Transcription factors interact with RNA to regulate genes.

Transcription factors (TFs) orchestrate the gene expression programs that define each cell's identity. The canonical TF accomplishes this with two domains, one that binds specific DNA sequences and the other that binds protein coactivators or corepressors. We find that at least half of TFs also bind RNA, doing so through a previously unrecognized domain with sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat. RNA binding contributes to TF function by promoting the dynamic association between DNA, RNA, and TF on chromatin. TF-RNA interactions are a conserved feature important for vertebrate development and disrupted in disease. We propose that the ability to bind DNA, RNA, and protein is a general property of many TFs and is fundamental to their gene regulatory function.

Groundwater is a hidden global keystone ecosystem.

Groundwater is a vital ecosystem of the global water cycle, hosting unique biodiversity and providing essential services to societies. Despite being the largest unfrozen freshwater resource, in a period of depletion by extraction and pollution, groundwater environments have been repeatedly overlooked in global biodiversity conservation agendas. Disregarding the importance of groundwater as an ecosystem ignores its critical role in preserving surface biomes. To foster timely global conservation of groundwater, we propose elevating the concept of keystone species into the realm of ecosystems, claiming groundwater as a keystone ecosystem that influences the integrity of many dependent ecosystems. Our global analysis shows that over half of land surface areas (52.6%) has a medium-to-high interaction with groundwater, reaching up to 74.9% when deserts and high mountains are excluded. We postulate that the intrinsic transboundary features of groundwater are critical for shifting perspectives towards more holistic approaches in aquatic ecology and beyond. Furthermore, we propose eight key themes to develop a science-policy integrated groundwater conservation agenda. Given ecosystems above and below the ground intersect at many levels, considering groundwater as an essential component of planetary health is pivotal to reduce biodiversity loss and buffer against climate change.

Comapping Cellular Content and Extracellular Matrix with Hemodynamics in Intact Arterial Tissues Using Scanning Immunofluorescent Multiphoton Microscopy.

Deviation of blood flow from an optimal range is known to be associated with the initiation and progression of vascular pathologies. Important open questions remain about how the abnormal flow drives specific wall changes in pathologies such as cerebral aneurysms where the flow is highly heterogeneous and complex. This knowledge gap precludes the clinical use of readily available flow data to predict outcomes and improve treatment of these diseases. As both flow and the pathological wall changes are spatially heterogeneous, a crucial requirement for progress in this area is a methodology for acquiring and comapping local vascular wall biology data with local hemodynamic data. Here, we developed an imaging pipeline to address this pressing need. A protocol that employs scanning multiphoton microscopy was developed to obtain three-dimensional (3D) datasets for smooth muscle actin, collagen, and elastin in intact vascular specimens. A cluster analysis was introduced to objectively categorize the smooth muscle cells (SMC) across the vascular specimen based on SMC actin density. Finally, direct quantitative comparison of local flow and wall biology in 3D intact specimens was achieved by comapping both heterogeneous SMC data and wall thickness to patient-specific hemodynamic results.

Intermediate Levels of Predation and Nutrient Enrichment Enhance the Activity of Ibuprofen-Degrading Bacteria.

Water is the most indispensable natural resource; yet, organic pollution of freshwater sources is widespread. In recent years, there has been increasing concern over the vast array of emerging organic contaminants (EOCs) in the effluent of wastewater treatment plants (WWTPs). Several of these EOCs are degraded within the pore space of riverbeds by active microbial consortia. However, the mechanisms behind this ecosystem service are largely unknown. Here, we report how phosphate concentration and predator-prey interactions drive the capacity of bacteria to process a model EOC (ibuprofen). The presence of phosphate had a significant positive effect on the population growth rate of an ibuprofen-degrading strain. Thus, when phosphate was present, ibuprofen removal efficiency increased. Moreover, low and medium levels of predation, by a ciliated protozoan, stimulated bacterial population growth. This unimodal effect of predation was lost under high phosphate concentration, resulting in the flattening of the relationships between predator density and population growth of ibuprofen degraders. Our results suggest that moderate nutrient and predation levels promote the growth rate of bacterial degraders and, consequently, the self-purifying capability of the system. These findings enhance our understanding of the mechanisms by which riverbed communities drive the processing of EOCs.

CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation.

Hematopoietic stem and progenitor cell (HSPC) formation and lineage differentiation involve gene expression programs orchestrated by transcription factors and epigenetic regulators. Genetic disruption of the chromatin remodeler chromodomain-helicase-DNA-binding protein 7 (CHD7) expanded phenotypic HSPCs, erythroid, and myeloid lineages in zebrafish and mouse embryos. CHD7 acts to suppress hematopoietic differentiation. Binding motifs for RUNX and other hematopoietic transcription factors are enriched at sites occupied by CHD7, and decreased RUNX1 occupancy correlated with loss of CHD7 localization. CHD7 physically interacts with RUNX1 and suppresses RUNX1-induced expansion of HSPCs during development through modulation of RUNX1 activity. Consequently, the RUNX1:CHD7 axis provides proper timing and function of HSPCs as they emerge during hematopoietic development or mature in adults, representing a distinct and evolutionarily conserved control mechanism to ensure accurate hematopoietic lineage differentiation.

Predicting regression of cervical intraepithelial neoplasia grade 2 in women under 25 years.

BACKGROUND: A number of retrospective and prospective studies have documented substantial rates of regression in cervical intraepithelial neoplasia grade 2 lesions in young women. Initial observational management of cervical intraepithelial neoplasia grade 2 is increasingly accepted as appropriate for women under 25 years of age with screen-detected abnormalities and is included in a number of clinical guidelines. However, there has been a paucity of large prospective studies on observational management with strict inclusion criteria. A number of important questions remain, specifically regarding the clinical variables that are associated with the risk of progression or persistence of disease. To investigate these factors and to ensure that young women with cervical intraepithelial neoplasia grade 2 undergoing observational management were being managed in a well-monitored and an appropriately informed fashion, we conducted a large, multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 in women under 25 years. OBJECTIVE: This study aimed to determine the regression rates and clinical, cytologic, and pathologic predictors of regression of cervical intraepithelial neoplasia grade 2 in women under 25 years undergoing observational management over 24 months. STUDY DESIGN: This study was a multicenter prospective study on observational management of cervical intraepithelial neoplasia grade 2 (ie, repeat colposcopy, cytology, and cervical biopsy every 6 months) for up to 24 months. A total of 615 consenting women under 25 years with newly-diagnosed, biopsy-proven cervical intraepithelial neoplasia grade 2 were recruited (from 2010 to 2016) through 16 hospital-based colposcopy units in New Zealand and Australia. RESULTS: At completion, 326 women had confirmed regression, 156 had persistent high-grade cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ, and 24 had unconfirmed regression (ie, first regression at the 24-month follow-up). A total of 109 women did not complete the protocol (41 because of delayed follow-up, 41 lost to follow-up, 22 elected treatment, 4 refused a biopsy, and 1 died of an unrelated cause). Confirmed regression was observed in 53% (326 of 615) of all women enrolled in the study and, when missing data were imputed, it was estimated that 64% of women (95% confidence interval, 60%-68%) would have experienced regression. Similarly, lesions regressed in 64% (326 of 506) of women who completed the observational protocol. Based on a multivariable analysis, detection of human papillomavirus 16 in a liquid-based cytology sample at the time of initial colposcopy decreased the chance of regression by 31% (risk ratio, 0.69; 95% confidence interval, 0.56-0.86; P<.001). In addition, at initial colposcopy, low-grade or normal colposcopic impression, later year of diagnosis, low-grade or normal cytology, and being a nonsmoker were all independently associated with an increased chance of regression. CONCLUSION: More than half of women under 25 years with cervical intraepithelial neoplasia grade 2 will regress to cervical intraepithelial neoplasia grade 1 or normal within 24 months without destructive treatment. The absence of human papillomavirus 16 is the most important predictor of regression.

Specific oxylipins enhance vertebrate hematopoiesis via the receptor GPR132.

Epoxyeicosatrienoic acids (EETs) are lipid-derived signaling molecules with cardioprotective and vasodilatory actions. We recently showed that 11,12-EET enhances hematopoietic induction and engraftment in mice and zebrafish. EETs are known to signal via G protein-coupled receptors, with evidence supporting the existence of a specific high-affinity receptor. Identification of a hematopoietic-specific EET receptor would enable genetic interrogation of EET signaling pathways, and perhaps clinical use of this molecule. We developed a bioinformatic approach to identify an EET receptor based on the expression of G protein-coupled receptors in cell lines with differential responses to EETs. We found 10 candidate EET receptors that are expressed in three EET-responsive cell lines, but not expressed in an EET-unresponsive line. Of these, only recombinant GPR132 showed EET-responsiveness in vitro, using a luminescence-based ß-arrestin recruitment assay. Knockdown of zebrafish gpr132b prevented EET-induced hematopoiesis, and marrow from GPR132 knockout mice showed decreased long-term engraftment capability. In contrast to high-affinity EET receptors, GPR132 is reported to respond to additional hydroxy-fatty acids in vitro, and we found that these same hydroxy-fatty acids enhance hematopoiesis in the zebrafish. We conducted structure-activity relationship analyses using both cell culture and zebrafish assays on diverse medium-chain fatty acids. Certain oxygenated, unsaturated free fatty acids showed high activation of GPR132, whereas unoxygenated or saturated fatty acids had lower activity. Absence of the carbon-1 position carboxylic acid prevented activity, suggesting that this moiety is required for receptor activation. GPR132 responds to a select panel of oxygenated polyunsaturated fatty acids to enhance both embryonic and adult hematopoiesis.

Calcification in Human Intracranial Aneurysms Is Highly Prevalent and Displays Both Atherosclerotic and Nonatherosclerotic Types.

OBJECTIVE: Although the clinical and biological importance of calcification is well recognized for the extracerebral vasculature, its role in cerebral vascular disease, particularly, intracranial aneurysms (IAs), remains poorly understood. Extracerebrally, 2 distinct mechanisms drive calcification, a nonatherosclerotic, rapid mineralization in the media and a slower, inflammation driven, atherosclerotic mechanism in the intima. This study aims to determine the prevalence, distribution, and type (atherosclerotic, nonatherosclerotic) of calcification in IAs and assess differences in occurrence between ruptured and unruptured IAs. Approach and Results: Sixty-five 65 IA specimens (48 unruptured, 17 ruptured) were resected perioperatively. Calcification and lipid pools were analyzed nondestructively in intact samples using high resolution (0.35 µm) microcomputed tomography. Calcification is highly prevalent (78%) appearing as micro (<500 µm), meso (500 µm-1 mm), and macro (>1 mm) calcifications. Calcification manifests in IAs as both nonatherosclerotic (calcification distinct from lipid pools) and atherosclerotic (calcification in the presence of lipid pools) with 3 wall types: Type I-only calcification, no lipid pools (20/51, 39%), Type II-calcification and lipid pools, not colocalized (19/51, 37%), Type III-calcification colocalized with lipid pools (12/51, 24%). Ruptured IAs either had no calcifications or had nonatherosclerotic micro- or meso-calcifications (Type I or II), without macro-calcifications. CONCLUSIONS: Calcification in IAs is substantially more prevalent than previously reported and presents as both nonatherosclerotic and atherosclerotic types. Notably, ruptured aneurysms had only nonatherosclerotic calcification, had significantly lower calcification fraction, and did not contain macrocalcifications. Improved understanding of the role of calcification in IA pathology should lead to new therapeutic targets.

Studies on gas exchange in the meadow spittlebug, Philaenus spumarius: the metabolic cost of feeding on, and living in, xylem sap.

Spittlebugs (superfamily Cercopoidea) live within a mass of frothy, spittle-like foam that is produced as a by-product of their xylem-feeding habits. The wet spittle represents a unique respiratory environment for an insect, potentially acting either as a reserve of trapped oxygen (O2) or as a significant barrier to O2 diffusion from the surrounding atmosphere. Feeding on xylem sap under tension is also assumed to be energetically expensive, potentially placing further constraints on their gas exchange. To understand the respiratory strategies used by spittlebugs, this study measured the PO2  within the spittle of the meadow spittlebug, Philaenus spumarius, as well as the non-feeding metabolic rate (RMR) and respiratory quotient (RQ) of both nymphs and adults. The metabolic rate of nymphs feeding on xylem was also measured. In separate experiments, the ability of a nymph to obtain O2 from bubbles while submerged in foam was determined using a glass microscope slide coated in an O2-sensitive fluorophore. We determined that P. spumarius breathes atmospheric O2 by extending the tip of its abdomen outside of its spittle, rather than respiring the O2 trapped in air bubbles within the foam. However, spittlebugs can temporarily use these air bubbles to breathe when forcibly submerged. V̇O2  and V̇CO2  did not differ statistically within life stages, giving a RQ of 0.92 for nymphs and 0.95 for adults. Feeding on xylem was found to increase the nymphs' V̇CO2  by only 20% above their RMR. From this cost of feeding, cibarial pump pressures were estimated to be between -0.05 and -0.26 MPa.

Comparing biotic drivers of litter breakdown across stream compartments.

Litter breakdown in the streambed is an important pathway in organic carbon cycling and energy transfer in the biosphere that is mediated by a wide range of streambed organisms. However, most research on litter breakdown to date has focused on a small fraction of the taxa that drive it (e.g. microbial vs. macroinvertebrate-mediated breakdown) and has been limited to the benthic zone (BZ). Despite the importance of the hyporheic zone (HZ) as a bioreactor, little is known about what, or who, mediates litter breakdown in this compartment and whether breakdown rates differ between the BZ and HZ. Here, we explore the relationship between litter breakdown and the variation in community structure of benthic and hyporheic communities by deploying two standardized bioassays (cotton strips and two types of commercially available tea bags) in 30 UK streams that encompass a range of environmental conditions. Then, we modelled these assays as a response of the streambed compartment and the biological features of the streambed assemblage (Prokaryota, Protozoa and Eumetazoa invertebrates) to understand the generality and efficiency of litter processing across communities. Litter breakdown was much faster in the BZ compared with the HZ (around 5 times higher for cotton strips and 1.5 times faster for the tea leaves). However, differences in litter breakdown between the BZ and the HZ were mediated by the biological features of the benthos and the hyporheos. Biomass of all the studied biotic groups, α-diversity of Eumetazoa invertebrates and metabolic diversity of Prokaryota were important predictors that were positively related to breakdown coefficients demonstrating their importance in the functioning of the streambed ecosystem. Our study uses a novel multimetric bioassay that is able to disentangle the contribution by Prokaryota, Protozoa and Eumetazoa invertebrates to litter breakdown. In doing so, our study reveals new insights into how organic matter decomposition is partitioned across biota and streambed compartments.

Depth and vertical hydrodynamics constrain the size structure of a lowland streambed community.

Abundance-body mass (N-M) relationships are prominent macroecological patterns and provide an integrated measurement of the structure and energy flow through natural communities. However, little is known about how N-M relationships are constrained by local environmental conditions. Here, we quantify how sediment depth and direction of surface-groundwater exchange (vertical hydrodynamics), two major drivers of the streambed ecology, determine N-M scaling in a sandy lowland European stream. Streambed assemblages included flagellates, ciliates, meiofauna and macroinvertebrates, and spanned five orders of magnitude in body mass. We detected a significant interaction of body mass with depth and vertical hydrodynamics with a sharp reduction in N-M slopes in the hyporheic zone and under upwelling conditions. These results revealed that streambed assemblages become more size-structured as environmental constraints increase with direct implications for the metabolic capacity and functioning of the system.

Flow-induced, inflammation-mediated arterial wall remodeling in the formation and progression of intracranial aneurysms.

OBJECTIVE: Unruptured intracranial aneurysms (UIAs) are relatively common lesions that may cause devastating intracranial hemorrhage, thus producing considerable suffering and anxiety in those affected by the disease or an increased likelihood of developing it. Advances in the knowledge of the pathobiology behind intracranial aneurysm (IA) formation, progression, and rupture have led to preclinical testing of drug therapies that would prevent IA formation or progression. In parallel, novel biologically based diagnostic tools to estimate rupture risk are approaching clinical use. Arterial wall remodeling, triggered by flow and intramural stresses and mediated by inflammation, is relevant to both. METHODS: This review discusses the basis of flow-driven vessel remodeling and translates that knowledge to the observations made on the mechanisms of IA initiation and progression on studies using animal models of induced IA formation, study of human IA tissue samples, and study of patient-derived computational fluid dynamics models. RESULTS: Blood flow conditions leading to high wall shear stress (WSS) activate proinflammatory signaling in endothelial cells that recruits macrophages to the site exposed to high WSS, especially through macrophage chemoattractant protein 1 (MCP1). This macrophage infiltration leads to protease expression, which disrupts the internal elastic lamina and collagen matrix, leading to focal outward bulging of the wall and IA initiation. For the IA to grow, collagen remodeling and smooth muscle cell (SMC) proliferation are essential, because the fact that collagen does not distend much prevents the passive dilation of a focal weakness to a sizable IA. Chronic macrophage infiltration of the IA wall promotes this SMC-mediated growth and is a potential target for drug therapy. Once the IA wall grows, it is subjected to changes in wall tension and flow conditions as a result of the change in geometry and has to remodel accordingly to avoid rupture. Flow affects this remodeling process. CONCLUSIONS: Flow triggers an inflammatory reaction that predisposes the arterial wall to IA initiation and growth and affects the associated remodeling of the UIA wall. This chronic inflammation is a putative target for drug therapy that would stabilize UIAs or prevent UIA formation. Moreover, once this coupling between IA wall remodeling and flow is understood, data from patient-specific flow models can be gathered as part of the diagnostic workup and utilized to improve risk assessment for UIA initiation, progression, and eventual rupture.

Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013-2014 in the United States.

BACKGROUND: The predominant strain during the 2013-2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009. METHODS: The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2-17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed. RESULTS: We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR-confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%-61%). Among fully vaccinated children aged 2-17 years, the effectiveness of LAIV4 was 17% (95% CI, -39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%-74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season. CONCLUSIONS: During 2013-2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States.

Illness Severity and Work Productivity Loss Among Working Adults With Medically Attended Acute Respiratory Illnesses: US Influenza Vaccine Effectiveness Network 2012-2013.

BACKGROUND: Influenza causes significant morbidity and mortality, with considerable economic costs, including lost work productivity. Influenza vaccines may reduce the economic burden through primary prevention of influenza and reduction in illness severity. METHODS: We examined illness severity and work productivity loss among working adults with medically attended acute respiratory illnesses and compared outcomes for subjects with and without laboratory-confirmed influenza and by influenza vaccination status among subjects with influenza during the 2012-2013 influenza season. RESULTS: Illnesses laboratory-confirmed as influenza (ie, cases) were subjectively assessed as more severe than illnesses not caused by influenza (ie, noncases) based on multiple measures, including current health status at study enrollment (≤7 days from illness onset) and current activity and sleep quality status relative to usual. Influenza cases reported missing 45% more work hours (20.5 vs 15.0; P < .001) than noncases and subjectively assessed their work productivity as impeded to a greater degree (6.0 vs 5.4; P < .001). Current health status and current activity relative to usual were subjectively assessed as modestly but significantly better for vaccinated cases compared with unvaccinated cases; however, no significant modifications of sleep quality, missed work hours, or work productivity loss were noted for vaccinated subjects. CONCLUSIONS: Influenza illnesses were more severe and resulted in more missed work hours and productivity loss than illnesses not confirmed as influenza. Modest reductions in illness severity for vaccinated cases were observed. These findings highlight the burden of influenza illnesses and illustrate the importance of laboratory confirmation of influenza outcomes in evaluations of vaccine effectiveness.

Serum and glucocorticoid-regulated kinase 1 regulates neutrophil clearance during inflammation resolution.

The inflammatory response is integral to maintaining health by functioning to resist microbial infection and repair tissue damage. Large numbers of neutrophils are recruited to inflammatory sites to neutralize invading bacteria through phagocytosis and the release of proteases and reactive oxygen species into the extracellular environment. Removal of the original inflammatory stimulus must be accompanied by resolution of the inflammatory response, including neutrophil clearance, to prevent inadvertent tissue damage. Neutrophil apoptosis and its temporary inhibition by survival signals provides a target for anti-inflammatory therapeutics, making it essential to better understand this process. GM-CSF, a neutrophil survival factor, causes a significant increase in mRNA levels for the known anti-apoptotic protein serum and glucocorticoid-regulated kinase 1 (SGK1). We have characterized the expression patterns and regulation of SGK family members in human neutrophils and shown that inhibition of SGK activity completely abrogates the antiapoptotic effect of GM-CSF. Using a transgenic zebrafish model, we have disrupted sgk1 gene function and shown this specifically delays inflammation resolution, without altering neutrophil recruitment to inflammatory sites in vivo. These data suggest SGK1 plays a key role in regulating neutrophil survival signaling and thus may prove a valuable therapeutic target for the treatment of inflammatory disease.

The ancient Britons: groundwater fauna survived extreme climate change over tens of millions of years across NW Europe.

Global climate changes during the Cenozoic (65.5-0 Ma) caused major biological range shifts and extinctions. In northern Europe, for example, a pattern of few endemics and the dominance of wide-ranging species is thought to have been determined by the Pleistocene (2.59-0.01 Ma) glaciations. This study, in contrast, reveals an ancient subsurface fauna endemic to Britain and Ireland. Using a Bayesian phylogenetic approach, we found that two species of stygobitic invertebrates (genus Niphargus) have not only survived the entire Pleistocene in refugia but have persisted for at least 19.5 million years. Other Niphargus species form distinct cryptic taxa that diverged from their nearest continental relative between 5.6 and 1.0 Ma. The study also reveals an unusual biogeographical pattern in the Niphargus genus. It originated in north-west Europe approximately 87 Ma and underwent a gradual range expansion. Phylogenetic diversity and species age are highest in north-west Europe, suggesting resilience to extreme climate change and strongly contrasting the patterns seen in surface fauna. However, species diversity is highest in south-east Europe, indicating that once the genus spread to these areas (approximately 25 Ma), geomorphological and climatic conditions enabled much higher diversification. Our study highlights that groundwater ecosystems provide an important contribution to biodiversity and offers insight into the interactions between biological and climatic processes.

Behavioral and technological interventions targeting glycemic control in a racially/ethnically diverse population: a randomized controlled trial.

BACKGROUND: Diabetes self-care by patients has been shown to assist in the reduction of disease severity and associated medical costs. We compared the effectiveness of two different diabetes self-care interventions on glycemic control in a racially/ethnically diverse population. We also explored whether reductions in glycated hemoglobin (HbA1c) will be more marked in minority persons. METHODS: We conducted an open-label randomized controlled trial of 376 patients with type 2 diabetes aged ≥18 years and whose last measured HbA1c was ≥7.5% (≥58 mmol/mol). Participants were randomized to: 1) a Chronic Disease Self-Management Program (CDSMP; n = 101); 2) a diabetes self-care software on a personal digital assistant (PDA; n = 81); 3) a combination of interventions (CDSMP + PDA; n = 99); or 4) usual care (control; n = 95). Enrollment occurred January 2009-June 2011 at seven regional clinics of a university-affiliated multi-specialty group practice. The primary outcome was change in HbA1c from randomization to 12 months. Data were analyzed using a multilevel statistical model. RESULTS: Average baseline HbA1c in the CDSMP, PDA, CDSMP + PDA, and control arms were 9.4%, 9.3%, 9.2%, and 9.2%, respectively. HbA1c reductions at 12 months for the groups averaged 1.1%, 0.7%, 1.1%, and 0.7%, respectively and did not differ significantly from baseline based on the model (P = .771). Besides the participants in the PDA group reporting eating more high-fat foods compared to their counterparts (P < .004), no other significant differences were observed in participants' diabetes self-care activities. Exploratory sub-analysis did not reveal any marked reductions in HbA1c for minority persons but rather modest reductions for all racial/ethnic groups. CONCLUSIONS: Although behavioral and technological interventions can result in some modest improvements in glycemic control, these interventions did not fare significantly better than usual care in achieving glycemic control. More research is needed to understand how these interventions can be most effective in clinical practice. The reduction in HbA1c levels found in our control group that received usual care also suggests that good routine care in an integrated healthcare system can lead to better glycemic control. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01221090.

The Scottish children's panels as a catalyst for civic engagement and child well-being.

Scotland's child welfare system has developed as hybrid of both residual and universal approaches and incorporates local involvement through trained volunteers participating in children's panels and community-based interventions. Furthermore, Scotland's move toward independence from the United Kingdom, called devolution in Scotland, has resulted in a resurgence of new recommendations focused on child well-being from birth through adolescence for all Scottish children. This article will explore policy development of Scotland's unique child welfare approach through the children's panels and the commitment to civic participation. It will expand on how recent initiatives, policy, and practice guidelines may have implications for providing a promising, sustainable model focused on child well-being, and may be useful for consideration in other cultural contexts that view liberty and civic engagement as core values.