Role of maternal hyperoxygenation testing to predict need for balloon atrial septostomy in fetal d-transposition of great arteries.

OBJECTIVES: Predicting whether balloon atrial septostomy (BAS) will be necessary after birth for fetuses with d-transposition of the great arteries (d-TGA) remains challenging. We sought to determine whether measurements obtained during fetal maternal hyperoxygenation (MH) testing can improve our ability to predict need for postnatal BAS. METHODS: Forty-one mothers carrying fetuses with d-TGA with either intact ventricular septum or small ventricular septal defect measuring <3mm underwent MH testing between 33-38 weeks gestation. Patent foramen ovale (PFO) size, measured by 2D and color Doppler, patent ductus arteriosus (PDA) shunting (all antegrade versus bidirectional) was assessed in room air (RA) and during MH, blinded to postnatal outcome. BAS status and timing were recorded. RESULTS: Postnatally, 23 neonates underwent BAS while 18 did not, and 14 subjects underwent emergent BAS within 3 hours of life. By univariate analysis, PFO size measured both in RA and MH and all antegrade shunting in the PDA during MH predicted BAS. During MH testing, median PFO size by 2D measured 2.5mm (interquartile range, IQR, 2-3mm) in fetuses who underwent emergent BAS versus 4.1mm (IQR 3.4-5mm) in fetuses who did not undergo BAS (p<0.001). By cutpoint analysis, PFO size during MH testing ≤ 3.2mm predicted need for emergent BAS with sensitivity 93% and specificity 78%. CONCLUSIONS: In d-TGA, measurement of PFO size and direction of PDA shunting during MH testing improves our ability to predict need for BAS postnatally, although additional study is needed. We propose incorporating third trimester MH testing when planning deliveries of d-TGA fetuses. This article is protected by copyright. All rights reserved.

Modeling the impact of high thermal conductivity paper on the performance and life of power transformers.

Degradation of insulation paper is a key contributor to the failure of power transformers. Insulation degradation accelerates at elevated temperatures, which highlights the potential for better thermal management to prolong life. While several studies have analyzed the benefits of high thermal conductivity oil for reducing temperatures inside a transformer, this study is an initial assessment of the benefits of high thermal conductivity paper on transformer life. Blending particulates with cellulosic fibers offers a pathway for high thermal conductivity paper (with good dielectric properties), which can reduce internal temperatures. Presently, life extensions that can be achieved by the use of such thermally conducting papers were estimated, with the thermal conductivity of the paper being the key parameter under study. The analytical-numerical thermal model used in this study was validated against experimental measurements in a distribution transformer, adding confidence to the utility of the model. This model was then used to provide estimates of hot-spot temperature reduction resulting from the use of papers with higher thermal conductivity than baseline. Transformer life was predicted conventionally by tracking the degree of polymerization of paper over time, based on an Arrhenius model. Results indicate that increasing the thermal conductivity of paper from 0.2 W/mK (baseline) to 1 W/mK reduces the hot spot temperature by 10 °C. While degradation significantly depends on the moisture and oxygen content, the model shows that such a temperature reduction can increase life for all conditions, by as much as a factor of three.

Risk of bias and limits of reporting in diagnostic accuracy studies for commercial point-of-care tests for respiratory pathogens.

Commercial point-of-care (POC) diagnostic tests for Group A Streptococcus, Streptococcus pneumoniae, and influenza virus have large potential diagnostic and financial impact. Many published reports on test performance, often funded by diagnostics companies, are prone to bias. The Standards for Reporting of Diagnostic Accuracy (STARD 2015) are a protocol to encourage accurate, transparent reporting. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool evaluates risk of bias and transportability of results. We used these tools to evaluate diagnostic test accuracy studies of POC studies for three respiratory pathogens. For the 96 studies analysed, compliance was <25% for 14/34 STARD 2015 standards, and 3/7 QUADAS-2 domains showed a high risk of bias. All reports lacked reporting of at least one criterion. These biases should be considered in the interpretation of study results.

A bibliographic exploration of nursing's scope of practice.

AIM: To conduct a bibliographic analysis of the indexed literature relating to scope of practice in nursing so as to identify underlying patterns in journal publication, volume of scholarly work over time, countries of origin, central contributors, academic affiliation and the major dimension of the studies conducted. METHODS: A systematic search of the Scopus database provided data that was then extracted and utilized to undertake a bibliometric analysis of published work relating to scope of practice. In addition to identification of aggregated metrics relating to the most frequently occurring journals and most cited authors, a co-word analysis was conducted. RESULTS: A total of 2730 articles with the term Scope of Practice in the Title, Abstract or Keywords were identified. Co-word analysis revealed five major themes - Changing Regulatory Environment; Health Care Drivers; Competence & Role Implementation; Policy Context; and Role Evolution & Role Differentiation. CONCLUSIONS AND POLICY IMPLICATIONS: From a policy perspective, we conclude that bibliographic analysis of the indexed literature is a useful technique that can augment our understanding of key regulatory issues such as scope of practice. However, the overemphasis on advanced practice in the scope of practice literature coupled with the increased interest in task shifting to support-personnel as governments pursue the goal of universal health coverage may leave nursing inadequately prepared to inform any evidence-based policy change.

Mortality of urban Aboriginal adults in Canada, 1991-2001.

OBJECTIVE: To compare mortality patterns for urban Aboriginal adults with those of urban non-Aboriginal adults. METHODS: Using the 1991-2001 Canadian census mortality follow-up study, our study tracked mortality to December 31, 2001, among a 15% sample of adults, including 16 300 Aboriginal and 2 062 700 non-Aboriginal persons residing in urban areas on June 4, 1991. The Aboriginal population was defined by ethnic origin (ancestry), Registered Indian status and/or membership in an Indian band or First Nation, since the 1991 census did not collect information on Aboriginal identity. RESULTS: Compared to urban non-Aboriginal men and women, remaining life expectancy at age 25 years was 4.7 years and 6.5 years shorter for urban Aboriginal men and women, respectively. Mortality rate ratios for urban Aboriginal men and women were particularly elevated for alcohol-related deaths, motor vehicle accidents and infectious diseases, including HIV/AIDS. For most causes of death, urban Aboriginal adults had higher mortality rates compared to other urban residents. Socio-economic status played an important role in explaining these disparities. CONCLUSION: Results from this study help fill a data gap on mortality information of urban Aboriginal people of Canada.

Mortality of urban Aboriginal adults in Canada, 1991-2001.

OBJECTIVE: To compare mortality patterns for urban Aboriginal adults with those of urban non-Aboriginal adults. METHODS: Using the 1991-2001 Canadian census mortality follow-up study, our study tracked mortality to December 31, 2001, among a 15% sample of adults, including 16 300 Aboriginal and 2 062 700 non-Aboriginal persons residing in urban areas on June 4, 1991. The Aboriginal population was defined by ethnic origin (ancestry), Registered Indian status and/or membership in an Indian band or First Nation, since the 1991 census did not collect information on Aboriginal identity. RESULTS: Compared to urban non-Aboriginal men and women, remaining life expectancy at age 25 years was 4.7 years and 6.5 years shorter for urban Aboriginal men and women, respectively. Mortality rate ratios for urban Aboriginal men and women were particularly elevated for alcohol-related deaths, motor vehicle accidents and infectious diseases, including HIV/AIDS. For most causes of death, urban Aboriginal adults had higher mortality rates compared to other urban residents. Socio-economic status played an important role in explaining these disparities. CONCLUSION: Results from this study help fill a data gap on mortality information of urban Aboriginal people of Canada.

SSR (spatially resolved refractometer): a null-seeking aberrometer.

The spatially resolved refractometer is an aberrometer used to measure the wave-front aberrations of the human eye. In its original form and the new configuration that we report, it uses the patient's perception in a psychophysical task to evaluate the wave-front errors at a variable number of loci (typically 40 or 160) across the cornea. This configuration includes pupil tracking and the ability to choose the measurement loci in software. An automated configuration that does not require patient input is also described.

MRI in the differential diagnosis of a sellar mass.

Whilst pituitary adenomas are the commonest cause of a sellar mass, there are a number of other neoplastic, infectious, inflammatory, developmental and vascular aetiologies that should be considered by the radiologist. We discuss and illustrate these lesions and indicate the various magnetic resonance imaging features that are helpful in formulating an appropriate differential diagnosis.

Immunostimulant oxidized beta-glucan conjugates.

beta-Glucans are polysaccharides that act as nonspecific immune system stimulants. However, many beta-Glucans are sparingly soluble in water. This work describes an oxidative procedure, which solubilizes the beta-Glucan from Saccharomyces cerevisiae and maintains its immunostimulatory properties. Furthermore, the carboxylates at the site of oxidation allow for the conjugation of small molecule immunostimulants. Both the parent oxidized beta-glucan and its conjugates with O-beta-alanyl-5-[6-(N,N'-dimethylamino)purin-9-yl]pentanol stimulate cytotoxic T-lymphocytes (CTLs), B cells and macrophages. In addition, they both stimulate natural killer (NK) cells, a property which the small molecule purine does not possess.

Optimal electrocardiographic leads for detecting acute myocardial ischemia.

This study identifies the most sensitive electrocardiographic leads for monitoring ST-segment changes caused by acute coronary ischemia. The data set consisted of 120-lead electrocardiograms (ECGs) digitally recorded during balloon-inflation angioplasty in 3 groups of patients with single-vessel disease (left anterior descending [LAD], 32; right coronary artery [RCA], 36; left circumflex [LCx], 23). The ST deviation was measured in all recorded leads during baseline and ischemic states, and its difference between these 2 states (DeltaST) was calculated at 352 sites and plotted as DeltaST maps. The patients in each group were divided, by means of DeltaST criteria, into subgroups of "responders" and "nonresponders." Mean DeltaSTs for each group/subgroup were calculated and standardized by the corresponding standard deviation (SD); these values were plotted as mean DeltaST and t maps. Sites where extrema of DeltaST occurred most frequently were sought in bootstrap trials, performed in each group/subgroup. The results suggest that the optimal sites for the ischemia-sensitive leads are: V(3) (+) and just below V(8) (-) for LAD-related ischemia; the left iliac crest (+) and above V(3) at the third intercostal space (-) for RCA-related ischemia; and just below V(8) (+) and above V(2) at the third intercostal space (-) for LCx-related ischemia. Three "optimal" bipolar leads using these sites registered, in the responders from the LAD, RCA, and LCx groups, mean DeltaST (+/-SD) of 232 +/- 59, 245 +/- 96 and 158 +/- 91 microV, respectively; the corresponding t values were 15.14, 9.90, and 6.75. In the 12-lead ECG, only lead V(3) approached optimal DeltaST and t values for the LAD responders (187 +/- 61 microV; t = 11.75) and lead III for the RCA responders (191 +/- 76 microV; t = 9.73), but even these values were significantly suboptimal (P = 0.0011 and P = 0.0120, respectively). We found that the "optimal" bipolar leads can be derived, to an excellent approximation, from the 12 standard leads or from 3 EASI leads (with 3 electrodes at Frank's transverse level and 1 on the manubrium), by using precalculated regression coefficients. By means of bootstrap trials, we estimated the mean sensitivity (SE) and the mean positive predictive value (PPV) with which 3 "optimal" vessel-specific leads could identify ischemia related to the LAD, RCA, and LCx arteries, in the test set, as (SE/PPV) 94.7/92.8%, 78.7/80.9%, and 81.5/80.9%. A similar diagnostic performance can be achieved by vessel-specific leads derived from the 12-lead ECG (93.0/93.4%, 76.6/82.0%, and 82.7/77.1%) and, interestingly, from the EASI lead system (97.8/88.4%, 78.0/80.2%, and 76.8/83.2%). Thus, although the "optimal" bipolar leads for detecting ischemia related to each of the 3 coronary arteries were found to require sampling outside the 12-lead ECG, these leads can be derived from the full set of 12 standard leads or--for clinical monitoring applications--from the EASI lead system by using fewer electrodes at convenient locations.

Unilateral fixed dilation of the pupil as a false-localizing sign with intracranial hemorrhage: case report and literature review.

OBJECTIVE AND IMPORTANCE: Although other focal signs may prove "false localizing," it is a neurosurgical axiom that unilateral fixed dilation of the pupil occurs ipsilateral to a supratentorial mass. CLINICAL PRESENTATION: A 25-year-old man collapsed with a dense right hemiplegia and a Glasgow Coma Scale score of 6 (eye opening, 1; motor, 4; verbal, 1) after rupture of a left middle cerebral artery aneurysm associated with an intrasylvian hematoma. Initially, both pupils had remained equal-sized and reactive: however, within hours, the right (contralateral) pupil became fixed and dilated (i.e., false localizing). For some time, the left (ipsilateral) pupil remained small and reactive; at emergency craniotomy, this also became fixed and equally dilated. INTERVENTION: After evacuation of the clot and wrapping of the aneurysm, both pupils rapidly became equal-sized and reactive. Twenty-four hours later, concurrent with massive left hemispheric swelling and a midline shift, the left (ipsilateral) pupil became unilaterally fixed and dilated (i.e., false localizing). Eventually, the right (contralateral) pupil also became fixed and dilated, concurrent with cardiovascular collapse. Death occurred within 10 hours. CONCLUSION: Unilateral fixed dilation of the pupil in patients with hemispheric mass lesions may be false localizing. Furthermore, disparate "herniating mechanisms" can arise despite mass effect emanating from the same side. Because such mechanisms cannot be witnessed, their nature remains speculative. An extensive review is contained in this article.

Synergistic anti-tumor activity of a novel immunomodulator, BCH-1393, in combination with cyclophosphamide.

N,N-dimethylaminopurine pentoxycarbonyl D-arginine (BCH-1393) is a novel low molecular weight synthetic immunomodulator that has been shown to significantly stimulate cytotoxic T-lymphocyte responses both in vitro and in vivo (Zacharie B, Gagnon L, Attardo G, Connolly TP, St-Denis Y, Penney CL. Synthesis and activity of 6-substituted purine linker amine immunostimulants. J. Med. Chem. 1997;40:2883-94). Prompted by this evidence, we extended evaluation of BCH-1393 for anticancer activity in syngeneic mouse experimental tumor models. Consistent with previous findings, in vitro assessment of BCH-1393 activity demonstrated a significant increase in the CTL responses in the range of 10(-9)-10(-5) M. Treatment of mice with four consecutive daily intraperitoneal injections at 25 and 50 mg/kg resulted in a significant increase of the relative percentage of blood CD4+, CD8+, NK and monocyte subsets without any evidence of toxicity. In vivo anti-tumor activity of BCH-1393 was evaluated, either alone or in combination with subtherapeutic doses of cyclophosphamide (Cy), against weakly immunogenic mouse breast carcinoma DA-3 and strongly immunogenic colon adenocarcinoma MC38. Daily intraperitoneal injection of BCH-1393 at 50 mg/kg alone was well tolerated but produced a relatively weak anti-tumor effect in both tumor models. However, a significant inhibition of tumor outgrowth and suppression of established tumor growth was observed when BCH-1393 was administered in combination with subtherapeutic doses of Cy. Combination treatment of 50 mg/kg BCH-1393 with 100 mg/kg Cy (given as single intravenous bolus injection) starting 2 days prior to DA-3 tumor cell inoculation prevented tumor outgrowth in 70-80% of treated mice. In the remaining 20-30% of mice that had developed tumors, a nearly complete (90%) tumor growth inhibition was observed at days 22-24 post tumor implant. In the MC38 tumor model, combination treatment of established tumors with BCH-1393 and Cy (CTX) at 50 mg/kg resulted in a significant delay in tumor growth compared to CTX treatment alone. The observed concomitant anti-tumor activity of BCH-1393 with cyclophosphamide warrants further investigation of this immunomodulator as an adjunctive treatment of cancer.

A case of Miller-Dieker syndrome in a family with neurofibromatosis type I.

The Miller-Dieker syndrome (type I lissencephaly) is a neuronal migration disorder which is associated with microdeletions in the short arm of chromosome 17. Neurofibromatosis type I (NF1) is an autosomal dominant condition associated with mutations in the long arm of chromosome 17, and characterised by neurofibromas, café-au-lait spots and axillary freckling. The neonatal period for a female infant born at 39 weeks gestation by emergency Caesarean section was complicated by frequent epileptic seizures as well as hypotonia. A computed tomography scan revealed evidence of lissencephaly, and chromosomal analysis showed a microdeletion on the short arm of chromosome 17 (17p13.3), confirming the diagnosis as Miller-Dieker syndrome. The child died at the age of 4 years and examination of the brain confirmed lissencephaly with a thickened cortex, deficient white matter, and grey matter heteropias. The mother had café-au-lait spots, and axillary freckling. In addition, the mother's and maternal grandmother's genetic analysis showed identical mutations in the neurofibromatosis I gene on the long arm of chromosome 17, confirming the diagnosis of NF1. The child did not possess the mutation. This case illustrates a rare neuronal migration disorder appearing in a child from a family with a history of NF1.

Identification of premature ovarian failure patients with underlying autoimmunity.

Although known causes of premature ovarian failure (POF) include X chromosome deletions, radiation and chemotherapy, and genetic defects of the gonadotropin hormones or receptors, at least one third to one half of cases remain idiopathic. A significant proportion of patients with apparently idiopathic POF have some evidence for an autoimmune etiology. However, the only gold standard for detecting autoimmune causes of immune ovarian destruction has been invasive ovarian biopsy. Serum antibodies to ovarian and other self-tissue have been described in up to one third of women with POF, but the tests are not well standardized, not well correlated with ovarian histology, and highly variable. Recently, specific defects of expression of cell surface markers on peripheral blood lymphocytes have been shown to identify, in population-based studies, individuals destined to develop autoimmune pancreatic destruction and type I diabetes mellitus, even before any other evidence of autoimmunity. We, therefore, sought to test the ability of cell surface marker expression in women with POF to identify autoimmune defects. Seventeen women with POF, 11 of whom had positive antibody titers to ovary, thyroid, or antinuclear antibody, were studied on at least two occasions and compared in blinded fashion with normal controls and patients with autoimmune type I diabetes mellitus. The most useful marker for identifying autoimmunity was the surface density of conformationally correct HLA class I molecules on macrophages, a structure essential for T cell education. Using this marker, 7 of the 9 patients with autoantibodies and 3 of the 8 patients without autoantibodies were identified as having evidence of a defect in self-antigen presentation similar to that of type I diabetics (chi-square, p = 0.03). Subsequent testing identified antismooth muscle antibodies in 1 of the women with a defect of HLA class I molecules but no previously identified autoimmunity. In addition, there were increased numbers of CD8 T cells in both autoimmune POF and insulin-dependent diabetes mellitus (IDDM) patients. Exclusive to POF patients was a statistically significant increase in CD8 density on T cells. This was most prominent in POF patients with an underlying autoimmune etiology. These data further support a role for autoimmunity in POF patients and suggest that the further development of cell surface markers in combination with other diagnostic tests could result in diagnosis before the development of complete ovarian failure. The possibility for disease-specific therapy to prevent further autoimmune ovarian damage in selected POF patients is also envisioned.

D-LysAsnProTyr tetrapeptide: a novel B-cell stimulant and stabilized bursin mimetic.

The tetrapeptide I (D-lysine-L-asparaginyl-L-prolyl-L-tyrosine or D-LysAsnProTyr), and analogue sequences, were synthesized and evaluated for the ability to stimulate immune cell subsets. These sequences were selected based on their perceived ability to readily adopt a beta-turn structure. In vitro immunological assays revealed a robust stimulation of mitogen activated B-cell proliferation and a modest to significant stimulation of cytotoxic T lymphocytes (CTLs). Further, this in vitro stimulation of B-cells was accompanied by an in vivo expansion of B-cells in C57BL/6 mice, as demonstrated by immunophenotyping experiments. Interestingly, a conformational analysis of the low energy conformers of I and the endogenous B-cell stimulant bursin (LysHisGlyNH2) shows that these molecules can be superimposed. However, I displayed significantly enhanced physiological stability. For a number of reasons, I may be a particularly useful vaccine adjuvant.

Extra-cranial branch of the internal carotid artery.

It has been argued in recent years that angiography is no longer essential before undertaking a carotid endarterectomy, relying solely on a carotid duplex scan. A case is presented where an extra-cranial branch of the internal carotid artery was found at surgery. This unexpected finding was obviated having obtained preoperative angiograms. Anomalies of the internal carotid artery are reviewed.

Unusual radiological appearance of a skull osteoma.

A 24-year-old woman presented with a 7-week history of headache and left frontal scalp swelling. A plain radiograph and CT demonstrated a 2-cm lytic lesion in the frontal bone which was excised via craniotomy. Histology showed this to be an osteoma. Osteomas very rarely, if ever, appear as lytic lesions. The differential and radiological diagnoses are discussed.

Thioamides: synthesis, stability, and immunological activities of thioanalogues of Imreg. Preparation of new thioacylating agents using fluorobenzimidazolone derivatives.

Imreg (Tyr1-Gly2-Gly3) is a well-known immunostimulant. However, it possesses a short half-life. Stabilized analogues of Imreg were prepared by a regioselective insertion in which peptide bonds at position 1,2 or 2,3 were replaced by thioamide linkages. This was achieved by using new thioacylating agents based on thioacyl-fluoro-N-benzimidazolone. The synthesis and properties of these reagents are described herein. This peptide modification enhanced significantly the half-life of the thioanalogues relative to Imreg in blood. The thioanalogues and Imreg were tested in vitro in T and B cell proliferation assays and for their ability to stimulate cytotoxic T-lymphocytes (CTLs). Only thiotyrosyl glycyl glycine 11 displayed some activity as evidenced by a weak stimulation of CTLs. On the basis of this activity and the increased stability, an in vivo immunological evaluation was undertaken. Immunophenotyping of 11 revealed a significant increase in activated CTL and NK cell populations in the spleen. This expansion was also accompanied by a significant stimulation of NK cells and the B cell proliferative response. Thioanalogues of Imreg were generally nontoxic, as exemplified by 11. The latter is a promising immunostimulant which may be targeted for cancer and viral infections, where CTLs and NK cells play an important role, or as a vaccine adjuvant where stimulation of antibody-producing B cells is important.

Unusual modality effects in less-skilled readers.

University students who were skilled or less-skilled readers were compared on tests of auditory information processing and immediate serial recall of auditory and visual digits. Reading skill was defined by performance on a pseudoword reading task. The good readers exhibited typical modality effects with higher recall of auditory than visual items from the last 3 serial positions. On the terminal list item, the less-skilled readers showed a modality effect comparable with that of the skilled readers, but on other list items the modality effect reversed and a visual superiority was obtained. Results were discussed in terms of C. G. Penney's (1989) separate-streams model of short-term verbal memory.