Seeking information and services associated with reproductive health among rural Peruvian young adults: exploratory qualitative research from Amazonas, Peru.

BACKGROUND: Sexual and reproductive health (SRH) literacy allows young adults to make informed decisions about health outcomes. In Peru, roughly one fifth of the population lives in rural areas, and little is known about where young adults in rural areas get their SRH information. The aim of this study was to identify what motivates and influences young adults to seek information and care related to SRH in three rural communities in the highlands of Northern Peru. METHODS: Five gender-stratified focus group discussions with a total of 24 participants, and nine follow-up interviews were conducted to generate in-depth narrative data and triangulate data from the target group. Participants were women and men aged 18-24. The focus group discussions and interviews explored sources of reproductive health information, the role of informal social networks, barriers to care, and primary health concerns of the target population. RESULTS: Main findings include: (1) The two greatest perceived SRH risks were unwanted pregnancy and abnormal discharge; (2) There appears to be limited concern about HIV or other sexually transmitted infections in the narratives; (3) There is a low quality of information concerning SRH, with discrepancies between the genders; (4) A broad spectrum of sources for SRH information were cited, including Internet, traditional healers, and specialized care; and varied by gender and life experience; (5) Having trust in the information source was the primary variable associated with uptake of services and/or access to information for both men and women. However, men reported more embarrassment around seeking services and information, whereas women faced more physical barriers. CONCLUSIONS: There is a lack of SRH information among young adults in some communities in the northern highlands of Peru. Both schools and health centers were noted as being trusted and established information sources for all genders so could be a key resource to explore as a way to disseminate information.

The Role of the Artery of Ligamentum Teres in Revascularization in Legg-Calve-Perthes Disease.

INTRODUCTION: A recent cadaveric study supported that most immature hips are supplied by the artery of ligamentum teres and suggested this medial vascular source may influence the pattern of revascularization in Legg-Calve-Perthes disease (LCPD). The purposes of this study were to characterize the perfusion pattern of the capital femoral epiphysis and determine the role of the artery of ligamentum teres in early revascularization of LCPD. METHODS: Retrospective review of perfusion magnetic resonance imaging (pMRI) from 64 hips in early stage LCPD (Waldenström stage I to IIa) was performed. Two independent graders categorized perfusion pattern based on the presence of perfusion medially (from artery of ligamentum teres) and/or laterally (from the medial femoral circumflex artery) on coronal and sagittal MRI series: type 1-lateral perfusion only, type 2-separate medial and lateral perfusion, or type 3-coalescent medial and lateral perfusion. Lateral pillar classification was obtained for hips that reached mid-fragmentation. RESULTS: We identified 64 patients (75% male) with mean age at diagnosis of 8.5±2.1 years. 36% (23/64) hips underwent pMRI during stage I and 64% (41/64) during stage IIa. pMRI revealed separate and distinct medial and lateral sources of perfusion (type 2) in 50% (32/64) hips. In stage I, the distribution of type 1/2/3 hips was found to be 26%/52%/22%. However, in stage IIa there was a nonsignificant trend toward greater coalescence of the medial and lateral perfusion with a distribution of type 1/2/3 of 7%/49%/44% (P=0.07). There was a nonsignificant trend toward weak negative linear correlation between lower initial perfusion grade and worsened lateral pillar classification at mid-fragmentation (r=-0.25, P=0.05). CONCLUSION: The presence of separate and distinct areas of perfusion of medial and lateral capital femoral epiphysis provides further evidence of the role of the ligamentum teres vessels in revascularization during the early stages of LCPD. The changes in perfusion pattern with disease progression likely reflect that medial femoral circumflex artery and ligamentum teres vessel revascularization occur separately, but ultimately coalesce posteriorly over time. LEVEL OF EVIDENCE: Level II-prognostic study.

Weightbearing and Activity Restriction Treatments and Quality of Life in Patients with Perthes Disease.

BACKGROUND: Weightbearing and activity restrictions are commonly prescribed during the active stages of Perthes disease. These restrictions, ranging from cast or brace treatment with nonweightbearing to full weightbearing with activity restrictions, may have a substantial influence on the physical, mental, and social health of a child. However, their impact on the patient's quality of life is not well-described. QUESTIONS/PURPOSES: After controlling for confounding variables, we asked (1) are restrictions on weightbearing and activity associated with physical health measures (as expressed by the Patient-Reported Outcome Measurement Information System [PROMIS] mobility, PROMIS pain interference, and PROMIS fatigue) of children in the active stages of Perthes disease? (2) Are these restrictions associated with poorer scores for mental health measures (PROMIS depressive symptoms and PROMIS anxiety)? (3) Are these restrictions associated with poorer scores for social health measures (PROMIS peer relationships)? METHODS: Between 2013 and 2020, 211 patients with Perthes disease at a single institution were assigned six PROMIS measures to assess physical, mental, and social health. Patients who met the following eligibility criteria were analyzed: age 8 to 14 years old, completion of six PROMIS measures, English-speaking, and active stage of Perthes disease (Waldenstrom Stage I, II, or III). Weightbearing and activity restrictions were clinically recommended to patients in the initial through early reossification stages of Perthes disease when patients had increasing pain, loss of hip motion, loss of hip containment, progression of femoral head deformity, increased hip synovitis, and femoral head involvement on MRI or as a postoperative regimen. Patients were categorized into four intervention groups based on weightbearing and activity regimen. We excluded 111 patients who did not meet the inclusion criteria. The following six pediatric self-report PROMIS measures were assessed: mobility, pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Of the 100 patients, 36 were categorized into the no-restriction regimen, 27 into the mild-restriction regimen, 25 into the moderate-restriction regimen, and 12 into the severe-restriction regimen at the time of PROMIS administration. The median (range) age at diagnosis was 8 years old (range 2 to 13 years). There were 85 boys and 15 girls. Eleven patients had hips in Waldenstrom Stage I, 10 were in Stage II, and 79 were in Stage III. Forty-four patients had hips classified as lateral pillar B and 47 patients as lateral pillar C. Nine patients had not reached the mid-fragmentation stage for appropriate lateral pillar classification by the time they took the PROMIS survey. ANOVA was used to compare differences between the mean PROMIS T-scores of these weightbearing/activity regimens. Results were assessed with a significance of p < 0.05 and adjusted for Waldenstrom stage, gender, age at diagnosis, and history of major surgery using multivariate regression analysis. RESULTS: After controlling for confounding variables, the mild- (ß regression coefficient -15 [95% CI -19 to -10]; p < 0.001), moderate- (ß -19 [95% CI -24 to -14]; p < 0.001), and severe- (ß -25 [95% CI -30 to -19]; p < 0.001) restriction groups were associated with worse mobility T-scores compared with the no-restriction group, but no association was detected for the pain interference or fatigue measures. Weightbearing and activity restrictions were not associated with mental health measures (depressive symptoms and anxiety). Weightbearing and activity restrictions were not associated with social health measures (peer relationships). Earlier Waldenstrom stage was associated with worse pain interference (ß 10 [95% CI 2 to 17]; p = 0.01) and peer relationships scores (ß -8 [95% CI -15 to -1]; p = 0.03); female gender was linked with worse depressive symptoms (ß 7 [95% CI 2 to 12]; p = 0.005) and peer relationships scores (ß -6 [95% CI -12 to 0]; p = 0.04); and earlier age at diagnosis was associated with worse peer relationships scores (ß 1 [95% CI 0 to 2]; p = 0.03). History of major surgery had no connection to any of the six PROMIS measures. CONCLUSION: We found that weightbearing and activity restriction treatments are associated with poorer patient-reported mobility in the active stages of Perthes disease after controlling for Waldenstrom stage, gender, age at diagnosis, and history of surgery. Weightbearing/activity restrictions, however, are not associated with pain interference, fatigue, depressive symptoms, anxiety, and peer relationships. Understanding how these treatments are associated with quality of life in patients with Perthes disease can aid in decision-making for providers, help set expectations for patients and their parents, and provide opportunities for better education and preparation. Because of the chronic nature of Perthes disease, future studies may focus on longitudinal trends in patient-reported outcomes to better understand the overall impact of this disease and its treatment. LEVEL OF EVIDENCE: Level III, therapeutic study.

Bearing fruit: Piloting a novel judgment bias task in an American black bear.

Judgment bias tasks can reveal changes in affect in animals as a function of environmental manipulations such as provision of enrichment. We assessed affect in an American black bear across seasonal changes in availability of a mulberry bush. We used a novel judgment bias task in which the background color of a touchscreen signaled whether the left or right positioned stimulus was correct. The bear learned the conditional rule in which the correct action for the white background (choose left) resulted in three pieces of food and the correct action for the black background (choose right) resulted in one piece of food. On probe trials involving intermediate gray backgrounds, left side responses indicated optimism and right side responses indicated pessimism. Tests took place at the beginning, middle, and end of mulberry season and again nearing the end of the summer and early fall before hibernation. The bear showed the most optimistic responses during the phase involving increased opportunities for foraging on mulberry. A follow-up experiment confirmed that the bear preferred three food items over one food item, suggesting the quantity-based discrimination was in fact salient to this bear. This is the first evidence for conditional discrimination learning in a black bear, validating the task to assess changes in affect.

Does Early Proximal Femoral Varus Osteotomy Shorten the Duration of Fragmentation in Perthes Disease? Lessons From a Prospective Multicenter Cohort.

BACKGROUND: The prognosis of Legg-Calvé-Perthes disease (LCPD) is dependent upon several factors, with the length and severity of the fragmentation stage among the most important. Previous retrospectively collected data from a single center have suggested that early proximal femoral varus osteotomy (PFO) may shorten the length of fragmentation and allow 34% of patients to bypass fragmentation altogether resulting in less femoral head deformity. The purpose of this study was to validate these findings in a prospectively collected multicenter cohort. METHODS: Patients with LCPD treated with early PFO (during Waldenström stage I) were prospectively followed with serial radiographs at 3-month intervals until a minimum of 2-year follow-up. Waldenström stages and lateral pillar class were determined by mode assessments from 3 pediatric orthopaedic surgeons. The duration of fragmentation was defined as the interval between the first radiographs demonstrating features of stage IIa and stage IIIa. "Complete" bypass was defined as the absence of stage IIa or IIb findings on sequential radiographs with no development of femoral head deformity or collapse. "Partial" bypass was defined as the absence of advanced features of fragmentation and femoral head collapse (stage IIb). RESULTS: Forty-six patients (80% male individuals) with initial stage LCPD and a mean age of 8.2±1.2 years were identified. The weighted kappa statistics for Waldenström staging and lateral pillar classifications showed excellent (0.833) and substantial (0.707) agreement, respectively. Ninety-eight percent of patients (45/46) underwent some period of fragmentation lasting between 91 and 518 days; the median duration was 206 days (interquartile range, 181 to 280). One patient (2%) bypassed fragmentation completely; 8 patients (17%) demonstrated partial bypass. Patients who completely or partially bypassed fragmentation experienced significantly less severe lateral pillar collapse (P=0.016) and shorter fragmentation duration (P=0.001). CONCLUSIONS: In this prospective multicenter cohort, we found a lower rate of fragmentation bypass than previously reported. Nonetheless, our data support the previous contention that early PFO may shorten fragmentation and minimize collapse in LCPD compared with historical controls. Further study with larger cohorts and a more rigorous definition of what constitutes bypass is warranted to clarify the effect of early PFO on the reparative biology of LCPD. LEVEL OF EVIDENCE: Level IV-therapeutic study.

Validation of Pediatric Self-Report Patient-Reported Outcomes Measurement Information System (PROMIS) Measures in Different Stages of Legg-Calvé-Perthes Disease.

OBJECTIVES: Patient-reported outcomes (PRO) assessing health-related quality of life (HRQoL) are important outcome measures, especially in Legg-Calvé-Perthes disease (LCPD) where symptoms (pain and limping), activity restrictions, and treatments vary depending on the stage of the disease. The purpose of this study was to investigate the validity of the Patient-reported Outcomes Measurement Information System (PROMIS) for measuring HRQoL of patients with LCPD in various stages of the disease. METHODS: This is a multicenter validity study. Patients with LCPD between 4 and 18 years old were included and classified into modified Waldenström stages of disease: Early (1 or 2A), Late (2B or 3), or Healed (4). Seven PROMIS domains were collected, including Pain Interference, Fatigue, Mobility, Depression, Anger, Anxiety, and Peer Relationships. Convergent, discriminant, and known group validity was determined. RESULTS: A total of 190 patients were included (mean age: 10.4±3.1 y). All 7 domains showed the worst scores in patients in the Early stage (known group validity). Within each domain, all domains positively correlated to each other (convergent validity). Patients who reported more anxiety, depression, and anger were associated with decreased mobility and increased fatigue and pain. Peer relationships had no to weak associations with other domains (discriminant validity). CONCLUSIONS: PROMIS has construct validity in measuring the HRQoL of patients in different stages of LCPD, suggesting that PROMIS has potential to serve as a patient-reported outcome tool for this population. LEVEL OF EVIDENCE: Diagnostic level III study.

A behavioral design approach to improving a Chagas disease vector control campaign in Peru.

BACKGROUND: Individual behavior change is a critical ingredient in efforts to improve global health. Central to the focus on behavior has been a growing understanding of how the human brain makes decisions, from motivations and mindsets to unconscious biases and cognitive shortcuts. Recent work in the field of behavioral economics and related fields has contributed to a rich menu of insights and principles that can be engineered into global health programs to increase impact and reach. However, there is little research on the process of designing and testing interventions informed by behavioral insights. METHODS: In a study focused on increasing household participation in a Chagas disease vector control campaign in Arequipa, Peru, we applied Datta and Mullainathan's "behavioral design" approach to formulate and test specific interventions. In this Technical Advance article we describe the behavioral design approach in detail, including the Define, Diagnosis, Design, and Test phases. We also show how the interventions designed through the behavioral design process were adapted for a pragmatic randomized controlled field trial. RESULTS: The behavioral design framework provided a systematic methodology for defining the behavior of interest, diagnosing reasons for household reluctance or refusal to participate, designing interventions to address actionable bottlenecks, and then testing those interventions in a rigorous counterfactual context. Behavioral design offered us a broader range of strategies and approaches than are typically used in vector control campaigns. CONCLUSIONS: Careful attention to how behavioral design may affect internal and external validity of evaluations and the scalability of interventions is needed going forward. We recommend behavioral design as a useful complement to other intervention design and evaluation approaches in global health programs.

Behavioral and hormonal responses to the availability of forage material in Western lowland gorillas (Gorilla gorilla gorilla).

We investigated how forage material affects indicators of welfare in three male Western lowland gorillas (Gorilla gorilla gorilla) at the Detroit Zoo. In addition to their maintenance diet and enrichment foods, the gorillas generally received forage material four times a week. From this baseline, we systematically manipulated how much forage material the group received on a weekly basis, with either daily or bi (twice)-weekly presentation of browse (mulberry, Morus sp.) or alfalfa hay. We collected behavioral data (60 hr per gorilla) and measured fecal glucocorticoid metabolites (FGM). Mixed models indicated that the presence of forage material significantly increased time feeding (F2,351 = 9.58, p < 0.001), and decreased rates of noncontact aggression (F2,351 = 3.69, p = 0.03), and regurgitation and reingestion (F2,353 = 4.70, p = 0.01). Regurgitation and reingestion were never observed during the condition when forage material was provided daily. When forage material was provided, time spent feeding was similar across gorillas, compared to a disproportionately greater amount of time spent feeding by the dominant individual when forage material was absent. Providing forage material in addition to the regular diet likely created more opportunities for equitable feeding for the subordinate gorillas. FGM concentrations did not vary based on the presence or type of forage material available and, instead, likely reflected group social dynamics. In general, alfalfa and mulberry had similar impacts on behavior, indicating that alfalfa can be an adequate behavioral substitute during times when browse is less readily available for gorillas housed in seasonally variable climates.

Quantity estimation and comparison in western lowland gorillas (Gorilla gorilla gorilla).

We investigated the quantity judgment abilities of two adult male western lowland gorillas (Gorilla gorilla gorilla) by presenting discrimination tasks on a touch-screen computer. Both gorillas chose the larger quantity of two arrays of dot stimuli. On some trials, the relative number of dots was congruent with the relative total area of the two arrays. On other trials, number of dots was incongruent with area. The gorillas were first tested with static dots, then with dots that moved within the arrays, and finally on a task where they were required to discriminate numerically larger subsets within arrays of moving dots. Both gorillas achieved above-chance performance on both congruent and incongruent trials with all tasks, indicating that they were able to use number as a cue even though ratio of number and area significantly controlled responding, suggesting that number was not the only relevant dimension that the gorillas used. The pattern of performance was similar to that found previously with monkeys and chimpanzees but had not previously been demonstrated in gorillas within a computerized test format, and with these kinds of visual stimuli.

Catcalls: exotic cats discriminate the voices of familiar caregivers.

Background: The ability to differentiate familiar from unfamiliar humans has been considered a product of domestication or early experience. Few studies have focused on voice recognition in Felidae despite the fact that this family presents the rare opportunity to compare domesticated species to their wild counterparts and to examine the role of human rearing. Methods: We tested whether non-domesticated Felidae species recognized familiar human voices by exposing them to audio playbacks of familiar and unfamiliar humans. In a pilot study, we presented seven cats of five species with playbacks of voices that varied in familiarity and use of the cats' names. In the main study, we presented 24 cats of 10 species with unfamiliar and then familiar voice playbacks using a habituation-dishabituation paradigm. We anticipated that human rearing and use of the cats' names would result in greater attention to the voices, as measured by the latency, intensity, and duration of responses regardless of subject sex and subfamily. Results: Cats responded more quickly and with greater intensity (e.g., full versus partial head turn, both ears moved versus one ear twitching) to the most familiar voice in both studies. They also responded for longer durations to the familiar voice compared to the unfamiliar voices in the main study. Use of the cats' name and rearing history did not significantly impact responding. These findings suggest that close human contact rather than domestication is associated with the ability to discriminate between human voices and that less social species may have socio-cognitive abilities akin to those of more gregarious species. With cats of all species being commonly housed in human care, it is important to know that they differentiate familiar from unfamiliar human voices.

Redesigning Recruitment and Engagement Strategies for Virtual Culinary Medicine and Medical Nutrition Interventions in a Randomized Trial of Patients with Uncontrolled Type 2 Diabetes.

In-person culinary medicine (CM) can improve health behaviors, but its translation to virtual platforms and impact on diabetes outcomes are not well described. We designed a pragmatic trial comparing the effectiveness of virtual CM (eCM) to Medical Nutrition Therapy on diabetes outcomes among patients with uncontrolled diabetes within a safety-net healthcare system. All participants were provided cooking equipment and food from a food pantry. Due to low initial eCM participation, recruitment was paused, and eight semi-structured interviews were conducted to solicit feedback on study appeal, operations, and barriers to participation. Rapid thematic analysis was used to modify study operations. We found that participants were interested in the study and motivated by health concerns. While they valued food distribution and cooking equipment, they highlighted transportation barriers and conflicts with the pick-up time/location. Some eCM participants expressed discomfort with the virtual platform or preferred to observe rather than cook along. Study operations were modified by (1) moving supply pick-up to a familiar community clinic and diversifying food pick-up locations; (2) offering an in-person orientation to the program to increase comfort with the virtual platform; (3) emphasizing the credibility and relatability of the eCM instructor and encouraging participation of family members. This redesign led to the recruitment of 79 participants, of whom 75% attended at least one class. In conclusion, participant feedback informed pragmatic changes in study operations that increased engagement in this ongoing trial and may inform future eCM program design.

Testing for the "Blues": Using the Modified Emotional Stroop Task to Assess the Emotional Response of Gorillas.

We adapted the emotional Stroop task developed for primates to test whether gorillas would show response slowing for images of 'negative' compared to images of 'positive' items placed within previously reinforced borders. Three zoo-housed male gorillas participated in six phases of an emotional Stroop paradigm. In Phase One, they learned to select blue borders over yellow borders in a forced choice task presented on the touchscreen. In Phase Two, neutral yellow or blue two-dimensional shapes were placed within the borders. On congruent trials, blue images were presented within both blue and yellow borders. On incongruent trials, yellow images were placed within both blue and yellow borders. We continued to use these trials as control trials in subsequent phases. We predicted that response latencies would be slower and accuracy would be lower on incongruent trials. Although the gorillas responded more quickly to incongruent trials, in contrast to predictions, they were more accurate on congruent trials, consistent with predictions. Therefore, we proceeded with Phase Three in which photographs of images assumed to have positive and negative valences for the gorillas were placed within the borders. On test trials, the same positive or negative image was placed within both borders. In Phase Four, a positive image was paired with a negative image on each trial and the positive image appeared in either the blue (congruent trials) or yellow border (incongruent trials). Phases Five and Six replicated Phases Three and Four with images of novel positive and negative items. The gorillas responded more quickly on congruent trials compared to incongruent trials on test trials but not on control trials throughout Phases 3-6. These findings provide some validation for the emotional Stroop task to test attentional shift with emotionally valenced items.

A Food for All Seasons: Stability of Food Preferences in Gorillas across Testing Methods and Seasons.

Decisions about which foods to use during training and enrichment for captive animals may be based on invalid assumptions about individuals' preferences. It is important to assess the stability of food preferences given that one-time preferences are often used to inform which items are offered over a longer period of time. Presenting preference assessments using images of food items allows control over factors such as size, scent, and inadvertent cueing but requires validation. We presented three male gorillas with choices between randomly selected pairs of actual food items from their morning meal using PVC feeders. We also presented the gorillas with two-alternative forced-choice tests between images of these foods on a touchscreen computer. Ranked preferences were correlated across method and seasons. Furthermore, gorillas selected images of preferred over less preferred foods in a validation task on the touchscreen. However, selections of some food items changed within sessions, suggesting that preference may be relative to other contextual factors. Researchers should assess how choices affect subsequent preferences to understand whether animals demonstrate absolute preferences for particular food items, or prefer variety.

What is the adult experience of Perthes' disease? : initial findings from an international web-based survey.

AIMS: Perthes' disease is an uncommon hip disorder with limited data on the long-term outcomes in adulthood. We partnered with community-based foundations and utilized web-based survey methodology to develop the Adult Perthes Survey, which includes demographics, childhood and adult Perthes' disease history, the University of California Los Angeles (UCLA) Activity Scale item, Short Form-36, the Hip disability and Osteoarthritis Outcome Score, and a body pain diagram. Here we investigate the following questions: 1) what is the feasibility of obtaining > 1,000 survey responses from adults who had Perthes' disease using a web-based platform?; and 2) what are the baseline characteristics and demographic composition of our sample? METHODS: The survey link was available publicly for 15 months and advertised among support groups. Of 1,505 participants who attempted the Adult Perthes survey, 1,182 completed it with a median timeframe of 11 minutes (IQR 8.633 to 14.72). Participants who dropped out were similar to those who completed the survey on several fixed variables. Participants represented 45 countries including the USA (n = 570; 48%), UK (n = 295; 25%), Australia (n = 133; 11%), and Canada (n = 46; 4%). Of the 1,182 respondents, 58% were female and the mean age was 39 years (SD 12.6). RESULTS: Ages at onset of Perthes' disease were < six years (n = 512; 43%), six to seven years (n = 321; 27%), eight to 11 years (n = 261; 22%), and > 11 years (n = 76; 6%), similar to the known age distribution of Perthes' disease. During childhood, 40% (n = 476) of respondents had at least one surgery. Bracing, weightbearing restriction, and absence of any treatment varied significantly between USA and non-USA respondents (p < 0.001, p = 0.002, and p < 0.001, respectively). As adults, 22% (n = 261) had at least one total hip arthroplasty, and 30% (n = 347) had any type of surgery; both more commonly reported among women (p = 0.002). CONCLUSION: While there are limitations due to self-sampling, our study shows the feasibility of obtaining a large set of patient-reported data from adults who had childhood Perthes' from multiple countries. Cite this article: Bone Jt Open 2022;3(5):404-414.

Prolonged non-weightbearing treatment decreases femoral head deformity compared to symptomatic treatment in the initial stage of Legg-Calvé-Perthes disease.

The purpose of this study is to investigate the potential benefit of using prolonged non-weightbearing (PNWB) as a treatment option for early-stage Legg-Calvé-Perthes disease (LCPD). An Institutional Review Board (IRB) approved this retrospective study of patients with LCPD and ≥2-year follow-up. Patients 6-12 years of age were included if treatment began in Waldenstrom stage 1 or 2A. PNWB consisted of ≥6 months of non- or toe-touch weightbearing. PNWB was recommended if perfusion MRI demonstrated ≥40% hypoperfusion of the femoral head and parents decided against operative treatment. The control group consisted of symptomatically treated patients. Deformity index and epiphyseal quotient were measured at 2-year follow-up. Stulberg classification and sphericity deviation score (SDS) were determined at skeletal maturity or at a minimum of 5-year follow-up. When treatment was initiated in Waldenstrom stage 1, the PNWB group had significantly less femoral head deformity, including deformity index (0.21 vs. 0.52; P < 0.001), epiphyseal quotient (69% vs. 43%; P < 0.001), SDS (18 vs. 52; P = 0.004), and Stulberg (50% good vs. 0% good; P = 0.044). The PNWB group mean hypoperfusion was 68%, indicating severe hypoperfusion. Duration of recommended non-weight bearing in the PNWB group was 11.5 months (range 7-17 months). Despite severe femoral head hypoperfusion, PNWB begun during the initial stage of LCPD decreased femoral head deformity. PNWB should be considered a treatment option for patients/parents who do not wish to pursue operative intervention in early-stage LCPD with substantial hypoperfusion. Level of Evidence III - retrospective comparative study.

Upregulation of Endothelin-1 May Predict Chemotherapy-Induced Cardiotoxicity in Women with Breast Cancer.

As survival in breast cancer patients from newer therapies increases, concerns for chemotherapy-induced cardiotoxicity (CIC) have offset some of these benefits, manifesting as a decline in left ventricular ejection fraction (LVEF). Patients receiving anthracycline-based chemotherapy followed by trastuzumab are at risk for CIC. Previous research evaluating whether clinical biomarkers predict cardiotoxicity has been inconsistent. Recently, angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) have been shown to play a role in breast tumor growth. We evaluated ATR1 and ET1 expression in breast cancer tissue and its association with CIC. A total of 33 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were analyzed by immunohistochemistry (IHC) and qRT-PCR. We found that ET1 expression was increased in patients with an LVEF ≤ 50% (p = 0.032) with a lower LVEF correlating with higher ET1 expression (r = 0.377, p = 0.031). In patients with a change in LVEF of greater than 10%, greater ET1 expression was noted compared to those without a change in LVEF (p = 0.017). Increased ET1 expression in breast tumor tissue is associated with reduced LVEF. Future studies need to examine whether ET1 may be a tissue biomarker that helps predict the risk of developing CIC in women with breast cancer.

Trpc6 Promotes Doxorubicin-Induced Cardiomyopathy in Male Mice With Pleiotropic Differences Between Males and Females.

Background: Doxorubicin is a widely used and effective chemotherapy, but the major limiting side effect is cardiomyopathy which in some patients leads to congestive heart failure. Genetic variants in TRPC6 have been associated with the development of doxorubicin-induced cardiotoxicity, suggesting that TRPC6 may be a therapeutic target for cardioprotection in cancer patients. Methods: Assessment of Trpc6 deficiency to prevent doxorubicin-induced cardiac damage and function was conducted in male and female B6.129 and Trpc6 knock-out mice. Mice were treated with doxorubicin intraperitoneally every other day for a total of 6 injections (4 mg/kg/dose, cumulative dose 24 mg/kg). Cardiac damage was measured in heart sections by quantification of vacuolation and fibrosis, and in heart tissue by gene expression of Tnni3 and Myh7. Cardiac function was determined by echocardiography. Results: When treated with doxorubicin, male Trpc6-deficient mice showed improvement in markers of cardiac damage with significantly reduced vacuolation, fibrosis and Myh7 expression and increased Tnni3 expression in the heart compared to wild-type controls. Similarly, male Trpc6-deficient mice treated with doxorubicin had improved LVEF, fractional shortening, cardiac output and stroke volume. Female mice were less susceptible to doxorubicin-induced cardiac damage and functional changes than males, but Trpc6-deficient females had improved vacuolation with doxorubicin treatment. Sex differences were observed in wild-type and Trpc6-deficient mice in body-weight and expression of Trpc1, Trpc3 and Rcan1 in response to doxorubicin. Conclusions: Trpc6 promotes cardiac damage following treatment with doxorubicin resulting in cardiomyopathy in male mice. Female mice are less susceptible to cardiotoxicity with more robust ability to modulate other Trpc channels and Rcan1 expression.

In or out: Response slowing across housing conditions as a measure of affect in three Western lowland gorillas (Gorilla gorilla gorilla).

BACKGROUND: Individuals experiencing negative affect have shown response slowing, a longer latency to respond in relation to baseline, when presented with aversive stimuli. We assessed response slowing in three male gorillas housed in a bachelor group as a function of daytime and nighttime housing arrangements. METHODS: In both experiments, three gorillas were rewarded for touching a single image (baseline, non-threatening gorilla or threatening gorilla) on a touchscreen. In Experiment One, they completed 48 50-trial sessions across combinations of three nested daytime and three nighttime conditions. In Experiment Two, they completed eight 50-trial sessions with novel stimuli across two daytime conditions, which were nested within two nighttime conditions. Housing conditions represented different amounts of space and degree of choice. We predicted that the gorillas would show response slowing to threatening stimuli when space and choice were restricted. RESULTS: We did not observe response slowing in Experiment One, although daytime and nighttime conditions interacted to predict response latencies. The gorillas responded more slowly when they had access to indoors and outdoors overnight compared to when they were in their stalls or together in an indoor habitat, but only if they had been given access to both indoors and outdoors or locked in the indoor habitat the day before. In Experiment Two, the gorillas did show response slowing to threatening stimuli, but this pattern did not interact with housing conditions. Our results, although limited by a small sample, are somewhat consistent with those of a previous study that did not find significant response slowing for apes as a function of aversive testing conditions, although the procedure has been effective in identifying dysregulated fear (high fear in low threat conditions) in macaques. The utility of this paradigm for testing affect in apes awaits further evaluation.

Increasing participation in a vector control campaign: a cluster randomised controlled evaluation of behavioural economic interventions in Peru.

OBJECTIVE: To assess the efficacy of strategies informed by behavioural economics for increasing participation in a vector control campaign, compared with current practice. DESIGN: Pragmatic cluster randomised controlled trial. SETTING: Arequipa, Peru. PARTICIPANTS: 4922 households. INTERVENTIONS: Households were randomised to one of four arms: advanced planning, leader recruitment, contingent group lotteries, or control. MAIN OUTCOME MEASURES: Participation (allowing the house to be sprayed with insecticide) during the vector control campaign. RESULTS: In intent-to-treat analyses, none of the interventions increased participation compared with control (advanced planning adjusted OR (aOR) 1.07 (95% CI 0.87 to 1.32); leader recruitment aOR 0.95 (95% CI 0.78 to 1.15); group lotteries aOR 1.12 (95% CI 0.89 to 1.39)). The interventions did not improve the efficiency of the campaign (additional minutes needed to spray house from generalised estimating equation regressions: advanced planning 1.08 (95% CI -1.02 to 3.17); leader recruitment 3.91 (95% CI 1.85 to 5.97); group lotteries 3.51 (95% CI 1.38 to 5.64)) nor did it increase the odds that houses would be sprayed in an earlier versus a later stage of the campaign cycle (advanced planning aOR 0.94 (95% CI 0.76 to 1.25); leader recruitment aOR 0.68 (95% CI 0.55 to 0.83); group lotteries aOR 1.19 (95% CI 0.96 to 1.47)). A post hoc analysis suggested that advanced planning increased odds of participation compared with control among households who had declined to participate previously (aOR 2.50 (95% CI 1.41 to 4.43)). CONCLUSIONS: Achieving high levels of household participation is crucial for many disease prevention efforts. Our trial was not successful in improving participation compared with the existing campaign. The trial highlights persistent challenges to field experiments as well as lessons about the intervention design process, particularly understanding barriers to participation through a behavioural lens. TRIAL REGISTRATION NUMBER: American Economic Association AEARCTR-0000620.

Ambiguous Results When Using the Ambiguous-Cue Paradigm to Assess Learning and Cognitive Bias in Gorillas and a Black Bear.

Cognitive bias tests are frequently used to assess affective state in nonhumans. We adapted the ambiguous-cue paradigm to assess affective states and to compare learning of reward associations in two distantly related species, an American black bear and three Western lowland gorillas. Subjects were presented with three training stimuli: one that was always rewarded (P), one that was never rewarded (N) and one that was ambiguous (A) because its reward association depended on whether it had been paired with P (PA pairing) or N (NA pairing). Differential learning of NA and PA pairs provided insight into affective state as the bear and one gorilla learned NA pairs more readily, indicating that they focused on cues of reinforcement more than cues of non-reinforcement, whereas the opposite was true of one gorilla. A third gorilla did not learn either pairings at above chance levels. Although all subjects experienced difficulty learning the pairings, we were able to assess responses to A during probe trials in the bear and one gorilla. Both responded optimistically, but it was difficult to determine whether their responses were a true reflection of affective state or were due to preferences for specific stimuli.