feeding behavior of dairy cows is altered in response to diet-induced negative energy balance, and if this response varies depending on dietary particle size distribution. Multiparous Holstein cows (n = 30; days in milk = 59 ± 5; parity = 2.8 ± 0.19), producing 44.6 ± 1.2 kg/d of milk, were fed (on a dry matter basis) a lactating diet [net energy of lactation (NEL) = 1.66 Mcal/kg; 68% forage, including 1.8% wheat straw] during a 2-wk baseline period. To induce negative energy balance, cows were then exposed for 3 wk to 1 of 2 diets formulated for a 20% reduction in energy available for milk (NEL = 1.58 Mcal/kg; 73% forage, including 17.2% wheat straw). These diets were identical, only varying in straw chop length: (1) long straw diet (LS): straw chopped with a 10.2-cm screen, or (2) short straw diet (SS): straw chopped with a 2.54-cm screen. Cows consumed 25.6 ± 0.26 kg/d during the baseline period. Dry matter intake decreased on the experimental diets; dry matter intake was greater for the SS diet as compared with the LS diet (23.1 vs. 22.5 kg/d; standard error = 0.47). During the baseline period, cow serum nonesterified fatty acids (NEFA) and blood β-hydroxybutyrate averaged 0.27 ± 0.02 and 0.71 ± 0.05 mmol/L, respectively. During the experimental period, NEFA and β-hydroxybutyrate averaged 0.34 and 1.04 mmol/L, respectively, with a peak of NEFA (0.63 ± 0.06 mmol/L) occurring 4 d after dietary change. During baseline, cows produced 42.3 ± 0.33 kg/d of milk; milk yield was decreased for both SS cows and LS cows during the experimental period (SS = 39.0, LS = 37.8 kg/d; standard error = 0.67). On the experimental diets, cows spent more time eating (266.8 vs. 221.8 min/d), had longer meal lengths (46.9 vs. 37.5 min/meal), and consumed fewer meals (7.1 vs. 7.7 meals/d) compared with the baseline period. Within the experimental period, LS cows spent more time eating per day than SS cows (LS = 281.3, SS = 252.2 min/d). During the baseline period cows sorted against long particles (>19 mm), did not sort medium particles (8 to 19 mm), and sorted for short (4 to 8 mm) and fine (

The objective of this study was to investigate the effect of 2 gradual weaning programs and 2 locations of solid feed within individual calf pens on feed intake, growth, and behavior of calves fed milk by an automated milk feeder. Using a 2 × 2 factorial design, 60 female calves were randomly assigned to 1 of 2 weaning treatments and 1 of 2 solid feed placement treatments. Calves were assigned to a continuous gradual weaning program (CG) or a multi-step gradual weaning program (MG). Calves assigned to the CG treatment had their milk allocation reduced in small, equal increments from 12.5 L/d on d 43 to 2 L/d on d 56. Calves assigned to the MG treatment were offered 10 L/d on d 43 to 45, 8 L/d on d 46 to 49, 6 L/d on d 50 to 52, and 3 L/d on d 53 to 56. Solid feed was placed either at the front of the pen adjacent (ADJ) to where the automated milk feeder offered milk or at the back of the pen on the opposite (OPP) side from where the milk was offered. All calves were offered 12.5 L/d of milk replacer from d 2 to 42, fresh solid feed (5% chopped wheat straw mixed with 95% calf starter pellet) from d 5 onward, and ad libitum water starting d 0. Calves were weaned from d 43 to 56 and additionally monitored from d 57 to 70. No interactions of effects of weaning and feed location treatment were detected. Both MG and CG calves had similar water and solid feed consumption, blood β-hydroxybutyrate concentrations, and behavior. By design, calves on the CG treatment consumed greater amounts of milk during the weaning phase than MG treatment calves (6.7 vs. 6.3 L/d), which resulted in milk drinking behavior differing between the treatments during the weaning phase. Although average daily gain and body weights were similar between treatments, MG calves had greater middle girth gain during wk 7 compared with CG calves (0.6 vs. 0.3 cm/d). Calves on the ADJ treatment consumed 16.7% more solid feed and 0.55 L/d more milk during the preweaning phase compared with OPP treatment calves. In all 3 phases, ADJ treatment calves consumed more water than OPP treatment calves. The ADJ calves spent more time consuming solid feed during the 10-wk period. The ADJ treatment calves had 10% greater average daily gain compared with OPP treatment calves during the preweaning phase. Overall, the results indicate that both gradual weaning treatments resulted in similar performance and behavior. However, placement of solid feed next to the milk source was demonstrated to increase feed, water, and milk intake during the preweaning stage, contributing to greater growth.

The objective of this study was to determine the effects of adding molasses-based liquid feed to a high-straw dry cow diet on intake, behavior, health, and performance of dairy cows across the transition period. Holstein cows (n = 40) entering their second lactation or greater were enrolled at dry-off (∼45 d before expected calving) and assigned to 1 of 2 treatments: a high-straw dry cow total mixed ration (TMR) with either (1) no molasses [CON; n = 20; 10.7% crude protein (CP), 1.45 Mcal/kg of net energy for lactation (NEL)] or (2) supplemented with 1 kg/cow daily [dry matter (DM) basis] of molasses-based liquid feed (LF; n = 20; 11.2% CP, 1.49 Mcal/kg of NEL). At calving all cows were fed the same lactating TMR (14.9% CP, 1.68 Mcal/kg of NEL) and followed for 28 d. During the dry period, cows fed the LF diet had greater DM intake (15.3 ± 0.24 vs. 13.4 ± 0.24 kg/d) and tended to have a shorter interval between meals (192.8 ± 8.38 vs. 216.5 ± 7.97 min) and more frequent meals (6.3 ± 0.27 vs. 5.6 ± 0.27 meals/d), while consuming their feed faster (0.09 ± 0.001 vs. 0.08 ± 0.001 kg of DM/min) compared with cows fed the CON diet. Regardless of treatment, cows sorted [100% × (actual intake/predicted intake)] against the longest ration particles (>19 mm), with cows fed the CON diet sorting more against these (81.1 ± 2.6 vs. 93.9 ± 2.6%). Cows fed the CON diet did not sort for or against short particles ( 4 mm; 100.2 ± 0.31%), but cows fed the LF diet tended to sort against these (99.2 ± 0.31%). Post-calving, cows fed the LF diet did not sort for long particles (98.5 ± 1.1%), but cows fed the CON diet continued to sort against these (96.3 ± 1.1%). Cows fed the LF diet had higher mean reticulorumen pH in the dry period (6.4 ± 0.05 vs. 6.2 ± 0.06 pH), in the first week after calving (CON = 5.7 ± 0.06 pH, LF = 5.8 ± 0.06 pH), and tended to have higher mean reticulorumen pH in the second week after calving (CON = 5.7 ± 0.06 pH, LF = 5.9 ± 0.06 pH). The results suggest that supplementing a molasses-based liquid feed in high-straw dry cow diets may improve intake and consistency in nutrients consumed during the dry period and in early lactation, as well as possibly promoting better rumen health across the transition period.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Acute kidney recovery (AKR) is a recently described phenomenon observed after transcatheter aortic valve replacement (TAVR) and is more frequent than acute kidney injury (AKI). To determine the incidence and predictors of AKR between surgical aortic valve replacement (SAVR) and TAVR, we examined patients with chronic kidney disease and severe aortic stenosis who underwent SAVR or TAVR procedure between 2007 and 2017; excluding age65 or90, dialysis, endocarditis, non-aortic valve stenosis, or patients died within 48-hours postprocedure. AKR was defined as an increase of estimated glomerular filtration rate (eGFR)25% and AKI as decrease in eGFR25% at discharge. Stroke, mortality, major bleeding, transfusion, and length of stay were examined. Multivariate logistic regression analysis was used to examine predictors of AKR. There were 750 transcatheter and 1,062 surgical patients and 319 pairs after propensity matching. AKR was observed in 26% TAVR versus 23.2% SAVR, p = 0.062. Highest recovery was in patients with eGFR30 for both TAVR (33.7%) and SAVR (34.5%) patients. Independent predictors of AKR were ejection fraction50% (odds ratio [OR] 1.66, 95% confidence interval [CI] 1.02 to 2.71, p = 0.042), female gender (OR 1.66, 95% CI 1.1 to 2.5, p = 0.015), and obesity (OR 1.5, 95% CI 1.04-2.3, p = 0.032). Diabetes was a negative predictor of AKR (OR 0.55, 95% CI 0.36 to 0.84, p = 0.005). AKR was associated with improved secondary clinical outcomes compared with AKI. In conclusion, AKR is a generalizable phenomenon occurring frequently and similarly among transcatheter or surgical aortic valve patients. Diabetes is a negative predictor of AKR, possibly indicative of less reversible kidney disease.

BACKGROUND CONTEXT Traumatic spinal cord injury can have a dramatic effect on a patient's life. The degree of neurologic recovery greatly influences a patient's treatment and expected quality of life. This has resulted in the development of machine learning algorithms (MLA) that use acute demographic and neurologic information to prognosticate recovery. The van Middendorp et al. (2011) (vM) logistic regression (LR) model has been established as a reference model for the prediction of walking recovery following spinal cord injury as it has been validated within many different countries. However, an examination of the way in which these prediction models are evaluated is warranted. The area under the receiver operators curve (AUROC) has been consistently used when evaluating model performance, but it has been shown that AUROC overemphasizes the most common event resulting in an inaccurate assessment when the data are imbalanced. Furthermore, there is evidence that the use of more advanced MLA, such as an unsupervised k-means model, may show superior performance compared to LR as they can handle a larger number of features. PURPOSE The first objective of the study was to assess the performance of both an unsupervised MLA and LR model with complete admission neurologic information against the vM and Hicks models. Second, a comparison between the accuracy of the AUROC and the F1-score will be made to determine which method is superior for the assessment of diagnostic performance of prediction models on large-scale datasets. STUDY DESIGN Retrospective review of a prospective cohort study. PATIENT SAMPLE The Rick Hansen Spinal Cord Injury Registry (RHSCIR) was used in this study. All patients enrolled between 2004 and 2017 with complete neurologic examination and Functional Independence Measure outcome data at ≥1 year follow-up or who could walk at discharge were included. The prognostic variables included age (dichotomized at ≥65 years old); American Spinal Injury Association Impairment Scale (AIS) grade; and individual motor, light touch, and pinprick score from L2 to S1. OUTCOME MEASURES The Functional Independence Measure locomotor score was used to assess independent walking ability at discharge or 1-year follow-up. METHODS An unsupervised MLA with k=2 was chosen in order to identify a “walk” cluster and a “not walk” cluster. Model performance was assessed through the development of a receiver operating characteristic curve with associated AUROC and a precision-recall curve with associated F1-score. The study and the RHSCIR are supported by funding from Health Canada, Western Economic Diversification Canada, and the Governments of Alberta, British Columbia, Manitoba, and Ontario. These funders had no role in the study or study reporting and the authors have no conflicts of interest to report. RESULTS No clinically relevant differences were found between with the use of an unsupervised MLA with a greater amount of initial neurologic information compared to the established standards for any AIS classification. Although demonstrated for all separate AIS classifications, most notably, the AUROC for the vM (0.78) and Hicks models (0.76) were found to be superior to that of the new LR model (0.72); however, the vM and Hicks models had more than double the amount of false negative classifications compared to the LR. The F1-scores between these three models were also found to be different but with the vM and Hicks models being lower than the LR (0.85, 0.81, and 0.89, respectively). CONCLUSIONS No clinically relevant differences were found between the use of an unsupervised MLA with complete admission neurologic information compared to the previously validated standards; however, when comparing the performance of the AUROC and F1-score, the AUROC showed inaccurate prognostic performance when there was an imbalance toward a greater amount of false negatives. Importantly, the F1-score did not succumb to this imbalance. As AUROC has been used as the standard when evaluating performance of prediction models, consideration as to whether this is the most appropriate method is warranted. Future work should focus on comparing AUROC and F1-scores with other previously validated models.

The study investigated the effect of chop length of wheat straw in a high-straw dry cow diet on the feeding behavior, health, and performance of Holstein dairy cows across the transition period. Forty cows were enrolled at dry off, approximately 45 d before expected calving, and assigned to 1 of 2 dietary treatments containing (on a dry matter basis) 36% corn silage, 35% dry cow pellet, and 29% wheat straw. Diets were formulated to target an energy consumption of 19 Mcal/d of net energy for lactation per cow. The diets differed in the chop length of wheat straw: (1) long straw chopped with a 10.16-cm screen (LDD; n = 20), or (2) short straw chopped with a 2.54-cm screen (SDD; n = 20). Dietary treatments were fed throughout the dry period. Feeding behavior, rumination time, and reticulorumen pH were monitored electronically, and feed samples were collected to determine feed sorting. Blood samples were taken weekly, and body condition scores and body weights were taken every 2 wk. Postcalving, all cows were fed the same lactating cow total mixed ration for 28 d; the same measurements were recorded with the addition of daily milk yield and twice weekly milk components. During the dry period, cows fed the SDD treatment consumed more dry matter (15.6 vs. 15.0 kg/d), had more consistent dry matter intake in the week leading up to calving, had a faster feeding rate, consumed 0.4 kg/meal more, and had 0.6 fewer meals per day. No differences were observed in rumination time or mean reticulorumen pH between treatments in both the dry and lactating period. Regardless of treatment during the dry period, cows sorted against the long particles (19 mm) and in favor of the short particles (8,4 mm), but cows fed the LDD treatment sorted to a greater extent than cows fed the SDD treatment. Dietary treatment in the dry period did not influence feed sorting behavior postcalving. Cows fed the LDD treatment had a greater daily change (decline) in rumen pH in the first week postcalving and had a greater blood β-hydroxybutyrate concentration in the third week postcalving. Overall, the results from this study indicate that feeding shorter chopped wheat straw in a high-straw dry cow diet improved intake, reduced sorting during the dry period, and resulted in greater metabolic health and rumen stability in early lactation.

Comparison of bacterial counts (BCs) among common bedding types used for dairy cows, including straw, is needed. There is concern that the microbial content of organic bedding is elevated and presents risks for dairy cow udder health and milk quality. The objectives of this study were to investigate: (1) % DM and BCs (Streptococcus spp., all gram-negatives and specifically Klebsiella spp.) in different types of bedding sampled, and to investigate housing and farm management factors associated with % DM and BCs; (2) if bedding type was associated with hygiene of cow body parts (lower-legs, udder, upper-legs and flank) and housing and management factors associated with hygiene and (3) bedding types associated with higher BCs in cow milk at the farm level and bulk tank milk and management factors that were associated with highest BCs. Seventy farms (44 free-stall and 26 tie-stall) in Ontario, Canada were visited 3 times, 7 days apart from October 2014 to February 2015. At each visit, composite samples of unused and used bedding were collected for % DM determination and bacterial culture. Used bedding samples were collected from the back third of selected stalls. Data were analyzed using multivariable linear mixed models. Bedding classification for each farm were: new sand (n = 12), straw and other dry forage (n = 33), wood products (shavings, sawdust; n = 17) and recycled manure solids (RMSs)-compost, digestate (n = 8). In used bedding, across all bedding samples, sand was driest, compared to straw and wood, and RMS; higher % DM was associated with lower Streptococcus spp. count. Streptococcus spp. and all Gram-negative bacteria counts increased with increasing days since additional bedding was added. Gram-negative bacteria counts in used bedding varied with type: RMS = 16.3 ln colony-forming units (cfu)/mL, straw = 13.8 ln cfu/mL, new sand = 13.5 ln cfu/mL, and wood = 10.3 ln cfu/mL. Klebsiella spp. counts in used bedding were lower for wood products (5.9 ln cfu/mL) compared to all other bedding types. Mean cow SCC tended to be higher on farms with narrower stalls. Farms with mattress-based stalls had a higher prevalence of cows with dirty udders compared to those using a deep bedding system (often inorganic sand). Wider stalls were associated with lower bulk milk bacteria count. Lower % DM of used bedding was associated with higher bulk milk bacteria count. In conclusion, bedding management may have a profound impact on milk quality, bacterial concentrations in the bedding substrates, and cow hygiene.

This study evaluated the effect on dairy cows of the partial replacement of whole plant corn silage (WPCS) with corn ear fibrous coproduct (CEFC) in diets with concentrate coproducts from citrus and corn on dry matter intake (DMI), lactation performance, digestibility, and chewing behavior. Holstein dairy cows (n = 20) in 5, 4 × 4 Latin squares (21-d periods) were fed a combination of strategies for feeding fibrous coproducts in a 2 × 2 factorial arrangement of the following treatments: (1) forage feeds: the partial replacement of WPCS (CS) with CEFC (CO), and (2) concentrate feeds: the partial replacement of wet corn gluten feed (GF) with a blend of pelleted citrus and corn distillers dried grains (CD) to have isonitrogenous diets. The concentrations of physically effective neutral detergent fiber (NDF

Male dairy calf welfare is a key issue in the Canadian cattle industry. The welfare of male dairy calves can be explored through the aspects of health and biological functioning, affective states, and natural living. Presently, the main welfare issues associated with the production of male dairy calves include morbidity and mortality, colostrum and feeding management, transportation, isolation, castration and disbudding, and euthanasia. Opportunities to improve male dairy calf welfare include improving accepted industry practices, enhancing education and compliance with industry codes of practice, and increasing veterinarian involvement in on-farm animal welfare. The benefits of improving male dairy calf welfare include maintenance of the cattle industry’s social license and improved producer mental health and occupational satisfaction. The main barriers to improving male dairy calf welfare are economics and cultural attitudes within the industry towards male dairy calves.

Our objectives were to evaluate the effects of complete replacement of supplementary inorganic salts of trace minerals (STM) by organic trace minerals (OTM) in both pre- and postpartum diets on feeding behavior, ruminal fermentation, rumination activity, energy metabolism, and lactation performance in dairy cows. Pregnant cows and heifers (n = 273) were blocked by parity and body condition score and randomly assigned to either STM or OTM diets at 45 ± 3 d before their expected calving date. Both groups received the same diet, except for the source of trace minerals (TM). The STM group was supplemented with Co, Cu, Mn, and Zn sulfates and Na selenite, whereas the OTM group was supplemented with Co, Cu, Mn, and Zn proteinates and selenized yeast. Treatments continued until 156 days in milk and pre- and postpartum diets were formulated to meet 100% of recommended levels of each TM in both treatments, taking into consideration both basal and supplemental levels. Automatic feed bins were used to assign treatments to individual cows and to measure feed intake and feeding behavior. Rumination activity was monitored by sensors attached to a collar from wk -3 to 3 relative to calving. Blood metabolites were evaluated on d -21, -10, -3, 0, 3, 7, 10, 14, 23, and 65 relative to calving. Ruminal fluid samples were collected using an ororuminal sampling device on d -21, 23, and 65 relative to calving, for measurement of ruminal pH and concentration of volatile fatty acids. Cows were milked twice a day and milk components were measured monthly. Cows supplemented with OTM tended to have longer daily feeding time (188 vs. 197 min/d), and greater dry matter intake (DMI; 12.9 vs. 13.3 kg), and had a more positive energy balance (3.6 vs. 4.2 Mcal/d) and shorter rumination time per kg of dry matter (DM; 40.1 vs. 37.5 min/kg of DM) than cows supplemented with STM during the prepartum period. In the postpartum period, OTM increased DMI in multiparous cows (24.1 vs. 24.7 kg/d) but not in primiparous cows (19.1 vs. 18.7 kg/d). The difference in DMI of multiparous cows was more evident in the first 5 wk of lactation, when it averaged 1 kg/d. Milk yield was not affected by treatment in multiparous cows (44.1 vs. 44.2 kg/d); however, primiparous cows supplemented with OTM had lesser yields than primiparous cows supplemented with STM (31.9 vs. 29.8 kg/d). Cows supplemented with OTM had a greater percentage of protein in milk (3.11 vs. 3.17%), reduced concentration of nonesterified fatty acids in serum (0.45 vs. 0.40 mmol/L), and rumination activity (30.1 vs. 27.8 min/kg of DM) than cows supplemented with STM. At the end of the transition period, cows supplemented with OTM had reduced molar proportion of acetate, reduced pH, and tended to have a greater concentration of total volatile fatty acids in ruminal fluid. In conclusion, complete replacement of STM by OTM caused modest changes in rumen fermentation, feeding behavior, energy metabolism, and performance of dairy cows, improving postpartum DMI in multiparous cows and reducing circulating levels of nonesterified fatty acids. The pre-absorptive effects of TM source and the parity specific responses on performance warrant further research.

The aim of this study was to evaluate specific risk factors and their impact on hospital readmission risk following delivery in pregnancies affected by the hypertensive disease of pregnancy (HDP).We performed a 10-year case-control study for patients who delivered at our institution and whose antenatal courses were complicated by HDP. The primary outcome was the identification of specific patient factors contributing to readmission. HDP pregnancies experiencing readmission for HDP signs and/or symptoms were used as the cases, with HDP pregnancies not experiencing readmission randomly selected as controls. Maternal age, gestational age at delivery, gravidity, parity, and mode of delivery (vaginal including operative, or cesarean) were recorded. Mean systolic and diastolic blood pressures were calculated over the 24 h preceding discharge. The most recent laboratory values preceding discharge for serum creatinine, lactate dehydrogenase, aspartate aminotransferase, alanine transaminase, and platelets were also recorded. The presence or absence of prescribed antihypertensive medication was recorded for initial hospitalization. Postpartum readmission was defined as within 30 days of delivery. Exclusion criteria involved readmission for non-HDP cause and maternal age less than 17 at delivery.Within the study timeframe, 3601 patients with pregnancies complicated with HDP were identified. Of these, 34 patients were readmitted within 30 days postpartum for signs and/or symptoms of HDP after exclusion criteria were applied A cohort of 50 controls were used for comparison for a total of 84 participants. A diagnosis of pre-eclampsia was significantly associated with readmission (This study suggests that readmission overall for the hypertensive disease of pregnancy is rare, but that patient variables of increasing parity and presence of severe features were associated with postpartum readmission. Knowledge of these variables may assist physicians in the identification of HDP patients who are at higher risk for readmission.

Collecting data to understand violence against women and children during and after the COVID-19 pandemic is essential to inform violence prevention and response efforts. Although researchers across fields have pivoted to remote rather than in-person data collection, remote research on violence against women, children and young people poses particular challenges. As a group of violence researchers, we reflect on our experiences across eight studies in six countries that we redesigned to include remote data collection methods. We found the following areas were crucial in fulfilling our commitments to participants, researchers, violence prevention and research ethics: (1) designing remote data collection in the context of strong research partnerships; (2) adapting data collection approaches; (3) developing additional safeguarding processes in the context of remote data collection during the pandemic; and (4) providing remote support for researchers. We discuss lessons learnt in each of these areas and across the research design and implementation process, and summarise key considerations for other researchers considering remote data collection on violence.

Ketosis in dairy cattle is primarily diagnosed based on the concentrations of ketone bodies in the blood, milk, or urine. Cow-side tests using these fluids are available for rapid detection of elevated concentrations of ketone bodies. Although these tests have been extensively validated, the performance of different tests has not been compared over time. Our objectives were to investigate the relationship between point-of-care diagnostic tests measuring the concentrations of β-hydroxybutyrate (BHB) in blood (BT; Precision Xtra, Abbott Laboratories), BHB in milk (MT; Keto-Test, Elanco), and acetoacetate (AcAc) in urine (UT; Ketostix, Bayer Corporation) through cases of ketosis. Holstein cows (n = 148) were screened daily for hyperketonemia (HYK; blood BHB ≥1.2 mmol/L) from 3 to 16 d in milk (DIM); moreover, milk and urine samples were collected concomitantly and tested for ketones (ketosis thresholds: 100 µmol/L milk BHB and 5 mg/dL urine AcAc). Of the animals screened (n = 148), 74% were diagnosed with HYK. When diagnosed with HYK, cows were treated with propylene glycol orally once daily for 5 d. After the day of diagnosis (d 0), hyperketonemic cows were retested with BT, MT, and UT for 3 d (d 1, 2, and 3). We assessed the diagnostic test performance and time to ketosis (survival analyses and Cox proportional hazards models) of MT and UT compared with BT. Considering all paired samples (before and after diagnosis of HYK), MT had 61% sensitivity and 91% specificity, whereas the UT had 77% sensitivity and 94% specificity compared with BT. The specificity of MT and UT increased from d 0 to d 1, decreased on d 2, and increased on d 3. The median time to diagnosis of ketosis in blood was 5 DIM (95% CI 5 to 7 DIM); moreover, MT and UT had 2 d greater median time to diagnosis of ketosis compared with the BT [7 DIM (6 to 11 d); and 7 DIM (6 to 13 d), respectively]. We concluded that the UT is a more sensitive predictor of blood BHB concentration than the MT. The UT and MT tests diagnosed ketotic cows approximately 2 d later than the BT. The possible consequences of delay in detection of ketosis in milk and urine should be investigated.

The objective of this study was to determine the effect of a biologically normal plane of nutrition compared with a limited plane on the primary outcome wound healing, and one dose of nonsteroidal anti-inflammatory drug (NSAID) compared with 2 on the secondary outcomes: lying behavior, haptoglobin concentrations, and mechanical nociceptive threshold (MNT) in calves disbudded via cautery iron. Eighty female Holstein calves were enrolled at birth, individually housed, and fed via a Calf Rail system (Förster Technik). A 2 × 2 factorial design was used to assess the effect of plane of nutrition and an additional NSAID. Calves were randomly assigned to a biologically normal plane of nutrition (BN; offered up to 15 L/d) or a limited plane (LP; offered up to 6 L/d) and to receive one or 2 doses of meloxicam. All calves received a lidocaine cornual nerve block and a subcutaneous injection of meloxicam 15 min before cautery disbudding at 18 to 25 d of age, and half the calves received an additional injection of meloxicam (0.5 mg/kg) 3 d after disbudding. Tissue type present, wound diameter, and wound depth were evaluated 2 times per week for 7 to 8 wk as measures of wound healing, lying behavior was recorded beginning 1 to 2 wk before disbudding until 7 to 8 wk after as a behavioral indicator of pain, haptoglobin concentrations were measured once per day for 7 d after disbudding, and MNT was evaluated 2 times/wk for 3 wk. Survival analyses were analyzed using Cox regression models (wound healing) and continuous data were analyzed using mixed-effect linear regression models. Only 12% of horn buds were completely healed by 7 to 8 wk after disbudding and 54% had re-epithelized at this time. At any time, wounds from BN calves were more likely to have had re-epithelization occur compared with wounds from LP calves (hazard ratio: 1.93, 95% CI: 1.18-3.14). Wounds from calves that received only one dose of NSAID were more likely to have re-epithelization occur, compared with wounds from calves given 2 doses (hazard ratio: 1.87, 95% CI: 1.15-3.05). Wounds from BN calves had smaller diameters and depths over time beginning on wk 3 compared with LP calves. Wounds from calves that received an additional NSAID had larger diameters and depths over time beginning on wk 4 and 3 respectively, compared with calves that only received one dose of NSAID. Calves that received an extra NSAID tended to be less sensitive 7, 10, and 17 d after disbudding compared with calves that only received one dose and spent less time lying in the week after disbudding. Calves on the BN milk program were more active compared with LP calves with lower lying times, fewer lying bouts per day, and longer average lying bouts. Our results indicate that a BN milk feeding program for calves can result in faster healing times and more activity, and that providing an extra NSAID 3 d after disbudding appears to slow the healing process but may result in less pain experienced by the calf 1 to 2 wk after the procedure. This study is also among the first to demonstrate that after the complete removal of the horn bud, wounds can take more than 8 weeks to re-epithelize and fully heal.

Background Africa is the global region where modern-slavery is most prevalent, especially among women and girls. Despite the severe health consequences of human trafficking, evidence on the risks and experiences of trafficked adolescents and young women is scarce for the region. This paper addresses this gap by exploring the intersections between violence, migration and exploitation among girls and young women identified as trafficking survivors in Nigeria and Uganda. Methods We conducted secondary analysis of the largest routine dataset on human trafficking survivors. We used descriptive statistics to report the experiences of female survivors younger than 25 years-old from Nigeria and Uganda. We also conducted 16 semi-structured interviews with adolescents identified as trafficked in both countries. We used thematic analysis to explore participants’ perceptions and experiences before, during and after the trafficking situation. Results Young female survivors of human trafficking in Nigeria and Uganda are exposed to a range of experiences of violence before migration, during transit and at destination. The qualitative data revealed that children and adolescents migrated to escape family poverty, violence and neglect. They had very low levels of education and most had their studies interrupted before migrating. Family members and close social contacts were the most common intermediaries for their migration. During transit, sexual violence and hunger were common, especially among Nigerians. Participants in both the quantitative and qualitative studies reported high levels of violence, deception, coercion, withheld wages and poor working conditions at destination. The adolescents interviewed in the qualitative study reported severe mental suffering, including suicide attempts. Only one reported the prosecution of perpetrators. Conclusions Our findings suggest that interventions to prevent or mitigate the negative impact of adverse childhood experiences can contribute to preventing the trafficking of adolescents in Nigeria and Uganda. These interventions include social protection mechanisms, universal access to education, social service referrals and education of parents and carers. Importantly, effective prevention also needs to address the systemic conditions that makes trafficking of female adolescents invisible, profitable and inconsequential for perpetrators.

To identify and characterize demographic and socioeconomic factors associated with delays in cochlear implantation (CI) in children.Retrospective.Tertiary pediatric CI referral center.All patients under 18 years of age receiving CI between March 2018 and February 2020.CI.Primary outcome measures included age at implantation and time from hearing loss diagnosis and candidacy evaluation to CI.Seventy-two patients were identified (44% women, average age at implantation 4.9 yr). Age at implantation was older in patients with public, rather than private, insurance (6.0 ± 0.8 yr versus 3.1 ± 0.7 yr, p = 0.007) and those from low-income areas (8.6 ± 7.6 yr versus 2.4 ± 3.0 yr, p = 0.007). Time between hearing loss diagnosis and implantation was longer in publicly insured patients (4.1 ± 0.6 yr versus 2.2 ± 0.5 yr, p = 0.014). Time between identification as a CI candidate and implantation was longer in publicly insured patients (721 ± 107d versus 291 ± 64 d, p = 0.001). Among children with congenital profound hearing loss, publicly insured patients continued to be older at implantation (1.9 ± 0.2 versus 1.0 ± 0.2 yr, p = 0.008). Latinx children were more often publicly insured whereas white children were more often privately insured (p 0.05). Publicly insured patients had delays in the pre-CI workup, including, in no particular order, vestibular evaluation (621 ± 132 d versus 197 ± 67 d, p = 0.007), developmental evaluation (517 ± 106 d versus 150 ± 56 d, p = 0.003), speech evaluation (482 ± 107 d versus 163 ± 65 d, p = 0.013), and children's implant profile (ChIP) assessment (572 ± 107d versus 184 ± 59d, p = 0,002). On ChIP evaluation, concerns regarding educational environment and support were higher in Spanish-speaking children (p = 0.024; p = 2.6 × 10-4) and children with public insurance (p = 0.016; p = 0.002).Disparities in access to CI continue to affect timing of pediatric cochlear implantation.