Factors influencing general practice nurse's implementation of culturally responsive care, using normalization process theory: A cross-sectional study.

AIMS: To explore levers and barriers to providing culturally responsive care for general practice nurses (GPNs) using normalization process theory. DESIGN: A self-administered online cross-sectional survey. METHODS: A participatory co-designed adapted version of the normalization of complex interventions measure (NoMAD) validated tool was distributed to a convenience sample of GPNs between December 2022 and February 2023. The sample comprised of GPNs working in general practice services in Ireland (n = 122). Data were analysed using descriptive and analytical statistics (Pearson correlations) and principles of content analysis. This study was conducted and reported in line with the Consensus-Based Checklist for Reporting of Survey Studies (CROSS). RESULTS: GPNs in this study indicated their familiarity with, acknowledged the importance of and were committed to, providing culturally responsive care. However, implementing culturally responsive care in daily practice was problematic due to insufficient education and training, scarcity of resources and supports and a lack of organizational leadership. Subsequently, GPNs experience difficulties adapting everyday practices to respond appropriately to the care needs of culturally and linguistically diverse (CaLD) patients. CONCLUSION: This analysis highlights the necessity of exploring the intricacies of factors that influence capabilities and capacity for providing culturally responsive care. Despite demonstrating awareness of the importance of providing nursing care that responds to the needs of CaLD patients, GPNs do not have full confidence or capacity to integrate culturally responsive care into their daily work practices. IMPACT: Using normalization process theory, this study elucidates for the first time how GPNs in Ireland make sense of, legitimize, enact and sustain culturally responsive care as a routine way of working. It illuminates the multitude of micro-level (individual), meso-level (organizational) and macro-level (structural) factors that require attention for normalizing culturally responsive care in general practice services. PATIENT OR PUBLIC CONTRIBUTION: The study question was identified in a participatory research prioritization for Irish research about migrant health that involved migrants in the process.

Time to re-envisage culturally responsive care: Intersection of participatory health research and implementation science.

AIM: In the context of widening societal diversity, culturally and linguistically diverse patients continue to experience inequities in healthcare access and deficiencies in standards of nursing care. Re-framing culturally responsive care as a complex intervention spanning multiple interacting factors at micro, meso and macro levels is an essential prerequisite for addressing knowledge translation gaps into everyday nursing practice. To this end, this paper proposes and explicates the potential of applying synergistic participatory implementation methodologies for developing effective implementation strategies with impact at individual and wider structural levels. DESIGN: Discussion Paper. DATA SOURCES: A co-design case study is presented as an example of combining normalization process theory and participatory learning and action to investigate and support the implementation of culturally responsive care in general practice nursing. IMPLICATIONS FOR NURSING: Enacting culturally responsive health care is inherently complex in that it is influenced by multiple interacting factors. Viewing culturally responsive care as a complex intervention and incorporating a synergistic participatory implementation science approach offers possibilities for addressing the documented shortcomings in the implementation of culturally responsive nursing care. CONCLUSION: There is a need to move away from conventional approaches to conceptualizing and generating evidence on culturally responsive care. Incorporating participatory implementation methodologies can provide a new lens to investigate and support whole system implementation strategies. IMPACT: The combination of participatory and implementation methodologies is both theoretically and empirically informed. Engaging stakeholders in the co-design and co-production of evidence and solutions to long standing problems has the potential to increase the likelihood of influencing iterative and sustainable implementation and changes to clinical practice and systems. PATIENT OR PUBLIC CONTRIBUTION: This work is part of a wider programme of participatory health research on migrant health, partnering with a non-governmental organization that supports migrants.

Rates of neutropenia in adults with influenza A or B: a retrospective analysis of hospitalised patients in South East Queensland during 2015.

Neutropenia in adult patients is often attributed to intercurrent viral infections; however, there are limited data describing the frequency or natural history of this phenomenon. We examined all patients presenting to three large hospitals in the Metro South region of South East Queensland with laboratory-confirmed influenza A or B throughout the 2015 influenza season (January-October). Four hundred and thirty-six patients were studied and 15.3% of this cohort were neutropenic (absolute neutrophil count <2.0 × 109 /L) with no identifiable cause other than the influenza. Importantly, the majority of cases were mild, with absolute neutrophil count remaining >1.0 × 109 /L. The incidence of neutropenia was significantly higher in association with influenza B than influenza A (18.3% vs 10.3%). We conclude that mild, transient neutropenia is common among patients with influenza infection and advise that it should not cause alarm or invite specific investigation unless severe or prolonged.

Blood, sweat, and tears: developing clinically relevant protein biosensors for integrated body fluid analysis.

Biosensors are being developed to provide rapid, quantitative, diagnostic information to clinicians in order to help guide patient treatment, without the need for centralised laboratory assays. The success of glucose monitoring is a key example of where technology innovation has met a clinical need at multiple levels ­ from the pathology laboratory all the way to the patient's home. However, few other biosensor devices are currently in routine use. Here we review the challenges and opportunities regarding the integration of biosensor techniques into body fluid sampling approaches, with emphasis on the point-of-care setting.

Controlling fast-electron-beam divergence using two laser pulses.

This Letter describes the first experimental demonstration of the guiding of a relativistic electron beam in a solid target using two colinear, relativistically intense, picosecond laser pulses. The first pulse creates a magnetic field that guides the higher-current, fast-electron beam generated by the second pulse. The effects of intensity ratio, delay, total energy, and intrinsic prepulse are examined. Thermal and Kα imaging show reduced emission size, increased peak emission, and increased total emission at delays of 4-6 ps, an intensity ratio of 10∶1 (second:first) and a total energy of 186 J. In comparison to a single, high-contrast shot, the inferred fast-electron divergence is reduced by 2.7 times, while the fast-electron current density is increased by a factor of 1.8. The enhancements are reproduced with modeling and are shown to be due to the self-generation of magnetic fields. Such a scheme could be of considerable benefit to fast-ignition inertial fusion.

Ballistic focusing of polyenergetic protons driven by petawatt laser pulses.

By using a thick (250 µm) target with 350 µm radius of curvature, the intense proton beam driven by a petawatt laser is focused at a distance of ∼1 mm from the target for all detectable energies up to ∼25 MeV. The thickness of the foil facilitates beam focusing as it suppresses the dynamic evolution of the beam divergence caused by peaked electron flux distribution at the target rear side. In addition, reduction in inherent beam divergence due to the target thickness relaxes the curvature requirement for short-range focusing. Energy resolved mapping of the proton beam trajectories from mesh radiographs infers the focusing and the data agree with a simple geometrical modeling based on ballistic beam propagation.

Laser-driven fast electron collimation in targets with resistivity boundary.

We demonstrate experimentally that the relativistic electron flow in a dense plasma can be efficiently confined and guided in targets exhibiting a high-resistivity-core-low-resistivity-cladding structure analogous to optical waveguides. The relativistic electron beam is shown to be confined to an area of the order of the core diameter (50 µm), which has the potential to substantially enhance the coupling efficiency of electrons to the compressed fusion fuel in the Fast Ignitor fusion in full-scale fusion experiments.

Spectral enhancement in the double pulse regime of laser proton acceleration.

The use of two separate ultraintense laser pulses in laser-proton acceleration was compared to the single pulse case employing the same total laser energy. A double pulse profile, with the temporal separation of the pulses varied between 0.75-2.5 ps, was shown to result in an increased maximum proton energy and an increase in conversion efficiency to fast protons by up to a factor of 3.3. Particle-in-cell simulations indicate the existence of a two stage acceleration process. The second phase, induced by the main pulse preferentially accelerates slower protons located deeper in the plasma, in contrast to conventional target normal sheath acceleration.

Neurotransmitter plasticity at the molecular level.

Contrary to long-held assumptions, recent work indicates that neurons may profoundly change transmitter status during development and maturity. For example, sympathetic neurons, classically regarded as exclusively noradrenergic or cholinergic, can also express putative peptide transmitters such as substance P. This neuronal plasticity is directly related to membrane depolarization and sodium ion influx. The same molecular mechanisms and plastic responses occur in mature as well as developing neurons. Further, contrary to traditional teaching, adult primary sensory neurons may express the catecholaminergic phenotype in vivo. Transmitter plasticity is not restricted to the peripheral nervous system: ongoing studies of the brain nucleus locus ceruleus in culture indicate that specific extracellular factors elicit marked transmitter changes. Consequently, neurotransmitter expression and metabolism are dynamic, changing processes, regulated by a variety of defined factors. Transmitter plasticity adds a newly recognized dimension of flexibility to nervous system function.

Lactose drives Enterococcus expansion to promote graft-versus-host disease.

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Impact of cytokine gene polymorphisms on graft-vs-host disease.

Allogeneic hematopoietic stem cell transplantation (SCT) remains the only available curative therapy for hematological malignancy. It does, however, result in significant morbidity and mortality, predominantly as a consequence of infections, leukemic relapse and graft-vs-host disease (GVHD). While differences in human leukocyte antigen (HLA) molecules between donor and host make a crucial contribution to the alloreactivity driving the donor-antihost response, the cytokine milieu consisting of molecules that both promote and regulate the alloresponse after transplantation is also critical. As such, genetic studies correlating donor and/or host cytokine polymorphisms with disease outcomes have provided useful insight into disease pathogenesis, often confirming effects that have been dissected in animal models of the disease. It is now clear that the polymorphic expression of key cytokines (particularly tumor necrosis factor and interleukin 10) has a demonstrable effect on disease outcome and overall transplant-related mortality. Consideration of the role of genetic polymorphisms in GVHD severity and procedural mortality associated with SCT will lead to improvements in patient outcome such that the addition of non-HLA genetic typing of potential donors will allow optimization of donor selection for a given recipient. This review provides a discussion of the current state of the literature regarding polymorphic expression of the key GVHD cytokines and their capacity to predict clinical disease outcome.

Calibration of pertussis toxin BRP batch 1 in a standardised CHO cell-based clustering assay.

The European Pharmacopoeia (Ph. Eur.) pertussis toxin (PT) Biological Reference Preparation (BRP) is used as a working standard for safety testing of acellular pertussis vaccines as prescribed in the Ph. Eur. monographs 1356 "Pertussis vaccine (acellular, component, adsorbed)" and 1595 "Pertussis vaccine (acellular, co-purified, adsorbed)". The BRP was calibrated in 2006 in the murine histamine sensitisation test (HIST) against the World Health Organization (WHO) 1st International Standard (IS) for PT. In recent years, there have been increasing efforts to replace the in vivo test with in vitro methods. The Chinese hamster ovary (CHO) cell clustering assay has been used for many years by manufacturers to monitor residual PT activity in detoxified non-adjuvanted bulks. More recently a standardised protocol has been developed for this assay and a PT reference preparation was needed. Due to low stocks, the WHO 1st International Standard for Pertussis Toxin (JNIH-5) needed to be replaced and therefore a joint study between the European Directorate for the Quality of Medicines & HealthCare (EDQM) and WHO was initiated to calibrate the PT BRP for the CHO clustering assay and to replace the IS. The collaborative study involved 14 laboratories from Europe, North America and Asia. The outcome of the study confirmed that the BRP is suitable for use as a reference preparation in the CHO clustering assay. The material was assigned a potency of 1360 IU per vial for the CHO clustering assay.

Development of a curated Hershberger database.

A systematic literature review was conducted to identify Hershberger bioassays for ∼3200 chemicals including those used to validate the OECD/US EPA guideline assay, US EPA's chemicals screened for endocrine activity, and the library of chemicals run in US EPA 's ToxCast in vitro assays. For 134 chemicals that met pre-defined criteria, experimental results were extracted into a database used to characterize uncertainty in results and evaluate the concordance of the Hershberger assay with other in vivo rodent studies that measure androgen-responsive endpoints. Of 25 chemicals tested in >1 Hershberger study, 28% had disagreements between studies (i.e. ≥1 positive and ≥1 negative study), and of the 65 chemicals tested in Hershberger studies and other in vivo studies with androgen-responsive endpoints, 43% indicated disagreements, though in some cases these may be explained by differences in study designs or physiology of the animal model. Ultimately, 49 chemicals were identified with reproducible androgen pathway responses confirmed in ≥2 in vivo rodent studies that could be considered reference chemicals useful for validating alternative methods.

Evaluation of androgen assay results using a curated Hershberger database.

A set of 39 reference chemicals with reproducible androgen pathway effects in vivo, identified in the companion manuscript [1], were used to interrogate the performance of the ToxCast/Tox 21 androgen receptor (AR) model based on 11 high throughput assays. Cytotoxicity data and specificity confirmation assays were used to distinguish assay loss-of-function from true antagonistic signaling suppression. Overall agreement was 66% (19/29), with ten additional inconclusive chemicals. Most discrepancies were explained using in vitro to in vivo extrapolation to estimate equivalent administered doses. The AR model had 100% positive predictive value for the in vivo response, i.e. there were no false positives, and chemicals with conclusive AR model results (agonist or antagonist) were consistently positive in vivo. Considering the lack of reproducibility of the in vivo Hershberger assay, the in vitro AR model may better predict specific AR interaction and can rapidly and cost-effectively screen thousands of chemicals without using animals.

Active manipulation of the spatial energy distribution of laser-accelerated proton beams.

The spatial energy distributions of beams of protons accelerated by ultrahigh intensity (>10(19)Wcm2) picosecond laser pulse interactions with thin foil targets are investigated. Using separate, low intensity (<10(13)Wcm2) nanosecond laser pulses, focused onto the front surface of the target foil prior to the arrival of the high intensity pulse, it is demonstrated that the proton beam profile can be actively manipulated. In particular, results obtained with an annular intensity distribution at the focus of the low intensity beam are presented, showing smooth proton beams with a sharp circular boundary at all energies, which represents a significant improvement in the beam quality compared to irradiation with the picosecond beam alone.

In search of acceptable alternatives to the murine histamine sensitisation test (HIST): what is possible and practical?

The 'International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: In Search of Acceptable Alternatives to the Murine Histamine Sensitization Test (HIST): What is Possible and Practical?' was held on 4 and 5 March 2015 in London, United Kingdom. Participants discussed the results of the data generated from an international collaborative study (BSP114 Phase 2) sponsored by the European Directorate for the Quality of Medicines & Health Care (EDQM) to determine if a modified Chinese hamster ovary (CHO) cell-based clustering assay is a suitable alternative to replace HIST. Workshop participants agreed that protocol transferability demonstrated in the collaborative study indicates that a standardised CHO cell assay is adequate for measuring pure PTx in reference preparations. However, vaccine manufacturers would still need to demonstrate that the method is valid to detect or measure residual PTx in their specific adjuvanted products. The 2 modified CHO cell protocols included in the study (the Direct and the Indirect Methods) deserve further consideration as alternatives to HIST. Using the CHO cell assay, an in vitro alternative, for acellular pertussis (aP) vaccine batch release testing would reduce the number of animals used for aP vaccine safety testing. A strategic, stepwise adoption plan was proposed, in which the alternative test would be used for release purposes first, and then, once sufficient confidence in its suitable performance has been gained, its use would be extended to stability testing.

Glucocorticoid influence on tyrosine hydroxylase activity in mouse locus coeruleus during postnatal development.

Administration of corticosterone (10 mg/kg, ip, twice daily for 3 days) to mice during the second week of postnatal development led to an increase of tyrosine hydroxylase (TH) activity in the locus coeruleus, but not in the substantia nigra. The corticosterone effect was observed only transiently during this developmental period. Tritiated corticosterone can bind to a cytosol fraction prepared from mouse locus coeruleus, with a specific binding capacity of 110 fmol/mg protein. There is a correlation between the ability of various steroids to increase TH activity and their binding to the cytosol glucocorticoid receptor. Cortexolone and progesterone, two antiglucocorticoids that can bind to the cytosol receptor, were found to abolish the effect of corticosterone in increasing TH activity. It appears that the noradrenergic neurons in the locus coeruleus may be target cells for glucocorticoids, and that the glucocorticoid effect on TH may be a receptor-mediated mechanism.

Human brainstem catecholamine neuronal anatomy as indicated by immunocytochemistry with antibodies to tyrosine hydroxylase.

Immunocytochemistry based on antibodies to tyrosine hydroxylase is used to identify catecholaminergic neurons in the human brain stem. An atlas is provided and the distribution of structures compared with that in other animals and with biochemical and catecholamine fluorescent data from humans. Broad agreement of results increases the confidence with which tyrosine hydroxylase-like immunoreactivity can be used to trace catecholaminergic pathways in human postmortem material. As compared to most studies of other animals there are striking increases in populations of upper pontine and mesencephalic catecholaminergic neurons in the human. Distinct cytoarchitectonic features, consistent differences in tyrosine hydroxylase immunoreactive staining intensity and regional variations in substance P innervation indicate complexity within the substantia nigra. Human catecholaminergic neurons are prominent in the midline of the ventral tegmentum and the upper parts of the central tegmental tracts. A bundle of tyrosine hydroxylase-immunoreactive axons runs between the latter regions and a cluster of smaller catecholaminergic neurons which lie in the oblique band of axons joining ventrolateral and dorsomedial medullary catecholaminergic groups. There are more catecholaminergic neurons within and closely related to the superior cerebellar peduncles than have been described in other species. Anatomically, the central compact nucleus of the locus coeruleus appears to be related to several nearby catecholaminergic cell groups. The data provided are being used as a basis for neuropathologic studies of human neurological diseases.

Short and long-term effects of reserpine on the concentration of 1-(4-hydroxy-3-methoxyphenyl)-ethane-1,2-diol (MOPEG-SO4) in the brain of the rat.

1 Reserpine (1.25 mg/kg i.p.) induced an increase (172% of controls) in the concentration of 1-(4-hydroxy-3-methoxyphenyl)-ethane-1,2-diol sulphate (MOPEG-SO(4)) in rat brain and a decrease in the noradrenaline (NA) concentration to 50% of controls 2 h after injection. At this time the MOPEG-SO(4)/NA ratio was 0.28. Thereafter the MOPEG-SO(4) concentration declined and the NA concentration decreased further to 28% of control.2 Higher doses of reserpine (2.5 and 5 mg/kg i.p.) did not induce a larger increase in the concentration of MOPEG-SO(4).3 While a second dose of reserpine (1.25 mg/kg i.p.) given 24 h after the first did not increase the MOPEG-SO(4) concentration, amphetamine (5.0 mg/kg i.p.) administration or electrical stimulation significantly increased the concentration of MOPEG-SO(4).4 NA and MOPEG-SO(4) concentrations were examined during 5 days after a single dose of reserpine (1.25 mg/kg i.p.). While the concentration of NA started to return towards normal after 24 h, that of MOPEG-SO(4) remained at approximately 70% of controls during the entire period.5 The probenecid-induced accumulation rate of MOPEG-SO(4) was significantly lower 3 and 4 days after reserpine and returned to the control value on the fifth day. At this time the concentration of NA had reached 50% of the control value.6 These experiments indicate that MOPEG-SO(4) is not the major metabolite of NA during the initial phase of reserpine-induced NA release. Reserpine acts on the storage pool while amphetamine (like electrical stimulation) acts on the functional pool. During the first phase of post-drug recovery, there is a clear decrease in NA output which appears to be regulated by the concentration of NA in the storage pool.

Adrenal influence on tyrosine hydroxylase activity in superior cervical ganglion.

The involvement of adrenal hormones as regulatory factors in maintaining physiological levels of tyrosine hydroxylase (TH) was examined in mouse superior cervical ganglion. Following bilateral adrenalectomy, TH activity in the ganglion fell at a slow but steady rate, reaching 60-65% of the control levels after 2 weeks. Decentralization is known also to reduce TH activity in the ganglion. The effects of adrenalectomy and decentralization were therefore compared, and they were found to be additive, indicating different mechanisms in the two cases. The reduction of TH activity following adrenalectomy was not prevented by replacement with corticosterone (0.5 mg/kg, daily). However, replacement with epinephrine (4 mg/kg, daily) completely prevented the fall of TH activity in adrenalectomized animals. Isoproterenol, a beta-adrenergic receptor agonist, was as effective as epinephrine in preventing the reduction of TH activity following adrenalectomy. Furthermore, in intact animals, chronic administration of SKF 64139, an inhibitor of adrenal PNMT which depletes circulating epinephrine levels, also reduced ganglionic TH activity to the same level as that after adrenalectomy. These results indicate that epinephrine, but not corticosterone, is the adrenal factor required for physiological maintenance of normal levels of TH in the superior cervical ganglion.