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Introduction: Prompt, high-quality pre-hospital emergency medical services (EMS) can significantly reduce morbidity and mortality. The goal of this study was to identify factors that compromise efficiency and quality of pre-hospital emergency care in Rwanda, and explore the opportunities for a mobile health (mHealth) tool to address these challenges. Methods: In-depth interviews were conducted with 21 individuals representing four stakeholder groups: EMS dispatch staff, ambulance staff, hospital staff, and policymakers. A semi-structured interview guide explored participants’ perspectives on all aspects of the pre-hospital emergency care continuum, from receiving a call at dispatch to hospital handover. Participants were asked how the current system could be improved, and the potential utility of an mHealth tool to address existing challenges. Interviews were audio-recorded, and transcripts were thematically analyzed using NVivo. Results: Stakeholders identified factors that compromise the efficiency and quality of care across the prehospital emergency care continuum: triage at dispatch, dispatching the ambulance, locating the emergency, coordinating patient care at scene, preparing the receiving hospital, and patient handover to the hospital. They identified four areas where an mHealth tool could improve care: efficient location of the emergency, streamline communication for decision making, documentation with real-time communication, and routine data for quality improvement. While stakeholders identified advantages of an mHealth tool, they also mentioned challenges that would need to be addressed, namely: limited internet bandwidth, capacity to maintain and update software, and risks of data security breaches that could lead to stolen or lost data. Conclusion: Despite the success of Rwanda's EMS system, this study highlights factors across the care continuum that could compromise quality and efficiency of prehospital emergency care. Mobile health tools hold great promise to address these challenges, but contextual issues need to be considered to ensure sustainability of use.

Time of day is a critical factor for most biological functions, but concepts from the field of chronobiology have yet to be fully translated to clinical practice. Circadian rhythms, generated internally and synchronised to the external environment, promote function and support survival in almost every living species. Fetal circadian rhythms can be observed in utero from 30weeks gestation, coupled to the maternal rhythm, but synchronise to the external environment only after birth. Important cues for synchronisation include the light/dark cycle, the timing of feeding, and exposure to melatonin in breast milk. Disruption to these cues may occur during admission to the neonatal intensive care unit. This can impair the development of circadian rhythms, and influence survival and function in the neonatal period, with a potential to impact health and well-being throughout adult life. Here we outline the rationale and evidence to support a chronobiological approach to neonatal care., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: To investigate whether palmaris longus interposition or flexor carpi radialis ligament reconstruction and tendon interposition improve the outcome of trapezial excision for the treatment of basal joint arthritis after a minimum follow-up of 5 years., Methods: We randomized 174 thumbs with trapeziometacarpal osteoarthritis into 3 groups to undergo simple trapeziectomy, trapeziectomy with palmaris longus interposition, or trapeziectomy with ligament reconstruction and tendon interposition using 50% of the flexor carpi radialis tendon. A K-wire was passed across the trapezial void and retained for 4 weeks, and a thumb spica was used for 6 weeks in all 3 groups. We reviewed 153 thumbs after a minimum of 5 years (median, 6 y; range, 5-18 y) after surgery with subjective and objective assessments of thumb pain, function, and strength., Results: There was no difference in the pain relief achieved in the 3 treatment groups, with good results in 120 (78%) patients. Grip strength and key and tip pinch strengths did not differ among the 3 groups and range of movement of the thumb was similar. Few complications persisted after 5 years, and these were distributed evenly among the 3 groups. Compared with the results at 1 year in the same group of patients, the good pain relief achieved was maintained in the longer term, irrespective of the type of surgery. While improvements in grip strength achieved at 1 year after surgery were preserved, the key and tip pinch strengths deteriorated with time, but the type of surgery did not influence this., Conclusions: The outcomes of these 3 variations of trapeziectomy were similar after a minimum follow-up of 5 years. There appears to be no benefit to tendon interposition or ligament reconstruction in the longer term., (Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

To determine whether immune stimulation could reduce acute myelogenous leukemia (AML) lethality, dendritic cells (DCs) were pulsed with AML antigens and used as vaccines or generated in vivo by Flt3 ligand (Flt3L), a potent stimulator of DC and natural killer (NK) cell generation. Mice were then challenged with AML cells. The total number of splenic anti-AML cytotoxic T-lymphocyte precursors (CTLPs) present at the time of challenge was increased 1.9-fold and 16.4-fold by Flt3L or DC tumor vaccines, respectively. As compared with the 0% survival of controls, 63% or more of recipients of pulsed DCs or Flt3L survived long term. Mice given AML cells prior to DC vaccines or Flt3L had only a slight survival advantage versus non-treated controls. NK cells or NK cells and T cells were found to be involved in the antitumor responses of Flt3L or DCs, respectively. DC vaccines lead to long-term memory responses but Flt3L does not. Syngeneic bone marrow transplantation (BMT) recipients were analyzed beginning 2 months post-BMT. In contrast to the uniform lethality in BMT controls given AML cells, recipients of either Flt3L or DC vaccines had a significant increase in survival. The total number of splenic anti-AML CTLPs at the time of AML challenge in BMT controls was 40% of concurrently analyzed non-BMT controls. Flt3L or DC vaccines increased the total anti-AML CTLPs 1.4-fold and 6.8-fold, respectively. Neither approach was successful when initiated after AML challenge. It was concluded that DC vaccines and Flt3L administration can enhance an AML response in non-transplanted or syngeneic BMT mice but only when initiated prior to AML progression.

Dendritic cells (DCs) represent a family of ontogenically distinct leukocytes involved in immune response regulation. The ability of DCs to stimulate T-cell immunity has led to their use as vectors for immunotherapy vaccines. However, it is unclear whether and to what degree in vitro-generated DCs are representative of DCs that develop in vivo. Treatment of mice with human Flt3 ligand (FL) dramatically increases the number of DCs. We report here that administration of FL to healthy human volunteers increased the number of circulating CD11c(+ )IL-3Ralpha(low) DC (mean 44-fold) and CD11c(-) IL-3Ralpha(high) DC precursors (mean 12-fold). Moreover, the CD11c(+ )DCs were efficient stimulators of T cells in vitro. Thus, FL can expand the number of circulating, functionally competent human DCs in vivo.

The ligand for the receptor tyrosine kinase fms-like tyrosine kinase 3 (flt3), also referred to as fetal liver kinase-2 (flk-2), has an important role in hematopoiesis. The flt3 ligand (flt3L) is a growth factor for hematopoietic progenitors and induces hematopoietic progenitor and stem cell mobilization in vivo. In addition, when mice are treated with flt3L immature B cells, natural killer (NK) cells and dendritic cells (DC) are expanded in vivo. To further elucidate the role of flt3L in hematopoiesis, mice lacking flt3L (flt3L-/-) were generated by targeted gene disruption. Leukocyte cellularity was reduced in the bone marrow, peripheral blood, lymph nodes (LN), and spleen. Thymic cellularity, blood hematocrit, and platelet numbers were not affected. Significantly reduced numbers of myeloid and B-lymphoid progenitors were noted in the BM of flt3L-/- mice. In addition a marked deficiency of NK cells in the spleen was noted. DC numbers were also reduced in the spleen, LN, and thymus. Both myeloid-related (CD11c(++) CD8alpha(-)) and lymphoid-related (CD11c(++) CD8alpha(+)) DC numbers were affected. We conclude that flt3L has an important role in the expansion of early hematopoietic progenitors and in the generation of mature peripheral leukocytes.

Peripheral blood progenitor cells (PBPC) are increasingly being used in the clinic as a replacement for bone marrow (BM) in the transplantation setting. We investigated the capacity of several different growth factors, including human flt3 ligand (FL), alone and in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF ) or granulocyte colony-stimulating factor (G-CSF ), to mobilize colony forming cells (CFU) into the peripheral blood (PB) of mice. Mice were injected subcutaneously (SC) with growth factors daily for up to 10 days. Comparing the single agents, we found that FL alone was superior to GM-CSF or G-CSF in mobilizing CFU into the PB. FL synergized with both GM-CSF or G-CSF to mobilize more CFU, and in a shorter period of time, than did any single agent. Administration of FL plus G-CSF for 6 days resulted in a 1,423-fold and 2,717-fold increase of colony-forming unit-granulocyte-macrophage (CFU-GM) and colony-forming unit granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM) in PB, respectively, when compared with control mice. We also followed the kinetics of CFU numerical changes in the BM of mice treated with growth factors. While GM-CSF and G-CSF alone had little effect on BM CFU over time, FL alone increased CFU-GM and CFU-GEMM threefold and fivefold, respectively. Addition of GM-CSF or G-CSF to FL did not increase CFU in BM over levels seen with FL alone. However, after the initial increase in BM CFU after FL plus G-CSF treatment for 3 days, BM CFU returned to control levels after 5 days treatment, and CFU-GM were significantly reduced (65%) after 7 days treatment, when compared with control mice. Finally, we found that transplantation of FL or FL plus G-CSF-mobilized PB cells protected lethally irradiated mice and resulted in long-term multilineage hematopoietic reconstitution.

Defining what nurses do and why has been the endeavour of many researchers, both academic and clinical. Nursing interventions are a fundamental component of nursing practice and a focus on accountability means that nurses must be able to justify their actions. The sensoristrain experience of intensive care patients is widely acknowledged in nursing literature, though without the use of the word 'sensoristrain'. The aim in this paper is to place patients, their experience and the role of nurses within the practical framework of a suitable nursing theory which will elucidate and guide everyday practice in preventing and alleviating the causes (stressors), symptoms (reactions) and emotional aftermatch. Nursing interventions appropriate for the three modalities of intervention elucidated by the Neuman systems theory have been outlined, paralleled by a discussion of how these could relate to the three dimensions of nursing care: comfort care; knowing the patient; and the therapeutic presence of the nurse. Nurses must use each opportunity to advance practice through emphasizing the value of nursing in today's cost-conscious health care climate. In order to do this, and to ensure nurses' continued presence at the bedside, clear articulation of the contribution of nursing interventions to improved patient outcomes is essential.

Psychological disturbances that patients may experience during admission to intensive care units (ICUs) can have distressing implications for their emotional and physical integrity, progress and subsequent recovery. It is widely believed by practitioners and reflected in professional literature that these disturbances are precipitated by sensory deprivation or overload in the physical environment of intensive care units. In this paper the sources and mechanism of the sensory imbalances experienced by these patients are examined. A new concept--sensoristrain--has been developed in an attempt to promote awareness and improve understanding of the phenomenon among nurses. Once this has been achieved, assessment and identification of patients at risk are optimized and appropriate interventions can be formulated. Using an eclectic approach to analyse sensoristrain, both causes and effects of the phenomenon have been identified from the literature. This information has been combined with practical examples in the development of a model of the concept sensoristrain. The paper concludes by outlining the resulting implications for nursing practice, which may be used to guide future research both in concept development and identification of effective prevention of the phenomenon conceptualized and interventions if it occurs.

We have investigated the effects of in vivo treatment with flt3 ligand (FL) on murine hematopoiesis, including mobilization of progenitors into the peripheral blood (PB). Mice were injected once daily with 10 micrograms recombinant human FL for 15 days. On days 3, 5, 8, 10, 15, and 22, mice were killed and analyzed for the number of leukocytes and colony-forming units (CFU) in bone marrow (BM), spleen, and PB. Splenic and PB cellularity increased with time in FL-treated mice. In the spleen, there was an increase in B cells, myeloid cells, and nucleated erythroid cells; in the PB, there was an increase in lymphocytes, granulocytes, and monocytic cells. The maximal number of CFU in the BM was observed after 3 days of FL treatment, giving 3.7- and 7.3-fold increases in CFU-granulocyte-macrophage (CFU-GM) and CFU-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM), respectively, compared with mouse serum albumin (MSA)-treated controls. After 8 days of FL treatment, there was a maximal 123- and 108-fold increase in splenic CFU-GM and CFU-GEMM, respectively. The maximal number CFU-GM and CFU-GEMM were seen in PB on day 10, with 537- and 585-fold increases, respectively. Burst-forming units-erythroid (BFU-E) increased in the same time frame as those of CFU-GM and CFU-GEMM in BM, spleen, and PB, although the magnitude was not as great. Primitive day-13 CFU-spleen (CFU-S) and phenotypically defined stem cells were also mobilized into the PB of FL-treated mice with similar kinetics and magnitude to that of CFU-GM and CFU-GEMM. We conclude from these studies that FL, when administered as a single agent, is a potent mobilizer of hematopoietic progenitors into the PB.

A ligand for the tyrosine kinase receptor flt3/flk-2, referred to here as flt3 ligand (flt3L), was recently cloned. The effect of flt3L on purified human CD34+ progenitor cells was examined. flt3 receptor (flt3R) was detected on the surface of human bone marrow cells that were enriched for CD34 expression. The effects of flt3L and the c-kit ligand Steel factor (SLF) on hematopoietic progenitors were compared in clonal colony assays. Both factors synergized with Pixy321 (interleukin-3 [IL-3]-granulocyte-macrophage colony-stimulating factor fusion protein) to induce granulocytic-monocytic (GM) and high proliferative potential (HPP) colonies and synergized with Pixy321 + erythropoietin (EPO) to induce multipotent granulocytic-erythroid-monocytic-megakaryocytic colonies. Although SLF had a potent effect on colony formation of erythroid restricted progenitor cells (burst-forming unit-erythroid), no effect by flt3L was observed. The addition of flt3L to irradiated long-term marrow cultures seeded with CD34+ cells augmented both total and progenitor cell production. Ex vivo expansion studies with isolated CD34+ bone marrow cells from normal donors showed that flt3L alone supported maintenance of both GM and HPP progenitors for 3 to 4 weeks in vitro. The addition of flt3L to a growth factor combination of IL-1 alpha + IL-3 + IL-6 + EPO resulted in a synergistic effect on progenitor cell expansion comparable to that observed with the addition of SLF to IL-1 alpha + IL-3 + IL-6 + EPO. These data show a function for flt3L in the regulation of both primitive multipotent and lineage-committed hematopoietic progenitor cells.

The ability of Steel factor (SLF) to stimulate the growth of immature thymocytes alone and in combination with IL-7 was assessed. In suspension cultures of CD4-/CD8- thymocytes, SLF itself did not induce significant proliferation, but in combination with IL-7, it induced a greater response than did IL-7 alone. In fetal thymus lobe submersion cultures, SLF stimulated the growth of cells to a magnitude similar to that of IL-7 and the combination resulted in a synergistic response. Phenotypic analysis of these cells revealed that SLF in comparison to IL-7 stimulated the growth of a less mature population. The synergistic growth stimulated by the combination of IL-7 and SLF occurred in a population of IL-2R+/CD4-/CD8-/CD3- cells. Cells grown in SLF expressed low levels of IL-2R and overnight culture in IL-7 dramatically increased IL-2R expression. Thus, these results are consistent with the hypothesis that SLF stimulates the growth of a less mature thymocyte population than does IL-7.

Using a fragment of the murine flt3 ligand as a probe, we have succeeded in cloning a human flt3 ligand from a human T-cell lambda gt10 cDNA library. The human and murine ligands are 72% identical at the amino acid level. Analysis of multiple cDNA clones shows that alternative splicing of the human flt3 mRNA can occur at a number of positions. A recombinant soluble form of the human flt3 ligand stimulates the proliferation and colony formation of a subpopulation of human bone marrow cells that are CD34+ and are enriched for primitive hematopoietic cells. In addition, the human flt3 ligand also stimulates the proliferation of cells expressing murine flt3 receptors. Northern blot analysis shows widespread expression of flt3 ligand mRNA transcripts in human tissues.