Associations between nutritional energy delivery, bioimpedance spectroscopy and functional outcomes in survivors of critical illness.

BACKGROUND: Patients who survive critical illness frequently develop muscle weakness that can impact on quality of life; nutrition is potentially a modifiable risk factor. The present study aimed to explore the associations between cumulative energy deficits (using indirect calorimetry and estimated requirements), nutritional and functional outcomes. METHODS: A prospective single-centre observational study of 60 intensive care unit (ICU) patients, who were mechanically ventilated for at least 48 h, was conducted. Cumulative energy deficit was determined from artificial nutrition delivery compared to targets. Measurements included: (i) at recruitment and ICU discharge, weight, fat-free mass (bioimpedance spectroscopy) and malnutrition (Subjective Global Assessment score B/C); (ii) at awakening and ICU discharge, physical function (Physical Function in Intensive Care Test-scored) and muscle strength (Medical Research Council sum-score (MRC-SS). ICU-acquired weakness was defined as a MRC-SS score of less than 48/60. RESULTS: The median (interquartile range) cumulative energy deficit compared to the estimated targets up to ICU day 12 was 3648 (2514-5650) kcal. Adjusting for body mass index, age and severity of illness, cumulative energy deficit (per 1000 kcal) was independently associated with greater odds of ICU-acquired weakness [odds ratio (OR) = 2.1, 95% confidence interval (CI) = 1.4-3.3, P = 0.001] and malnutrition (OR = 1.9, 95% CI = 1.1-3.2, P = 0.02). In similar multivariable linear models, cumulative energy deficit was associated with reductions in fat-free mass (-1.3 kg; 95% CI = -2.4 to -0.2, P = 0.02) and physical function scores (-0.6 points; 95% CI = -0.9 to -0.3, P = 0.001). CONCLUSIONS: Cumulative energy deficit from artificial nutrition support was associated with reduced functional outcomes and greater loss of fat-free mass in ventilated ICU patients.

Masculinisation of the zebra finch song system: roles of oestradiol and the Z-chromosome gene tubulin-specific chaperone protein A.

Robust sex differences in brain and behaviour exist in zebra finches. Only males sing, and forebrain song control regions are more developed in males. The factors driving these differences are not clear, although numerous experiments have shown that oestradiol (E2 ) administered to female hatchlings partially masculinises brain and behaviour. Recent studies suggest that an increased expression of Z-chromosome genes in males (ZZ; females: ZW) might also play a role. The Z-gene tubulin-specific chaperone A (TBCA) exhibits increased expression in the lateral magnocellular nucleus of the anterior nidopallium (LMAN) of juvenile males compared to females; TBCA+ cells project to the robust nucleus of the arcopallium (RA). In the present study, we investigated the role of TBCA and tested hypotheses with respect to the interactive or additive effects of E2 and TBCA. We first examined whether E2 in hatchling zebra finches modulates TBCA expression in the LMAN. It affected neither the mRNA, nor protein in either sex. We then unilaterally delivered TBCA small interfering (si)RNA to the LMAN of developing females treated with E2 or vehicle and males treated with the aromatase inhibitor, fadrozole, or its control. In both sexes, decreasing TBCA in LMAN reduced RA cell number, cell size and volume. It also decreased LMAN volume in females. Fadrozole in males increased LMAN volume and RA cell size. TBCA siRNA delivered to the LMAN also decreased the projection from this brain region to the RA, as indicated by anterograde tract tracing. The results suggest that TBCA is involved in masculinising the song system. However, because no interactions between the siRNA and hormone manipulations were detected, TBCA does not appear to modulate effects of E2 in the zebra finch song circuit.

Anomalous origin of 4 coronary ostia from the right sinus of Valsalva in a patient with hypertrophic cardiomyopathy.

Anomalous origin of 4 separate coronary ostia from a single coronary sinus has rarely been reported. We report what is to our knowledge a previously undescribed variation characterized by the left anterior descending, left ramus, left circumflex, and right coronary arteries originating from separate ostia in the right sinus of Valsalva. In addition, the autopsy disclosed features of hypertrophic cardiomyopathy, rarely associated with congenital coronary anomalies.

BrainImageJ: a Java-based framework for interoperability in neuroscience, with specific application to neuroimaging.

The Human Brain Project consortium continues to struggle with effective sharing of tools. To facilitate reuse of its tools, the Stanford Psychiatry Neuroimaging Laboratory (SPNL) has developed BrainImageJ, a new software framework in Java. The framework consists of two components-a set of four programming interfaces and an application front end. The four interfaces define extension pathways for new data models, file loaders and savers, algorithms, and visualization tools. Any Java class that implements one of these interfaces qualifies as a BrainImageJ plug-in-a self-contained tool. After automatically detecting and incorporating new plug-ins, the application front end transparently generates graphical user interfaces that provide access to plug-in functionality. New plug-ins interoperate with existing ones immediately through the front end. BrainImageJ is used at the Stanford Psychiatry Neuroimaging Laboratory to develop image-analysis algorithms and three-dimensional visualization tools. It is the goal of our development group that, once the framework is placed in the public domain, it will serve as an interlaboratory platform for designing, distributing, and using interoperable tools.

Edge complexity and partial volume effects.

PURPOSE: The accuracy of MR brain image segmentation is limited by so-called partial volume effects. We hypothesized that "edge complexity" (i.e., tissue class interface border complexity) significantly influences the magnitude of such effects. METHOD: To investigate partial volume effects and provide a vehicle for validation of segmentation algorithm accuracy in brain MRI. We developed a computer simulation, the "gigabrain." The simulation is based on interpolated (supersampled) data from actual MR studies. The voxels are assigned to one of five compartments (gray matter, white matter, CSF, fat, or "background"), the compartment interfaces are "jittered" to add high frequency "signal" or "edge complexity," and the voxels are populated with appropriate values determined from human data, low pass filtered (based on the MR scanner's point spread function), and subsampled back to the sampling and voxel size of the original MR data set. RESULTS: In comparison studies with actual phantoms and human MR data, our simulation approach was able to produce images whose appearance and quantitative values were comparable with the actual data, but only when edge complexity was added to the original MR data. CONCLUSION: Edge complexity is a significant source of partial volume effects. MR simulations must include edge complexity to adequately test segmentation algorithms.

Reliability and validity of an algorithm for fuzzy tissue segmentation of MRI.

PURPOSE: A new multistep, volumetric-based tissue segmentation algorithm that results in fuzzy (or probabilistic) voxel description is described. This algorithm is designed to accurately segment gray matter, white matter, and CSF and can be applied to both single channel high resolution and multispectral (multiecho) MR images. METHOD: The reliability and validity of this method are evaluated by assessing (a) the stability of the algorithm across time, rater, and pulse sequence; (b) the accuracy of the method when applied to both real and synthetic image datasets; and (c) differences in specific tissue volumes between individuals with a specific genetic condition (fragile X syndrome) and normal control subjects. RESULTS: The algorithm was found to have high reliability, accuracy, and validity. The finding of increased caudate gray matter volume associated with the fragile X syndrome is replicated in this sample. CONCLUSION: Since this segmentation approach incorporates "fuzzy" or probabilistic methods, it has the potential to more accurately address partial volume effects, anatomical variation within "pure" tissue compartments, and more subtle changes in tissue volumes as a result of disease and treatment. The method is a component of software that is available in the public domain and has been implemented on an inexpensive personal computer thus offering an attractive and promising method for determining the status and progression of both normal development and pathology of the CNS.

A phase I trial of neutron brachytherapy for the treatment of malignant gliomas.

We performed a phase I trial to test the feasibility of neutron brachytherapy using californium-252 (252Cf) as the sole source of radiation, and to determine the maximum tolerable dose (MTD), for the treatment of malignant gliomas. Previous studies using external beam neutron radiation have shown that neutrons are capable of totally eradicating malignant gliomas. However, in most cases, fatal widespread radiation necrosis resulted. Radioactive implants are a logical method of increasing the dose to the tumour and decreasing the dose to normal brain. 252Cf is a relatively stable neutron-emitting isotope suitable for implant therapy. The study was an open ended dose-escalation study. All radiation was delivered by using only 252Cf implants, without external beam therapy of any type. The first dose step was 900 neutron cGy (ncGy); each subsequent step was increased by 100 ncGy. Three patients with newly diagnosed malignant gliomas were entered at each dose step, and the number was increased to six patients in dose steps at which necrosis of brain occurred. The study ended when two patients at any dose step developed radiation necrosis of brain outside the prescribed radiation field. 33 patients were entered into the study. 10 patients developed scalp necrosis associated with scalp doses above 900 ncGy. The study ended when two patients at the 1300 ncGy dose step developed radiation necrosis of brain. We conclude: (1) neutron brachytherapy using 252Cf as the sole source of radiation is a feasible treatment for malignant gliomas; (2) the scalp tolerates less neutron radiation than the brain; (3) the MTD (and the recommended dose for a phase II trial) of interstitial neutron brachytherapy is 1200 ncGy.

The quality improvement strategy.

To prepare for managed competition, many hospitals now focus on service quality as a means to improve their competitive position. To aid in decisions about where best to direct limited resources, managers need physician feedback about how the hospital's services compare with its competitors' services (competitive advantage) and about the degree to which the hospital's services fall short of, meet, or exceed physicians' expectations (customer satisfaction). This article describes a strategy for acquiring information about competitive advantage and customer satisfaction and for using the information to identify optimal service improvement opportunities. It then presents a step-by-step application of the Quality Improvement Strategy (QIS) for a large urban hospital.

The treatment perspectives of physicians, citizens, and state legislators.

This study addresses the dilemma of physicians to act both as an agent of their patients and as an agent of society. We contrasted the perceptions of physicians, citizens at large, and state legislators about 11 topics related to physician decision making regarding the management of care for seriously ill patients. Significant and interpretable differences were found between physicians and citizens, although there were no differences between these two groups and the state legislators. However, even the obtained differences were fewer and smaller than expected. These results suggest that lay, legislative, and medical viewpoints may be less at odds with each other than the literature would suggest, and reaching an accord on at least some aspects of health policy may not be as difficult as generally is assumed.

A template for rigid stereotaxic afterloading brachytherapy of the brain.

PURPOSE: This paper describes a system for the implantation of rigid stainless steel afterloading tubes into the brain using a stereotaxic head frame for both localization and treatment. METHODS AND MATERIALS: The stereotaxic frame is attached to the skull throughout the treatment, and the afterloading tubes are both rigid and fixed to the frame. The source positions are therefore fixed relative to the skull throughout the irradiation. Design and construction of templates, afterloading tubes and clamps are discussed in detail. RESULTS: The rigidity of the resulting implant provides accurate and immobile positioning of the planned isodose distribution relative to the defined treatment volume and makes it possible to carefully and rapidly plan a source loading which will best cover the volume of interest. The source template is not in contact with the patient at any time. The afterloading tubes are held strictly parallel during treatment, allowing for rapid and versatile preplanning prior to surgical placement. Placement options are enhanced by using a set of rotating templates. CONCLUSION: This system has been used for over 60 procedures without any mechanical or safety problems and has provided a significant improvement in both the speed and confidence of localization and treatment planning. There are significant advantages of such a system for High Dose Rate Afterloading Brachytherapy.

Personal importance, motivation, and performance of older adults.

This investigation was conducted to examine whether older adults would improve their performance when given statements intended to make them feel important to a research study as well as statements concerning their over-all well-being. Women (n = 14) and men (n = 15) with mean ages of 76.0 yr. and 75.1 yr., respectively, were randomly assigned into a control group, a positive reinforcement group, and a group given statements of personal importance. Dependent measures on a rotary pursuit task, screw-and-nut assembly task, and an interest questionnaire were obtained during three separate visits. Data were analyzed with a 3 x 3 (Groups x Days) analysis of variance. While no significant group effects were found on any measure, a significant main effect was obtained for days, indicative of learning.

A regulatory gene as a novel visible marker for maize transformation.

The temporal and spatial patterns of anthocyanin pigmentation in the maize plant are determined by the presence or absence of the R protein product, a presumed transcriptional activator. At least 50 unique patterns of pigmentation, conditioned by members of the R gene family, have been described. In this study, microprojectiles were used to introduce into maize cells a vector containing the transcription unit from one of these genes (Lc) fused to a constitutive promoter. This chimeric gene induces cell autonomous pigmentation in tissues that are not normally pigmented by the Lc gene. As a reporter for gene expression studies in maize, R is unique because it can be quantified in living tissue simply by counting the number of pigmented cells following bombardment. R may also be useful as a visible marker for selecting stably transformed cell lineages that can give rise to transgenic plants.

The Ds1 transposable element acts as an intron in the mutant allele Adh1-Fm335 and is spliced from the message.

The Ds-induced maize Adh1 allele Adh1-Fm335 retains its anaerobic regulation and normal transcription start site despite the presence of the 405 bp Ds element in the 5' untranslated leader region of the gene. The steady state level of Adh1-specific transcript is reduced to about 1% that of the progenitor or revertant alleles. Run-on transcription studies show that the reduced level of Adh1 specific mRNA is not attributable to a decreased transcription rate. S1 mapping indicates that the Ds element is spliced from the Adh1-Fm335 transcript using a donor site 14 bp into the Ds element and an acceptor site at the 3' junction of the Ds element with the flanking genome DNA.

cDNA and protein sequence of a major pea seed albumin (PA 2 : Mr≈26 000).

Pea albumin 2 (PA2:Mr≈26000) is a major component of the albumin fraction derived from aqueous salt extracts of pea seed. Sodium dodecylsulfate-polyacrylamide gel electrophoresis and chromatography on DEAE-Sephacel resolve PA2 into two closely related components (PA2a and PA2b). A cDNA clone coding for one of these components has been sequenced and the deduced amino acid sequence compared with partial, chemically-determined sequences for cyanogen bromide peptides from both PA2 components. Complete amino acid sequences were obtained for the C-terminal peptides. The PA2 molecule of 230 amino acids contains four imperfect repeat sequences each of approximately 57 amino acids in length.The combined sequence data, together with a comparison of PA2-related polypeptides produced in vitro and in vivo, indicate that PA2 is synthesized without a signal sequence and does not undergo significant post-translational modification. Although both forms of PA2 contain Asn-X-Thr consensus sequences, neither form is glycosylated. Accumulation of PA2 contributes approximately 11% of the sulfur-amino acids in pea seeds (cysteine plus methionine equals 2.6 residues percent). Suppression of levels of PA2 polypeptides and their mRNAs in developing seeds of sulfur-deficient plants is less marked than that for legumin, in spite of the lower content of sulfur-amino acids in legumin.

The flu shot study: using multiattribute utility theory to design a vaccination intervention.

Differences between the multiattribute utility (MAU) profiles of participants who had previously gotten flu shots and those who had not done so were used to design an informational brochure urging influenza vaccination. The effectiveness of the MAU brochure was evaluated in a VA ambulatory care clinic with a long-standing influenza vaccination program. The target population for the intervention was high-risk clinic patients who had not gotten a shot the previous year. Participants received either a letter urging them to get a flu shot, or a letter plus the informational brochure. A significantly larger proportion of the patients who received the brochure got shots; 36% versus 23% for the letter only. While a 13 percentage point increase is modest, influenza and related complications (preventable through vaccination) are the fourth-leading killers of older persons. Adding a MAU-based brochure to an ongoing vaccination program is inexpensive and may save additional lives.

Gene structure, protein structure, and regulation of the synthesis of a sulfur-rich protein in pea seeds.

Two low molecular weight pea seed albumins (Mr approximately 6000 and approximately 4000) have been characterized by protein, cDNA, and gene sequencing. Both proteins are encoded by separate regions of the same mRNA species. The initial translation product is a preproprotein from which a signal sequence is removed co-translationally. The resultant proprotein (PA1) is then cleaved post-translationally to yield the mature form of the two albumins (PA1a and PA1b). Comparison of cDNA and protein sequences suggests that at least four different PA1 genes are expressed in the pea genome. Both PA1a and PA1b have an unusually high cysteine content (7.5 and 16.2%, respectively). Pea seeds developing under suboptimal levels of sulfur nutrient supply contain reduced levels of PA1 mRNA and accumulate greatly reduced levels of PA1a and PA1b in the mature seed. In vitro transcription studies showed that this reduced level of PA1 mRNA resulted from reduced post-transcriptional stability rather than an altered rate of transcription of the PA1 gene. In contrast, during normal seed development, the level of PA1 mRNA seems to be under transcriptional control. Sequence comparisons reveal some homology between PA1 and a number of low molecular weight proteins from seeds of a wide range of mono- and dicotyledonous plants.

Developing and testing a decision model for predicting influenza vaccination compliance.

Influenza vaccination has long been recommended for elderly high-risk patients, yet national surveys indicate that vaccination compliance rates are remarkably low (20 percent). We conducted a study to model prospectively the flu shot decisions and subsequent behavior of an elderly and/or chronically diseased (at high risk for complications of influenza) ambulatory care population at the Seattle VA Medical Center. Prior to the 1980-81 flu shot season, a random (stratified by disease) sample of 63 patients, drawn from the total population of high-risk patients in the general medicine clinic, was interviewed to identify patient-defined concerns regarding flu shots. Six potential consequences of influenza and nine of vaccination were emphasized by patients and provided the content for a weighted hierarchical utility model questionnaire. The utility model provides an operational framework for (1) obtaining subjective value and relative importance judgments from patients; (2) combining these judgments to obtain a prediction of behavioral intention and behavior for each patient; and, if the model is valid (predictive of behavior), (3) identifying those factors which are most salient to patient's decisions and subsequent behavior. Prior to the 1981-82 flu season, the decision model questionnaire was administered to 350 other high-risk patients from the same general medicine clinic population. The decision model correctly predicted behavioral intention for 87 percent and vaccination behavior for 82 percent of this population and, more importantly, differentiated shot "takers" and "nontakers" along several attitudinal dimensions that suggest specific content areas for clinical compliance intervention strategies.