Developing the Blueprint for Youth Suicide Prevention.

Suicide and suicidal behavior among youth and young adults are a major public health crisis, exacerbated by the COVID-19 pandemic and demonstrated by increases in suicidal ideation and attempts among youth. Supports are needed to identify youth at risk and intervene in safe and effective ways. To address this need, the American Academy of Pediatrics and the American Foundation for Suicide Prevention, in collaboration with experts from the National Institute of Mental Health, developed the Blueprint for Youth Suicide Prevention ( Blueprint ) to translate research into strategies that are feasible, pragmatic, and actionable across all contexts in which youth live, learn, work, and play. In this piece, we describe the process of developing and disseminating the Blueprint. Through a summit and focus meetings, cross-sectoral partners convened to discuss the context of suicide risk among youth; explore the landscape of science, practice, and policy; build partnerships; and identify strategies for clinics, communities, and schools-all with a focus on health disparities and equity. These meetings resulted in 5 major takeaways: (1) suicide is often preventable; (2) health equity is critical to suicide prevention; (3) individual and systems changes are needed; (4) resilience should be a key focus; and (5) cross-sectoral partnerships are critical. These meetings and takeaways then informed the content of the Blueprint , which discusses the epidemiology of youth and young adult suicide and suicide risk, including health disparities; the importance of a public health framework; risk factors, protective factors, and warning signs; strategies for clinical settings, strategies for community and school settings; and policy priorities. Following the process description, lessons learned are also discussed, followed by a call to action for the public health community and all who serve and support youth. Finally, key steps to establishing and sustaining partnerships and implications for policy and practice are discussed.

Developing simulation games to advance public health nursing competence in baccalaureate education.

We describe the development of an innovative baccalaureate nursing education strategy for public health nursing. Virtual simulation pedagogy is known to be effective for acute care nursing practice while less known for public health nursing. Three Canadian nursing schools, the Canadian Association of Schools of Nursing (CASN), and the Canadian Alliance of Nurse Educators using Simulation (CAN-Sim) partnered to develop three public health nursing virtual simulation games. Learners work through unfolding population health scenarios, simulating public health nursing practice focused on entry level public health nursing competencies. Each game fosters clinical reasoning and collaborative, community decision-making to respond to population health issues during community assessment, evidence-informed health promotion planning, and evaluation processes. A companion guide was developed to support best practices in implementing virtual simulation and promote optimum student learning using the public health nursing games.

The effect of ammonia on canine polymorphonuclear cells.

Hyperammonaemia is a common complication of liver disease in dogs. High concentrations of ammonia can be detrimental to dogs with liver disease for several reasons, notably by causing hepatic encephalopathy (HE) which describes the wide range of neurological abnormalities ranging from altered behaviour to seizures that are well recognised complications in dogs with hepatic disorders. In human patients with liver disease, hyperammonaemia has also been linked to the development of other systemic complications such as dysregulation of the innate immune system. In contrast, the effects of hyperammonaemia on the canine innate immune system is currently unknown. The aim of this study was to investigate the effects of ammonia on the oxidative burst activity of canine polymorphonuclear cells in vitro. Blood obtained from healthy dogs (n = 8) was incubated with escalating concentrations of ammonia ranging from 0 to 250 µM, and the percentage of cells experiencing an oxidative burst was evaluated using a commercial kit (Phagoburst™) and flow cytometry. The spontaneous oxidative burst was evaluated without stimulation and also following stimulation with E coli. The pH of the blood was also measured at the differing ammonia concentrations. There was an increase in the percentage of cells experiencing a spontaneous oxidative burst from ammonia concentrations of 125 µM (p = <0.05) and above (p = <0.01), with a 4.9 fold increase at 200 µM (p = < 0.001). In those cells stimulated with E coli, incubation with increasing ammonia concentrations did not result in a significant difference in oxidative burst from baseline (p = 0.953). There was no statistically significant difference between the pH of the blood at the various ammonia concentrations (p = 0.2) suggesting that the difference in spontaneous oxidative burst was due to the ammonia rather than simply a change in pH conditions. In summary, the spontaneous oxidative burst of neutrophils was significantly increased from baseline. This supports a potential role of ammonia in contributing to innate immune system dysfunction in dogs with liver disease, and may present a future therapeutic target.

A Microfluidic Platform for Precision Small-volume Sample Processing and Its Use to Size Separate Biological Particles with an Acoustic Microdevice.

A major advantage of microfluidic devices is the ability to manipulate small sample volumes, thus reducing reagent waste and preserving precious sample. However, to achieve robust sample manipulation it is necessary to address device integration with the macroscale environment. To realize repeatable, sensitive particle separation with microfluidic devices, this protocol presents a complete automated and integrated microfluidic platform that enables precise processing of 0.15-1.5 ml samples using microfluidic devices. Important aspects of this system include modular device layout and robust fixtures resulting in reliable and flexible world to chip connections, and fully-automated fluid handling which accomplishes closed-loop sample collection, system cleaning and priming steps to ensure repeatable operation. Different microfluidic devices can be used interchangeably with this architecture. Here we incorporate an acoustofluidic device, detail its characterization, performance optimization, and demonstrate its use for size-separation of biological samples. By using real-time feedback during separation experiments, sample collection is optimized to conserve and concentrate sample. Although requiring the integration of multiple pieces of equipment, advantages of this architecture include the ability to process unknown samples with no additional system optimization, ease of device replacement, and precise, robust sample processing.

Community differentiation and kinship among Europe's first farmers.

Community differentiation is a fundamental topic of the social sciences, and its prehistoric origins in Europe are typically assumed to lie among the complex, densely populated societies that developed millennia after their Neolithic predecessors. Here we present the earliest, statistically significant evidence for such differentiation among the first farmers of Neolithic Europe. By using strontium isotopic data from more than 300 early Neolithic human skeletons, we find significantly less variance in geographic signatures among males than we find among females, and less variance among burials with ground stone adzes than burials without such adzes. From this, in context with other available evidence, we infer differential land use in early Neolithic central Europe within a patrilocal kinship system.

Cell signalling and radiation survival: the impact of protein phosphatases.

PURPOSE: This review will examine the role of phosphatases in cancer cell signalling and also outline emerging findings regarding the influence of phosphatases on tumor cell survival after ionising radiation. CONCLUSION: The exposure of tumour cells to clinically relevant doses of ionising radiation causes DNA damage and rapidly activates a series of signaling cascades involved in cell survival (reviewed in (Valerie et al. 2007 )). The role of kinases in this signalling has been extensively studied, but the role of phosphatases is less well defined. There is an abundance of literature implicating phosphatases in cell cycle control, cell growth and survival but there has been much less reported on the involvement of these enzymes as determinants of radiosensitivity. Recent studies, however, suggest that phosphatases may modulate tumor cell radiosensitivity and may be targets for the enhancement of radiotherapy.

Phosphatase inhibition and cell survival after DNA damage induced by radiation.

The activity of certain kinases can promote cell survival after DNA damage, but the role of phosphatases in determining cell fate, although documented, is much less well defined. We sought to define a role for phosphatases in radiation survival and identify potential targets for intervention. By using naturally occurring inhibitors and siRNA we have assessed inhibition of four serine/threonine phosphatases PP1, PP2A, PHLPP and PHLPPL in a panel of tumor cell lines with H-, K- or N-ras mutations or with EGFR activation for effects on tumor cell radiosensitivity. Calyculin A, which inhibits both PP1 and PP2A reduced radiation survival in SQ20B cells (overexpressing EGFR). Okadaic acid, which preferentially inhibits PP2A showed less effect in SQ20B cells suggesting a greater involvement of PP1 in modulating radiosensitivity of these cells. T24 cells (H-Ras mutant) appeared equally sensitive to both inhibitors. The suggestion from inhibitors that PP1 might be important in radiosensitivity was supported by the greater sensitization obtained after knocking down expression of the catalytic sub-unit of PP1 over that seen after PP2A knockdown. Knocking down the PP2C like phosphatase PHLPPL also increased radiosensitivity in all cell lines tested where a second isoform PHLPP had little effect. These data suggest that targeted inhibition of phosphatase activity may be an alternative to kinase inhibition to enhance radiosensitivity in tumors.

Porphyrin-based photocatalytic lithography.

Photocatalytic lithography couples light with photoreactive coated mask materials to pattern surface chemistry. We excite porphyrins to create radical species that photocatalytically oxidize, and thereby pattern, chemistries in the local vicinity. The technique advantageously is suited for use with a wide variety of substrates. It is fast and robust, and the wavelength of light does not limit the resolution of patterned features. We have patterned proteins and cells to demonstrate the utility of photocatalytic lithography in life science applications.

Patient perceptions of quality in discharge instruction.

The present study investigates patient perceptions of the quality of discharge instruction by assessing inpatients' ratings of care and service in the United States over the past 5 years (1997-2001) (n = 4,901,178). As expected, patients' ratings of "instructions given about how to care for yourself at home" showed a strong, consistent positive relationship with overall patient satisfaction from 1997 through 2001. Nevertheless, patient satisfaction with discharge instructions decreased significantly each year (p < 0.001). Patients gave lower ratings to the quality of discharge instruction than to the overall quality of their hospital stay which indicates a failure to match the quality delivered among other services within the hospital. Patient assessments of discharge instruction quality varied systematically among conditions. Patients with musculoskeletal diseases and disorders (MDC-8) rated discharge instruction considerably lower than all other patient groups. Patients' age, sex, self-described health status and length of stay did not predict patients' evaluations of discharge instructions. U.S. hospitals may not be meeting existing AMA and JCAHO standards for patient education and discharge.

DIELECTROPHORESIS-BASED MICROFLUIDIC SEPARATION AND DETECTION SYSTEMS.

Diagnosis and treatment of human diseases frequently requires isolation and detection of certain cell types from a complex mixture. Compared with traditional separation and detection techniques, microfluidic approaches promise to yield easy-to-use diagnostic instruments tolerant of a wide range of operating environments and capable of accomplishing automated analyses. These approaches will enable diagnostic advances to be disseminated from sophisticated clinical laboratories to the point-of-care. Applications will include the separation and differential analysis of blood cell subpopulations for host-based detection of blood cell changes caused by disease, infection, or exposure to toxins, and the separation and analysis of surface-sensitized, custom dielectric beads for chemical, biological, and biomolecular targets. Here we report a new particle separation and analysis microsystem that uses dielectrophoretic field-flow fractionation (DEP-FFF). The system consists of a microfluidic chip with integrated sample injector, a DEP-FFF separator, and an AC impedance sensor. We show the design of a miniaturized impedance sensor integrated circuit (IC) with improved sensitivity, a new packaging approach for micro-flumes that features a slide-together compression package and novel microfluidic interconnects, and the design, control, integration and packaging of a fieldable prototype. Illustrative applications will be shown, including the separation of different sized beads and different cell types, blood cell differential analysis, and impedance sensing results for beads, spores and cells.