The adrenergic control of corticotrophin secretion

1. A highly selective alpha-1 adrenoceptor agonist that crosses the blood brain barrier stimulated the secretion of corticotrophin (ACTH) in man and in the rat in a dose - dependent manner. The effect was blocked by selective alpha-1 antagonists which also cross the blood brain barrier. It was concluded that activation of alpha-1 adrenoceptors stimulates ACTH secretion. A considerable amount of evidence obtained in the rat and in man suggested that the stimulant alpha-1 adrenoceptors are located in the brain, rather than directly on the pituitary gland or in the periphery. In the rat, the alpha-1 adrenoceptors stimulate ACTH secretion predominantly by activating hypothalamic vasopressin neurones. 2. Intravenous infusions of adrenaline and dopamine did not stimulate ACTH secretion or enhance the ACTH response to the corticotrophin releasing factor (CRF-41) in man. It was concluded that circulating catecholamines do not stimulate ACTH secretion under physiological conditions, and the peripheral sympathoadrenal response to stress is not responsible for the accompanying increase in ACTH secretion. 3. Activation of endogenous catecholamines increased ACTH secretion, suggesting that the stimulant alpha-1 adrenoceptors are innervated by catecholaminergic neurones and are likely to be physiologically relevant. 4. The physiological significance of the stimulant alpha-1 adrenoceptors in man was demonstrated in two situations: the cortisol secretory pattern during waking hours and the ACTH and cortisol responses to food ingestion were both enhanced by an alpha-1 agonist and reduced by an alpha-1 antagonist. Cortisol secretion at night and in response to hypoglycaemia were unaffected by an alpha-1 antagonist, suggesting that alpha-1 adrenoceptors mediate some but not all of the stimuli to ACTH secretion. 5. During some conditions of increased ACTH secretion, inhibitory alpha-2 adrenoceptors are activated and they limit the ACTH response. 6. The potential clinical applications of this work are discussed

DYNAMIC SOIL-STRUCTURE RESPONSE ANALYSIS OF AN IRAQI SOIL BASED ON GEOPHYSICAL TESTING

In this paper, soil – pore fluid behavior of a silo under an earthquake loading is investigated. To predict the response of the silo with the soil surrounding it, ‘the linear-elastic constitutive model’ is adopted with soil properties; shear modulus and damping ratio; are strains and cycle independent. A computer program using dynamic stiffness matrix analyses (DSMA) for predicting and analyzing the model was established using FORTRAN coding. The program is based on geophysical values (such as primary velocity (vp), shear velocity (vs), modulus of elasticity (E), mass density (), shear modulus (G),….etc). The values were obtained from field test results for the soil under a silo located in Kirkuk, Iraq. To check and compare the obtained results, the computer program (MSC/NASTRAN) is used also for predicting and analyzing the same problem. This second program uses input values such as shear modulus (G), modulus of elasticity (E), mass density () and damping ratio () obtained from conventional laboratory tests. From the two aforementioned analyses, comparisons between the results of the relevant two programs are made. Though program “MSC/NASTRAN” visualizes a realistic behavior of the silo under dynamic loading, due to full response results are expressed for each node, the dynamic stiffness matrix analyses program (DSMA) gives only the maximum value for the horizontal and vertical displacements at that node. Despite of that, program DSMA relies on realistic values of geophysical tests obtained from the field directly.As a conclusion from this study, the soil-structure interaction zone for the silo at Kirkuk under investigation using both analyses show excellent agreement between the results. The agreement in this study turns out to be more than 95% close between the two algorithms. The easiness through which geophysical field tests are conducted, the simplicity of carrying out the required calculations and the reliability of the results makes the dynamic stiffness matrix analysis method (DSMA) highly recommended. It can give an excellent directive about the response of structures resting on soils and subjected to dynamic loads

Effects of Internal Gas Explosion on an Underwater Tunnel Roof

An underwater reinforced concrete tunnel roof is subjected to an internal gas explosion. Dynamic analyses are performed for three cases, namely, (1) an uncoupled solution, (2) class II coupling analysis and (3) full model with class I and II couplings. Three load cases are considered, dead (gravity) load, uniformly distributed vertical loads from sand and water and finally an internal pressure gas explosion. Linear and non-linear constitutive relationships are considered for the materials constituting the gas explosion problem. Results include time deflection of tunnel roof, time histories of stresses in vertical reinforcing bars and contours of concrete stresses for tunnel roof. By conducting analyses from various models, the question whether the tunnel would be damaged to such an extent that its serviceability would be impaired is investigated

THREE-DIMENSIONAL FINITE ELEMENT ANALYSES OF A SINGLE PILE IN AN ELASTOPLASTIC CLAYEY SOIL

A three-dimensional coupled finite element analysis algorithm is developed to predict the behaviour of single piles in clay. Three dimensional 20-noded brick elements are used in the analyses carried out on three documented field studies. Each node carries four degrees of freedom, three being for displacements in the three perpendicular space dimensions while the fourth is allocated for pore water pressure. The behaviour of the material of the pile is idealized through a linear elastic constitutive relationship while that for the soil by the Modified Cam-Clay model both extended to cover three-dimensional characteristics. The load-displacement results from the developed algorithm on the three selected problems from literature show a very good agreement with the observations. Moreover, the build-up of pore fluid pressures and their dissipations were found to be consistent with field measurements also.

Modified Stability Functions with Shear Effects for Non-PrismaticMembers in Steel Plane Frames

The mathematical model of the tapered struts subjected to axial load is solved to obtain the modified stability functions due to shear effect as well as bending effects. The stability functions are derived for a wide range of non-prismatic struts then compared in graphical curves with stability functions excluding shear effects. The stability functions for non-prismatic members under compressive and tensile axial loads are developed for the purpose of expressing both effects of bending and shear in a beamcolumn stiffness at any value of axial force under the buckling limi

DETERMINATION OF DEPTH OF PLACEMENT OF TUNNELS AND CAVITIES BY THE BOUNDARY ELEMENT METHOD

A boundary element numerical algorithm has been developed for the determination of stresses and deformations around cavities and tunnels. A study of the influence of depth below the ground surface on the distribution of stresses and deformations around cavities and tunnels is presented in this paper. The soil is assumed to behave linearly elastic. A computer program has been built to perform the numerical computations. The results show that with increasing the depth of placement of tunnel or opening below the ground surface, the settlements decrease. The maximum stresses occur at the haunches of the tunnel rather than at the crown. For the circular cavity that is considered in this paper, it was found that with increasing the depth below the ground surface (depth/tunnel diameter > 3), the surface settlements do not exceed 6 % from those obtained for the case of no-cavity condition

EFFECT OF TRANSVERSE BASE RESTRAINT ON THE CRACKING BEHAVIOR OF MASSIVE CONCRETE

The effect of considering the third dimension in mass concrete members on its cracking behavior is investigated in this study. The investigation includes thermal and structural analyses of mass concrete structures. From thermal analysis, the actual temperature distribution throughout the mass concrete body was obtained due to the generation of heat as a result of cement hydration in addition to the ambient circumstances. This was performed via solving the differential equations of heat conduction and convection using the finite element method. The finite element method was also implemented in the structural analysis adopting the concept of initial strain problem. Drying shrinkage volume changes were calculated using the procedure suggested by ACI Committee 209 and inverted to equivalent temperature differences to be added algebraically to the temperature differences obtained from thermal analysis. Willam-Warnke model with five strength parameters is used in modeling of concrete material in which cracking and crushing behavior of concrete can be included. The ANSYS program was employed in a modified manner to perform the above analyses. A thick concrete slab of 1.5m in thickness and 10m in length was analyzed for different widths 2, 4, 8, and 10m to produce different aspect ratios (B/L) of 0.2, 0.4, 0.8, and 1.0 respectively. The results of the analyses show an increase in cracking tendency of mass concrete member as the aspect ratio of the same member is increased due to the effect of transverse base restraint. Accordingly, such effect cannot be ignored in the analysis of base restrained mass concrete structures subjected to temperature and drying shrinkage volume changes

Baghdad’s thirdspace: Between liminality, anti-structures and territorial mappings

Wedged in-between the dense urban grain of Baghdad, blast walls of t-shaped concrete have littered the streets and neighbourhoods since 2003, after the US led invasion. The idiosyncrasy of these walls lies in their exaggerated spatial liminality. They appear, change location and disappear overnight, and on a daily basis, leaving Iraqis to navigate through labyrinths of in-between spaces. This article critically reveals the new social and power structures that have emerged in the context of the city in response to the condition resulting from this unique urban intervention. This uncanny spatial and social condition of permanent liminality will be analysed through Victor Turner’s critical theories of liminality and anti-structure coupled with Edward Soja’s theory of Thirdspace, interpreting, through a series of territorial mappings, a complex liminal condition in a contested and disrupted city

Life\u27s Essential 8: Optimizing Health in Older Adults

The population worldwide is getting older as a result of advances in public health, medicine, and technology. Older individuals are living longer with a higher prevalence of subclinical and clinical cardiovascular disease (CVD). In 2010, the American Heart Association introduced a list of key prevention targets, known as Life\u27s Simple 7 to increase CVD-free survival, longevity, and quality of life. In 2022, sleep health was added to expand the recommendations to Life\u27s Essential 8 (eat better, be more active, stop smoking, get adequate sleep, manage weight, manage cholesterol, manage blood pressure, and manage diabetes). These prevention targets are intended to apply regardless of chronologic age. During this same time, the understanding of aging biology and goals of care for older adults further enhanced the relevance of prevention across the range of functions. From a biological perspective, aging is a complex cellular process characterized by genomic instability, telomere attrition, loss of proteostasis, inflammation, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. These aging hallmarks are triggered by and enhanced by traditional CVD risk factors leading to geriatric syndromes (eg, frailty, sarcopenia, functional limitation, and cognitive impairment) which complicate efforts toward prevention. Therefore, we review Life\u27s Essential 8 through the lens of aging biology, geroscience, and geriatric precepts to guide clinicians taking care of older adults

Prognosis of heart failure recorded in primary care, acute hospital admissions, or both: a population-based linked electronic health record cohort study in 2.1 million people

Aims: The prognosis of patients hospitalized for worsening heart failure (HF) is well described but not that of patients managed solely in non-acute settings such as primary care or secondary outpatient care. We assessed the distribution and prognostic differences for patients with HF either recorded in primary care (including secondary out-patient care) (PC), hospital admissions alone, or known in both contexts. Methods and Results: This study was part of the CALIBER programme, comprising linked data from primary care, hospital admissions, and death-certificates for 2.1 million inhabitants of England. We identified 89,554 patients with incident HF, of whom 23,547(26%) were recorded in PC but never hospitalised, 30,629(34%) in hospital admissions but not known in PC, 23,681(26%) in both, and 11,697(13%) in death-certificates only. Highest prescription rates of ACEi, betablockers, and minerocorticoid receptor antagonists was found in patients known in both contexts. The respective 5-year survival in the first three groups was 43.9% (95%CI 43.2-44.6%), 21.7% (95%CI 21.1-22.2%), and 39.8% (95%CI 39.2-40.5%), compared to 88.1% (95%CI 87.9-88.3%) in the age and sex matched general population. Conclusion: In the general population, one in four patients with HF will not be hospitalised for worsening HF within a median follow up of 1.7 years, yet they still have a poor five-year prognosis. Patients admitted to hospital with worsening HF but not known with HF in primary care have the worst prognosis and management. Mitigating the prognostic burden of HF requires greater consistency across primary- and secondary care in the identification, profiling and treatment of patients