Development of clinical guidelines for service provision of functional electrical stimulation to support walking: mixed method exploration of stakeholder views.

BACKGROUND: Over the past 20 years Functional Electrical Stimulation (FES) has grown in clinical use to support walking in people with lower limb weakness or paralysis due to upper motor neuron lesions. Despite growing consensus regarding its benefits, provision across the UK and internationally is variable. This study aimed to explore stakeholder views relating to the value of a clinical guideline focusing on service provision of FES to support walking, how people might use it and what should be included. METHODS: A mixed methods exploration sought the views of key stakeholders. A pragmatic online survey (n = 223) focusing on the study aim was developed and distributed to the email distribution list of the UK Association for Chartered Physiotherapists Interested in Neurology (ACPIN). In parallel, a qualitative service evaluation and patient public involvement consultation was conducted. Two group, and seven individual interviews were conducted with: FES-users (n = 6), their family and carers (n = 3), physiotherapists (n = 4), service providers/developers (n = 2), researchers (n = 1) and distributors of FES (n = 1). Descriptive analysis of quantitative data and framework analysis of qualitative data were conducted. RESULTS: Support for clinical guideline development was clear in the qualitative interviews and the survey results. Survey respondents most strongly endorsed possible uses of the clinical guideline as ensuring best practice and supporting people seeking access to a FES service. Data analysis and synthesis provided clear areas for inclusion in the clinical guidelines, including current research evidence and consensus relating to who is most likely to benefit and optimal service provision as well as pathways to access this. Specific areas for further investigation were summarised for inclusion in the first stage of a Delphi consensus study. CONCLUSIONS: Key stakeholders believe in the value of a clinical guideline that focuses on the different stages of service provision for FES to support walking. A Delphi consensus study is being planned based on the findings.

"Just too busy living in the moment and surviving": barriers to accessing health care for structurally vulnerable populations at end-of-life.

BACKGROUND: Despite access to quality care at the end-of-life (EOL) being considered a human right, it is not equitable, with many facing significant barriers. Most research examines access to EOL care for homogenous 'normative' populations, and as a result, the experiences of those with differing social positioning remain unheard. For example, populations experiencing structural vulnerability, who are situated along the lower rungs of social hierarchies of power (e.g., poor, homeless) will have unique EOL care needs and face unique barriers when accessing care. However, little research examines these barriers for people experiencing life-limiting illnesses and structural vulnerabilities. The purpose of this study was to identify barriers to accessing care among structurally vulnerable people at EOL. METHODS: Ethnography informed by the critical theoretical perspectives of equity and social justice was employed. This research drew on 30 months of ethnographic data collection (i.e., observations, interviews) with structurally vulnerable people, their support persons, and service providers. Three hundred hours of observation were conducted in homes, shelters, transitional housing units, community-based service centres, on the street, and at health care appointments. The constant comparative method was used with data collection and analysis occurring concurrently. RESULTS: Five significant barriers to accessing care at EOL were identified, namely: (1) The survival imperative; (2) The normalization of dying; (3) The problem of identification; (4) Professional risk and safety management; and (5) The cracks of a 'silo-ed' care system. Together, findings unveil inequities in accessing care at EOL and emphasize how those who do not fit the 'normative' palliative-patient population type, for whom palliative care programs and policies are currently built, face significant access barriers. CONCLUSIONS: Findings contribute a nuanced understanding of the needs of and barriers experienced by those who are both structurally vulnerable and facing a life-limiting illness. Such insights make visible gaps in service provision and provide information for service providers, and policy decision-makers alike, on ways to enhance the equitable provision of EOL care for all populations.

Regulation of fas ligand expression during activation-induced cell death in T cells by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase.

Activation-induced cell death (AICD) is a mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). Although c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in apoptosis in various cell types, the mode of regulation of FasL expression during AICD in T cells by these two MAPKs is incompletely understood. To investigate the regulatory roles of these two MAPKs, we analyzed the kinetics of TCR-induced p38 MAPK and JNK activity and their regulation of FasL expression and AICD. We report that both JNK and p38 MAPK regulate AICD in T cells. Our data suggest a novel model of T cell AICD in which p38 MAPK acts early to initiate FasL expression and the Fas-mediated activation of caspases. Subsequently, caspases stimulate JNK to further upregulate FasL expression. Thus, p38 MAPK and downstream JNK converge to regulate FasL expression at different times after T cell receptor stimulation to elicit maximum AICD.

Volumetric sampling strategies for heterogeneous brainstem nuclei.

Many brainstem nuclei are heterogeneous structures in which neuronal and glial populations are unevenly distributed, and focal normal or pathologic deviations in cell density, so-called "features," are found. Examples of features include subnuclei, focal neuronal loss, and focal gliosis. We present a statistical test that justifies an investigator's claim that a feature is present in a nucleus at a selected level of confidence after completion of a cell counting experiment. The computer program developed for the test also indicates the most probable location of the feature within the nucleus, and its most probable density and length, and potentially allows one to make comparisons of feature characteristics among cases. We also present quantitative guidelines for the selection of a sampling periodicity in a heterogeneous nucleus before a cell counting experiment. Sampling periodicity is based upon analysis of computer-generated simulations of the nucleus with features of different sizes; for each feature the probability of Type I (false positives) and Type II (false negatives) errors are examined against one another. Type II error rate is dependent upon feature length and density, acceptable Type I error rate, and sampling periodicity. Feature detection is important for devising sampling strategies in brainstem nuclei.

Transesophageal echocardiography in pediatric congenital heart disease.

The uses of transesophageal echocardiography have expanded dramatically over the last decade. With advances in technology, this imaging modality has become readily available for evaluation of the complex pediatric population with congenital heart disease. This article discusses the many uses of transesophageal echocardiography in this population, in the outpatient setting, in the peri-operative period, and in the cardiac catheterization laboratory.

What is "powder free"? Characterisation of powder aerosol produced during simulated use of powdered and powder free latex gloves.

OBJECTIVES: To characterise the distribution of particle size and mass of glove powder aerosol released from powdered and powder free non-sterile latex gloves under controlled conditions. METHODS: Gravimetric sampling and aerodynamic particle size analysis were performed during simulated use of gloves on a prosthetic hand in a chamber designed to minimise background particle concentrations. RESULTS: Aerosol was detectable for both powdered and powder free gloves under both aggressive and non-aggressive handling conditions. Most of the particles detected had aerodynamic diameter less than 10 microm. CONCLUSION: Powder free gloves were not entirely free of powder aerosol. Particles from both powdered and powder free gloves are sufficiently fine to penetrate into the thoracic region of the respiratory tract.

Failure in immune regulation begets IDDM in NOD mice.

The nonobese diabetic (NOD) mouse model of insulin-dependent diabetes mellitus (IDDM) has provided evidence which suggests that an important mechanism of the induction of this T-cell-mediated autoimmune disease is a failure in immune regulation. The role of T-cell immune dysregulation in the initiation of diabetes is the focus of this review. Immunological mechanisms such as T-cell anergy and deficient T-cell-mediated suppression are discussed as mediators of IDDM susceptibility. In particular, T helper (Th) 2 cell anergy may be responsible for defective regulation of autoreactive effector T-cells. Therapies designed to overcome these T-cell-mediated deficiencies may prevent IDDM onset.

ZAP-70 is essential for the T cell antigen receptor-induced plasma membrane targeting of SOS and Vav in T cells.

Translocation of the SOS and Vav GDP/GTP exchange factors proximal to Ras and Rac GTPases localized in the plasma membrane glycolipid-enriched microdomains is a pivotal step required for T cell antigen receptor-induced T cell activation. Here we demonstrate that the T cell antigen receptor zeta-chain-associated ZAP-70 kinase and T cell antigen receptor zeta-chain immunoreceptor tyrosine-based activation motifs are essential for the membrane recruitment of SOS and Vav. Plasma membrane targeting of SOS or Vav begins with the assembly of ZAP-70 with Grb-2 and SOS. The subsequent tyrosine phosphorylation of LAT (linker for activation of T cell) by ZAP-70 leads to a shift in equilibrium from the ZAP-70.Grb-2.SOS(Vav) complex to the (Vav)SOS.Grb-2.LAT complex. This shift results in the targeting of SOS and Vav into glycolipid-enriched microdomains and initiation of the Ras and Rac signaling cascades involved in T cell activation, proliferation, and cytokine production.

Differential expression of CC chemokines and the CCR5 receptor in the pancreas is associated with progression to type I diabetes.

We investigated the biological role of CC chemokines in the Th1-mediated pathogenesis of spontaneous type I diabetes in nonobese diabetic (NOD) mice. Whereas an elevated ratio of macrophage inflammatory protein-1alpha (MIP-1alpha):MIP-1beta in the pancreas correlated with destructive insulitis and progression to diabetes in NOD mice, a decreased intrapancreatic MIP-1alpha:MIP-1beta ratio was observed in nonobese diabetes-resistant (NOR) mice. IL-4 treatment, which prevents diabetes in NOD mice by polarizing intraislet Th2 responses, decreased CCR5 expression in islets and potentiated a high ratio of MIP-1beta and monocyte chemotactic protein-1 (MCP-1): MIP-1alpha in the pancreas. Furthermore, NOD.MIP-1alpha-/- mice exhibited reduced destructive insulitis and were protected from diabetes. Neutralization of MIP-1alpha with specific Abs following transfer of diabetogenic T cells delayed the onset of diabetes in NOD.Scid recipients. These studies illustrate that the temporal expression of certain CC chemokines, particularly MIP-1alpha, and the CCR5 chemokine receptor in the pancreas is associated with the development of insulitis and spontaneous type I diabetes.