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Search Results: 1 - 10 of 178492 matches for " Alan E Jones "
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Modeling the effects of tetanus vaccination on chronically infected HIV patients
Laura E. Jones,Alan S. Perelson
Physics , 2001,
Abstract: T-cell activation plays a critical role in the initiation and propagation of HIV-1 infection and yet transient activation of the immune system is a normal response to immunization. In this study we extend a simple of model of HIV infection to include T cell activation by vaccination. We then show that the model can reproduce many but not all of the features of the post-tetanus immunization rise in viral load observed and reported on by Stanley et al., [N. Engl. J. Med., 334:1222--1230 (1996)]. Amplitudes and approximate timing of post-immunization maximum viremia were matched in nine of twelve cases; in patients with double peaks of nearly equal amplitude the later peaks were matched. Patients with single early peaks in their viremia were best fit with relatively high antigen clearance rate constants, while patients with early and late peaks in viremia of equal or nearly equal amplitude were best-fit with much lower clearance rates. The rate of clearance may depend on the level of pre-existing antibody, which in turn would be expected to depend on the time since the individual under study received a previous tetanus vaccination.
Opportunistic infection as a cause of transient viremia in chronically infected HIV patients under treatment with HAART
Laura E. Jones,Alan S. Perelson
Quantitative Biology , 2004, DOI: 10.1016/j.bulm.2005.01.006
Abstract: When highly active antiretroviral therapy is administered for long periods of time to HIV-1 infected patients, most patients achieve viral loads that are ``undetectable'' by standard assay (i.e., HIV-1 RNA $ < 50$ copies/ml). Yet despite exhibiting sustained viral loads below the level of detection, a number of these patients experience unexplained episodes of transient viremia or viral "blips". We propose here that transient activation of the immune system by opportunistic infection may explain these episodes of viremia. Indeed, immune activation by opportunistic infection may spur HIV replication, replenish viral reservoirs and contribute to accelerated disease progression. In order to investigate the effects of concurrent infection on chronically infected HIV patients under treatment with highly active antiretroviral therapy (HAART), we extend a simple dynamic model of the effects of vaccination on HIV infection [Jones and Perelson, JAIDS 31:369-377, 2002] to include growing pathogens. We then propose a more realistic model for immune cell expansion in the presence of pathogen, and include this in a set of competing models that allow low baseline viral loads in the presence of drug treatment. Programmed expansion of immune cells upon exposure to antigen is a feature not previously included in HIV models, and one that is especially important to consider when simulating an immune response to opportunistic infection. Using these models we show that viral blips with realistic duration and amplitude can be generated by concurrent infections in HAART treated patients.
Arterial pressure optimization in the treatment of septic shock: a complex puzzle
Alan E Jones, Stephen Trzeciak, R Phillip Dellinger
Critical Care , 2010, DOI: 10.1186/cc8194
Abstract: In the previous issue of Critical Care Dünser and colleagues presented the results of post-hoc analysis that add another piece to the puzzle of understanding optimal arterial pressure goals in the treatment of sepsis [1]. The authors examine data from a control group of severe sepsis patients enrolled in an interventional trial that mandated hemo dynamic management to specific therapeutic targets, one of which was achievement of a mean arterial pressure (MAP) of 70 mmHg or higher through the use of vasopressors. Dunser and colleagues analyzed the association between the average MAP, both as a continuous variable and grouped into quartiles, and mortality. What they found was no association between average MAP, or MAP quartiles above 70 mmHg, and 28-day mortality. They did, however, report an association between vasopressor load and mortality.In his classic text Physiology of Shock published in 1950, Dr Carl J Wiggers wrote 'In short, there are no patho-gnomonic signs of shock ... The instability of a patient's condition, along with progressive deterioration, constitutes the best evidence of shock. In the assessment of such determination, the trend of arterial pressures remains one of our best criteria' [2]. For over a century, arterial hypotension has been intensely studied as a central cause of organ hypoperfusion and subsequent organ injury in critically ill patients. This includes patients with hemorrhage [2], heterogeneous populations of pre-hospital patients [3] and emergency department patients [4], and specific disease states such as pulmonary embolism [5], acute myocardial infarction [6], post-cardiac arrest syndrome [7], and sepsis [8]. Because of both the universal availability of its measurement and its association with severity of illness, medical care providers frequently use blood pressure to communicate with each other about the hemodynamic stability of patients.We agree with the authors' contention that consensus recommendation of a goal for MAP as a
End expiratory oxygen concentrations to predict central venous oxygen saturation: an observational pilot study
Alan E Jones, Karl Kuehne, Michael Steuerwald, Jeffrey A Kline
BMC Emergency Medicine , 2006, DOI: 10.1186/1471-227x-6-9
Abstract: Prospective observational study of a convenience sample of hemodialysis patients age > 17 years with existing upper extremity central venous catheters were enrolled. Using a portable respiratory device, we collected both tidal breathing and end expiratory oxygen and carbon dioxide concentrations, volume and flow on each patient. Simultaneous ScVO2 measurements were obtained via blood samples collected from the hemodialysis catheter. Two models were used to predict ScVO2: 1) Best-fit multivariate linear regression equation incorporating all respiratory variables; 2) MathCAD to model the decay curve of EtO2 versus expiratory volume using the least squares method to estimate the pO2 that would occur at <20% of total lung capacity.From 21 patients, the correlation between EtO2 and measured ScVO2 yielded R2 = 0.11. The best fit multivariate equation included EtCO2 and EtO2 and when solved for ScVO2, the equation yielded a mean absolute difference from the measured ScVO2 of 8 ± 6% (range -18 to +17%). The predicted ScVO2 value was within 10% of the actual value for 57% of the patients. Modeling of the EtO2 curve did not accurately predict ScVO2 at any lung volume.We found no significant correlation between EtO2 and ScVO2. A linear equation incorporating EtCO2 and EtO2 had at best modest predictive accuracy for ScVO2.The mixed venous oxygen saturation (SVO2) is widely used in clinical practice to assess shock states and the physiologic response to resuscitation [1,2]. The central venous oxygen saturation (ScVO2) measurement correlates closely with SVO2 and when necessary can be substituted as a less invasive surrogate to the SVO2 [3]. When combined with other parameters, the use of ScVO2 measurements for guiding resuscitation has been shown in one study to improve mortality in patients with septic shock [4]. Both the SVO2 and ScVO2 measurements require central venous cannulation and a catheter to be placed in either the right atrium or pulmonary artery, thus limiting the f
New Material of Beelzebufo, a Hyperossified Frog (Amphibia: Anura) from the Late Cretaceous of Madagascar
Susan E. Evans, Joseph R. Groenke, Marc E. H. Jones, Alan H. Turner, David W. Krause
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087236
Abstract: The extant anuran fauna of Madagascar is exceptionally rich and almost completely endemic. In recent years, many new species have been described and understanding of the history and relationships of this fauna has been greatly advanced by molecular studies, but very little is known of the fossil history of frogs on the island. Beelzebufo ampinga, the first named pre-Holocene frog from Madagascar, was described in 2008 on the basis of numerous disarticulated cranial and postcranial elements from the Upper Cretaceous (Maastrichtian) Maevarano Formation of Madagascar. These specimens documented the presence of a hyperossified taxon that differed strikingly from extant Malagasy frogs in its large size and heavy coarse cranial exostosis. Here we describe and analyse new, articulated, and more complete material of the skull, vertebral column, and hind limb, as well as additional isolated elements discovered since 2008. μCT scans allow a detailed understanding of both internal and external morphology and permit a more accurate reconstruction. The new material shows Beelzebufo to have been even more bizarre than originally interpreted, with large posterolateral skull flanges and sculptured vertebral spine tables. The apparent absence of a tympanic membrane, the strong cranial exostosis, and vertebral morphology suggest it may have burrowed during seasonally arid conditions, which have been interpreted for the Maevarano Formation from independent sedimentological and taphonomic evidence. New phylogenetic analyses, incorporating both morphological and molecular data, continue to place Beelzebufo with hyloid rather than ranoid frogs. Within Hyloidea, Beelzebufo still groups with the South American Ceratophryidae thus continuing to pose difficulties with both biogeographic interpretations and prior molecular divergence dates.
Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis
Jessica M. F. Hall,desAnges Cruser,Alan Podawiltz,Diana I. Mummert,Harlan Jones,Mark E. Mummert
Dermatology Research and Practice , 2012, DOI: 10.1155/2012/403908
Abstract: Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity) and alters antigen presentation by epidermal Langerhans cells (adaptive immunity). Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis. 1. Introduction Psychological stress can trigger the activation of numerous physiological responses, including the endocrine, nervous, and immune systems [1–7]. Nearly 100 years ago, Cannon hypothesized that the release of substances (adrenalin, epinephrine, etc.) by the adrenal medulla during “pain and the major emotions” (fear, rage, and asphyxia) was an evolutionary adaptation for survival [8]. For example, an encounter with a predator induces an acute psychological stress which in turn activates the release of substances from the adrenal medulla. Substances released by the adrenal medulla induce profound physiological changes (increased circulation to the lungs, heart and limbs; increased cardiac vigor and increased sugar content in the blood; cessation of the activities of the alimentary canal) that endow the intended prey to flee or to fight. However, the connotation of emotional distress as an adaptation for survival has dramatically changed for most modern humans. Today, for example, there may be psychological stress due to divorce or unemployment, with the peripheral physiological
One year mortality of patients treated with an emergency department based early goal directed therapy protocol for severe sepsis and septic shock: a before and after study
Michael A Puskarich, Michael R Marchick, Jeffrey A Kline, Michael T Steuerwald, Alan E Jones
Critical Care , 2009, DOI: 10.1186/cc8138
Abstract: We performed a longitudinal analysis of a prospective before and after study conducted at a large urban ED. Adult patients were enrolled if they had suspected infection, 2 or more systemic inflammatory response criteria, and either systolic blood pressure (SBP) <90 mmHg after a fluid bolus or lactate >4 mM. Exclusion criteria were: age <18 years, no aggressive care desired, or need for immediate surgery. Clinical and outcomes data were prospectively collected on consecutive eligible patients for 1 year before and 2 years after implementing EGDT. Patients in the pre-implementation phase received non-protocolized care at attending physician discretion. The primary outcome was mortality at one year.285 subjects, 79 in the pre- and 206 in the post-implementation phases, were enrolled. Compared to pre-implementation, post-implementation subjects had a significantly lower ED SBP (72 vs. 85 mm Hg, P < 0.001) and higher sequential organ failure assessment score (7 vs. 5, P = 0.0004). The primary outcome of 1 year mortality was observed in 39/79 (49%) pre-implementation subjects and 77/206 (37%) post-implementation subjects (difference 12%; P = 0.04).Implementation of EGDT for the treatment of ED patients with severe sepsis and septic shock was associated with significantly lower mortality at one year.The rate of hospitalizations due to severe sepsis doubled during the past decade with estimates indicating that approximately 750,000 persons are affected annually in the USA [1]. Age-adjusted population-based mortality from severe sepsis appears to be increasing and sepsis currently ranks as the 10th leading cause of death in the USA [2]. Although much of the therapy for severe sepsis occurs in intensive care units (ICU), as many as 500,000 cases of severe sepsis are initially managed in emergency departments (EDs) annually, with an average ED length of stay of five hours [3]. These data underscore the importance of ED diagnosis and therapeutic intervention for severe sepsis.P
Non-obstetric vaginal trauma  [PDF]
Ian S. C. Jones, Alan O’Connor
Open Journal of Obstetrics and Gynecology (OJOG) , 2013, DOI: 10.4236/ojog.2013.31005

Objective: To describe the mechanism, injury pattern and management of women who present to the Emergency Department with non-obstetric vaginal trauma. Methods: A retrospective, single institution case series was carried out. Data was sourced from medical records of women who presented to the Emergency Department and Royal Brisbane and Women’s Hospital between 2007 and 2011. Records of possible injuries to the vagina were assessed to determine incidence, age, site, type of injury, mechanism of injury and whether urinary retention required treatment. Results: Vaginal non-obstetric trauma was found in 11 of 519 cases resulting in lacerations or tears. Injuries were due to consensual coitus, other forms of sexual activity and self harm. Acute urinary retention did not occur in any case but two cases required resuscitation. Site of injury was most common high in the vagina. Conclusion: Non-obstetric vaginal injuries are uncommon (incidence 2.1%). All cases require assessment for vulvar, vaginal, urethral, anal and bony pelvis injuries. This may require examination under anaesthesia. Social worker and psychological support is important to reduce the incidence of long-term psychological problems.

The Effects of Mary Rose Conservation Treatment on Iron Oxidation Processes and Microbial Communities Contributing to Acid Production in Marine Archaeological Timbers
Joanne Preston, Andrew D. Smith, Eleanor J. Schofield, Alan V. Chadwick, Mark A. Jones, Joy E. M. Watts
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0084169
Abstract: The Tudor warship the Mary Rose has reached an important transition point in her conservation. The 19 year long process of spraying with polyethylene glycol (PEG) has been completed (April 29th 2013) and the hull is air drying under tightly controlled conditions. Acidophilic bacteria capable of oxidising iron and sulfur have been previously identified and enriched from unpreserved timbers of the Mary Rose, demonstrating that biological pathways of iron and sulfur oxidization existed potentially in this wood, before preservation with PEG. This study was designed to establish if the recycled PEG spray system was a reservoir of microorganisms capable of iron and sulfur oxidization during preservation of the Mary Rose. Microbial enrichments derived from PEG impregnated biofilm collected from underneath the Mary Rose hull, were examined to better understand the processes of cycling of iron. X-ray absorption spectroscopy was utilised to demonstrate the biological contribution to production of sulfuric acid in the wood. Using molecular microbiological techniques to examine these enrichment cultures, PEG was found to mediate a shift in the microbial community from a co-culture of Stenotrophomonas and Brevunidimonas sp, to a co-culture of Stenotrophomonas and the iron oxidising Alicyclobacillus sp. Evidence is presented that PEG is not an inert substance in relation to the redox cycling of iron. This is the first demonstration that solutions of PEG used in the conservation of the Mary Rose are promoting the oxidation of ferrous iron in acidic solutions, in which spontaneous abiotic oxidation does not occur in water. Critically, these results suggest PEG mediated redox cycling of iron between valence states in solutions of 75% PEG 200 and 50% PEG 2000 (v/v) at pH 3.0, with serious implications for the future use of PEG as a conservation material of iron rich wooden archaeological artefacts.
Towards More Efficient Assessments: Increasing Information from Objective Examinations  [PDF]
Alan E. Dugdale
Creative Education (CE) , 2013, DOI: 10.4236/ce.2013.46A007

Objective examination questions are widely used to assess students knowledge, but the standard MCQ with a stem followed by 4 - 6 possible answers one of which is chosen as correct is very inefficient. Simple changes to the format can treble the information gained. Information theory is the tool for assessing the information content of electronic and other communications. The “bit” is the unit of information and equals on true/false choice. I have applied basic information theory to objective questions. The standard MCQ with a stem, a choice of 4 possible answers (mark one answer true) and an expected correct answer rate of 70% yields 1.36 bits. A MTFQ with 4 choices where the student must answer true/false to every possible answer gives 3.52 bits of information. By adding a “dont know” option the same MTFQ gives 4.72 bits of information, 350% of the standard MCQ. Thirty MTFQ with dont know give the same information about students knowledge as 100 standard MCQs. The effort needed to set, sit and mark is the same for both. Small changes to the format of objective questions give large gains in efficiency. We should balance these gains against possible disadvantages.

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