Showing papers by "University of Virginia published in 1993"

The role of secondary brain injury in determining outcome from severe head injury.

Abstract: As triage and resuscitation protocols evolve, it is critical to determine the major extracranial variables influencing outcome in the setting of severe head injury. We prospectively studied the outcome from severe head injury (GCS score < or = 8) in 717 cases in the Traumatic Coma Data Bank. We investigated the impact on outcome of hypotension (SBP < 90 mm Hg) and hypoxia (Pao2 < or = 60 mm Hg or apnea or cyanosis in the field) as secondary brain insults, occurring from injury through resuscitation. Hypoxia and hypotension were independently associated with significant increases in morbidity and mortality from severe head injury. Hypotension was profoundly detrimental, occurring in 34.6% of these patients and associated with a 150% increase in mortality. The increased morbidity and mortality related to severe trauma to an extracranial organ system appeared primarily attributable to associated hypotension. Improvements in trauma care delivery over the past decade have not markedly altered the adverse influence of hypotension. Hypoxia and hypotension are common and detrimental secondary brain insults. Hypotension, particularly, is a major determinant of outcome from severe head injury. Resuscitation protocols for brain injured patients should assiduously avoid hypovolemic shock on an absolute basis.

On the Use of Polynomial Regression Equations As An Alternative to Difference Scores in Organizational Research

Abstract: For decades, difference scores have been widely used in studies of congruence in organizational research. Although methodological problems with difference scores are well known, few viable alternat...

Shallow water analogy for a ballistic field effect transistor: New mechanism of plasma wave generation by dc current.

Abstract: We demonstrate that electrons in a ballistic field effect transistor behave as a fluid similar to shallow water. Phenomena similar to wave and soliton propagation, hydraulic jump, and others should take place in this electron fluid. We show that a relatively slow electron flow should be unstable because of plasma wave amplification due to the reflection from the device boundaries. This provides a new mechanism for the generation of tunable far infrared electromagnetic radiation.

Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase

Abstract: The guanosine triphosphate (GTP)-binding protein Ras functions in regulating growth and differentiation; however, little is known about the protein interactions that bring about its biological activity. Wild-type Ras or mutant forms of Ras were covalently attached to an insoluble matrix and then used to examine the interaction of signaling proteins with Ras. Forms of Ras activated either by mutation (Gly12Val) or by binding of the GTP analog, guanylyl-imidodiphosphate (GMP-PNP) interacted specifically with Raf-1 whereas an effector domain mutant, Ile36Ala, failed to interact with Raf-1. Mitogen-activated protein kinase (MAP kinase) activity was only associated with activated forms of Ras. The specific interaction of activated Ras with active MAP kinase kinase (MAPKK) was confirmed by direct assays. Thus the forming of complexes containing MAPKK activity and Raf-1 protein are dependent upon the activity of Ras.

Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3',5'-monophosphate

Abstract: Mitogen-activated protein (MAP) kinases p42mapk and p44mapk are activated in cells stimulated with epidermal growth factor (EGF) and other agents. A principal pathway for MAP kinase (MAPK) activation by EGF consists of sequential activations of the guanine nucleotide exchange factor Sos, the guanosine triphosphate binding protein Ras, and the protein kinases Raf-1, MAPK kinase (MKK), and MAPK. Because adenosine 3',5'-monophosphate (cAMP) does not activate MAPK and has some opposing physiologic effects, the effect of increasing intracellular concentrations of cAMP with forskolin and 3-isobutyl-1-methylxanthine on the EGF-stimulated MAPK pathway was studied. Increased concentrations of cAMP blocked activation of Raf-1, MKK, and MAPK in Rat1hER fibroblasts, accompanied by a threefold increase in Raf-1 phosphorylation on serine 43 in the regulatory domain. Phosphorylation of Raf-1 in vitro and in vivo reduces the apparent affinity with which it binds to Ras and may contribute to the blockade by cAMP.

A Network Model of Organization Formation

Abstract: This paper presents a network model of organization formation and builds upon theories of social and socioeconomic exchange. The model explains the transformation of exchange relationships from a s...

Power system observability with minimal phasor measurement placement

Abstract: The placement of a minimal set of phasor measurement units (PMUs) so as to make the system measurement model observable, and thereby linear, is investigated. A PMU placed at a bus measures the voltage as well as all the current phasors at that bus, requiring the extension of the topological observability theory. In particular, the concept of spanning tree is extended to that of spanning measurement subgraph with an actual or a pseudomeasurement assigned to each of its branches. The minimal PMU set is found through a dual search algorithm which uses both a modified bisecting search and a simulated-annealing-based method. The former fixes the number of PMUs while the latter looks for a placement set that leads to an observable network for a fixed number of PMUs. In order to accelerate the procedure, an initial PMU placement is provided by a graph-theoretic procedure which builds a spanning measurement subgraph according to a depth-first search. From computer simulation results for various test systems it appears that only one fourth to one third of the system buses need to be provided with PMUs in order to make the system observable. >

Maintaining Mobility in Late Life. I. Demographic Characteristics and Chronic Conditions

Abstract: To assess the role of demographic factors and chronic conditions in maintaining mobility in older persons, this study utilized longitudinal data collected as part of the Established Populations for Epidemiologic Studies of the Elderly between 1981 and 1987 on 6,981 men and women aged 65 years and older in East Boston, Massachusetts; Iowa and Washington counties, Iowa; and New Haven, Connecticut. Results are presented for those who at baseline reported intact mobility, defined as the ability to climb stairs and walk a half mile without help, and who were followed annually for up to 4 years for changes in mobility status. Age, income, education, and chronic conditions present at baseline and occurring during follow-up were evaluated for their association with loss of mobility. Over the follow-up period, 55.1% of subjects maintained mobility, 36.2% lost mobility, and 8.7% died without evidence of mobility loss prior to death. In both men and women, increasing age and lower income levels were associated with increased risk of losing mobility, even after controlling for the presence of chronic conditions at baseline. After adjustment for age, income, and chronic conditions, lower education levels were a significant risk factor for mobility loss in men, but not in women. Baseline reports of previous heart attack, stroke, high blood pressure, diabetes, dyspnea, and exertional leg pain were associated with small but significant risks for mobility loss. There was a stepwise increase in the risk of mobility loss according to the number of chronic conditions present at baseline that was very consistent between men and women. The occurrence during the study of a new heart attack, stroke, cancer, or hip fracture was associated with a substantially greater risk of mobility loss than was associated with the presence of these conditions at baseline.

Introspecting about Reasons can Reduce Post-Choice Satisfaction

Abstract: This study tested the prediction that introspecting about the reasons for one's preferences would reduce satisfaction with a consumer choice Subjects evaluated two types of posters and then chose one to take home Those instructed to think about their reasons chose a different type of poster than control subjects and, when contacted 3 weeks later, were less satisfied with their choice When people think about reasons, they appear to focus on attributes of the stimulus that are easy to verbalize and seem like plausible reasons but may not be important causes of their initial evaluations When these attributes imply a new evaluation of the stimulus, people change their attitudes and base their choices on these new attitudes Over time, however, people's initial evaluation of the stimulus seems to return, and they come to regret choices based on the new attitudes

Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex.

Abstract: Two related cellular proteins, p80 and p85 (cortactin), become phosphorylated on tyrosine in pp60src-transformed cells and in cells stimulated with certain growth factors. The amino-terminal half of cortactin is comprised of multiple copies of an internal, tandem 37-amino acid repeat. The carboxyl-terminal half contains a distal SH3 domain. We report that cortactin is an F-actin-binding protein. The binding to F-actin is specific and saturable. The amino-terminal repeat region appears to be both necessary and sufficient to mediate actin binding, whereas the SH3 domain had no apparent effect on the actin-binding activity. Cortactin, present in several different cell types, is enriched in cortical structures such as membrane ruffles and lamellipodia. The properties of cortactin indicate that it may be important for microfilament-membrane interactions as well as transducing signals from the cell surface to the cytoskeleton. We suggest the name cortactin, reflecting the cortical subcellular localization and its actin-binding activity.

Quantitative planar rest-redistribution 201Tl imaging in detection of myocardial viability and prediction of improvement in left ventricular function after coronary bypass surgery in patients with severely depressed left ventricular function.

Abstract: BACKGROUNDAlthough many patients with multivessel coronary artery disease (CAD) and severely depressed left ventricular (LV) function will benefit from coronary artery bypass graft surgery (CABG), surgeons may be reluctant to perform CABG on these patients without evidence of myocardial viability in regions of severe asynergy. We hypothesized that quantitative planar rest-redistribution 201Tl imaging would identify viable myocardium and predict improved regional and global function after revascularization in patients with depressed LV function and CAD.METHODS AND RESULTSTwenty-one patients (mean LV ejection fraction, 0.27 +/- 0.05) were studied. Regional and global LV functions were evaluated before and 8 weeks after CABG with radionuclide ventriculography. Segments were prospectively classified as showing normal, mildly reduced, or severely reduced viability on the basis of quantitative analysis of defect severity and redistribution on planar resting 201Tl imaging. By 201Tl criteria, 90% of hypokinetic s...

Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor.

Abstract: Thrombin has been implicated in the stimulation of smooth muscle cell (SMC) proliferation that contributes to post angioplasty restenosis. The present studies demonstrated that human alpha-thrombin was a potent and efficacious mitogen for cultured rat aortic SMC, stimulating an increase in 3H-thymidine incorporation, as well as an increase in cell number at 1 to 10 nM concentration. gamma-Thrombin, which is enzymatically active but lacks fibrinogen clotting activity, stimulated SMC mitogenesis but was approximately 10-fold less potent than alpha-thrombin. In contrast, D-phenylalanyl-L-propyl-L-arginyl-chloromethyl ketone-alpha-thrombin, which lacked enzymatic activity, had no mitogenic effect. Diisopropylfluorophosphate-alpha-thrombin failed to stimulate mitogenesis except at concentrations having equivalent enzymatic activity as that of alpha-thrombin at its threshold for mitogenesis. Thus, thrombin-induced proliferation was dependent on enzymatic activity. A 14-residue peptide (SFLLRNPNDKYEPF) corresponding to amino acids 42 through 55 of the human thrombin receptor (Vu, T. K., D. T. Hung, V. I. Wheaton, and S. R. Coughlin, 1991. Cell. 64:1057-1068) had full efficacy in stimulating SMC proliferation. Reversing the first two amino acids of this peptide abolished mitogenic activity. Northern analysis demonstrated that SMC expressed a single mRNA species that hybridized to a labeled thrombin receptor cDNA probe. These findings indicate that alpha-thrombin stimulates SMC proliferation via the proteolytic activation of a receptor very similar or identical to that previously identified.

Regenerative proliferation in inner ear sensory epithelia from adult guinea pigs and humans

Abstract: Supporting cells in the vestibular sensory epithelia from the ears of mature guinea pigs and adult humans proliferate in vitro after treatments with aminoglycoside antibiotics that cause sensory hair cells to die. After 4 weeks in culture, the epithelia contained new cells with some characteristics of immature hair cells. These findings are in contrast to expectations based on previous studies, which had suggested that hair cell loss is irreversible in mammals. The loss of hair cells is responsible for hearing and balance deficits that affect millions of people.

Sensitization and Exposure to Indoor Allergens as Risk Factors for Asthma among Patients Presenting to Hospital

Abstract: To investigate the role of indoor allergens in adult patients with acute asthma, we conducted a case-controlled study on patients presenting to an emergency room One hundred and fourteen patients and 114 control subjects were enrolled over a 1-yr period in Wilmington, Delaware Sera were assayed for total IgE, and for IgE antibodies to dust mites, cat dander, cockroach, grass pollen, and ragweed pollen Dust was obtained from 186 homes and assayed for dust mite, cat, and cockroach allergens IgE antibodies to mite, cat, and cockroach were each significantly associated with asthma, and this association was very strong among participants without medical insurance and among African Americans Among 99 uninsured participants, sensitization to one of the indoor allergens (> 200 RAST units) was present in 28 of 57 asthmatics and in one of 42 control subjects (odds ratio, 39; confidence interval, 94 to 166) For cat and cockroach the combination of sensitization and presence of allergen in the house was significantly associated with asthma Furthermore, there was a strong inverse relationship between IgE antibodies to cat and to cockroach, and the risk of this sensitization was in large part restricted to homes or areas with high levels of allergen Thirty-eight percent of the asthmatics, but only 8% of the control subjects, were allergic to one of the three indoor allergens, and had high levels of the relevant allergen in their houses (odds ratio, 74; confidence interval, 33 to 165)(ABSTRACT TRUNCATED AT 250 WORDS)

Pharyngeal Fat in Obstructive Sleep Apnea

Abstract: Although most patients with obstructive sleep apnea (OSA) are obese, it is not known how obesity contributes to airway collapse during sleep. The purpose of this study was to determine whether the volume of adipose tissue adjacent to the pharyngeal airway in humans is related to the degree of OSA. We studied 30 subjects, nine without OSA and 21 with OSA; two subjects were studied before and after weight loss. Adipose tissue was detected with magnetic resonance imaging using T1-weighted spin echo sequences. The volume of adipose tissue adjacent to the upper airway was determined by measuring the volume of all pixels in the intensity range of adipose tissue within the region bounded by the ramus of the mandible, the spine, the anterior border of the soft palate, and the hard palate. Polysomnography was performed with conventional techniques. All subjects had a collection of adipose tissue adjacent to the upper airway; the volume of this adipose tissue correlated with the number of apneas plus hypopneas per hour of sleep (r = 0.59, p < 0.001). Both patients who lost weight and had fewer apneas and hypopneas had a marked decrease in the pharyngeal adipose tissue volume. We conclude that adipose tissue is deposited adjacent to the pharyngeal airway in patients with OSA and that the volume of this tissue is related to the presence and degree of OSA.

Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions.

Abstract: The integrin family of heterodimeric cell surface receptors play critical roles in multiple biological processes by mediating cellular adhesion to the extracellular matrix (ECM). Adhesion triggers intracellular signaling cascades, including tyrosine phosphorylation and elevation of [Ca2+]i. The Focal Adhesion Kinase (FAK or pp125FAK), a protein tyrosine kinase that colocalizes with integrins in cellular focal adhesions, is a prime candidate for a mediator of integrin signaling events. Here we report an analysis of the domain structure of FAK in which we have identified a contiguous stretch of 159 amino acids within the COOH terminus essential for correct subcellular localization. When placed in the context of an unrelated cytosolic protein, this Focal Adhesion Targeting (FAT) sequence functions to efficiently mediate the focal adhesion localization of this fusion protein. Furthermore, this analysis suggests that pp125FAK cannot be activated oncogenically by mutation. This result could be explained if pp125FK either exhibits a narrow substrate specificity or is diametrically opposed by cellular phosphatases or other cellular processes.

Specificity in the efferent projections of the nucleus accumbens in the rat: comparison of the rostral pole projection patterns with those of the core and shell.

Abstract: The efferent connections of the rostral pole of the rat accumbens, where distinct core and shell subterritories can not be identified, were examined with the aid of the anterogradely transported plant lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L), for comparison with the previously reported projection patterns of the accumbal core and shell. Injection sites and transported PHA-L were evaluated with the aid of reference to adjacent sections processed to display substance P or calbindin 28 kD immunoreactivities, i.e., markers that demonstrate the core and shell. Lateral parts of the rostral pole gave rise to a “core-like” projection system that involved the rostroventral globus pallidus, subcommissural ventral pallidum, entopeduncular nucleus and an adjacent part of the lateral hypothalamus, lateral ventral tegmental area, dorsal pars compacta, and structures in the lateral mesencephalic tegmentum and central grey. The medial part of the rostral pole gave rise to a “shell-like” innervation of the subcommissural ventral pallidum, lateral preoptic region, lateral hypothalamus, ventral tegmental area, dorsalmost pars compacta, retrorubral field, lateral midbrain tegmentum, and central grey. In contrast to the large numbers of axon varicosities observed through the entire length of lateral hypothalamus following shell injections, dense accumulations of axon collaterals and varicosities in hypothalamus were limited to the levels of origin of the stria medullaris bundle and entopeduncular nucleus and to the posterlateral region following medial injections. The medial part of the rostral pole contributed some projections to preoptic and sublenticular regions, but not to the bed nucleus of the stria terminalis. Noteworthy concentrations of calbindin immunoreactive cells observed in the lateral rostral pole correlate with the origin of the “basal ganglia-like” projection system, provoking the speculation that ventral striatal calbindin immunoreactive cells contribute principally to basal ganglia-like projections while cells lacking calbindin immunoreactivity contribute to the innervation of hypothalamus and midbrain tegmentum. © 1993 Wiley-Liss, Inc.

Developmental theories of parental contributors to antisocial behavior

Abstract: In view of the increased interest in a developmental approach to psychopathology, and mounting evidence of the importance of parent-child interactions in the etiology of early antisocial behavior, the following questions were posed for this review. What theories of parent-child relationships and family management techniques are available? How developmental are they, how specific and transactional are they relative to parent and child behaviors involved? And how well do they cover the period in which antisocial behavior develops? Six theories have some developmental features but the attachment theories (by L. A. Sroufe, B. Egeland, and M. T. Greenberg) and two social learning theories (by G. R. Patterson and J. Martin) are most clearly developmental. They postulate reciprocal interactions of parent and child, and transformations in the form of normative changes in the child or changes in family processes. The social learning theories of Patterson and Martin are most specific, microanalytic in fact, as to the interaction processes involved, and the attachment theories at least specify kinds of behavior involved and also do not rely on traits or types of influence as their units of analysis. Conceptualization is most weak and overly general between late infancy and the preschool years. This gap makes it difficult to link attachment and social learning theories, both of which have driven a large number of studies. A bridging theory is offered to link the two sets of theories in the critical period involved.

Experimental observation of magnetism in rhodium clusters.

Abstract: We have observed giant magnetic moments in clusters of rhodium, ${\mathrm{Rh}}_{\mathit{n}}$(n=12--32), consistent with ferromagnetic ordering of the 4d electrons. Ferromagnetic behavior has not been reported previously in pure 4d transition metals. Rhodium clusters are superparamagnetic at 93 K, with magnetic moments of between 0.3 and 1.1${\mathrm{\ensuremath{\mu}}}_{\mathit{B}}$ per atom. We find that ${\mathrm{Rh}}_{15}$, ${\mathrm{Rh}}_{16}$, and ${\mathrm{Rh}}_{19}$ have magnetic moments per atom that are significantly larger than those of adjacent cluster sizes.

A retrospective analysis of pituitary apoplexy.

Abstract: Thirty-seven patients with pituitary apoplexy were analyzed with an emphasis on clinical presentation and visual outcome. Their mean age was 56.6 years, with a male to female ratio of 2:1. Presenting symptoms included headache (95%), vomiting (69%), ocular paresis (78%), and reduction in visual fields (64%) or acuities (52%). Computed tomographic scanning correctly identified pituitary hemorrhage in only 46% of those scanned. Thirty-six patients underwent transsphenoidal decompression. By immunostaining criteria, null-cell adenomas were the most frequent tumor type (50%). Long-term steroid or thyroid hormone replacement therapy was necessary in 82% and 89% of patients, respectively. Long-term desmopressin therapy was required in 11%, and 64% of the male patients required testosterone replacement therapy. Surgery resulted in improvement in visual acuity deficits in 88%, visual field deficits in 95%, and ocular paresis in 100%. Analysis of the degree of improvement in preoperative visual deficits with the timing of the surgery demonstrated that those who underwent surgery within a week of apoplexy had significant recovery in their visual acuities. In the stable, conscious patient with residual vision in each eye, surgical decompression should be performed as soon as possible, because delays beyond 1 week may retard the return of visual function.

Reexamining the “Minimal Effects” Model in Recent Presidential Campaigns

Abstract: Although much recent work suggests that contemporary presidential campaigns have more powerful electoral effects than were seen in previous decades, there has been little research that examines the actual effect of recent campaigns on individual vote choice. Using the 1980 NES panel study, I show that the overwhelming majority of individual votes can be accounted for from attitudes such as party identification and presidential approval that are measured before the political conventions, and that changes in orientations during the campaign had limited effects on individual vote choice and negligible consequences for the electoral outcome. Moreover, models derived from the 1980 panel data can predict with a great deal of accuracy the aggregate outcomes of the 1984 and 1988 presidential contests. I argue that the results support an "activation" model of campaign effects in recent elections: rather than simply reinforcing individuals' preexisting vote intentions, the campaigns served mainly to activate existi...

Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome)

Abstract: BACKGROUND The Lennox-Gastaut syndrome is a childhood disorder characterized by multiple types of seizures, mental retardation, characteristic electroencephalographic abnormalities, and resistance to standard antiepileptic drugs. Felbamate is an investigational antiepileptic drug with a preclinical profile that suggests it would be effective in patients with multiple types of seizures. In controlled clinical trials, felbamate was superior to placebo in reducing the frequency of refractory partial-onset seizures. METHODS We studied the efficacy of felbamate in 73 patients ranging in age from 4 to 36 years who had the Lennox-Gastaut syndrome. During a 28-day base-line phase, the patients received their usual antiepileptic therapies. At the end of this phase, felbamate or placebo was administered for 70 days in addition to the current antiepileptic medications. The dosage of felbamate was titrated during the first 14 days of the treatment phase to a maximum of 45 mg per kilogram of body weight per day or 3600 mg per day, whichever was less. The primary efficacy variables were the total number of seizures counted during a four-hour period of video recording, parents' or guardians' global evaluations of the patients' quality of life, and the total number of atonic seizures, as reported by parents or guardians. RESULTS The patients treated with felbamate had a 34 percent decrease in the frequency of atonic seizures, as compared with a 9 percent decrease in the patients who received placebo (P = 0.01). The felbamate-treated patients had a 19 percent decrease in the total frequency of seizures, as compared with a 4 percent increase in the placebo group (P = 0.002). The global-evaluation scores were significantly higher in the felbamate group than in the placebo group from day 49 to the end of the study. There were no significant differences in the frequency of seizures occurring during video monitoring, but there was a significant reduction (P = 0.017) in the number of tonic-clonic seizures during the maintenance period in the felbamate group. The types and frequency of side effects were similar in the two treatment groups. CONCLUSIONS Felbamate is beneficial in patients with the Lennox-Gastaut syndrome.

Evidence of inorganic chlorine gases other than hydrogen chloride in marine surface air

Abstract: We report the first measurements of inorganic chlorine gases in the marine atmosphere using a new tandem mist chamber method. Surface air was sampled during four days including one diel cycle in January, 1992, at Virginia Key, Florida. Concentrations of HCl* (including HCl, ClNO3, ClNO2, and NOCl) were in the range 40 to 268 pptv and concentrations of Cl2* (including Cl2 and any HOCl not trapped in the acidic mist chamber) were in the range <26 to 254 pptv Cl. Concentrations of Cl2* increased during the night, and decreased after sunrise as HCl* concentrations increased by similar amounts. The measurements suggest an unknown source of either HOCl or Cl2 to the marine atmosphere. Photochemical model calculations indicate that photolysis of the observed Cl2* would yield a chlorine atom (Cl•) concentration of order 104–105 cm−3. Oxidation by Cl• would then represent a significant sink for alkanes and dimethylsulfide (DMS) in the marine boundary layer. The cycling of Cl• could provide either a source or a sink for O3, depending on NOX levels.

A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study.

Abstract: ✓ Because of their action as cerebral vasodilators, dihydropyridine calcium antagonists have received intense scrutiny for their potential benefit in ameliorating the devastating consequences of delayed cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH). From October, 1987, to September, 1989, 41 North American neurosurgical centers in the Cooperative Aneurysm Study accrued 906 patients with recent (Days 0 to 7) aneurysmal SAH into a prospective randomized double-blind placebo-controlled trial of high-dose intravenous nicardipine to test whether treatment with this agent improved overall outcome. Eligible patients received 0.15 mg/kg/hr of either nicardipine or placebo by continuous infusion for up to 14 days following hemorrhage. The 449 patients randomly assigned to the nicardipine-treated group and the 457 patients assigned to the placebo-treated group were balanced with regard to prognostic factors for ischemic deficits from vasospasm and for overall outcome. Other medical and surgi...