Dionysian Hard Sphere Packings Are Mechanically Stable at Vanishingly Low Densities.

High strength-to-weight ratio materials can be constructed by either maximizing strength or minimizing weight. Tensegrity structures and aerogels take very different paths to achieving high strength-to-weight ratios but both rely on internal tensile forces. In the absence of tensile forces, removing material eventually destabilizes a structure. Attempts to maximize the strength-to-weight ratio with purely repulsive spheres have proceeded by removing spheres from already stable crystalline structures. This results in a modestly low density and a strength-to-weight ratio much worse than can be achieved with tensile materials. Here, we demonstrate the existence of a packing of hard spheres that has asymptotically zero density and yet maintains finite strength, thus achieving an unbounded strength-to-weight ratio. This construction, which we term Dionysian, is the diametric opposite to the Apollonian sphere packing which completely and stably fills space. We create tools to evaluate the stability and strength of compressive sphere packings. Using these we find that our structures have asymptotically finite bulk and shear moduli and are linearly resistant to every applied deformation, both internal and external. By demonstrating that there is no lower bound on the density of stable structures, this work allows for the construction of arbitrarily lightweight high-strength materials.

Jamming Energy Landscape is Hierarchical and Ultrametric.

The free energy landscape of mean-field marginal glasses is ultrametric. We demonstrate that this feature persists in finite three-dimensional systems that are out of equilibrium by finding sets of minima, which are nearby in configuration space. By calculating the distance between these nearby minima, we produce a small region of the distance metric. This metric exhibits a clear hierarchical structure and shows the signature of an ultrametric space. That such a hierarchy exists for the jamming energy landscape provides direct evidence for the existence of a marginal phase along the zero temperature jamming line.

Infant antibiotic exposures and early-life body mass.

OBJECTIVES: To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life. DESIGN: Longitudinal birth cohort study. SUBJECTS: A total of 11 532 children born at 2500 g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991-1992. MEASUREMENTS: Exposures to antibiotics during three different early-life time windows (<6 months, 6-14 months, 15-23 months), and indices of body mass at five time points (6 weeks, 10 months, 20 months, 38 months and 7 years). RESULTS: Antibiotic exposure during the earliest time window (<6 months) was consistently associated with increased body mass (+0.105 and +0.083 s.d. unit, increase in weight-for-length Z-scores at 10 and 20 months, P<0.001 and P=0.001, respectively; body mass index (BMI) Z-score at 38 months +0.067 s.d. units, P=0.009; overweight OR 1.22 at 38 months, P=0.029) in multivariable, mixed-effect models controlling for known social and behavioral obesity risk factors. Exposure from 6 to 14 months showed no association with body mass, while exposure from 15 to 23 months was significantly associated with increased BMI Z-score at 7 years (+0.049 s.d. units, P=0.050). Exposures to non-antibiotic medications were not associated with body mass. CONCLUSIONS: Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6-14 months, 15-23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.

Nutrition and the psychoneuroimmunology of postpartum depression.

Postpartum depression (PPD) is a relatively common and often severe mood disorder that develops in women after childbirth. The aetiology of PPD is unclear, although there is emerging evidence to suggest a psychoneuroimmune connection. Additionally, deficiencies in n-3 PUFA, B vitamins, vitamin D and trace minerals have been implicated. This paper reviews evidence for a link between micronutrient status and PPD, analysing the potential contribution of each micronutrient to psychoneuroimmunological mechanisms of PPD. Articles related to PPD and women's levels of n-3 PUFA, B vitamins, vitamin D and the trace minerals Zn and Se were reviewed. Findings suggest that while n-3 PUFA levels have been shown to vary inversely with PPD and link with psychoneuroimmunology, there is mixed evidence regarding the ability of n-3 PUFA to prevent or treat PPD. B vitamin status is not clearly linked to PPD, even though it seems to vary inversely with depression in non-perinatal populations and may have an impact on immunity. Vitamin D and the trace minerals Zn and Se are linked to PPD and psychoneuroimmunology by intriguing, but small, studies. Overall, evidence suggests that certain micronutrient deficiencies contribute to the development of PPD, possibly through psychoneuroimmunological mechanisms. Developing a better understanding of these mechanisms is important for guiding future research, clinical practice and health education regarding PPD.

Flow and fracture in drying nanoparticle suspensions.

Drying aqueous suspensions of monodisperse silica nanoparticles can fracture in remarkable patterns. As the material solidifies, evenly spaced cracks invade from the drying surface, with individual cracks undergoing intermittent motion. We show that the growth of cracks is limited by the advancement of the compaction front, which is governed by a balance of evaporation and flow of fluid at the drying surface. Surprisingly, the macroscopic dynamics of drying show signatures of molecular-scale fluid effects.

An ongoing initiative to reach rural family nurse practitioner students.

The challenges we have encountered in educating rural nurses to become nurse practitioners are not unique to Penn State but rather are similar to those encountered by other programs with similar missions. As emphasized in these reports, providing distance education to distance nurse practitioner students requires patience and flexibility. Also emphasized is that, although the numbers of rural nurses educated to become practitioners may be few, their impact on the rural community is magnified many times over. For our program, the difficulties encountered putting this rural initiative in place have been more than compensated for by the enthusiasm of our students and faculty and the very positive support we have received from practitioners and clients in the rural community. As a result of the plan described, we now have the opportunity to reach into the rural community itself for local, qualified nurses committed to providing primary healthcare to their own neighbors. We encourage other programs to do the same.

Understanding cytokines. Part I: Physiology and mechanism of action.

This is the first of a 2-part article on understanding cytokines. Cytokines are intercellular signaling proteins released from virtually all nucleated cells that influence growth and cellular proliferation in a wide range of tissues. Cytokines have immune modulating effects and are understood to control most of the physical and psychological symptoms associated with infection and inflammation. Cytokines also influence reproduction and bone remodeling. Dysregulation of the cytokine cellular system has significant implications in the development of a variety of illnesses, including most autoimmune disorders, many diseases of the cardiovascular system, osteoporosis, asthma, and depression. For nurses to be adequately informed when caring for clients with chronic illnesses and to be sufficiently knowledgeable when evaluating client outcomes, an understanding of the physiology of cytokines, the occurrences of dysregulation, and the role of cytokines in health and illness is essential. In Part I of this review, cytokine physiology is presented, with an emphasis on characteristics, categories, and mechanism of action. Specific instances of cytokine function in health and disease and implications for nursing research and practice are presented in Part II.

Understanding cytokines. Part II: Implications for nursing research and practice.

Cytokines are small signaling proteins released from a variety of cells that influence virtually every aspect of growth and development and every host response to infection, injury, and inflammation. Because of their widespread and potent effects across the life span, cytokines without a doubt influence nursing research and practice. From physiological and adaptive effects of cytokines to cytokine-induced diseases, nurses and nursing care are involved. Part II of this review highlights a few of the many examples of cytokines functioning in response to infection and inflammation, during the processes of reproduction, and in a variety of pathophysiological states. Implications for nursing research and practice are emphasized.

Gonadotropin modulation of interleukin-1 secretion.

OBJECTIVE: To determine the influence of pituitary gonadotropins, which increase dramatically in concentration at ovulation and in the early years of the postmenopausal transition, on inflammatory cytokine production. DESIGN: Cross-sectional population sampling, in vitro experimentation. PARTICIPANTS: Healthy subjects, including six men, five women between the ages of 18 and 35 years, and four women who were four to 20 years past menopause. METHOD: Isolated peripheral blood mononuclear cells were incubated with physiological concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The concentrations of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) secreted into the supernatants were measured by enzyme-linked immunosorbent assays. RESULTS: Under basal conditions, FSH stimulated IL-1 beta secretion by cells isolated from women in the follicular phase. Under conditions of cellular activation with bacterial lipopolysaccharide, FSH and LH interacted to inhibit IL-1 beta secretion by cells isolated from all groups. The gonadotropins had no significant influence on IL-6 secretion regardless of donor group or cellular activation state. CONCLUSION: The results of this study support the concept that gonadotropins may contribute to the changes in IL-1 beta secretion that occur at the periovulatory and postmenopausal periods.

The readability of printed education materials regarding hormone replacement therapy.

In summary, HRT is a preventative medication that has been shown to decrease the incidence of heart disease and osteoporosis. It also has been shown to reduce symptoms of menopause and to increase the quality of life of users. Choosing to begin and maintain HRT is a personal and complicated decision. In evaluating the risks and benefits of HRT for any one woman, that woman and her primary care provider must individualize her past and current medical history, her family history, and her lifestyle. Together they must come to a decision that best represents the health, social needs, and desires of the patient. Individualizing HRT is difficult for a woman to do on her own, and it is time-consuming for a practitioner. Using PEMs to clarify the benefits and risks of HRT can be very beneficial to a woman considering such therapy. PEMs, however, are not a substitute for one-on-one education, and especially are not appropriate for teaching if their level of technical difficulty is beyond the scope of a patient's comprehension. This study suggests that many of the PEM's provided to women on the subject of HRT are failing to reach their target audiences because of their level of reading difficulty. A stated objective identified in the national initiative Healthy People 2000 (U.S. Department of Health and Human Services, 1997) is to "Increase to at least 90% the proportion of perimenopausal women who have been counseled about the benefits and risks of hormone replacement therapy for the prevention of osteoporosis." PEMs are one way to reach this objective, provided they are understandable to the clientele of focus.

Endometriosis: pathophysiology, diagnosis, and treatment.

Endometriosis is the presence of endometrial tissue outside of the uterine cavity, most commonly surrounding the ovaries and fallopian tubes. It is relatively common disorder in reproductive-age women and is associated with significant pain and morbidity. In most cases, the spread of extrauterine endometrial tissue appears to result from retrograde menstruation and capillary or lymph dissemination. Endometrial cells implanted ectopically respond to cyclical changes in estrogen and progesterone with proliferation and secretion. Their presence in extrauterine areas can initiate immune and inflammatory responses that lead to pain and peritoneal adhesions, and may interfere with fertility. Diagnosis is based on the occurrence of cyclical symptoms and surgical validation via laparoscopy or laparotomy. Treatment is aimed at alleviating pain and preventing complications. Most treatments work by reducing estrogen levels and/or menstrual cycling. A primary practitioner must understand not only the medical aspects of this disease, but the enormous social and psychologic costs as well.

An iterative method for training multilayer networks with threshold functions.

Concerns the problem of finding weights for feed-forward networks in which threshold functions replace the more common logistic node output function. The advantage of such weights is that the complexity of the hardware implementation of such networks is greatly reduced. If the task to be learned does not change over time, it may be sufficient to find the correct weights for a threshold function network off-line and to transfer these weights to the hardware implementation. This paper provides a mathematical foundation for training a network with standard logistic function nodes and gradually altering the function to allow a mapping to a threshold unit network. The procedure is analogous to taking the limit of the logistic function as the gain parameter goes to infinity. It is demonstrated that, if the error in a trained network is small, a small change in the gain parameter will cause a small change in the network error. The result is that a network that must be implemented with threshold functions can first be trained using a traditional back propagation network using gradient descent, and further trained with progressively steeper logistic functions. In theory, this process could require many repetitions. In simulations, however, the weights have be successfully mapped to a true threshold network after a modest number of slope changes. It is important to emphasize that this method is only applicable to situations for which off-line learning is appropriate.

Effect of magnesium sulfate on the vascular actions of norepinephrine and angiotensin II.

Magnesium sulfate is used for seizure prophylaxis in patients with preeclampsia. It also has significant effects on calcium metabolism and could, therefore, alter the pressor response to calcium-dependent vasoconstrictors. The present in vivo rat study examined the effect of magnesium sulfate to alter the pressor response to norepinephrine (NE) and angiotensin II (A II). Magnesium doses were chosen to approximate those used in treating preeclampsia. NE resulted in a significant rise in mean arterial pressure (delta MAP, 46 +/- 3.7 mmHg; p < 0.001). A II also resulted in a significant rise in MAP (delta MAP, 23 +/- 3.6 mmHg, p < 0.02). Magnesium sulfate alone had no significant effect on MAP but attenuated the pressor response to both NE (delta MAP, 16 +/- 1.5 mmHg) and A II (delta MAP, 12 +/- 2.5 mmHg). After discontinuation of the magnesium sulfate infusion, the control pressor responses to NE and A II were again seen (delta MAP, 39 +/- 3.5 mmHg and delta MAP, 28 +/- 4.2 mmHg, respectively). Although magnesium sulfate is not a primary antihypertensive agent, it may have effects on blood pressure by attenuating the actions of circulating vasoconstrictors.

Suggested mechanism for the selective excretion of glucosylated albumin. The effects of diabetes mellitus and aging on this process and the origins of diabetic microalbuminuria.

In previous studies in the Sprague-Dawley rat, Williams and coworkers reported the phenomenon of selective urinary excretion of glucosylated albumin (editing, i.e., the percent glucosylation of urinary albumin is more than that of plasma albumin) by the mammalian kidney. Ghiggeri and coworkers subsequently found that the extent of editing is reduced in human diabetics. Moreover, the reduction in editing in diabetes correlates inversely with levels of microalbuminuria. We also find reduction in the extent of editing in diabetic humans. We find a striking inverse correlation not only with the magnitude of microalbuminuria but also with the extent of plasma albumin glucosylation. In contrast, we found little correlation between the reduction in editing and the duration of diabetes in human subjects. Stz induced diabetes in the Sprague-Dawley rat is associated with a striking and rapid reduction in editing which develops virtually with the same kinetics exhibited by the appearance of hyperglycemia. This loss of editing is rapidly reversed by daily administration of insulin but not by aldose reductase inhibitors. Mannitol infusion in anesthetized Wistar rats resulted in an increase in urine volume, GFR, and microalbuminuria, and was also accompanied by a marked reduction in editing. This reduction was rapidly reversed by a cessation of mannitol infusion. We propose here that glucosylated albumin (in contrast to unmodified albumin) is not reabsorbed by the proximal tubule, and thus, is preferentially excreted in the urine. We postulate that the increase in GFR which emerges as a consequence of increased plasma osmolality in diabetes mellitus delivers more albumin to the proximal tubule than can be reabsorbed. This results in a dilution of excreted glucosylated albumin molecules by excreted unmodified albumin, which appears as the early microscopic albuminuria of diabetes. Paradoxically, the fall in apparent editing is accompanied by an absolute increase in the total quantity of glucosylated albumin excreted. In contrast, we found that editing of glucosylated albumin by the normal kidney is found to gradually decline as a function of age without the appearance of microalbuminuria. This suggests that a different mechanism operates to produce the loss of editing seen with aging in man, and as clearly (but in a shorter absolute time intervals) in the Fischer-344 rat.

Central role for angiotensin in control of adrenal catecholamine secretion.

Angiotensin II (ANG II) is required for unimpaired adrenal reflex secretion of catecholamines after hemorrhage in the dog. To test if ANG II acts centrally, experiments were performed under general anesthesia on bilaterally or sham-nephrectomized dogs hemorrhaged at 25 ml/kg. Ventriculocisternal perfusion of ANG II or its antagonist saralasin was accomplished via needles inserted in the left lateral cerebral ventricle and cisterna magna. Mean arterial pressure and adrenal secretion of catecholamines were measured before and after hemorrhage. Nephrectomized dogs receiving only artificial cerebrospinal fluid (CSF) by ventriculocisternal perfusion had a very small adrenal response to hemorrhage compared with animals receiving ANG II intraventricularly (IVT) (at 10 and 100 pg . kg-1 . min-1). This effect of ANG II IVT also depended on the rate of IVT infusion. Peripheral infusion of ANG II (10 pg . kg-1 . min-1) had no effect on adrenal catecholamine secretion. Animals with intact kidneys given saralasin IVT (0.06 ng/min) responded similarly to nephrectomized dogs receiving only CSF IVT. Intravenous saralasin did not blunt the response to hemorrhage. Thus ANG II appears to support catecholamine secretion via a central mechanism. This mechanism is physiologically significant because either nephrectomy or functional elimination of ANG II by saralasin greatly attenuates the adrenal medullary response to hemorrhage in vivo.

Temperature sensitivity of the renin-angiotensin system in Ambystoma tigrinum.

The presence of a renin-angiotensin system was demonstrated in the poikilotherm Ambystoma tigrinum, commonly called the tiger salamander. Standard radioimmunoassay techniques were employed to measure the intrarenal renin activity (IRA) and the plasma renin activity (PRA) of A. tigrinum kept at either 5 or 20 degrees C. Basal IRA and PRA values were not affected by the temperature at which the animals were maintained. Intraperitoneal injection of the beta-adrenergic agonist isoproterenol, however, increased PRA only in those animals maintained at 20 degrees C. This is consistent with the hypothesis of a temperature sensitivity of the renal adrenergic system in vivo. In addition, we were able to demonstrate the existence of a contractile response of Ambystoma vascular smooth muscle to angiotensin II that was blocked by the competitive inhibitor saralasin.

Temperature-induced conversion of the renal adrenoreceptor: modulating renin release.

The release of renin from dog cortical kidney slice preparations incubated in a physiological salt solution can be modulated by alpha- and beta-adrenergic drugs. When given to slices maintained at 37 degrees C, the beta-agonists isoproterenol (ISP) and norepinephrine stimulated renin release from the slices. When the slices were maintained at 20 degrees C, the beta-agonists had no effect on renin release. However, the alpha-agonist phenylephrine inhibited renin release from the slices incubated at 20 degrees C in a dose-dependent manner, whereas its effect on slices incubated at 37 degrees C was less pronounced. The change in response of the slices from beta dominant at 37 degrees C to alpha dominant at 20 degrees C appeared to be a receptor phenomenon. When the cortical slices were incubated with the irreversible alpha-antagonist phenoxybenzamine (POB) at 20 degrees C for 1 h, they were unable to respond to ISP when returned to 37 degrees C. However, POB had no effect on the response of slices to ISP when given at 37 degrees C. It appears that with a decrease in temperature the renal beta-receptors demonstrate properties normally associated with alpha-receptors, namely the potential to be blocked by POB. This may be due to an interconversion of the renal alpha- and beta-adrenoceptors.