"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.

Integrated molecular signature of disease: analysis of influenza virus-infected macaques through functional genomics and proteomics.

Recent outbreaks of avian influenza in humans have stressed the need for an improved nonhuman primate model of influenza pathogenesis. In order to further develop a macaque model, we expanded our previous in vivo genomics experiments with influenza virus-infected macaques by focusing on the innate immune response at day 2 postinoculation and on gene expression in affected lung tissue with viral genetic material present. Finally, we sought to identify signature genes for early infection in whole blood. For these purposes, we infected six pigtailed macaques (Macaca nemestrina) with reconstructed influenza A/Texas/36/91 virus and three control animals with a sham inoculate. We sacrificed one control and two experimental animals at days 2, 4, and 7 postinfection. Lung tissue was harvested for pathology, gene expression profiling, and proteomics. Blood was collected for genomics every other day from each animal until the experimental endpoint. Gross and microscopic pathology, immunohistochemistry, viral gene expression by arrays, and/or quantitative real-time reverse transcription-PCR confirmed successful yet mild infections in all experimental animals. Genomic experiments were performed using macaque-specific oligonucleotide arrays, and high-throughput proteomics revealed the host response to infection at the mRNA and protein levels. Our data showed dramatic differences in gene expression within regions in influenza virus-induced lesions based on the presence or absence of viral mRNA. We also identified genes tightly coregulated in peripheral white blood cells and in lung tissue at day 2 postinoculation. This latter finding opens the possibility of using gene expression arrays on whole blood to detect infection after exposure but prior to onset of symptoms or shedding.

Effect of endothelial cell-based iNOS gene transfer on cavernosal eNOS expression and mouse erectile responses.

Inducible nitric oxide synthase (iNOS) gene transfer is reported to augment erectile responses in rats, although it is also shown to impair vasorelaxation in cerebral arteries. We investigated the effect of endothelial cell-based iNOS gene transfer on endothelial NOS (eNOS) expression and mouse erectile responses. Human coronary artery endothelial cells (EC) transduced with empty vector (control) or iNOS were grown in culture and transplanted into the corpus cavernosum of severe combined immunodeficient mice. Endothelial NOS expression was compared in control and iNOS-transduced cells grown in the presence or absence of a selective iNOS inhibitor, L-N6- (1-iminoethyl) lysine hydrochloride (L-NIL). At 3-5 days after cell transplantation, we recorded intracorporal pressure (ICP) responses to cavernosal nerve stimulation and measured cavernosal total NO and eNOS protein expression. In this study, EC transduced with iNOS produced significantly more NO than controls but exhibited a twofold downregulation of eNOS protein and mRNA. This effect was reversed by L-NIL. In vivo, the cell-based gene transfer of iNOS led to significantly increased ICP responses, compared to mice transplanted with control ECs. Consistent with the in vitro data, cavernosal lysates had significantly reduced eNOS expression. In conclusion, EC gene transfer of iNOS downregulates EC expression of eNOS by an NOS-dependent mechanism. In the cavernosum of mice transplanted with Inos-transduced EC, nerve-stimulated erectile responses were augmented by the short-term gene transfer. However, our findings suggest that iNOS gene transfer may have deleterious effects on endothelial function if used as a treatment for erectile dysfunction.

Stability of parathyroid hormone ex vivo in haemodialysis patients.

BACKGROUND: The stability of parathyroid hormone (PTH) in blood ex vivo is a significant practical problem for laboratories and clinicians. Several studies have suggested that PTH is more stable in blood collected into a potassium edetate (EDTA) preservative. METHODS: To confirm that this was applicable to renal dialysis patients using our assay (Nichols chemiluminescence), we examined PTH stability in 13 patients with end-stage renal failure using three different blood collection tubes. RESULTS: PTH remained stable in EDTA plasma for up to 48 h at room temperature. PTH was significantly reduced in serum collected into plain tubes after 2 h, and after 4 h in serum collected into serum separator tubes, at room temperature. CONCLUSION: In the assessment of renal osteodystrophy, the use of EDTA plasma can confer significant benefit, especially in busy laboratories where rapid frozen separation of blood may be hard to achieve.

Effects of compression on language evolution.

For many adaptive complex systems information about the environment is not simply recorded in a look-up table, but is rather encoded in a theory, schema, or model, which compresses information. The grammar of a language can be viewed as such a schema or theory. In a prior study [Teal et al., 1999] we proposed several conjectures about the learning and evolution of language that should follow from these observations: (C1) compression aids in generalization; (C2) compression occurs more easily in a "smooth," as opposed to a "rugged," problem space: and (C3) constraints from compression make it likely that natural languages evolve towards smooth string spaces. This previous work found general, if not complete support for these three conjectures. Here we build on that study to clarify the relationship between Minimum Description Length (MDL) and error in our model and examine evolution of certain languages in more detail. Our results suggest a fourth conjecture: that all else being equal, (C4) more complex languages change more rapidly during evolution.

Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction.

Leptin serves as a humoral link coupling the status of energy reserves to the functional activity of the reproductive system. Leptin is thought to act through melanocortinergic pathways in the brain to regulate ingestive behaviors; however, whether melanocortins mediate leptin's actions on the neuroendocrine-reproductive axis is unknown. We tested this hypothesis first by determining whether the effects of leptin on feeding behavior and reproduction in the ob/ob mouse could be blocked by the melanocortin receptor (MC-R) antagonist SHU9119 and second, by examining the effects of the MC-R agonist MTII on feeding and the endocrine-reproductive system. Administered by intracerebroventricular injections, leptin inhibited food intake, raised plasma gonadotropin levels, and increased seminal vesicle weights compared with controls; SHU9119 (intracerebroventricularly) attenuated leptin's effects on food intake and body weight but did not alter leptin's stimulatory effect on the reproductive axis. MTII (intracerebroventricularly and intraperitoneally) decreased food intake and increased body temperature compared with controls but had no effect on the reproductive-endocrine axis. These results suggest that although leptin acts centrally through melanocortinergic pathways to inhibit ingestive behaviors and stimulate metabolism, leptin's activational effect on the reproductive axis is likely to be mediated by other, unknown neuroendocrine circuits.

Acronema sippewissettensis Gen. Nov. Sp. Nov., microbial mat bicosoecid (Bicosoecales = Bicosoecida).

A heterotrophic mastigote from the flat laminated Microcoleus-dominated intertidal microbial mat at the Sippewissett salt marsh, Cape Cod, Massachusetts, was isolated into monoprotist culture in the same anoxic medium that led to spirochete and other anaerobic bacterial enrichments. The protist grew vigorously and was transferred indefinitely in oxic marine medium. Videomicroscopy as well as scanning and transmission electron microscopy were used to document its features. The swimming and perching behavior, nutritional mode (bactivory) and morphology including ultra-structure identify it as an aloricate bicosoecid. The presence of heteromorphic acronematic undulipodia, bilateral bipartite tubular mastigonemes, absence of a cytostome, absence of extrusomes, and presence of "Dauerstadien" (duration stages) distinguish this from other Cafeteriaceae bicosoecids. Cell division involves a closed intranuclear spindle. The unspecialized bicosoecid morphology and behavior juxtaposed with oomycete-like vesicles and mastigonemes suggest that this protist may be an extant descendant of a common ancestor of bicosoecids and other stramenopiles (e.g. labyrinthulids, thraustochytrids and oomycetes). A new genus and species, Acronema sippewissettensis, are proposed.

Free-living spirochetes from Cape Cod microbial mats detected by electron microscopy.

Spirochetes from microbial mats and anaerobic mud samples collected in salt marshes were studied by light microscopy, whole mount and thin section transmission electron microscopy. Enriched in cellobiose-rifampin medium, selective for Spirochaeta bajacaliforniensis, seven distinguishable spirochete morphotypes were observed. Their diameters ranged from 0.17 micron to > 0.45 micron. Six of these morphotypes came from southwest Cape Cod, Massachusetts: five from Microcoleus-dominated mat samples collected at Sippewissett salt marsh and one from anoxic mud collected at School Street salt marsh (on the east side of Eel Pond). The seventh morphotype was enriched from anoxic mud sampled from the north central Cape Cod, at the Sandy Neck salt marsh. Five of these morphotypes are similar or identical to previously described spirochetes (Leptospira, Spirochaeta halophila, Spirochaeta bajacaliforniensis, Spirosymplokos deltaeiberi and Treponema), whereas the other two have unique features that suggest they have not been previously described. One of the morphotypes resembles Spirosymplokos deltaeiberi (the largest free-living spirochete described), in its large variable diameter (0.4-3.0 microns), cytoplasmic granules, and spherical (round) bodies with composite structure. This resemblance permits its tentative identification as a Sippewissett strain of Spirosymplokos deltaeiberi. Microbial mats samples collected in sterile Petri dishes and stored dry for more than four years yielded many organisms upon rewetting, including small unidentified spirochetes in at least 4 out of 100 enrichments.

Laboratory blunders revisited.

Blunders which occurred over a 1 year period in the clinical chemistry departments of two health districts were recorded and categorized according to type and detection stage. A blunder was defined as an incident leading to an incorrect result/set of results either being reported or detected at the final checking-out stage in the laboratory. Of the total of 120 blunders--which is a blunder rate of less than 0.1% of requests--53 (44%) were detected at the final checking-out stage. Blunders detected after the report had left the laboratory were divided into those subsequently picked up by laboratory personnel (23); those detected by clinicians (19); and those by external quality assessment schemes (21). The types of blunder were fairly equally distributed between the booking-in (36), analysis (38), and reporting (35) stages of the laboratory process. A formal review of blunders detected in laboratories is a valuable aid to overall performance.

Serum lipids, lipoproteins and macrovascular disease in non-insulin-dependent diabetics: a possible new approach to prevention.

The relationship between macrovascular disease and serum lipids, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL), and subfraction cholesterol, and apolipoproteins has been examined in 53 female and 95 male patients with non-insulin-dependent diabetes mellitus (NIDDM). In males, those with macrovascular disease had higher serum and LDL cholesterol concentrations than those without. In females, those with macrovascular disease had higher levels of serum triglyceride, cholesterol, LDL cholesterol, as well as lower HDL, HDL2, and HDL3 cholesterol and apoprotein A-1, than those without. On multivariate analysis, LDL cholesterol was the most important association with macrovascular disease in males and apoprotein A-1 in females. In a subgroup of 36 patients, a double-blind placebo controlled study using bezafibrate or placebo, in addition to conventional oral hypoglycaemic therapy over 4 months, showed falls in serum and LDL cholesterol and in serum triglyceride and a rise in HDL cholesterol in the treated group. These changes should reduce the incidence of macrovascular disease in NIDDM and we suggest further prospective studies of such therapy in addition to conventional oral hypoglycaemic agents.

Chlorpropamide lowers serum and lipoprotein cholesterol in insulin-dependent diabetes.

Changes in serum lipids and lipoproteins were examined during eight weeks chlorpropamide therapy in eight C-peptide negative, insulin-dependent diabetic patients (mean age 40 years, mean onset of diabetes 20 years). Chlorpropamide was found to have a generalized cholesterol lowering effect (progressive significant fall in mean total cholesterol, LDL-C, HDL-C, and HDL3-C) with no significant change in the ratio of high-density lipoprotein to low-density lipoprotein cholesterol which was independent of insulin secretion.