Convex Hulls, Oracles, and Homology

This paper presents a new algorithm for the convex hull problem, which is based on a reduction to a combinatorial decision problem POLYTOPE-COMPLETENESS-COMBINATORIAL, which in turn can be solved by a simplicial homology computation. Like other convex hull algorithms, our algorithm is polynomial (in the size of input plus output) for simplicial or simple input. We show that the ``no''-case of POLYTOPE-COMPLETENESS-COMBINATORIAL has a certificate that can be checked in polynomial time (if integrity of the input is guaranteed).Comment: 11 pages, 2 figure

Sources of human urinary epinephrine

Sources of human urinary epinephrine. The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight normal subjects (CON) and 5 older, heavier hypertensives (OHH) ate a light breakfast along with ascorbic acid supplementation and had intravenous and arterial lines placed. They received an infusion of 3H-E and had an oral water load. During the final hour of 3H-E infusion, urine and arterial blood samples were collected for 3H-E and E levels. After the 3H-E infusion was abruptly discontinued, arterial blood samples were collected to measure 3H-E kinetics. The total body clearance of 3H-E was about 2,500ml/min from plasma and clearance of 3H-E to urine was about 170ml/min. CON had plasma E levels of 43 ± 4 pg/ml. Their predicted rate of clearance of E from plasma to urine of 7,471 ± 865 pg/min was less than (P = 0.018) the actual urinary E excretion of 15,037 ± 2,625 pg/min. Thus, 43 ± 9% of urinary E in CON was apparently derived from renal sources and not filtered from blood. Among OHH 85 ± 4% of urinary E was derived from the kidney, significantly (P < 0.01) different from CON. The OHH also produced much more urinary E than predicted from plasma 3H-E clearance into urine (P = 0.03). A major fraction of urinary E is not filtered from the blood stream but is apparently derived from the kidney. A small fraction of urinary E may be derived from E stored in nerve endings along with norepinephrine, but this probably represents less than 2% of urinary E. Renal cleavage of E sulfate into E may be another potential source of urinary E. Some, and perhaps most, urinary E not filtered from the bloodstream is derived from renal N-methylation of norepinephrine as the human kidney has two enzymes capable of converting norepinephrine to E. In conclusion, a major portion of urinary E is derived from the kidney and not filtered from the bloodstream. This is an important factor in the interpretation of urine E levels. Renal E could alter renal blood flow, electrolyte reabsorption, and renin release prior to excretion into urine

Hypovolemia Induced Orthostatic Hypotension in Presyncopal Astronauts and Normal Subjects Relates to Hypo-Sympathetic Responsiveness

Circulating blood volume is reduced during spaceflight, leaving astronauts hemodynamically compromised after landing. Because of this hypovolemia, crew members are able to withstand a postflight 10 minute upright tilt test only if they are able to mount a hyper-sympathetic response. Previous work from this laboratory has shown that about 30% of astronauts, primarily female, have postflight sympathetic responses to tilt that are equal to or less than their preflight responses and thus, they become presyncopal. Part of the mission of the cardiovascular lab at the Johnson Space Center is to identify susceptible crewmembers before flight so that individualized countermeasures can be prescribed. The goal of this study was to develop a ground based model of hypovolemia that could be used for this purpose We tested the hypothesis that hypovolemia alone, in the absence of spaceflight, would reproduce the landing day rate of presyncope during upright tilt in normal volunteers. Further, we hypothesized that, during hypovolemia, subjects who had sympathetic responses that were equal to or less than their normovolemic responses would become presyncopal during upright tilt tests. We studied 20 subjects, 13 male and 7 female, on two separate occasions: during normovolemia and hypovolemia. We induced hypovolemia with intravenous furosemide 40 hours prior to the experiment day, followed by a 10MEq Na diet. On the normovolemia and hypovolemia test days, plasma volume, tilt tolerance and supine and standing arterial pressure, heart rate and plasma norepinephrine levels were measured. A two factor, repeated measures analysis of variance was performed to examine the differences between group (presyncopal vs. non-presyncopal) and day (normovolemia vs. hypovolemia) effects. There were no differences in baseline arterial pressure between normovolemia and hypovolemia or between presyncopal and non-presyncopal groups, but heart rates were higher with hypovolemia in both groups (presyncopal: 70 5 bpm vs. 63 3 bpm, P = 0.003, non-presyncopal: 59 2 bpm vs. 52 2 bpm, P = 0.003). Similar to patterns reported after flight, non-presyncopal subjects had greater norepinephrine responses to tilt during hypovolemia compared to normovolemia (580 79 vs. 298 37 pg/ml, P < 0.05), but presyncopal subjects did not (180 44 vs. 145 32 pg/ml, P = NS). This new model has the potential to accelerate the development of countermeasures and save flight resources. It can be used to identify astronauts who will become presyncopal on landing day, so that prospective, individualized countermeasures can be developed. In addition, it can also be used to screen candidate countermeasures prior to requests for bed rest or inflight resources

Lesen bewegt: Gemeinsam 3.000 Schritte extra

Bewegung bestimmt im Allgemeinen leider zu wenig unseren Alltag, obwohl sie gerade für unsere Gesundheit von elementarer Bedeutung ist. Nur wer auch körperlich fit ist, kann den Herausforderungen unserer Zeit gerecht werden, den Berufsalltag meistern und ein selbstbestimmtes Leben führen. Wer sich von Büchern bewegen lässt, vergisst dabei oft, sich selbst körperlich zu betätigen. Die Kampagne empfiehlt daher „Jeden Tag 3.000 Schritte extra“. Buchhandlungen und Bibliotheken in ganz Deutschland waren aufgefordert, diese Empfehlung aufzugreifen und ihre Kundinnen und Kunden sowie Besucherinnen und Besucher auf ihre Weise durch besondere Aktionen zu einem gesundheitsbewussten Umgang mit dem eigenen Körper zu motivieren

Disassociation between glomerular hyperfiltration and extracellular volume in diabetic rats

Disassociation between glomerular hyperfiltration and extracellular volume in diabetic rats. The relationship of the development of glomerular hyperfiltration in diabetes to changes in extracellular fluid volume has not been previously examined. To accomplish this task, male Wistar rats were chronically cannulated in the bladder, femoral artery and vein. Control measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), extracellular fluid volume (ECF), and urinary sodium excretion were performed on two separate days prior to infusion of streptozotocin (65 mg/kg body wt i.v.). After infusion of streptozotocin, the IDDM rats were separated into two groups: untreated IDDM group of rats and IDDM rats treated with insulin at doses sufficient to normalize blood glucose (Ultralente, 2 to 8 IU/day). A third group of normal non-diabetic rats served as time controls. Measurements of renal function occurred at 1, 4, 7, 11, and 15 days after infusion of streptozotocin. Blood glucose in the non-diabetic measurement period averaged 137 ± 30 mg/dl and increased from 412 ± 55 after 24 hours in the untreated diabetic rats to 533 ± 33 mg/dl after 15 days of IDDM. The time controls and the insulin-treated diabetic rats did not differ in blood glucose values at the time measurements were performed. Glomerular filtration rate increased from 1.0 ± 0.1 to 1.7 ± 0.1 ml/min/100g body wt by day 15 in the untreated diabetic rats with significant increases in GFR within 24 hours. GFR of both time controls and the insulin-treated IDDM rats did not significantly vary during the time of the study. The increase in GFR in the untreated IDDM group was associated with a concomitant increase in RPF. However, ECF decreased in both the insulin treated and untreated groups by one day after streptozotocin infusion and was less than control throughout the 15 day IDDM measurement period. Therefore, the data indicate that the development of hyperfiltration in IDDM is not caused by ECF expansion and cannot be temporally linked to changes in ECF

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease

Hemodynamic Effects of Midodrine After Space Flight in Astronauts Without Orthostatic Hypotension

Orthostatic hypotension and presyncope are common and potentially serious risks for astronauts returning from space. Susceptible subjects fail to generate an adequate adrenergic response to upright posture. The -1 adrenergic agonist, midodrine, may be an effective countermeasure. We tested the hypothesis that midodrine would have no negative hemodynamic effect on healthy astronauts returning from space. Five male astronauts participated in preflight and postflight tilt testing on a control flight as well as on the test flights, where midodrine (10 mg, orally) was administered after landing, approximately 1 hour before testing. None of these astronauts exhibited orthostatic hypotension or presyncope before or after either flight. Midodrine did not cause any untoward reactions in these subjects before or after flight, in fact a modest beneficial effect was seen on postflight tachycardia (p=0.036). These data show that midodrine protected against post-spaceflight increases in heart rate, without having any adverse hemodynamic effects on non-presyncopal, male astronauts. Among these subjects, midodrine was a safe cardiovascular countermeasure

Pinyon and Juniper Encroachment into Sagebrush Ecosystems Impacts Distribution and Survival of Greater Sage-Grouse

AbstractIn sagebrush (Artemisia spp.) ecosystems, encroachment of pinyon (Pinus spp.) and juniper (Juniperus spp.; hereafter, “pinyon-juniper”) trees has increased dramatically since European settlement. Understanding the impacts of this encroachment on behavioral decisions, distributions, and population dynamics of greater sage-grouse (Centrocercus urophasianus) and other sagebrush obligate species could help benefit sagebrush ecosystem management actions. We employed a novel two-stage Bayesian model that linked avoidance across different levels of pinyon-juniper cover to sage-grouse survival. Our analysis relied on extensive telemetry data collected across 6 yr and seven subpopulations within the Bi-State Distinct Population Segment (DPS), on the border of Nevada and California. The first model stage indicated avoidance behavior for all canopy cover classes on average, but individual grouse exhibited a high degree of heterogeneity in avoidance behavior of the lowest cover class (e.g., scattered isolated trees). The second stage modeled survival as a function of estimated avoidance parameters and indicated increased survival rates for individuals that exhibited avoidance of the lowest cover class. A post hoc frailty analysis revealed the greatest increase in hazard (i.e., mortality risk) occurred in areas with scattered isolated trees consisting of relatively high primary plant productivity. Collectively, these results provide clear evidence that local sage-grouse distributions and demographic rates are influenced by pinyon-juniper, especially in habitats with higher primary productivity but relatively low and seemingly benign tree cover. Such areas may function as ecological traps that convey attractive resources but adversely affect population vital rates. To increase sage-grouse survival, our model predictions support reducing actual pinyon-juniper cover as low as 1.5%, which is lower than the published target of 4.0%. These results may represent effects of pinyon-juniper cover in areas with similar ecological conditions to those of the Bi-State DPS, where populations occur at relatively high elevations and pinyon-juniper is abundant and widespread

The roles of TNF-α and the soluble TNF receptor I on sleep architecture in OSA

Patients with obstructive sleep apnea (OSA) have been described to have increased levels of inflammatory cytokines (particularly TNF-α) and have severely disturbed sleep architecture. Serum inflammatory markers, even in normal individuals, have been associated with abnormal sleep architecture. Not much is known about the role the TNF receptor plays in the inflammation of OSA nor if it is associated with changes in sleep architecture or arousals during the night. We hypothesized that the TNF receptor might play an important role in the inflammation as well as sleep architecture changes in patients with OSA. Thirty-six patients with diagnosed (AHI &gt; 15) but untreated OSA were enrolled in this study. Baseline polysomnograms as well as TNF-α and soluble TNF receptor I (sTNF-RI) serum levels were obtained on all patients. We evaluated the association between serum levels of TNF-α and sTNF-RI with various polysomongraphic characteristics, including sleep stages and EEG arousals. sTNF-RI levels were significantly correlated with snore arousals (r value 0.449, p value 0.009), spontaneous movement arousals (r value 0.378, p value 0.025), and periodic limb movement arousals (r value 0.460, p value 0.008). No statistically significant correlations were observed with TNF-α to any polysomnographic variables. To control for statistical significance with multiple comparisons, a MANOVA was performed with TNF-α and sTNF-RI as dependent variables and sleep architecture measures and arousals as independent variables. The model for sTNF-RI was statistically significant (F value 2.604, p value 0.03), whereas the model for TNF-α was not, suggesting sleep quality significantly affects sTNF-RI. Hierarchal linear regression analysis demonstrated that sTNF-RI was independently associated with spontaneous movement arousal index scores after controlling for age, body mass index, and sleep apnea severity. These findings suggest that sTNF-RI is associated with arousals during sleep, but not with other measures in patients with OSA