Multisystem ALK-Positive Histiocytosis With DCTN1::ALK Fusion in an Adult, Responsive to Alectinib: Case Report and Literature Review.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis has emerged as a clinically relevant diagnosis featuring a wide span of clinical presentations, which are unified by the presence of ALK-positive histiocytes on histopathology and molecular drivers involving the ALK kinase gene. This report presents an adult case of multisystem ALK-positive histiocytosis with xanthogranuloma-like features on histopathology that was responsive to ALK inhibition, and includes a review of ALK-positive histiocytoses with cutaneous involvement reported in the literature. A 56-year-old male developed a widespread eruption of red-brown papules on the face, trunk, and upper extremities. Histopathological evaluation revealed a well-circumscribed, nodular dermal infiltrate of epithelioid histiocytes with Touton giant cells, rare bizarre multinucleated cells, and focal emperipolesis. The lesional cells were positive for CD68 and ALK1 immunohistochemical stains, and negative for CD1a. Next-generation sequencing identified a DCTN1::ALK fusion. On imaging, he was found to have bone, lung, soft tissue, and salivary gland involvement. ALK inhibition was initiated with alectinib, resulting in rapid improvement of cutaneous lesions and eventual complete resolution of abnormal imaging findings, which was sustained at 24 months of follow-up. This case adds to the spectrum of ALK-positive histiocytoses and further demonstrates the positive response with targeted therapy.

The Role of Serum Albumin and Secretory Phospholipase A2 in Sepsis.

Sepsis is caused by a dysregulated host response to an infection that leads to cascading cell death and eventually organ failure. In this study, the role of inflammatory response serum secretory phospholipase A2 (sPLA2) and albumin in sepsis was investigated by determining the activities of the two proteins in serial serum samples collected on different days from patients with sepsis after enrollment in the permissive underfeeding versus standard enteral feeding protocols in an intensive care unit. Serum sPLA2 and albumin showed an inverse relationship with increasing sPLA2 activity and decreasing albumin membrane-binding activity in patients with evolving complications of sepsis. The activities of sPLA2 and albumin returned to normal values more rapidly in the permissive underfeeding group than in the standard enteral feeding group. The inverse sPLA2-albumin activity relationship suggests a complex interplay between these two proteins and a regulatory mechanism underlying cell membrane phospholipid homeostasis in sepsis. The decreased albumin-membrane binding activity in patients' serum was due to its fatty acid-binding sites occupied by pre-bound fatty acids that might alter albumin's structure, binding capacities, and essential functions. The sPLA2-albumin dual serum assays may be useful in determining whether nutritional intervention effectively supports the more rapid recovery of appropriate immune responses in critically ill patients with sepsis.

Role of coal ash morphology and composition in delivery and transport of trace metals in the aquatic environment.

Fly ash is predominately the inorganic byproduct of coal combustion for electrical power generation. It is composed of aluminosilicates with Fe, Mg, K, and Ca forming submicron to 100 µm spheres and amorphous particles. During combustion trace elements are incorporated into the heterogenous fine particles that can pose risks to the environment and human health. This study combines optical, rock magnetic, and geochemical analyses of fly ash originating from Appalachian coal to develop an integrated suite of environmental coal ash tracers. The non-magnetic portion of power plant fly ash has higher abundance of clear spheres and clear amorphous particles, combined with enrichment of As, B, Th, Ba, Li, Se, Cd, Pb, and Tl. The magnetic fraction is enriched in opaque and orange spheres and Cu, U, V, Mo, Cr, Ni, and Co. Plerospheres occur in either fraction. We investigated ash-bearing fluvial sediment from Emory-Clinch River system that was impacted by the instantaneous TVA spill in 2008 and Hyco Lake in North Carolina that was contaminated by chronic releases of fly ash since 1964. Five years after the TVA spill, most ash in the riverbed reflects one population with trace element concentrations proportional to percent total ash. This relationship does not hold for As and Se, volatile elements associated with the outer surface of clear spheres, which are affected by river transport. At Hyco Lake, small clear and opaque spheres correlate with trace elements released from storage ponds. The combination of trace elements, fly ash morphology and rock magnetism provides a powerful set of tools to assess the distribution of ash and potential impact on the environment. We conclude that dispersal of fly ash to the aquatic environment, especially small clear and opaque spheres, should be avoided in favor of dry landfills.

Achieving equitable access to incretin-based therapies in cardiovascular care.

The role of incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP1RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists, in the management of type 2 diabetes mellitus (T2DM) and obesity has been increasingly recognized, along with significant cardiovascular (CV) benefits. Despite the clinical efficacy of incretin-based therapies, high costs, suboptimal access, limited insurance coverage, and therapeutic inertia present substantial barriers to widespread adoption. Overcoming these obstacles is essential for the equitable initiation, access, and utilization of incretin-based therapies. Clinicians must make targeted efforts to ensure health equity in the use of these and other advanced therapies.

Public health and system approach in eliminating disparities in hypertensive disorders and cardiovascular outcomes in non-Hispanic Black women across the pregnancy life course.

Hypertension is one of the leading risk factors for cardiovascular disease. The ACC/AHA/Multisociety hypertension guideline covered all aspects of the recommendations for optimal blood pressure diagnosis and management to improve cardiovascular outcomes. Despite this, there remains a growing prevalence of hypertension within the United States, largely in non-Hispanic Black women at earlier stages of their life course. This highlights the evident racial disparities, but offers a targeted opportunity for improved outcomes. With hypertension increasingly seen in the antenatal and immediate postpartum period, and obstetrics societies weighing in on the need to alter pharmacotherapy initiation goals, national initiatives have purposefully targeted pregnant and postpartum women in an effort to improve outcomes. This same energy must also re-focus health care efforts across the entire health continuum. Public health and system strategies are in place to do so, with the strongest enforcing initiatives as early as childhood with a greater focus on primordial prevention.

School personnel well-being: Advancing measurement, best practices, and policy. Section 2: Role of traumatic experiences in educator well-being.

The special issue, "School Personnel Well-Being: Advancing Measurement, Best Practices, and Policy," showcases empirical quantitative and qualitative research that presents a range of social-ecological factors that directly and indirectly associate with school personnel well-being, trauma, and safety in prekindergarten through 12th grade schools. This introduction article represents Section 2 of the special issue reviewing eight articles that focus on the Role of Traumatic Experiences in Educator Well-Being. Collectively, these studies increase awareness of school personnel trauma experiences and make important contributions to the field. We offer lessons learned from the studies and directions for research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Homelessness and Risk of End-Stage Kidney Disease and Death in Veterans With Chronic Kidney Disease.

Importance: Adults experiencing homelessness in the US face numerous challenges, including the management of chronic kidney disease (CKD). The extent of a potentially greater risk of adverse health outcomes in the population with CKD experiencing homelessness has not been adequately explored. Objective: To evaluate the association between a history of homelessness and the risk of end-stage kidney disease (ESKD) and death among veterans with incident CKD. Design, Setting, and Participants: This retrospective cohort study was conducted between January 1, 2005, and December 31, 2017. Participants included veterans aged 18 years and older with incident stage 3 to 5 CKD utilizing the Veterans Health Administration health care network in the US. Patients were followed-up through December 31, 2018, for the occurrence of ESKD and death. Analyses were performed from September 2022 to October 2023. Exposure: History of homelessness, based on utilization of homeless services in the Veterans Health Administration or International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Homelessness was measured during the 2-year baseline period prior to the index date of incident CKD. Main Outcomes and Measures: The primary outcomes were ESKD, based on initiation of kidney replacement therapy, and all-cause death. Adjusted hazard ratios (HRs) were calculated to compare veterans with a history of homelessness with those without a history of homelessness. Results: Among 836 361 veterans, the largest proportion were aged 65 to 74 years (274 371 veterans [32.8%]) or 75 to 84 years (270 890 veterans [32.4%]), and 809 584 (96.8%) were male. A total of 26 037 veterans (3.1%) developed ESKD, and 359 991 (43.0%) died. Compared with veterans who had not experienced homelessness, those with a history of homelessness showed a significantly greater risk of ESKD (adjusted HR, 1.15; 95% CI, 1.10-1.20). A greater risk of all-cause death was also observed (HR, 1.48; 95% CI, 1.46-1.50). After further adjustment for body mass index, comorbidities, and medication use, results were attenuated for all-cause death (HR, 1.09; 95% CI, 1.07-1.11) and were no longer significant for ESKD (HR, 1.04; 95% CI, 0.99-1.09). Conclusions and Relevance: In this cohort study of veterans with incident stage 3 to 5 CKD, a history of homelessness was significantly associated with a greater risk of ESKD and death, underscoring the role of housing as a social determinant of health.

Tackling the Disproportionate Burden of Resistant Hypertension in US Black Adults.

PURPOSE OF REVIEW: Elevated blood pressure is the leading modifiable risk factor for cardiovascular morbidity and mortality in the US. Older individuals, Black adults, and those with comorbidities such as chronic kidney disease, have higher levels of uncontrolled and resistant hypertension. This review focuses on resistant hypertension, specifically in the US Black population, including potential benefits and limitations of current and investigational agents to address the disparate toll. RECENT FINDINGS: There is a necessity to implement public health measures, including early screening, detection, and evidence-based hypertension treatment with lifestyle, approved and investigational agents. The evidence highlights the importance of implementing feasible and cost-effective public health measures to advocate for early screening, detection, and appropriate treatment of hypertension. A team-based approach involving physicians, advanced practice nurses, physician assistants, pharmacists, social workers, and clinic staff to implement proven approaches and the delivery of care within trusted community settings may mitigate existing disparities.

Northern Gannet foraging trip length increases with colony size and decreases with latitude.

Density-dependent competition for food influences the foraging behaviour and demography of colonial animals, but how this influence varies across a species' latitudinal range is poorly understood. Here we used satellite tracking from 21 Northern Gannet Morus bassanus colonies (39% of colonies worldwide, supporting 73% of the global population) during chick-rearing to test how foraging trip characteristics (distance and duration) covary with colony size (138-60 953 breeding pairs) and latitude across 89% of their latitudinal range (46.81-71.23° N). Tracking data for 1118 individuals showed that foraging trip duration and maximum distance both increased with square-root colony size. Foraging effort also varied between years for the same colony, consistent with a link to environmental variability. Trip duration and maximum distance also decreased with latitude, after controlling for colony size. Our results are consistent with density-dependent reduction in prey availability influencing colony size and reveal reduced competition at the poleward range margin. This provides a mechanism for rapid population growth at northern colonies and, therefore, a poleward shift in response to environmental change. Further work is required to understand when and how colonial animals deplete nearby prey, along with the positive and negative effects of social foraging behaviour.

Fatigue by the Chalder Questionnaire and post-hemodialysis recovery in a population of predominantly African descent: The PROHEMO.

BACKGROUND/OBJECTIVE: A high prevalence of fatigue and a positive association between fatigue and post-hemodialysis recovery have been reported in predominantly white populations of maintenance hemodialysis (MHD) patients. The present study evaluates associations between self-reported fatigue by the 11-item Chalder Fatigue Questionnaire (CFQ-11) and the need for post-hemodialysis recovery in a predominantly African-descent MHD population. METHODS: A total of 233 patients (94% Black or Mixed-Race) participating in the "Prospective Study of the Prognosis of Patients on Maintenance Hemodialysis" (PROHEMO), Salvador, Brazil were recruited for this cross-sectional study. The CFQ-11 was used to measure fatigue: <4 for absent or mild, ⩾4 for moderate to severe. Patients were also asked if they needed some time to recover after the hemodialysis. Logistic regression was used to estimate odds ratio (OR) of the association with adjustments for age, sex, race, educational level, economic class level, diabetes, hearth failure, and hemoglobin. RESULTS: Mean age was 51.5 ± 12.5 years. Moderate to severe fatigue (⩾4 points) was observed in 70.8% (165/233), and absent or mild fatigue (<4 points) in 29.2% (68/233). Compared to patients with fatigue scores <4 (20.6%), the need for post-hemodialysis recovery was 2.5 times greater in patients with fatigue scores ⩾4 (52.7%). The covariate-adjusted logistic regression OR was 4.60, 95% CI: 2.27, 9.21. CONCLUSION: This study in MHD patients of predominantly African descent supports self-reported fatigue assessed by the CFQ-11 as a relevant predictor of the need for post-hemodialysis recovery. The results offer a rationale for investigating whether interventions to prevent fatigue reduce the need of post-hemodialysis recovery.

Low-Frequency Raman Spectroscopy on Amorphous Poly(Ether Ether Ketone) (PEEK).

Low-frequency peaks in the Raman spectra of amorphous poly(ether ether ketone) (PEEK) were investigated. An amorphous sample with zero crystallinity, as confirmed by wide-angle X-ray diffraction, was used in this study. In a previous study, two peaks were observed in the low-frequency Raman spectra of the crystallized samples. Among these, the peaks at 135 cm-1 disappeared for the amorphous sample. Meanwhile, for the first time, the peak at 50 cm-1 was observed in the crystallized sample. Similar to the peak at 135 cm-1, the peak at 50 cm-1 disappeared in the amorphous state, and its intensity increased with increasing crystallinity. The origins of the two peaks were associated with the Ph-CO-Ph-type intermolecular vibrational modes in the simulation. This suggests that the Ph-CO-Ph vibrational mode observed in the low-frequency region of PEEK was strongly influenced by the intermolecular order.

Sustained Reduction of Elevated Intact Parathyroid Hormone Concentrations with Extended-Release Calcifediol Slows Chronic Kidney Disease Progression in Secondary Hyperparathyroidism Patients.

INTRODUCTION: Chronic kidney disease (CKD) drives onerous human and healthcare costs, underscoring an urgent need to avert disease progression. Secondary hyperparathyroidism (SHPT) develops as CKD advances, and persistently elevated parathyroid hormone (PTH) may be nephrotoxic and associated with earlier dialysis onset. This study examines, for the first time, the hypothesis that sustained reduction of elevated intact PTH (iPTH) with extended-release calcifediol (ERC) reduces the nephrotoxic impact of SHPT and forestalls renal decline. METHODS: Changes in estimated glomerular filtration rate (eGFR) were analyzed post hoc in 126 adults with SHPT, stage 3-4 CKD, and low serum 25-hydroxyvitamin D (25D) treated for 1 year with ERC in pivotal trials. ERC was administered at 30 µg/day increasing, as needed, to 60 µg/day to achieve ≥30% reductions in iPTH. Calcium, phosphorus, 25D, 1,25-dihydroxyvitamin D (1,25D), iPTH, eGFR, fibroblast growth factor-23 (FGF23), bone turnover markers (BTMs), and urine albumin-to-creatinine ratio (uACR) were measured at baseline and regular intervals. Participants were categorized by achievement (or not) of sustained ≥30% iPTH reductions over the last 2 quarters of treatment to evaluate differences in eGFR decline. RESULTS: For all participants, 25D increased 58.5 ± 2.3 (SE) ng/mL (p < 0.001) by the end of treatment (EOT), 1,25D increased 10.1 ± 1.8 pg/mL (p < 0.001), iPTH decreased from 143.8 ± 5.8 pg/mL to 108.8 ± 7.2 (p < 0.001), BTMs improved (p < 0.01), and eGFR declined 2.2 ± 0.5 mL/min/1.73 m2 (p < 0.001). The rate of eGFR decline was >5-fold higher (p = 0.014) in participants who did not achieve sustained iPTH reductions of ≥30% (3.2 ± 0.7; 12.7 ± 2.2%) than in those who did (0.6 ± 0.8; 2.9 ± 2.4%). It was highest in the 30 participants who did not exhibit an iPTH lowering response in both of the last 2 quarters of treatment (5.4 ± 0.9; 20.9 ± 3.4%). Duration of iPTH reduction had no impact on safety parameters. Degree of iPTH reduction at EOT was also associated with slower CKD progression. CONCLUSION: Sustained reduction of elevated iPTH with ERC treatment was associated with slower rates of eGFR decline in patients with SHPT and stage 3-4 CKD without raising safety concerns. A prospective trial is warranted to confirm this finding.

Renal Denervation for the Treatment of Hypertension: A Scientific Statement From the American Heart Association.

Hypertension is a leading risk factor for cardiovascular morbidity and mortality. Despite the widespread availability of both pharmacological and lifestyle therapeutic options, blood pressure control rates across the globe are worsening. In fact, only 23% of individuals with high blood pressure in the United States achieve treatment goals. In 2023, the US Food and Drug Administration approved renal denervation, a catheter-based procedure that ablates the renal sympathetic nerves, as an adjunctive treatment for patients in whom lifestyle modifications and antihypertensive medications do not adequately control blood pressure. This approval followed the publication of multiple randomized clinical studies using rigorous trial designs, all incorporating renal angiogram as the sham control. Most but not all of the new generation of trials reached their primary end point, demonstrating modest efficacy of renal denervation in lowering blood pressure across a spectrum of hypertension, from mild to truly resistant. Individual patient responses vary, and further research is needed to identify those who may benefit most. The initial safety profile appears favorable, and multiple ongoing studies are assessing longer-term efficacy and safety. Multidisciplinary teams that include hypertension specialists and adequately trained proceduralists are crucial to ensure that referrals are made appropriately with full consideration of the potential risks and benefits. Incorporating patient preferences and engaging in shared decision-making conversations will help patients make the best decisions given their individual circumstances. Although further research is clearly needed, renal denervation presents a novel treatment strategy for patients with uncontrolled blood pressure.

BUILDing Engaged Mentors: Examining the Efficacy of BUILD-led Mentor Training.

The practice of mentorship is a critical focus in science, technology, engineering, mathematics, and medicine (STEMM) disciplines. This quasi-experimental study investigated the efficacy of undergraduate mentor training in biomedical sciences programs in the NIH-funded Building Infrastructure Leading to Diversity (BUILD) initiative comprised of research-rising institutions. We used data from the Higher Education Research Institute's Faculty Survey (2016-17 and 2019-20). In cross-sectional comparisons of 379 BUILD-trained faculty with 755 colleagues who were not BUILD-trained, those who participated in BUILD mentor training reported more engagement with mentees. Utilizing propensity score matching of 314 with longitudinal cases, mentoring confidence and engagement were stronger over time for BUILD-trained faculty. Findings suggest BUILD mentor training yields positive results for undergraduate mentors at research-rising institutions.

FimH-mannose noncovalent bonds survive minutes to hours under force.

The adhesin FimH is expressed by commensal Escherichia coli and is implicated in urinary tract infections, where it mediates adhesion to mannosylated glycoproteins on urinary and intestinal epithelial cells in the presence of a high-shear fluid environment. The FimH-mannose bond exhibits catch behavior in which bond lifetime increases with force, because tensile force induces a transition in FimH from a compact native to an elongated activated conformation with a higher affinity to mannose. However, the lifetime of the activated state of FimH has not been measured under force. Here we apply multiplexed magnetic tweezers to apply a preload force to activate FimH bonds with yeast mannan, then we measure the lifetime of these activated bonds under a wide range of forces above and below the preload force. A higher fraction of FimH-mannan bonds were activated above than below a critical preload force, confirming the FimH catch bond behavior. Once activated, FimH detached from mannose with multi-state kinetics, suggesting the existence of two bound states with a 20-fold difference in dissociation rates. The average lifetime of activated FimH-mannose bonds was 1000 to 10,000 s at forces of 30-70 pN. Structural explanations of the two bound states and the high force resistance provide insights into structural mechanisms for long-lived, force-resistant biomolecular interactions.

Monitoring mouse papillomavirus-associated cancer development using longitudinal Pap smear screening.

A substantial percentage of the population remains at risk for cervical cancer due to pre-existing human papillomavirus (HPV) infections, despite prophylactic vaccines. Early diagnosis and treatment are crucial for better disease outcomes. The development of new treatments heavily relies on suitable preclinical model systems. Recently, we established a mouse papillomavirus (MmuPV1) model that is relevant to HPV genital pathogenesis. In the current study, we validated the use of Papanicolaou (Pap) smears, a valuable early diagnostic tool for detecting HPV cervical cancer, to monitor disease progression in the MmuPV1 mouse model. Biweekly cervicovaginal swabs were collected from the MmuPV1-infected mice for viral DNA quantitation and cytology assessment. The Pap smear slides were evaluated for signs of epithelial cell abnormalities using the 2014 Bethesda system criteria. Tissues from the infected mice were harvested at various times post-viral infection for additional histological and virological assays. Over time, increased viral replication was consistent with higher levels of viral DNA, and it coincided with an uptick in epithelial cell abnormalities with higher severity scores noted as early as 10 weeks after viral infection. The cytological results also correlated with the histological evaluation of tissues harvested simultaneously. Both immunocompromised and immunocompetent mice with squamous cell carcinoma (SCC) cytology also developed vaginal SCCs. Notably, samples from the MmuPV1-infected mice exhibited similar cellular abnormalities compared to the corresponding human samples at similar disease stages. Hence, Pap smear screening proves to be an effective tool for the longitudinal monitoring of disease progression in the MmuPV1 mouse model. IMPORTANCE: Papanicolaou (Pap) smear has saved millions of women's lives as a valuable early screening tool for detecting human papillomavirus (HPV) cervical precancers and cancer. However, more than 200,000 women in the United States alone remain at risk for cervical cancer due to pre-existing HPV infection-induced precancers, as there are currently no effective treatments for HPV-associated precancers and cancers other than invasive procedures including a loop electrosurgical excision procedure (LEEP) to remove abnormal tissues. In the current study, we validated the use of Pap smears to monitor disease progression in our recently established mouse papillomavirus model. To the best of our knowledge, this is the first study that provides compelling evidence of applying Pap smears from cervicovaginal swabs to monitor disease progression in mice. This HPV-relevant cytology assay will enable us to develop and test novel antiviral and anti-tumor therapies using this model to eliminate HPV-associated diseases and cancers.

The effect of the level of data presentation on visual analysts' decisions.

Single-case design (SCD) is frequently utilized in research and applied settings to evaluate the effect of an intervention over time. Once collected, single-case data are typically graphed and analyzed visually in both research and practice contexts. Despite the ubiquity of visual analysis in SCD, this analytic framework has often been critiqued due to findings of limited reliability across visual analysts. Recent research has identified that the way a graph is constructed may contribute to the limitations of visual analysis. The present study sought to evaluate the effect of visually representing multiple measurement occasions as a single data point (e.g., combining measurements taken daily into a weekly composite data point) on visual analysts' decisions regarding the magnitude of an intervention effect. Eleven participants viewed identical data sets, plotted to show different numbers of measurement occasions combined as a single data point, and provided ratings regarding the magnitude of intervention effect depicted within the graph. Results indicated a significant main effect, with data sets with higher levels of data combination being rated as demonstrating significantly larger intervention effects. The results of the study provide additional support for standardization of data presentation and graph construction within SCD in both research and practice contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Centering students' voices in the exploration of in-classroom culturally responsive practices.

Scholars have developed culturally responsive frameworks and interventions to support educators as they aim to create inclusive and equitable classroom environments. Despite the number of frameworks on the topic, research on culturally responsive practices (CRPs) is limited by the lack of clear definitions or evidence on the effectiveness of in-classroom culturally responsive interventions. With the aim to understand which characteristics are important for in-classroom CRPs, this qualitative study explored students' perceptions of practices teachers use to respond to students' learning and cultural identities. We conducted 23 focus groups with 103 Black, Latine, and White students in middle and high school from two midwestern schools. After analyzing the data, we identified four overarching themes: (a) inclusive classroom instruction, (b) emotional safety in the classroom, (c) relational quality with the teachers, and (d) racism and other "isms" in the classroom. Students consistently commented on the importance of teacher support for students' emotional and academic well-being while also describing teachers that demeaned them or their peers, in turn, obstructing their learning. The findings hold promise to clarify and strengthen professional development CRP interventions as students offer insight about teacher cultural responsiveness and non-responsiveness.

Positive student-teacher relationships and exclusionary discipline practices.

Teacher-student relationships are beneficial for students and especially important in the middle school context. Suspensions are critical to reduce as it can be detrimental to the educational trajectory of students, particularly for marginalized students in underfunded schools. This study looked at the relations between teacher-student relationships and suspensions across the academic year in a sample of students (N = 541) and teachers (N = 51) in two urban school districts in the Midwest. A brief measure of teachers' perceptions of relationships with students completed in the fall of the academic year predicted the odds of receiving in-school suspension (ISS; odds ratio [OR] = 0.65) and out-of-school suspension (OSS; OR = 0.72) by the end of the school year. Student reports of the relationships were also associated with ISS (OR = 0.94), but not OSS. On average, teachers' report on the scale improved over the course of the school year (d = 0.11); however, student report of the relationships worsened (d = 0.30). The difference in the student report of the relationships from fall to spring was also associated with the odds of receiving ISS and OSS (ORs = 0.94). These findings suggest that student and teacher perceptions together are associated with harsh discipline practices that can negatively impact students' developmental trajectories. Relationships can change but direct action is necessary to develop, maintain, and repair relationships during the academic year.