Building A Comprehensive, Longitudinal Dataset to Advance Research on the Efficacy of State-Level Anti-bullying Legislation: 1999 to 2017.

Bullying is one of the most common forms of youth violence and is associated with myriad adverse consequences over the life course. There has been increasing interest in examining whether anti-bullying legislation is effective in preventing bullying victimization and its negative effects. However, a lack of data structures that comprehensively and longitudinally assess anti-bullying legislation and its provisions has hampered this effort. We provide 18 years of data (1999-2017) on anti-bullying legislation and amendments across 50 U.S. states and the District of Columbia, which we are making publicly available at LawAtlas.org. This article describes how the legal content analysis was conducted, provides information on the reliability of the coding, and details provisions of the legislation that were coded, such as funding provisions and enumerated groups (a total of 122 individual codes are provided). Over 90% of states had at least one amendment to their legislation during this 18-year period (range: 0-22; Mean = 6.1), highlighting both the evolving content of anti-bullying statutes and the importance of tracking these changes with longitudinal data. Additionally, we offer illustrative examples of the kinds of research questions that might be pursued with these new data. For instance, using survival analyses, we show that a variety of state characteristics (e.g., political leaning of state legislatures) predict time to adoption of key provisions of anti-bullying legislation (e.g., the comprehensiveness of legal provisions). Finally, we end with a discussion of how the dataset might be used in future research on the efficacy of anti-bullying legislation.

Trends in US State Public Health Emergency Laws, 2021-2022.

Objectives. To identify and categorize US state legislation introduced between January 1, 2021, and May 20, 2022, that addresses emergency health authority. Methods. We adapted standard policy surveillance methods to collect and code state bills and enacted laws limiting or expanding the emergency public health authority of state and local officials and agencies. Results. State legislators introduced 1531 bills addressing public health authority; 191 of those were enacted in 43 states and the District of Columbia, including 17 expanding and 65 contracting emergency authority, 163 regulating use, and 30 preempting local use of specific measures such as mask mandates. Conclusions. State laws setting the scope and limits of emergency authority are crucial to effective public health response. These laws are changing in ways that threaten to reduce response capacity. Tracking changes in health law infrastructure is important for evaluating changes in health authority and ensuring that stakeholders recognize these changes. Public Health Implications. The COVID-19 pandemic called for quick, decisive action to limit infections, and when the next outbreak hits, new laws limiting health authority will make such action even more difficult. (Am J Public Health. 2023;113(3):288-296. https://doi.org/10.2105/10.2105/AJPH.2022.307214).

Creating Compassion: Using Art for Empathy Learning with Urban Youth.

Social-emotional learning (SEL) curricula are being increasingly implemented with young children; however, access to comprehensive programs can be prohibitive for programs limited by finances, time, or other factors. This article describes an exploratory case study that investigates the use of creative activity in the direct promotion of empathy and indirect promotion of other social-emotional skills for early elementary children in an urban-based after-school setting. A novel curriculum, Creating Compassion, which combines art engagement with explicit behavioral instruction, serves as a promising avenue for social-emotional skill development, and has particular importance for children from low-income households. Five children from racially minoritized backgrounds in grades kindergarten and first attended the Creating Compassion group intervention. Group-level data and individual data of direct behavior ratings suggested a modest increase in empathy development, responsible decision-making, and self-management skills and thereby provide a preliminary basis for further effectiveness investigation. Suggestions for future research in this area are discussed in addition to social justice implications.

Education in the Time of COVID: At-a-Distance Training in Neuromusculoskeletal Ultrasonography.

Point of care ultrasound is important to the specialty of physical medicine and rehabilitation (PM&R) to aid in the diagnosis and treatment of a variety of neuromusculoskeletal conditions commonly seen in practice. However, across Canada, resident education of sonoanatomy skills is variable. There remain no standards in terms of how ultrasound is taught as part of the residency curriculum as set by the Royal College of Physicians and Surgeons of Canada. As such, residents are often required to find their own educational opportunities. This report describes an alternative approach to learning these skills that was inspired by disruption due to coronavirus disease 2019 in first year residency. This report explores how a PM&R resident was able to develop valuable ultrasound skills from home using not only textbooks and videos, but also new and novel teleguidance technology, namely an ultrasound probe that connects to a clinician's own smart devices to display images.

Trends Over Time and Jurisdiction Variability in Supplemental Security Income and State Supplementary Payment Programs for Children With Disabilities.

CONTEXT: Nearly 1.2 million children with disabilities received federally administered Supplemental Security Income (SSI) payments in 2017. Based on a robust review of research and evaluation evidence and microsimulations, The National Academies of Sciences, Engineering, and Medicine committee identified modifications to SSI (ie, increasing the federal SSI benefit maximum by one-third or two-thirds) as 1 of 10 strategies that could reduce the US child poverty rate, improving child health and well-being on a population level. OBJECTIVE: Describing the availability and amount of SSI and State Supplementary Payment (SSP) program benefits to support families of children with disabilities may be a first step toward evaluating The National Academies of Sciences, Engineering, and Medicine-proposed modification to SSI as a potential poverty alleviation and health improvement tool for children with disabilities and their families. DESIGN: We used public health law research methods to characterize the laws (statutes and state agency regulations) governing the federal SSI program and SSP programs in the 50 states and District of Columbia from January 1, 1996, through November 1, 2018. RESULTS: The number of jurisdictions offering supplementary payments (SSP) was relatively stable between 1996 and 2018. In 2018, 23 US jurisdictions legally mandated that SSP programs were available for children. Among the states with SSP payment amounts in their codified laws, SSP monthly benefit amounts ranged from $8 to $64.35 in 1996 and $3.13 to $60.43 in 2018. CONCLUSION: Our initial exploration of SSI-related policies as a tool for improving the economic stability of children with disabilities and their families suggests that current SSPs, in combination with SSI, would not rise to the level of SSI increases proposed by The National Academies of Sciences, Engineering, and Medicine. Understanding more about how SSI and SSP reach children and work in combination with other federal and state income security programs may help identify policies and strategies that better support children with disabilities in low-income households.

Confronting the opioid epidemic: public opinion toward the expansion of treatment services in Virginia.

BACKGROUND: Public opinion polls have consistently shown Americans prefer treatment over arrest policies for opioid users. As the opioid epidemic remains a major health problem in the United States, it is important to determine the type of treatment policies the public would support. Theoretically, government should take into consideration the opinion of its constituents when deciding how to act. As such, the 2018 Virginia Commonwealth Public Policy Poll determined levels of support for the expansion of community-based treatment in one's community. RESULTS: Overall, the results showed 80% of Virginians (n = 788) supported the expansion of community-based treatment centers in their neighborhood, 69% supported the use of housing in their community, while less than half supported the provision of clean needles to IV drug users so they do not use dirty needles that could spread infection. Multivariate analyses revealed education, sex, and political party affiliation are significant factors in predicting support for the expansion of services. CONCLUSIONS: Given the lack of progress made by the government in reducing the supply and demand of drugs over the course of the war on drugs, it is time to move away from punitive policies to responsible and pragmatic approaches that include the expansion of community-based treatment.

What is the Fracture Risk in Patients at a Multidisciplinary Neuromuscular Clinic?

Many neuromuscular diseases (NMD) result in muscle weakness, immobility and greater fracture risk. The objective of this study is to determine the fracture risk of adult patients at a multidisciplinary NMD clinic. Fracture risk was calculated using the Fracture Risk Assessment Tool, the presence of osteoporosis was quantified using bone densitometry and contributing co-morbidities were screened through serum markers. Of the 36 patients studied, 47% were found to be of moderate and high fracture risk. Two thirds of these patients had not been previously screened or treated for osteoporosis. These findings suggest that NMD patients warrant routine screening for osteoporosis and early treatment to reduce fragility fracture.

Enhanced targeting of CML stem and progenitor cells by inhibition of porcupine acyltransferase in combination with TKI.

Tyrosine kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) has limited efficacy against leukemia stem cells (LSC) responsible for disease propagation, and most CML patients require continued TKI treatment to maintain remission. LSC maintenance is related, at least in part, to signals from the bone marrow microenvironment (BMM). Our previous studies have shown that Wnt signaling from the BMM contributes to preservation of CML LSC following TKI treatment. Secretion of Wnt ligands requires their modification by the O-acyl transferase Porcupine (PORCN). Here we investigated the activity of a potent and selective PORCN inhibitor, WNT974, against CML stem and progenitor cells. WNT974 efficiently antagonized Wnt signaling in human CML CD34+ cells, and in combination with the TKI nilotinib (NIL) significantly enhanced inhibition of proliferation and colony-forming potential of CML stem and progenitor cells and reduced their growth in immunodeficient mice in vivo, in comparison with NIL alone. Treatment of transgenic CML mice in vivo with NIL in combination with WNT974 significantly reduced leukemic stem and progenitor cell numbers, reduced regeneration of leukemic long-term hematopoietic stem cells in secondary transplant recipients, and enhanced survival of mice after discontinuation of treatment, in comparison with NIL alone. CML progenitors demonstrated enhanced sensitivity to Wnt stimulation, associated with increased expression of the FZD4 receptor. FZD4 knockdown inhibited CML progenitor growth. These results support further investigation of PORCN targeting to inhibit Wnt secretion and signaling and enhance targeting of CML stem cells while sparing their normal counterparts.

The different faces of impulsivity as links between childhood maltreatment and young adult crime.

Crime is a major public health and safety threat. Many studies have suggested that early exposure to child maltreatment increases an individual's risk for persistent serious crime in adulthood. Despite these findings about the connection between child maltreatment and criminal behavior, there is a paucity of empirically-based knowledge about the processes or pathways that link child maltreatment to later involvement in crime. Using a community sample of 337 young adults (ages 18-25) in a U.S. metropolitan area, the present study examined the role of various facets of impulsivity in linking child maltreatment to crime. A series of factor analyses identified three types of crime including property crime, violent crime, and fraud. Structural equation modelings were conducted to examine the associations among childhood maltreatment, four facets of impulsivity, and criminal behavior, controlling for sociodemographic information, family income and psychological symptoms. The present study found that child emotional abuse was indirectly related to property crime and fraud through urgency while a lack of premeditation mediates the relationship between child neglect and property crime. Child physical abuse was directly related to all three types of crime. Personality traits of urgency and lack of premeditation may play a significant role in the maltreatment-crime link. Preventive interventions targeting impulsivity traits such as urgency and a lack of premeditation might have promising impacts in curbing criminal behavior among maltreatment victims.

Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients.

INTRODUCTION: Several studies have indicated that autoimmune and neuroinflammatory processes contribute to the neurodegeneration of retinal ganglion cells in human glaucoma patients and in animal models. To test the involvement of cellular immune processes in the pathophysiology of retinal ganglion cell degeneration in vivo, we carried out adoptive transfer experiments from two independent genetic mouse models of glaucoma into normal recipient mice. RESULTS: Our findings indicate that transfer results in a progressive loss of retinal ganglion cells and their axons despite normal intraocular pressure in recipient mice. Signs of pan-retinal inflammation were not detected. Similar findings were obtained following transfer of isolated T-lymphocytes, but not after transfer of splenocytes from immune deficient glaucomatous mice. Transferred lymphocytes were detected integrated in the spleen and in the retinal ganglion cell layer of recipient animals, albeit at very low frequencies. Furthermore, we observed cell-cell interaction between transferred T-cells and recipient microglia along with focal microglial activation in recipient eyes. CONCLUSION: This study demonstrates that the pathophysiology of glaucomatous degeneration in the tested animal models includes T-cell mediated events that are capable of causing loss of healthy retinal ganglion cells.

Olfactory Orientation and Navigation in Humans.

Although predicted by theory, there is no direct evidence that an animal can define an arbitrary location in space as a coordinate location on an odor grid. Here we show that humans can do so. Using a spatial match-to-sample procedure, humans were led to a random location within a room diffused with two odors. After brief sampling and spatial disorientation, they had to return to this location. Over three conditions, participants had access to different sensory stimuli: olfactory only, visual only, and a final control condition with no olfactory, visual, or auditory stimuli. Humans located the target with higher accuracy in the olfaction-only condition than in the control condition and showed higher accuracy than chance. Thus a mechanism long proposed for the homing pigeon, the ability to define a location on a map constructed from chemical stimuli, may also be a navigational mechanism used by humans.

Modeling the impact of restoration efforts on phosphorus loading and transport through Everglades National Park, FL, USA.

Ecosystems of Florida Everglades are highly sensitive to phosphorus loading. Future restoration efforts, which focus on restoring Everglades water flows, may pose a threat to the health of these ecosystems. To determine the fate and transport of total phosphorus and evaluate proposed Everglades restoration, a water quality model has been developed using the hydrodynamic results from the M3ENP (Mike Marsh Model of Everglades National Park)--a physically-based hydrological numerical model which uses MIKE SHE/MIKE 11 software. Using advection-dispersion with reactive transport for the model, parameters were optimized and phosphorus loading in the overland water column was modeled with good accuracy (60%). The calibrated M3ENP-AD model was then modified to include future bridge construction and canal water level changes, which have shown to increase flows into ENP. These bridge additions increased total dissolved phosphorus (TP) load downstream in Shark Slough and decreased TP load in downstream Taylor Slough. However, there was a general decrease in TP concentration and TP mass per area over the entire model domain. The M3ENP-AD model has determined the mechanisms for TP transport and quantified the impacts of ENP restoration efforts on the spatial-temporal distribution of phosphorus transport. This tool can be used to guide future Everglades restoration decisions.

Induction of trabecular meshwork cells from induced pluripotent stem cells.

PURPOSE: Loss or dysfunction of trabecular meshwork (TM) cells has been associated with the development of pathologically elevated IOP, and it is conceivable that replacement of damaged TM cells could restore function to the TM. We propose that the use of TM-like cells derived from induced pluripotent stem cells (iPSCs) created from a patient's own dermal fibroblasts offers the best solution to this challenge. Here we demonstrate that mouse iPSCs can be induced to differentiate into TM-like cells suitable for autologous transplantation. METHODS: Directed induction of stem cell differentiation was achieved through coculture of mouse iPSCs with human TM cells for up to 21 days. The resultant TM-like cells (iPSC-TM) were characterized morphologically, immunohistochemically, and functionally. RESULTS: The iPSC-TM cells closely resembled cultured human TM cells morphologically and began to express many markers of TM cells while ceasing to express pluripotency markers such as Nanog, Oct4, and Sox2. Functionally, these cells developed the ability to phagocytose particles. Finally, exposure to dexamethasone or phorbol 12-myristate acetate caused a distinct increase in the production and secretion of myocilin and matrix metalloproteinase-3, respectively, behavior characteristic of TM cells. CONCLUSIONS: Our data demonstrate that iPSCs can be induced to assume a phenotype that resembles native TM cells in many important aspects. Not only do these cells represent a valuable research tool, but transplantation into glaucomatous eyes with elevated IOP may also restore function to the TM, resulting in re-establishment of IOP.

JAK2/STAT5 inhibition by nilotinib with ruxolitinib contributes to the elimination of CML CD34+ cells in vitro and in vivo.

Chronic myeloid leukemia (CML) stem cell survival is not dependent on BCR-ABL protein kinase and treatment with ABL tyrosine kinase inhibitors cures only a minority of CML patients, thus highlighting the need for novel therapeutic targets. The Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)5 pathway has recently been explored for providing putative survival signals to CML stem/progenitor cells (SPCs) with contradictory results. We investigated the role of this pathway using the JAK2 inhibitor, ruxolitinib (RUX). We demonstrated that the combination of RUX, at clinically achievable concentrations, with the specific and potent tyrosine kinase inhibitor nilotinib, reduced the activity of the JAK2/STAT5 pathway in vitro relative to either single agent alone. These effects correlated with increased apoptosis of CML SPCs in vitro and a reduction in primitive quiescent CML stem cells, including NOD.Cg-Prkdc(scid) IL2rg(tm1Wjl) /SzJ mice repopulating cells, induced by combination treatment. A degree of toxicity toward normal SPCs was observed with the combination treatment, although this related to mature B-cell engraftment in NOD.Cg-Prkdc(scid) IL2rg(tm1Wjl) /SzJ mice with minimal effects on primitive CD34(+) cells. These results support the JAK2/STAT5 pathway as a relevant therapeutic target in CML SPCs and endorse the current use of nilotinib in combination with RUX in clinical trials to eradicate persistent disease in CML patients.

Identification of genetic loci associated with primary angle-closure glaucoma in the basset hound.

PURPOSE: Primary angle-closure glaucoma (PACG) in dogs is usually caused by the gradual collapse of the iridocorneal angle and cleft, eventually leading to aqueous humor (AH) outflow obstruction. The condition occurs in several breeds of dogs and the prognosis for affected animals is typically poor. We have identified several basset hound (BH) pedigrees, as well as unrelated cases with characteristic PACG that in many aspects recapitulates PACG in human patients. The goal of this study was to utilize the BH PACG model to characterize the genetics of PACG, and potentially discover genetic factors contributing to PACG in humans and animals. METHODS: We conducted a genome-wide logistic regression test for association using 37 PACG cases and 41 unaffected controls. Population stratification and cryptic relatedness were assessed using a multidimensional scaling analysis. The expression of two candidate genes within the target tissues of the BH eye was assessed by immunohistochemistry. RESULTS: We report significant associations at two novel loci, specifically BICF2P31912 in COL1A2 on chromosome 14 with a per-allele odds ratio (OR, 95% confidence interval [CI]) of 3.35 (1.73-6.51), P(genome)=3.6×10⁻4; and BICF2P893476 residing in proximity to RAB22A on chromosome 24 with a per-allele OR (95% CI) of 3.93 (1.78-8.66), P(genome)=4.9×10⁻4. COL1A2 and RAB22A demonstrated widespread expression throughout the eye and were prominently noted in the ciliary body (CB), trabecular meshwork (TM), and iris. CONCLUSIONS: Our finding of two genetic associations supports the potential segregation of PACG risk-conferring variants in the BH. The genetic associations identified may contribute to mechanisms underlying the pathogenesis of PACG, which remain to be elucidated.

Role of altered growth factor receptor-mediated JAK2 signaling in growth and maintenance of human acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) is sustained by small populations of leukemia stem cells (LSCs) that can resist available treatments and represent important barriers to cure. Although previous studies have shown increased signal transducer and activator of transcription (STAT)3 and STAT5 phosphorylation in AML leukemic blasts, the role of Janus kinase (JAK) signaling in primary AML compared with normal stem cells has not been directly evaluated. We show here that JAK/STAT signaling is increased in LSCs, particularly from high-risk AML. JAK2 inhibition using small molecule inhibitors or interference RNA reduced growth of AML LSCs while sparing normal stem cells both in vitro and in vivo. Increased JAK/STAT activity was associated with increased expression and altered signaling through growth factor receptors in AML LSCs, including receptor tyrosine kinase c-KIT and FMS-related tyrosine kinase 3 (FLT3). Inhibition of c-KIT and FLT3 expression significantly inhibited JAK/STAT signaling in AML LSCs, and JAK inhibitors effectively inhibited FLT3-mutated AML LSCs. Our results indicate that JAK/STAT signaling represents an important signaling mechanism supporting AML LSC growth and survival. These studies support continued evaluation of strategies for JAK/STAT inhibition for therapeutic targeting of AML LSCs.

My owner, right or wrong: the effect of familiarity on the domestic dog's behavior in a food-choice task.

Dogs are strongly influenced by human behavior, and they readily form bonds with specific humans. Yet these lines of inquiry are not often combined. The goal of this study was to investigate whether such bonds would play a role in how dogs behave in response to human signals. Using various types of signals, we compared dogs' use of information from a familiar human (their owner) versus an unfamiliar human when choosing between two food containers. In some conditions, the owner indicated a container that gave food and a stranger indicated a container that did not; in other conditions, this was reversed. Dogs more often chose the container indicated by or nearest to their owner, even when this container never yielded a food reward. In two conditions, dogs chose at chance: a control condition in which both pointers were strangers and a condition in which the owner and stranger sat reading books and provided no social signal. This is the first study to directly compare owners to strangers in a single food-choice situation. Our results suggest that dogs make decisions by attending preferentially to social signals from humans with whom they have become familiar.

Lack of immunoglobulins does not prevent C1q binding to RGC and does not alter the progression of experimental glaucoma.

PURPOSE: The degeneration of retinal ganglion cells (RGC) in the glaucomatous retina is accompanied by activation of the classical complement cascade. The purpose of this study was to evaluate whether complement component C1q binding and activation of the complement cascade in the glaucomatous retina requires the presence of immunoglobulins. METHODS: Experimental glaucoma was induced in normal mice and those carrying a targeted deletion of the RAG1 gene. Binding of C1q to RGC and accumulation of C3 and C5b-9 was investigated using immunohistochemical and proteomic approaches. Damage to the optic nerve and RGC was determined and compared between the two strains. Complement activation and accumulation were also evaluated in vitro using dissociated retinal cell cultures. RESULTS: C1q was detected in the RGC layer in both RAG1(-/-) and control mice with elevated IOP, but not in mice with normal IOP. Proteomic analysis of retinal membrane fractions indicated that C1q and C3 are membrane bound to a similar degree in RAG1(-/-) and control mice with elevated IOP. The absence of Ig does not affect the rate of axonal damage or RGC loss. Furthermore, cultured RGC maintained in serum-free media are also C1q and C3 immunoreactive, demonstrating that Ig is not required for C1q binding to damaged RGC. CONCLUSIONS: Our data demonstrate that lack of immunoglobulins and mature T/B cells does not influence the progression of glaucoma. Furthermore, immunoglobulins do not appear to be required for C1q binding and complement cascade activation on damaged RGC. These findings suggest that C1q recognizes an alternative binding partner expressed by stressed RGC.