Outcome of assisted reproduction in women with congenital uterine anomalies: a prospective observational study.

OBJECTIVES: To assess the prevalence of congenital uterine anomalies, including arcuate uterus, and their effect on reproductive outcome in subfertile women undergoing assisted reproduction. METHODS: Consecutive women referred for subfertility between May 2009 and November 2015 who underwent assisted reproduction were included in the study. As part of the initial assessment, each woman underwent three-dimensional transvaginal sonography. Uterine morphology was classified using the modified American Fertility Society (AFS) classification of congenital uterine anomalies proposed by Salim et al. If the external contour of the uterus was uniformly convex or had an indentation of < 10 mm, but there was a cavity indentation, it was defined as arcuate or septate. Arcuate uterus was further defined as the presence of a concave fundal indentation with a central point of indentation at an obtuse angle. Subseptate uterus was defined as the presence of a septum, not extending to the cervix, with the central point of the septum at an acute angle; if the septum extended to the internal cervical os, the uterus was defined as septate. Reproductive outcomes, including live birth, clinical pregnancy and preterm birth, were compared between women with a normal uterus and those with a congenital uterine anomaly. Subgroup analysis by type of uterine morphology and logistic regression analysis adjusted for age, body mass index, levels of anti-Müllerian hormone, antral follicle count and number and day of embryo transfer were performed. RESULTS: A total of 2375 women were included in the study, of whom 1943 (81.8%) had a normal uterus and 432 (18.2%) had a congenital uterine anomaly. The most common anomalies were arcuate (n = 387 (16.3%)) and subseptate (n = 16 (0.7%)) uterus. The rate of live birth was similar between women with a uterine anomaly and those with a normal uterus (35% vs 37%; P = 0.47). The rates of clinical pregnancy, mode of delivery and sex of the newborn were also similar between the two groups. Preterm birth before 37 weeks' gestation was more common in women with uterine anomalies than in controls (22% vs 14%, respectively; P = 0.03). Subgroup analysis by type of anomaly showed no difference in the incidence of live birth and clinical pregnancy for women with an arcuate uterus, but indicated worse pregnancy outcome in women with other major anomalies (P = 0.042 and 0.048, respectively). CONCLUSIONS: Congenital uterine anomalies as a whole, when defined using the modified AFS classification, do not affect clinical pregnancy or live-birth rates in women following assisted reproduction, but do increase the incidence of preterm birth. The presence of uterine abnormalities more severe than arcuate uterus significantly worsens all pregnancy outcomes. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

IL-6 promotes CD4+ T-cell and B-cell activation during Plasmodium infection.

Humoral immunity develops in the spleen during blood-stage Plasmodium infection. This elicits parasite-specific IgM and IgG, which control parasites and protect against malaria. Studies in mice have elucidated cells and molecules driving humoral immunity to Plasmodium, including CD4+ T cells, B cells, interleukin (IL)-21 and ICOS. IL-6, a cytokine readily detected in Plasmodium-infected mice and humans, is recognized in other systems as a driver of humoral immunity. Here, we examined the effect of infection-induced IL-6 on humoral immunity to Plasmodium. Using P. chabaudi chabaudi AS (PcAS) infection of wild-type and IL-6-/- mice, we found that IL-6 helped to control parasites during primary infection. IL-6 promoted early production of parasite-specific IgM but not IgG. Notably, splenic CD138+ plasmablast development was more dependent on IL-6 than germinal centre (GC) B-cell differentiation. IL-6 also promoted ICOS expression by CD4+ T cells, as well as their localization close to splenic B cells, but was not required for early Tfh-cell development. Finally, IL-6 promoted parasite control, IgM and IgG production, GC B-cell development and ICOS expression by Tfh cells in a second model, Py17XNL infection. IL-6 promotes CD4+ T-cell activation and B-cell responses during blood-stage Plasmodium infection, which encourages parasite-specific antibody production.

Haemarthrosis model in mice: BSS - Bleeding Severity Score assessment system.

INTRODUCTION: The prophylactic administration of clotting factor concentrate is currently the most effective strategy for the prevention of joint bleeding. As new agents with different mechanisms of action and administration schedules are developed, it will be important to study them in relevant preclinical models. AIM: The aim of this study was the standardization of a mouse haemarthrosis model in a haemophilia mouse and the development and validation of a comprehensive bleeding assessment system, the Bleeding Severity Score (BSS). METHODS AND RESULTS: Four outcome measurements were assessed, two of which, the extra-articular bleeding score and intra-articular bleeding score, were determined to be the most reliable and were summarized into a BSS which was validated using a mouse haemarthrosis variability model. CONCLUSION: Using this model, the haemostatic effect of prospective drugs can be assessed in a clinically relevant joint bleeding model and will significantly increase the value of preclinical studies.

Synovial chemokine expression and relationship with knee symptoms in patients with meniscal tears.

OBJECTIVE: In patients with knee OA, synovitis is associated with knee pain and symptoms. We previously identified synovial mRNA expression of a set of chemokines (CCL19, IL-8, CCL5, XCL-1, CCR7) associated with synovitis in patients with meniscal tears but without radiographic OA. CCL19 and CCR7 were also associated with knee symptoms. This study sought to validate expression of these chemokines and association with knee symptoms in more typical patients presenting for meniscal arthroscopy, many who have pre-existing OA. DESIGN: Synovial fluid (SF) and biopsies were collected from patients undergoing meniscal arthroscopy. Synovial mRNA expression was measured using quantitative RT-PCR. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was administered preoperatively. Regression analyses determined if associations between chemokine mRNA levels and KOOS scores were independent of other factors including radiographic OA. CCL19 in SF was measured by ELISA, and compared to patients with advanced knee OA and asymptomatic organ donors. RESULTS: 90% of patients had intra-operative evidence of early cartilage degeneration. CCL19, IL-8, CCL5, XCL1, CCR7 transcripts were detected in all patients. Synovial CCL19 mRNA levels independently correlated with KOOS Activities of Daily Living (ADL) scores (95% CI [-8.071, -0.331], P = 0.036), indicating higher expression was associated with more knee-related dysfunction. SF CCL19 was detected in 7 of 10 patients, compared to 4 of 10 asymptomatic donors. CONCLUSION: In typical patients presenting for meniscal arthroscopy, synovial CCL19 mRNA expression was associated with knee-related difficulty with ADL, independent of other factors including presence of radiographic knee OA.

Quality indicators for human milk use in very low-birthweight infants: are we measuring what we should be measuring?

OBJECTIVE: The objective of this study was to compare the currently used human milk (HM) quality indicators that measure whether very low-birthweight (VLBW; <1500 g birthweight) infants 'ever' received HM and whether they were still receiving HM at discharge from the neonatal intensive care unit (NICU) to the actual amount and timing of HM received. STUDY DESIGN: This study used data from a large NIH-funded cohort study and calculated whether VLBW infants ever received HM (HM-Ever) and of these infants, the percentage who were still receiving HM at NICU discharge (HM-DC). Then, the HM-DC indicator (exclusive, partial and none) was compared with the amount and timing of HM feedings received by these same infants. RESULT: Of the 291 VLBW infants who met inclusion criteria, 285 received some HM (HM-Ever=98%). At NICU discharge (HM-DC), 24.2, 15.1 and 60.7% were receiving exclusive, partial and no HM, respectively. Of the 60.7% infants with no HM-DC, some had received higher amounts of HM during the NICU hospitalization than infants categorized as exclusive and partial for HM-DC. Of the infants with no HM-DC, 76.8 and 59.7% had received exclusive HM during the days 1-14 and days 1-28 exposure periods, respectively. CONCLUSION: The average daily dose (HM-DD; in ml kg(-1) d(-1)) and cumulative percentage (HM-PCT; as % of cumulative enteral intake) of HM feedings were sufficient to significantly reduce the risk of multiple morbidities, including late-onset sepsis, necrotizing enterocolitis, neurocognitive delay and rehospitalization, in the majority of the VLBW infants who were discharged with no HM-DC. Quality indicators that focus on the amount and timing of HM feedings in the NICU should be added to the HM-Ever and HM-DC measures.

Impact of early human milk on sepsis and health-care costs in very low birth weight infants.

OBJECTIVE: To study the incidence of sepsis and neonatal intensive care unit (NICU) costs as a function of the human milk (HM) dose received during the first 28 days post birth for very low birth weight (VLBW) infants. STUDY DESIGN: Prospective cohort study of 175 VLBW infants. The average daily dose of HM (ADDHM) was calculated from daily nutritional data for the first 28 days post birth (ADDHM-Days 1-28). Other covariates associated with sepsis were used to create a propensity score, combining multiple risk factors into a single metric. RESULT: The mean gestational age and birth weight were 28.1 ± 2.4 weeks and 1087 ± 252 g, respectively. The mean ADDHM-Days 1-28 was 54 ± 39 ml kg(-1) day(-1) (range 0-135). Binary logistic regression analysis controlling for propensity score revealed that increasing ADDHM-Days 1-28 was associated with lower odds of sepsis (odds ratio 0.981, 95% confidence interval 0.967-0.995, P=0.008). Increasing ADDHM-Days 1-28 was associated with significantly lower NICU costs. CONCLUSION: A dose-response relationship was demonstrated between ADDHM-Days 1-28 and a reduction in the odds of sepsis and associated NICU costs after controlling for propensity score. For every HM dose increase of 10 ml kg(-1) day(-1), the odds of sepsis decreased by 19%. NICU costs were lowest in the VLBW infants who received the highest ADDHM-Days 1-28.

Outbreak of zoonotic cutaneous leishmaniasis with local dissemination in Balkh, Afghanistan.

OBJECTIVES: In Afghanistan zoonotic cutaneous leishmaniasis (CL) due to Leishmania major has been less widely reported than anthroponotic CL due to L. tropica. However, an outbreak of zoonotic CL occurred amongst a group of British soldiers at a military camp near Mazar-e-Sharif in the Balkh province of northern Afghanistan in 2004. METHODS: A study was performed to assess the epidemiology, clinical features, parasitology results, treatment outcomes and environmental health measures associated with this incident. RESULTS: Twenty (17%) of 120 soldiers developed CL due to L. major and the risk of infection increased with the proximity of their accommodation to an area of recently cleared scrub, where many wild rodents were observed. Most cases had features of local dissemination, including secondary lesions from the pseudo-Koebner phenomenon, sporotrichoid lymphatic spread, lymphadenopathy and satellite papules or milia formation around healing lesions. Several cases responded poorly to fluconazole and low dose (10 mg/kg) sodium stibogluconate, which were considered suitable treatments at the time. Environmental health measures at the military camp were found to be deficient. CONCLUSIONS: Zoonotic CL due to L. major is a significant threat for foreign troops based in Balkh, Afghanistan and may present with unusually severe clinical features and be resistant to previously recommended treatments.

Lupus-specific health outcome measure for US patients: the LupusQoL-US version.

BACKGROUND: Patient-reported outcomes are valuable for the management of chronic diseases like systematic lupus erythematosus (SLE), but no measures have been validated for use in US-based patients with SLE. OBJECTIVES: To adapt and assess the validity and reliability of an SLE-specific quality of life (QoL) measure developed in the United Kingdom, the LupusQoL, for use in US-based patients with SLE. METHODS: Debriefing interviews of subjects with SLE guided the language modifications of the tool. The LupusQoL-US, SF-36 and EQ5D were administered. Internal consistency (ICR) and test-retest (TRT) reliability, convergent and discriminative validity were examined. Factor analyses were performed. RESULTS: The mean (SD) age of the 185 subjects with SLE was 42.5 (12.9) years. ICR and TRT of the eight domains ranged from 0.85 to 0.94 and 0.68 to 0.92, respectively. Related domains on the SF-36 correlated with the LupusQoL domains (physical health and physical function r = 0.73, physical health and role physical r = 0.57, emotional health and mental health r = 0.72, emotional health and role emotional r = 0.48, pain and bodily pain r = 0.66, fatigue and vitality r = 0.70, planning and social functioning r = 0.58). Most LupusQoL-US domains could discriminate between subjects with varied disease activity and damage. Principal component analysis disclosed five factors in the US version, with physical function, pain and planning items loading on one factor. CONCLUSIONS: These data provide evidence to support the psychometric properties of the LupusQoL-US, suggesting its utility as an assessment tool for patients with SLE in the USA.

Veterinary medicines in the environment.

The impact of veterinary medicines on the environment will depend on a number of factors including physicochemical properties, amount used and method of administration, treatment type and dose, animal husbandry practices, manure storage and handling practices, metabolism within the animal, and degradation rates in manure and slurry. Once released to the environment, other factors such as soil type, climate, and ecotoxicity also determine the environmental impact of the compound. The importance of individual routes into the environment for different types of veterinary medicines varies according to the type of treatment and livestock category. Treatments used in aquaculture have a high potential to reach the aquatic environment. The main routes of entry to the terrestrial environment are from the use of veterinary medicines in intensively reared livestock, via the application of slurry and manure to land, and by the use of veterinary medicines in pasture-reared animals where pharmaceutical residues are excreted directly into the environment. Veterinary medicines applied to land via spreading of slurry may also enter the aquatic environment indirectly via surface runoff or leaching to groundwater. It is likely that topical treatments have greater potential to be released to the environment than treatments administered orally or by injection. Inputs from the manufacturing process, companion animal treatments, and disposal are likely to be minimal in comparison. Monitoring studies demonstrate that veterinary medicines do enter the environment, with sheep dip chemicals, antibiotics, sealice treatments, and anthelmintics being measured in soils, groundwater, surface waters, sediment, or biota. Maximum concentrations vary across chemical classes, with very high concentrations being reported for the sheep dip chemicals. The degree to which veterinary medicines may adsorb to particulates varies widely. Partition coefficients (K(d)) range from low (0.61 L kg(-1)) to high (6000 L kg(-1)). The variation in partitioning for many of the compounds in different soils was significant (up to a factor of 30), but these differences could be not be explained by normalization to the organic carbon content of the soils. Thus, to arrive at a realistic assessment of the availability of veterinary medicines for transport through the soil and uptake into soil organisms, the K(oc) (which is used in many of the exposure models) may not be an appropriate measure. Transport of particle-associated substances from soil to surface waters has also been demonstrated. Veterinary medicines can persist in soils for days to years, and half-lives are influenced by a range of factors including temperature, pH, and the presence of manure. The persistence of major groups of veterinary medicines in soil, manure, slurry, and water varies across and within classes. Ecotoxicity data were available for a wide range of veterinary medicines. The acute and chronic effects of avermectins and sheep dip chemicals on aquatic organisms are well documented, and these substances are known to be toxic to many organisms at low concentrations (ng L(-1) to microg L(-1)). Concerns have also been raised about the possibility of indirect effects of these substances on predatory species (e.g., birds and bats). Data for other groups indicate that toxicity values are generally in the mg L(-1) range. For the antibiotics, toxicity is greater for certain species of algae and marine bacteria. Generally, toxicity values for antibacterial agents were significantly higher than reported environmental concentrations. However, because of a lack of appropriate toxicity data, it is difficult to assess the environmental significance of these observations with regard to subtle long-term effects.

Clinical trials in the 21st century: the case for participant-centered research.

Informed consumers of the 21st century increasingly will be hesitant to enroll in randomized clinical trials (RCTs) because they will be unwilling to (a) submit to random assignment; (b) complete assessments that are too lengthy, intrusive, or irrelevant; or (c) comply with protocols that do not meet their needs. Research centered on the needs and interests of participants is likely to engender greater participation and commitment than are traditional RCTs. Recommendations for making clinical trials more participant centered include: (a) expanding our conceptualizations of study validity, (b) involving consumers as advisers in the development and execution of clinical trials, and (c) offering participants reasonable alternatives to random assignment.

Effects of melatonin administration on daytime sleep after simulated night shift work.

Disturbed sleep and on-the-job sleepiness are widespread problems among night shift workers. The pineal hormone melatonin may prove to be a useful treatment because it has both sleep-promoting and circadian phase-shifting effects. This study was designed to isolate melatonin's sleep-promoting effects, and to determine whether melatonin could improve daytime sleep and thus improve night time alertness and performance during the night shift. The study utilized a placebo-controlled, double-blind, cross-over design. Subjects (n=21, mean age=27.0 +/- 5.0 years) participated in two 6-day laboratory sessions. Each session included one adaptation night, two baseline nights, two consecutive 8-h night shifts followed by 8-h daytime sleep episodes and one recovery night. Subjects took 1.8 mg sustained-release melatonin 0.5 h before the two daytime sleep episodes during one session, and placebo before the daytime sleep episodes during the other session. Sleep was recorded using polysomnography. Sleepiness, performance, and mood during the night shifts were evaluated using the multiple sleep latency test (MSLT) and a computerized neurobehavioral testing battery. Melatonin prevented the decrease in sleep time during daytime sleep relative to baseline, but only on the first day of melatonin administration. Melatonin increased sleep time more in subjects who demonstrated difficulty in sleeping during the day. Melatonin had no effect on alertness on the MSLT, or performance and mood during the night shift. There were no hangover effects from melatonin administration. These findings suggest that although melatonin can help night workers obtain more sleep during the day, they are still likely to face difficulties working at night because of circadian rhythm misalignment. The possibility of tolerance to the sleep-promoting effects of melatonin across more than 1 day needs further investigation.

Rural and urban Midwestern United States contraception practices.

To address a paucity of demographic data on rural United States contraception practices, 370 randomly selected menstruating women, age 13-55 years, living in rural and urban Illinois and Missouri answered interview questions. Women with relatively few children and living in urban areas were likely to practice contraception more than those with relatively few children and living in rural areas, p < 0.01. In Illinois, more rural (23%) than urban (2%) women chose sterilization, p < 0.01. Single status was more frequent in Chicago (41%) and rural Missouri (32%) than in rural Illinois (19%), p < 0.002, and extant research links single status with risk for HIV and other sexually transmitted diseases (STDs). Condom use did not differ significantly by locale, p > 0.05. Urban-rural differences in contraception practices may be a function of life style choices (e.g. urban women may practice contraception to postpone having children, whereas rural women may practice contraception to prevent having more children after families are complete). Results do not strongly support that locale differences in contraception practices are a function of concern about contracting STDs.

A multifactorial study of age bias among rehabilitation professionals.

OBJECTIVES: To assess different dimensions of age bias among rehabilitation professionals and to determine the effect of patient gender and behavior on these biases. DESIGN: Between-subjects questionnaire study. SETTING: Randomly selected institutions accredited with the Commission on the Accreditation of Rehabilitation Facilities (CARF). PARTICIPANTS: Nine hundred seventy-four rehabilitation professionals from 9 disciplines at 23 CARF-accredited facilities. INTERVENTIONS: Each professional received a vignette case history of an amputation patient who varied in age (36yr, 76yr), gender (male, female), and patient behavior (ideal, depressed, noncompliant). The vignette was followed by the Professional Bias Questionnaire (PBQ), which included 25 questions assessing the professionals' responses to the patient. MAIN OUTCOME MEASURES: Main effects and interaction effects for age, gender, and behavior for the PBQ. RESULTS: Factor analysis of the PBQ questionnaire yielded 4 reliable scales: the professional's judgment of the patient's psychologic neediness, postdischarge potential, worthiness for rehabilitation, and their personal reaction to working with the patient. Analyses of variance resulted in significant age by behavior interaction effects for 3 of the 4 scales. Older patients were viewed more negatively than equivalent younger patients when they were noncompliant. Professionals also had a more negative personal reaction to depressed older patients compared with equivalent younger patients. In contrast, gender bias was only found in 1 specific situation and did not interact with age bias. CONCLUSION: Several forms of bias toward older adult patients were found among rehabilitation professionals, but they were present only when patient behavior was less than ideal. Age bias continues to be a critical issue in the equity of rehabilitation services and should be addressed with training and policy changes.

Pharmacological treatments for alcoholism: revisiting lithium and considering buspirone.

OBJECTIVE: Previous research has suggested that both lithium and buspirone could lessen alcoholics' desire to drink as well as reduce the actual amounts of alcohol consumed. The purpose of this study was to compare lithium and buspirone monotherapy with placebo on outcomes of abstinence, alcohol quantity consumed, treatment retention and compliance, and medication side effects. METHODS: We conducted a randomized, double-blind, placebo-controlled, three-arm parallel group, clinical trial that compared lithium and buspirone with placebo in 156 alcohol-dependent men. RESULTS: Study retention rates for the three treatment groups at 3 and 6 months, respectively, were 61% and 46% for lithium, 44% and 27% for buspirone, and 52% and 38% for placebo (p = NS, for 3 and 6 months). Overall abstinence rates were 28% and 19% at 3 and 6 months, respectively. However, mean daily quantities of alcohol consumed and percentage of drinking days decreased significantly (p < 0.0001) over time in all treatment groups. Differential improvement was seen only for the decrement in quantity consumed in the buspirone group, compared with the placebo group, but only at a trend level (p = 0.07). According to pill counts, compliance did not differ significantly among the treatment groups. CONCLUSIONS: These results do not support the hypothesis that either lithium or buspirone, compared with placebo, produces differential reductions in alcohol consumption. The results suggest the need to enhance treatment retention to maximize outcomes.

Threats to validity in randomized clinical trials.

The purposes of this article are to present an overview of randomized clinical trials (RCTs) and describe some of the methodological problems inherent in using RCTs in nursing research. Many nursing intervention studies are fraught with problems that defy the stringent control criteria required for RCTs, leading to biased estimates of intervention efficacy. Five threats to validity in RCTs are presented, including problems related to (a) differential dropout, (b) random assignment, (c) identifying and maintaining an adequate control condition, (d) nonadherence to research protocols, and (e) assessment of clinically meaningful change. Three strategies are recommended for addressing some of the problems posed by RCTs and improving inference.

Discipline across generations.

The objective of this qualitative research was to understand how parents decide which discipline practices they will repeat from their childhoods. Participants chose not to repeat punishment practices when a strong, negative effect was remembered. However, some parents repeated physical punishment practices even when a strong, negative effect was remembered if they believed the practices were effective or culturally valued, if they were under stress, or if the parents lacked alternative strategies.

Intermittent bright light and exercise to entrain human circadian rhythms to night work.

Bright light can phase shift human circadian rhythms, and recent studies have suggested that exercise can also produce phase shifts in humans. However, few studies have examined the phase-shifting effects of intermittent bright light, exercise, or the combination. This simulated night work field study included eight consecutive night shifts followed by daytime sleep/dark periods (delayed 9 h from baseline). There were 33 subjects in a 2 x 2 design that compared 1) intermittent bright light (6 pulses, 40-min long each, at 5,000 lx) versus dim light and 2) intermittent exercise (6 bouts, 15-min long each, at 50-60% of maximum heart rate) versus no exercise. Bright light and exercise occurred during the first 6 h of the first three night shifts. The circadian phase marker was the demasked rectal temperature minimum. Intermittent bright-light groups had significantly larger phase delays than dim-light groups, and 94% of subjects who received bright light had phase shifts large enough for the temperature minimum to reach daytime sleep. Exercise did not affect phase shifts; neither facilitating nor inhibiting phase shifts produced by bright light.

Finding meaning through caregiving: development of an instrument for family caregivers of persons with Alzheimer's disease.

Systematic assessment of the positive aspects of caregiving has been limited by the lack of comprehensive, theoretically based, and psychometrically sound measures. This study developed and tested a measure primarily designed to assess positive aspects and ways that caregivers find meaning through their experience of caring for a person with dementia. The measure has three subscales: Loss/Powerlessness, which identifies difficult aspects of caregiving; Provisional Meaning, which identifies how caregivers find day-to-day meaning; and Ultimate Meaning, which identifies philosophical/religious/spiritual attributions associated with the experience of caregiving. The measure is useful for understanding the close relationship between both the difficult and positive aspects of caregiving and also may be used to identify a caregiver's strengths in clinical and research settings.

Behavior problems among young children in low-income urban day care centers.

The purposes of this study were to describe: (a) the frequency and correlates of behavior problems among a sample of 2- and 3-year-old children from low-income families as seen by their parents and day care teachers, (b) the degree to which parents and teachers agree about the children's behavior problems in their respective contexts, and (c) family characteristics that distinguish toddlers with behavior problems both at home and at day care from the rest of the sample. Parents of 133 toddlers from 10 Chicago day care centers completed measures of child behavior problems, child behavioral intensity, parenting self-efficacy, discipline strategies, and stress. Children's day care teachers also completed a measure of child behavior problems. Parent-reported behavior problems were associated with higher child behavioral intensity, greater parent stress, lower self-efficacy, and discipline strategies characterized by irritability, coercion, and inconsistency. Parent and teacher ratings on child behavior were correlated for boys' behavior problems only. Parents reported more child behavior problems than teachers. Approximately 8% of the children were rated as having behavior problems at home and at day care. Although most of the children are functioning well, many of these parents and toddlers are engaged in highly stressful and coercive relationships.