Science.gov

Sample records for pre-existing medical conditions

  1. Travellers with pre-existing medical conditions.

    PubMed

    Ericsson, Charles D

    2003-02-01

    Medical conditions that influence travel include those that compromise the immunity of the traveller and chronic underlying diseases or infirmities. The former includes HIV, transplantation, malignancy and its treatment, IgA deficiency, asplenia and use of immunocompromising drugs like corticosteroids. Chronic conditions include diabetes mellitus, end stage renal disease, diseases associated with compromised cardiac or pulmonary function and certain gastrointestinal diseases including cirrhosis. This review includes practical approaches to each of these conditions with attention to risk assessment and avoidance, vaccination when appropriate and not a risk to the compromised host, and arming the traveller with self-therapy and chemoprophylaxis. Since travellers with underlying conditions are often taking various medications the travel health practitioner must be alert for possible drug/drug interactions and must adjust dosages depending on the level of compromised renal or hepatic function. Finally, education of such travellers is paramount; they must understand that risk avoidance is critical and preventative modalities such as vaccination and chemoprophylaxis are never 100% efficacious. PMID:12615384

  2. Sports Dermatology: Part 1 of 2 Traumatic or Mechanical Injuries, Inflammatory Conditions, and Exacerbations of Pre-existing Conditions

    PubMed Central

    Sivek, Rachel; Marciniak, Brian

    2015-01-01

    Competitive athletes endure extreme bodily stress when participating in sports-related activities. An athlete’s skin is particularly susceptible to a wide array of repetitive physical and environmental stressors that challenge the skin’s protective function. Many unique dermatoses are well-known to the serious athlete due to countless hours of intense physical training, but are frequently unrecognized by many healthcare professionals. Sports dermatology is a distinctive, budding field of dermatology that focuses on dermatoses frequently encountered in athletes. Athletic skin problems are notoriously infectious in nature due to the inherent environment of close-contact physical activity. Nonetheless, other skin conditions can manifest or worsen with recurring mechanical or traumatic injury or exposure to environmental hazards. Additionally, sports-related activities may exacerbate other pre-existing dermatological conditions that may possibly be unknown to the athlete or clinician. The objective of this two-part review is to arm the astute physician with the fundamental knowledge of the range of dermatological conditions distinct to the competitive athlete. Knowledge of these cutaneous conditions in the context of specific sporting events will permit the clinician to manage these unique patients most effectively. Part one will focus on traumatic or mechanical injuries, inflammatory conditions, and exacerbations of pre-existing conditions frequently seen in athletes. PMID:26060516

  3. Comparison of maternal morbidity and medical costs during pregnancy and delivery between patients with gestational diabetes and patients with pre-existing diabetes

    PubMed Central

    Son, K H; Lim, N-K; Lee, J-W; Cho, M-C; Park, H-Y

    2015-01-01

    Aims To evaluate the effects of gestational diabetes and pre-existing diabetes on maternal morbidity and medical costs, using data from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Methods Delivery cases in 2010, 2011 and 2012 (459 842, 442 225 and 380 431 deliveries) were extracted from the Health Insurance Review and Assessment Service database. The complications and medical costs were compared among the following three pregnancy groups: normal, gestational diabetes and pre-existing diabetes. Results Although, the rates of pre-existing diabetes did not fluctuate (2.5, 2.4 and 2.7%) throughout the study, the rate of gestational diabetes steadily increased (4.6, 6.2 and 8.0%). Furthermore, the rates of pre-existing diabetes and gestational diabetes increased in conjunction with maternal age, pre-existing hypertension and cases of multiple pregnancy. The risk of pregnancy-induced hypertension, urinary tract infections, premature delivery, liver disease and chronic renal disease were greater in the gestational diabetes and pre-existing diabetes groups than in the normal group. The risk of venous thromboembolism, antepartum haemorrhage, shoulder dystocia and placenta disorder were greater in the pre-existing diabetes group, but not the gestational diabetes group, compared with the normal group. The medical costs associated with delivery, the costs during pregnancy and the number of in-hospital days for the subjects in the pre-existing diabetes group were the highest among the three groups. Conclusions The study showed that the rates of pre-existing diabetes and gestational diabetes increased with maternal age at pregnancy and were associated with increases in medical costs and pregnancy-related complications. PMID:25472691

  4. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or...

  5. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or...

  6. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or...

  7. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or...

  8. 5 CFR 894.102 - If I have a pre-existing dental or vision condition, may I join FEDVIP?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false If I have a pre-existing dental or vision... MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Administration and General Provisions § 894.102 If I have a pre-existing dental or...

  9. [Travelers with underlying medical conditions].

    PubMed

    Cailhol, Johann

    2015-04-01

    Travelers with pre-existing medical disease are at risk of exacerbation of their underlying disease during their journey but are also more susceptible to various infectious agents, which consequences could be much more severe than in healthy subjects. Prevention and education are primordial in order to optimize the trip. Each new prescription should be checked for potential drug/drug interactions. Malaria chemoprophylaxis should be considered if applicable, as well as mechanical protection against insect-bites. Vaccinations should be recommended after weighting risks and benefits, keeping in mind that live-attenuated vaccines are not recommended in case of cellular immune suppression. Prevention of travel- related diarrhea by general hygiene measures is of particular interest in this population. Thereafter, we are discussing specific preventive measure according to different medical conditions. PMID:26058202

  10. 15 CFR 922.47 - Pre-existing authorizations or rights and certifications of pre-existing authorizations or rights.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Pre-existing authorizations or rights and certifications of pre-existing authorizations or rights. 922.47 Section 922.47 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC...

  11. 15 CFR 922.47 - Pre-existing authorizations or rights and certifications of pre-existing authorizations or rights.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Pre-existing authorizations or rights and certifications of pre-existing authorizations or rights. 922.47 Section 922.47 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE...

  12. Pre-existing Antibody: Biotherapeutic Modality-Based Review.

    PubMed

    Gorovits, Boris; Clements-Egan, Adrienne; Birchler, Mary; Liang, Meina; Myler, Heather; Peng, Kun; Purushothama, Shobha; Rajadhyaksha, Manoj; Salazar-Fontana, Laura; Sung, Crystal; Xue, Li

    2016-03-01

    Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed. PMID:26821802

  13. A Double Whammy: Health Promotion Among Cancer Survivors with Pre-Existing Functional Limitations

    PubMed Central

    Volker, Deborah L.; Becker, Heather; Kang, Sook Jung; Kullberg, Vicki

    2012-01-01

    Purpose/Objectives To explore the experience of living with a cancer diagnosis within the context of a pre-existing functional disability and to identify strategies to promote health in this growing population of cancer survivors. Research Approach Qualitative descriptive Setting Four sites in the United States Participants 19 female cancer survivors with pre-existing disabling conditions Methodologic Approach Four focus groups were conducted. The audiotapes were transcribed and analyzed using content analysis techniques. Main Research Variables cancer survivor, disability, health promotion Findings Analytic categories included living with a cancer diagnosis, health promotion strategies, and wellness program development for survivors with pre-existing functional limitations. Participants described many challenges associated with managing a cancer diagnosis on top of living with a chronic disabling functional limitation. They identified strategies they used to maintain their health and topics to be included in health promotion programs tailored for this unique group of cancer survivors. Conclusions The “double whammy” of a cancer diagnosis for persons with pre-existing functional limitations requires modification of health promotion strategies and programs to promote wellness in this group of cancer survivors. Interpretation Nurses and other health care providers must attend to patients’ pre-existing conditions as well as the challenges of the physical, emotional, social, and economic sequelae of a cancer diagnosis. PMID:23269771

  14. 75 FR 45013 - Pre-Existing Condition Insurance Plan Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-30

    ... 2719A (regarding patient protections), published in the Federal Register on June 28, 2010 (75 FR 37188... of rape or incest, or where the life of the woman would be endangered. Exec. Order No. 13,535, 75...

  15. 78 FR 30218 - Pre-Existing Condition Insurance Plan Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... published July 10, 2010 (75 FR 45014) set forth and addressed key issues regarding administration of the... 12866 (58 FR 51735), a ``significant'' regulatory action is subject to review by the Office of... the July 30, 2010 interim final regulation (75 FR 45026). These benefits could take the form...

  16. 77 FR 52614 - Pre-Existing Condition Insurance Plan Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... Affordable Insurance Exchanges, 45 CFR 155.20 (77 FR 18310, March 27, 2012), and the premium tax credits, 26 CFR 1.36B-1(g) (77 FR 30377, May 23, 2012), issued by HHS and the Department of the Treasury... 30, 2010 (75 FR 45014). For the reasons explained below, HHS is now issuing an amendment to...

  17. Gate dielectric degradation: Pre-existing vs. generated defects

    SciTech Connect

    Veksler, Dmitry E-mail: gennadi.bersuker@sematech.org; Bersuker, Gennadi E-mail: gennadi.bersuker@sematech.org

    2014-01-21

    We consider the possibility that degradation of the electrical characteristics of high-k gate stacks under low voltage stresses of practical interest is caused primarily by activation of pre-existing defects rather than generation of new ones. In nFETs in inversion, in particular, defect activation is suggested to be associated with the capture of an injected electron: in this charged state, defects can participate in a fast exchange of charge carriers with the carrier reservoir (substrate or gate electrode) that constitutes the physical process underlying a variety of electrical measurements. The degradation caused by the activation of pre-existing defects, as opposed to that of new defect generation, is both reversible and exhibits a tendency to saturate through the duration of stress. By using the multi-phonon assisted charge transport description, it is demonstrated that the trap activation concept allows reproducing a variety of experimental results including stress time dependency of the threshold voltage, leakage current, charge pumping current, and low frequency noise. Continuous, long-term degradation described by the power law time dependency is shown to be determined by the activation of defects located in the interfacial SiO{sub 2} layer of the high-k gate stacks. The findings of this study can direct process optimization efforts towards reduction of as-grown precursors of the charge trapping defects as the major factor affecting reliability.

  18. Morbidity risks among older adults with pre-existing age-related diseases.

    PubMed

    Akushevich, Igor; Kravchenko, Julia; Ukraintseva, Svetlana; Arbeev, Konstantin; Kulminski, Alexander; Yashin, Anatoliy I

    2013-12-01

    Multi-morbidity is common among older adults; however, for many aging-related diseases there is no information for U.S. elderly population on how earlier-manifested disease affects the risk of another disease manifested later during patient's lifetime. Quantitative evaluation of risks of cancer and non-cancer diseases for older adults with pre-existing conditions is performed using the Surveillance, Epidemiology, and End Results (SEER) Registry data linked to the Medicare Files of Service Use (MFSU). Using the SEER-Medicare data containing individual records for 2,154,598 individuals, we empirically evaluated age patterns of incidence of age-associated diseases diagnosed after the onset of earlier manifested disease and compared these patterns with those in general population. Individual medical histories were reconstructed using information on diagnoses coded in MFSU, dates of medical services/procedures, and Medicare enrollment/disenrollment. More than threefold increase of subsequent diseases risk was observed for 15 disease pairs, majority of them were i) diseases of the same organ and/or system (e.g., Parkinson disease for patients with Alzheimer disease, HR=3.77, kidney cancer for patients with renal failure, HR=3.28) or ii) disease pairs with primary diseases being fast-progressive cancers (i.e., lung, kidney, and pancreas), e.g., ulcer (HR=4.68) and melanoma (HR=4.15) for patients with pancreatic cancer. Lower risk of subsequent disease was registered for 20 disease pairs, mostly among patients with Alzheimer's or Parkinson's disease, e.g., decreased lung cancer risk among patients with Alzheimer's (HR=0.64) and Parkinson's (HR=0.60) disease. Synergistic and antagonistic dependences in geriatric disease risks were observed among US elderly confirming known and detecting new associations of wide spectrum of age-associated diseases. The results can be used in optimization of screening, prevention and treatment strategies of chronic diseases among U.S. elderly

  19. PRESENCE OF PRE-EXISTING ANTIBODIES MEDIATE SURVIVAL IN SEPSIS

    PubMed Central

    Moitra, Rituparna; Beal, Dominic R.; Belikoff, Bryan G.; Remick, Daniel G.

    2011-01-01

    Sepsis is one of the leading causes of death in hospitals worldwide. Even with optimal therapy, severe sepsis results in 50% mortality, indicating variability in the response of individuals towards treatment. We hypothesize that the presence of pre-existing antibodies present in the blood before the onset of sepsis induced by cecal ligation and puncture (CLP) in mice, accounts for the differences in their survival. A Plasma Enhanced Killing (PEK) assay was performed to calculate the PEK capacity of plasma i.e. the ability of plasma to augment PMN killing of bacteria. PEK was calculated as PEK= (1/log (N)) × 100; where N= number of surviving bacteria; a higher PEK indicated better bacterial killing. A range of PEK in plasma collected from mice prior to CLP was observed, documenting individual differences in bacterial killing capacity. Mortality was predicted based on plasma IL-6 levels at 24 hr post CLP. Mice predicted to die (Die-P) had a lower PEK (<14) and higher peritoneal bacterial counts 24 hr post sepsis compared to those predicted to live (Live-P) with a PEK>16. Mice with PEK<14 were 3.1 times more likely to die compared to the PEK>16 group. To understand the mechanism of defense conferred by the pre-existing antibodies, binding of IgM or IgG to enteric bacteria was documented by flow cytometry. To determine the relative contribution of IgM or IgG, the immunoglobulins were specifically immuno-depleted from the naïve plasma samples and the PEK of the depleted plasma measured. Compared to naïve plasma, depletion of IgM had no effect on the PEK. However, depletion of IgG increased PEK suggesting that an inhibitory IgG binds to antigenic sites on bacteria preventing optimal opsonization of the bacteria. These data demonstrate that prior to CLP; circulating inhibitory IgG antibodies exist that prevent bacterial killing by PMNs in a CLP model of sepsis. PMID:21921828

  20. Ionospheric Current Closure of the Pre-existing Auroral Arc

    NASA Astrophysics Data System (ADS)

    Jiang, F.; Kivelson, M.; Strangeway, R. J.; Khurana, K. K.; Walker, R. J.; Weygand, J. M.

    2014-12-01

    An auroral substorm commences when a discrete auroral arc brightens and subsequently expands poleward and azimuthally. The arc that brightens is usually the most equatorward of several auroral arcs that remain quiescent for ~5 to ~60 minutes before the break-up commences. This arc is often referred to as the "pre-existing auroral arc (PAA)" or the "growth-phase arc". Till now, the ionospheric electrodynamics of the PAA has been studied extensively by ground radar, rockets and low-altitude spacecraft, and it is well established that the field-aligned currents (FAC) associated with the PAA in the ionosphere are current sheets that are narrow in latitude and elongated in longitude. However, it remains a question whether the ionospheric currents that connect the FAC pair of the PAA are meridional or azimuthal. In this study, we have identified ~180 PAA events from FAST measurements in 1998 and 1999 and used the statistics to investigate the ionospheric current closure of the PAA. We calculate the height-integrated Pedersen currents from the electric fields measured by FAST using an empirical ionospheric conductance model and infer the FAC density from the divergence of the Pedersen currents. We find that in the vicinity of the PAA, the FAC density inferred from the divergence of perpendicular currents mimics the trend of the FAC density inferred from magnetic perturbations seen on FAST, and that the boundaries between the upward and the downward FAC sheets inferred from two different approaches lie very close together. Additionally, the latitudinal gradient of the azimuthal component of the magnetic perturbation is much larger than the azimuthal gradient of the meridional component of the magnetic perturbation in the vicinity of the PAA, indicating that the density of a meridional current is much larger than that of an azimuthal current. Our observational analysis strongly suggests that the perpendicular current that closes the FAC pair of the PAA is a north

  1. Pre-Existing Rotator Cuff Tears as a Predictor of Outcomes in National Football League Athletes

    PubMed Central

    Gibbs, Daniel; Lynch, Thomas Sean; Gomberawalla, M. Mustafa; Schroeder, Greg; LaBelle, Mark; Hollett, Brian P.; Saltzman, Matthew; Nuber, Gordon W.

    2015-01-01

    Objectives: Fifty percent of all athletes at the National Football League (NFL) Combine report having had a shoulder injury at some point during their playing career. Rotator cuff tears are rare injuries in young athletes, but an increasing incidence has been noted amongst competitive football players. It is unknown how pre-existing rotator cuff tears affect career longevity and performance of NFL athletes. In Combine athletes with pre-existing rotator cuff tears, knowledge of outcomes may help athletes and physicians manage expectations of draft potential, career length and performance. Methods: The written medical evaluations of prospective professional American football athletes from 2003-2011 during the NFL Combine were compiled and evaluated. All players were evaluated for the diagnosis of a pre-existing rotator cuff tear and stratified based on whether or not they underwent surgical intervention. Athletes with rotator cuff tears, who were selected in the NFL draft, were matched by age, position, year, and round drafted to control draftees without significant documented shoulder pathology. Career statistics, including a previously established “Performance Score,” were compiled. The continuous variables of each cohort were compared using a Student's t-test. A Chi Squared test was performed to analyze the categorical data. Statistical significance was accepted with a p-value < 0.05. Results: Between the years of 2003 and 2011, 2,965 consecutive athletes were evaluated. Forty-nine athletes were identified with a pre-existing rotator cuff tear; twenty-two of these athletes underwent surgical intervention for their tear and 27 were treated non-operatively. Those who attended the NFL Combine with a history of a rotator cuff tear were significantly less likely to be drafted than those without a previous injury (55.1% vs. 77.5% respectively, p = 0.002) (Table 1A). The 27 drafted athletes with pre-existing rotator cuff tears played significantly fewer years (4.3 vs

  2. Surrogate-based optimization of hydraulic fracturing in pre-existing fracture networks

    NASA Astrophysics Data System (ADS)

    Chen, Mingjie; Sun, Yunwei; Fu, Pengcheng; Carrigan, Charles R.; Lu, Zhiming; Tong, Charles H.; Buscheck, Thomas A.

    2013-08-01

    Hydraulic fracturing has been used widely to stimulate production of oil, natural gas, and geothermal energy in formations with low natural permeability. Numerical optimization of fracture stimulation often requires a large number of evaluations of objective functions and constraints from forward hydraulic fracturing models, which are computationally expensive and even prohibitive in some situations. Moreover, there are a variety of uncertainties associated with the pre-existing fracture distributions and rock mechanical properties, which affect the optimized decisions for hydraulic fracturing. In this study, a surrogate-based approach is developed for efficient optimization of hydraulic fracturing well design in the presence of natural-system uncertainties. The fractal dimension is derived from the simulated fracturing network as the objective for maximizing energy recovery sweep efficiency. The surrogate model, which is constructed using training data from high-fidelity fracturing models for mapping the relationship between uncertain input parameters and the fractal dimension, provides fast approximation of the objective functions and constraints. A suite of surrogate models constructed using different fitting methods is evaluated and validated for fast predictions. Global sensitivity analysis is conducted to gain insights into the impact of the input variables on the output of interest, and further used for parameter screening. The high efficiency of the surrogate-based approach is demonstrated for three optimization scenarios with different and uncertain ambient conditions. Our results suggest the critical importance of considering uncertain pre-existing fracture networks in optimization studies of hydraulic fracturing.

  3. Molecular dynamics study on the interactions between helium projectiles and helium bubbles pre-existing in tungsten surfaces

    NASA Astrophysics Data System (ADS)

    Ding, Yuan; Ma, Chaoqiong; Li, Min; Hou, Qing

    2016-02-01

    Molecular dynamics simulations were performed to study the interactions between low-energy (⩽100 eV) helium (He) projectiles and helium bubbles pre-existing near tungsten (W) surfaces. It is observed that with increasing bubble size, the reflection coefficient of the He projectiles was reduced, and the channelling effect that could be observed with no pre-existing He bubble was depressed. The He projectiles can be captured by pre-existing He bubbles and also knock He atoms out of the bubbles. The spatial distribution of the single He atoms, including both the slowed-down projectiles and the knocked-out He atoms, was extracted. The single He atoms were found distributed around the bubbles in a region with the width of 3-5.5 in lattice lengths of W. Although the results were obtained for the interaction of He projectiles with isolated He bubbles pre-existing in W, they suggest that the reflection and retention status of He projectiles would change during the irradiation of high flux/fluence He on W surfaces due to the change of He bubbles coverage near W surfaces. The results can be coupled with Monte Carlo modelling in conditions closer to that in experiments of high flux/fluence He bombardments on W surfaces.

  4. The Near Earth Asteroid Medical Conditions List

    NASA Technical Reports Server (NTRS)

    Barr, Yael R.; Watkins, S. D.

    2011-01-01

    Purpose: The Exploration Medical Capability (ExMC) element is one of six elements within NASA s Human Research Program (HRP) and is responsible for addressing the risk of "the inability to adequately recognize or treat an ill or injured crewmember" for exploration-class missions. The Near Earth Asteroid (NEA) Medical Conditions List, constructed by ExMC, is the first step in addressing the above-mentioned risk for the 13-month long NEA mission. The NEA mission is being designed by NASA's Human Space Flight Architecture Team (HAT). The purpose of the conditions list is to serve as an evidence-based foundation for determining which medical conditions could affect a crewmember during the NEA mission, which of those conditions would be of concern and require treatment, and for which conditions a gap in knowledge or technology development exists. This information is used to focus research efforts and technology development to ensure that the appropriate medical capabilities are available for exploration-class missions. Scope and Approach: The NEA Medical Conditions List is part of a broader Space Medicine Exploration Medical Conditions List (SMEMCL), which incorporates various exploration-class design reference missions (DRMs). The conditions list contains 85 medical conditions which could occur during space flight and which are derived from several sources: Long-Term Surveillance of Astronaut Health (LSAH) in-flight occurrence data, The Space Shuttle (STS) Medical Checklist, The International Space Station (ISS) Medical Checklist, and subject matter expert opinion. Each medical condition listed has been assigned a clinical priority and a clinical priority rationale based on incidence, consequence, and mitigation capability. Implementation: The conditions list is a "living document" and as such, new conditions can be added to the list, and the priority of conditions on the list can be adjusted as the DRM changes, and as screening, diagnosis, or treatment capabilities

  5. 45 CFR 96.111 - Continuation of pre-existing regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Continuation of pre-existing regulations. 96.111 Section 96.111 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION BLOCK GRANTS Transition Provisions § 96.111 Continuation of pre-existing regulations. The regulations previously issued...

  6. Mining FDA drug labels for medical conditions

    PubMed Central

    2013-01-01

    Background Cincinnati Children’s Hospital Medical Center (CCHMC) has built the initial Natural Language Processing (NLP) component to extract medications with their corresponding medical conditions (Indications, Contraindications, Overdosage, and Adverse Reactions) as triples of medication-related information ([(1) drug name]-[(2) medical condition]-[(3) LOINC section header]) for an intelligent database system, in order to improve patient safety and the quality of health care. The Food and Drug Administration’s (FDA) drug labels are used to demonstrate the feasibility of building the triples as an intelligent database system task. Methods This paper discusses a hybrid NLP system, called AutoMCExtractor, to collect medical conditions (including disease/disorder and sign/symptom) from drug labels published by the FDA. Altogether, 6,611 medical conditions in a manually-annotated gold standard were used for the system evaluation. The pre-processing step extracted the plain text from XML file and detected eight related LOINC sections (e.g. Adverse Reactions, Warnings and Precautions) for medical condition extraction. Conditional Random Fields (CRF) classifiers, trained on token, linguistic, and semantic features, were then used for medical condition extraction. Lastly, dictionary-based post-processing corrected boundary-detection errors of the CRF step. We evaluated the AutoMCExtractor on manually-annotated FDA drug labels and report the results on both token and span levels. Results Precision, recall, and F-measure were 0.90, 0.81, and 0.85, respectively, for the span level exact match; for the token-level evaluation, precision, recall, and F-measure were 0.92, 0.73, and 0.82, respectively. Conclusions The results demonstrate that (1) medical conditions can be extracted from FDA drug labels with high performance; and (2) it is feasible to develop a framework for an intelligent database system. PMID:23617267

  7. Travelers with Disabilities and Medical Conditions

    MedlinePlus

    ... Claims Travel Tips Travel Bulletin Travel Checklist FAQ Disabilities and Medical Conditions To ensure your security, all ... other questions or concerns about traveling with a disability please contact passenger support . If you are approved ...

  8. The Space Medicine Exploration Medical Condition List

    NASA Technical Reports Server (NTRS)

    Watkins, Sharmi; Barr, Yael; Kerstman, Eric

    2011-01-01

    Exploration Medical Capability (ExMC) is an element of NASA s Human Research Program (HRP). ExMC's goal is to address the risk of the "Inability to Adequately Recognize or Treat an Ill or Injured Crewmember." This poster highlights the approach ExMC has taken to address this risk. The Space Medicine Exploration Medical Condition List (SMEMCL) was created to define the set of medical conditions that are most likely to occur during exploration space flight missions. The list was derived from the International Space Station Medical Checklist, the Shuttle Medical Checklist, in-flight occurrence data from the Lifetime Surveillance of Astronaut Health, and NASA subject matter experts. The list of conditions was further prioritized for eight specific design reference missions with the assistance of the ExMC Advisory Group. The purpose of the SMEMCL is to serve as an evidence-based foundation for the conditions that could affect a crewmember during flight. This information is used to ensure that the appropriate medical capabilities are available for exploration missions.

  9. Mechanical and microstructural development of Carrara marble with pre-existing deformation history in torsion experiments

    NASA Astrophysics Data System (ADS)

    Bruijn, R. H. C.; Burlini, L.; Kunze, K.

    2009-04-01

    The deformation behaviour of Carrara marble has been studied mostly by performing deformation experiments on initially undeformed samples. In this study, torsion experiments on Carrara marble with a pre-existing deformation history have been conducted and analysed in terms of both mechanical and microstructural development. Torsion experiments have been conducted to deform initially deformed Carrara marble samples until a bulk shear strain of gamma 1 or 2.6 was reached. For Carrara marble experiments typically yielding is followed by strain hardening until a peak stress is reached around a shear strain gamma = 1 , after which a weakening phase occurs. Weakening gradually develops into a steady-state creep. During hardening, a shear microstructure and CPO develops; afterwards dynamic recrystallization becomes increasingly effective resulting in pervasively recrystallized microstructure and recrystallization CPO at gamma 5 and higher. Starting material of the new experiments are sandwich samples consisting of three equally sized segments: a top segment previously deformed counter clockwise, an undeformed centre segment and a previously clockwise deformed segment in the bottom. Shear strain of the deformed bottom and top segments are equal in magnitude but opposite in sense and correspond with the shear strain of the actual experiments (e.g. sample of the gamma 1 experiment, consists of initially gamma 1 deformed top and bottom segments). All torsion experiments were conducted using a Paterson type internally heated gas-medium deformation apparatus equipped with a torsion actuator, under temperature and pressure conditions of 1000K and 300 MPa, respectively. Angular displacement rates during the experiments correspond to a strain rate of 3.0x10-4 s-1 at the outer cylinder periphery. The second deformation event imposed on the sandwich sample is always counter clockwise (or dextral). The sandwich experiment to gamma 1 shows a weakly developed strain partitioning

  10. Solid particle impingement erosion characteristics of cylindrical surfaces, pre-existing holes and slits

    NASA Technical Reports Server (NTRS)

    Rao, P. V.; Buckley, D. H.

    1983-01-01

    The erosion characteristics of aluminum cylinders sand-blasted with both spherical and angular erodent particles were studied and compared with results from previously studied flat surfaces. The cylindrical results are discussed with respect to impact conditions. The relationship between erosion rate and pit morphology (width, depth, and width to depth ratio) is established. The aspects of (1) erosion rate versus time curves on cylindrical surfaces; (2) long-term exposures; and (3) erosion rate versus time curves with spherical and angular particles are presented. The erosion morphology and characteristics of aluminum surfaces with pre-existing circular cylindrical and conical holes of different sizes were examined using weight loss measurements, scanning electron microscopy, a profilometer, and a depth gage. The morphological features (radial and concentric rings) are discussed with reference to flat surfaces, and the erosion features with spherical microglass beads. The similarities and differences of erosion and morphological features are highlighted. The erosion versus time curves of various shapes of holes are discussed and are compared with those of a flat surface. The erosion process at slits is considered.

  11. Asperger Syndrome: Associated Psychiatric and Medical Conditions.

    ERIC Educational Resources Information Center

    Ghaziuddin, Mohammad

    2002-01-01

    This article explores the association of medical and psychiatric conditions with Asperger syndrome, based mainly on publications from the last two decades. It examines comorbidity of Asperger syndrome with mood disorders, schizophrenia, obsessive-compulsive disorder, attention deficit/hyperactivity disorder, tic disorders, violence and aggression,…

  12. Simple scaling laws for the role of pre-existing and shock-induced microstructure on spall strength

    NASA Astrophysics Data System (ADS)

    Wilkerson, Justin; Ramesh, Kt

    2015-06-01

    Failure of ductile metals has long been attributed to void nucleation, growth, and finally coalescence leading to fracture. Under extreme loading conditions, a number of experimental investigations have demonstrated a strong rate-dependence in the dynamic tensile strength of such metals, which may be attributed to the fact that voids are constrained to grow at finite rates. Here we show that bounds on these void growth rates may be derived analytically by considering the constraints imposed by micro-inertia as well as relativistic dislocation drag. We then make use of these bounds to derive simple scaling laws for predicting the rate-dependence of spall strength. Though simple, the derived scaling laws compare well with experimental measurements and prove useful in shedding light on some of the more perplexing observations associated with spall failure. In particular, the scaling laws are helpful in understanding the role of pre-existing microstructure, e.g. second-phase particle spacing and grain size, on the spall strength of metals. Under typical loading conditions, we find that the spall strength is governed by this pre-existing microstructure with void growth governed primarily by micro-inertia. However, under the most extreme loading conditions, we find that the spall strength is governed instead by the shock-induced microstructure with growth mediated by dislocation emission. Lastly, we demonstrate how the scaling laws may be utilized to optimize the pre-existing microstructure, e.g. grain size considering the Hall-Petch effect, of a material for a particular application.

  13. Rapid selective sweep of pre-existing polymorphisms and slow fixation of new mutations in experimental evolution of Desulfovibrio vulgaris.

    PubMed

    Zhou, Aifen; Hillesland, Kristina L; He, Zhili; Schackwitz, Wendy; Tu, Qichao; Zane, Grant M; Ma, Qiao; Qu, Yuanyuan; Stahl, David A; Wall, Judy D; Hazen, Terry C; Fields, Matthew W; Arkin, Adam P; Zhou, Jizhong

    2015-11-01

    To investigate the genetic basis of microbial evolutionary adaptation to salt (NaCl) stress, populations of Desulfovibrio vulgaris Hildenborough (DvH), a sulfate-reducing bacterium important for the biogeochemical cycling of sulfur, carbon and nitrogen, and potentially the bioremediation of toxic heavy metals and radionuclides, were propagated under salt stress or non-stress conditions for 1200 generations. Whole-genome sequencing revealed 11 mutations in salt stress-evolved clone ES9-11 and 14 mutations in non-stress-evolved clone EC3-10. Whole-population sequencing data suggested the rapid selective sweep of the pre-existing polymorphisms under salt stress within the first 100 generations and the slow fixation of new mutations. Population genotyping data demonstrated that the rapid selective sweep of pre-existing polymorphisms was common in salt stress-evolved populations. In contrast, the selection of pre-existing polymorphisms was largely random in EC populations. Consistently, at 100 generations, stress-evolved population ES9 showed improved salt tolerance, namely increased growth rate (2.0-fold), higher biomass yield (1.8-fold) and shorter lag phase (0.7-fold) under higher salinity conditions. The beneficial nature of several mutations was confirmed by site-directed mutagenesis. All four tested mutations contributed to the shortened lag phases under higher salinity condition. In particular, compared with the salt tolerance improvement in ES9-11, a mutation in a histidine kinase protein gene lytS contributed 27% of the growth rate increase and 23% of the biomass yield increase while a mutation in hypothetical gene DVU2472 contributed 24% of the biomass yield increase. Our results suggested that a few beneficial mutations could lead to dramatic improvements in salt tolerance. PMID:25848870

  14. Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status.

    PubMed

    Melnik, Bodo C; Schmitz, Gerd; John, Swen; Carrera-Bastos, Pedro; Lindeberg, Staffan; Cordain, Loren

    2013-01-01

    Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual's pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. PMID:24225036

  15. Metabolic effects of milk protein intake strongly depend on pre-existing metabolic and exercise status

    PubMed Central

    2013-01-01

    Milk protein intake has recently been suggested to improve metabolic health. This Perspective provides evidence that metabolic effects of milk protein intake have to be regarded in the context of the individual’s pre-existing metabolic and exercise status. Milk proteins provide abundant branched-chain amino acids (BCAAs) and glutamine. Plasma BCAAs and glutamine are increased in obesity and insulin resistance, but decrease after gastric bypass surgery resulting in weight loss and improved insulin sensitivity. Milk protein consumption results in postprandial hyperinsulinemia in obese subjects, increases body weight of overweight adolescents and may thus deteriorate pre-existing metabolic disturbances of obese, insulin resistant individuals. PMID:24225036

  16. 14 CFR 67.313 - General medical condition.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false General medical condition. 67.313 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.313 General medical condition. The general medical standards for a third-class airman medical certificate are: (a)...

  17. 14 CFR 67.113 - General medical condition.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false General medical condition. 67.113 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.113 General medical condition. The general medical standards for a first-class airman medical certificate are: (a)...

  18. 14 CFR 67.213 - General medical condition.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false General medical condition. 67.213 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.213 General medical condition. The general medical standards for a second-class airman medical certificate are: (a)...

  19. 14 CFR 67.313 - General medical condition.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false General medical condition. 67.313 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.313 General medical condition. The general medical standards for a third-class airman medical certificate are: (a)...

  20. 14 CFR 67.113 - General medical condition.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false General medical condition. 67.113 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.113 General medical condition. The general medical standards for a first-class airman medical certificate are: (a)...

  1. 14 CFR 67.213 - General medical condition.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false General medical condition. 67.213 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.213 General medical condition. The general medical standards for a second-class airman medical certificate are: (a)...

  2. 14 CFR 67.313 - General medical condition.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false General medical condition. 67.313 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.313 General medical condition. The general medical standards for a third-class airman medical certificate are: (a)...

  3. 14 CFR 67.213 - General medical condition.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false General medical condition. 67.213 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.213 General medical condition. The general medical standards for a second-class airman medical certificate are: (a)...

  4. 14 CFR 67.113 - General medical condition.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false General medical condition. 67.113 Section...) AIRMEN MEDICAL STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.113 General medical condition. The general medical standards for a first-class airman medical certificate are: (a)...

  5. 13 CFR 120.922 - Pre-existing debt on the Project Property.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Pre-existing debt on the Project Property. 120.922 Section 120.922 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS... Project Property. In addition to its share of Project cost, a Third-Party Loan may include...

  6. Contributions Made by a Strengths-Oriented Intervention to Trusting Relationships within Pre-Existing Teams

    ERIC Educational Resources Information Center

    King, W. Bernt

    2012-01-01

    This qualitative study spotlighted a grounded theory regarding contributions to affect- and cognition-based trust by a strengths-oriented intervention in pre-existing teams. Using purposeful and convenience sampling, 18 participants in a strengths-oriented intervention from 2 different regions of the Pacific Northwest were selected. A…

  7. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 14 2013-04-01 2013-04-01 false Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross...

  8. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross...

  9. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross...

  10. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 14 2012-04-01 2012-04-01 false Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross...

  11. 26 CFR 20.2045-1 - Applicability to pre-existing transfers or interests.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 14 2014-04-01 2013-04-01 true Applicability to pre-existing transfers or interests. 20.2045-1 Section 20.2045-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Gross...

  12. Using an Electronic Highlighter to Eliminate the Negative Effects of Pre-Existing, Inappropriate Highlighting

    ERIC Educational Resources Information Center

    Gier, Vicki; Kreiner, David; Hudnell, Jason; Montoya, Jodi; Herring, Daniel

    2011-01-01

    The purpose of the present experiment was to determine whether using an active learning technique, electronic highlighting, can eliminate the negative effects of pre-existing, poor highlighting on reading comprehension. Participants read passages containing no highlighting, appropriate highlighting, or inappropriate highlighting. We hypothesized…

  13. Are There Pre-Existing Neural, Cognitive, or Motoric Markers for Musical Ability?

    ERIC Educational Resources Information Center

    Norton, Andrea; Winner, Ellen; Cronin, Karl; Overy, Katie; Lee, Dennis J.; Schlaug, Gottfried

    2005-01-01

    Adult musician's brains show structural enlargements, but it is not known whether these are inborn or a consequence of long-term training. In addition, music training in childhood has been shown to have positive effects on visual-spatial and verbal outcomes. However, it is not known whether pre-existing advantages in these skills are found in…

  14. Influence of pre-existing salt structures in the 3D pattern of multilayer folding

    NASA Astrophysics Data System (ADS)

    Fernandez, Naiara; Kaus, Boris J. P.; Collignon, Marine

    2014-05-01

    Upward movement of the Precambrian Hormuz salt in the Fars region of the Zagros is supposed to have started as early as Late Cretaceous. The Late Cretaceous - Tertiary deformation events that lead to the folding of the sedimentary cover in this area would have therefore, enhance the upward salt movement by squeezing the pre-existing salt structures. How these salt diapirs evolve under such compressive events has already been previously addressed using analogue models (e.g. Callot et al. 2012). The same authors observed that pre-existing salt structures control the size and geometry of folds in sandbox models. Our previous work has shown that 3D folding instability gives rise to a wide variety of fold shapes (e.g. from dome shape structures to long en echelon or straight anticlines), resulting of the interactions between growing fold segments. The three dimensional growth of these folds, the wavelength and the lateral propagation, is itself controlled by physical parameters. However, the existence of initial weak zones such as pre-existing salt plugs within the sedimentary cover can affect the development of such folds by localizing part of the deformation. In this study we have used numerical modeling to investigate how the fold pattern in 3D multilayer folding is affected by pre-existing salt structures. High-resolution 3D folding simulations (with and without pre-existing salt structures) were performed with the parallel code LaMEM. Cylindrically shaped diapirs with different diameters and heights have been added to a multilayer folding setup. The use of a finite element based landscape evolution model (both erosion and sedimentation) allows for initially buried salt diapirs to be exposed at the surface during folding evolution. Acknowledgements Funding was provided by the European Research Council under the European Community's Seventh Framework program (FP7/2007-2013) ERC Grant agreement #258830. 3D simulations are performed in the IBM Blue Gene/Q JUQUEEN

  15. Normal fault growth above pre-existing structures: insights from discrete element modelling

    NASA Astrophysics Data System (ADS)

    Wrona, Thilo; Finch, Emma; Bell, Rebecca; Jackson, Christopher; Gawthorpe, Robert; Phillips, Thomas

    2016-04-01

    In extensional systems, pre-existing structures such as shear zones may affect the growth, geometry and location of normal faults. Recent seismic reflection-based observations from the North Sea suggest that shear zones not only localise deformation in the host rock, but also in the overlying sedimentary succession. While pre-existing weaknesses are known to localise deformation in the host rock, their effect on deformation in the overlying succession is less well understood. Here, we use 3-D discrete element modelling to determine if and how kilometre-scale shear zones affect normal fault growth in the overlying succession. Discrete element models use a large number of interacting particles to describe the dynamic evolution of complex systems. The technique has therefore been applied to describe fault and fracture growth in a variety of geological settings. We model normal faulting by extending a 60×60×30 km crustal rift-basin model including brittle and ductile interactions and gravitation and isostatic forces by 30%. An inclined plane of weakness which represents a pre-existing shear zone is introduced in the lower section of the upper brittle layer at the start of the experiment. The length, width, orientation and dip of the weak zone are systematically varied between experiments to test how these parameters control the geometric and kinematic development of overlying normal fault systems. Consistent with our seismic reflection-based observations, our results show that strain is indeed localised in and above these weak zones. In the lower brittle layer, normal faults nucleate, as expected, within the zone of weakness and control the initiation and propagation of neighbouring faults. Above this, normal faults nucleate throughout the overlying strata where their orientations are strongly influenced by the underlying zone of weakness. These results challenge the notion that overburden normal faults simply form due to reactivation and upwards propagation of pre-existing

  16. 14 CFR 67.113 - General medical condition.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false General medical condition. 67.113 Section 67.113 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION First-Class Airman Medical Certificate § 67.113 General medical condition. The general medical...

  17. 14 CFR 67.213 - General medical condition.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false General medical condition. 67.213 Section 67.213 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Second-Class Airman Medical Certificate § 67.213 General medical condition. The general medical...

  18. 14 CFR 67.313 - General medical condition.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false General medical condition. 67.313 Section 67.313 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN MEDICAL STANDARDS AND CERTIFICATION Third-Class Airman Medical Certificate § 67.313 General medical condition. The general medical...

  19. The association of medical conditions and presenteeism.

    PubMed

    Burton, Wayne N; Pransky, Glenn; Conti, Daniel J; Chen, Chin-Yu; Edington, Dee W

    2004-06-01

    A self-reported measure of four domains of work impairment based on the Work Limitations Questionnaire was completed by 16,651 employees of a large financial services corporation. Using a multivariate model to control for coexisting conditions, age, and gender, significant relationships were observed between medical conditions and patterns of impaired work performance. Depression was highly associated with work limitations in time management (odds ratio [OR] = 2.05), interpersonal/mental functioning (OR = 2.50), and overall output (OR = 2.24). Arthritis (OR = 1.56) and low back pain (OR = 1.32) were associated with physical function limitations. These same two conditions were associated with limitations in mental/interpersonal functioning but with low back pain having the higher odds ratio (OR = 1.54 vs. 1.22). These results suggest that worksite interventions (eg, disease management programs) should be tailored to the unique effects observed with specific medical conditions. More targeted programs could have important benefits for productivity in the workplace. PMID:15194894

  20. Effects of pre-existing discontinuities on the residual strength of rock mass - Insight from a discrete element method simulation

    NASA Astrophysics Data System (ADS)

    Gao, F. Q.; Kang, H. P.

    2016-04-01

    When rock failure is unavoidable, the designer of engineering structures must know and account for the residual strength of the rock mass. This is particularly relevant in underground coal mine openings. Pre-existing discontinuities play an important role in the mechanical behavior of rock masses and thus it is important to understand the effects of such pre-existing discontinuities on the residual strength. For this purpose, the present study demonstrates a numerical analysis using a discrete element method simulation. The numerical results indicate that fracture intensity has no significant influence on the residual strength of jointed rock masses, independent of confining conditions. As confining pressures increase, both peak and residual strengths increase, with residual strength increasing at a faster rate. The finding was further demonstrated by analyzing documented laboratory compressive test data from a variety of rocks along with field data from coal pillars. A comprehensive interpretation of the finding was conducted using a cohesion-weakening-friction-strengthening (CWFS) model. The effect of rock bolts on rock mass strength was also evaluated by using a discrete element method model which suggested that rock bolts can significantly increases residual strength but have limited effect on increasing the peak strength of rock masses.

  1. Nivolumab for the treatment of malignant melanoma in a patient with pre-existing myasthenia gravis

    PubMed Central

    Maeda, Osamu; Yokota, Kenji; Atsuta, Naoki; Katsuno, Masahisa; Akiyama, Masashi; Ando, Yuichi

    2016-01-01

    ABSTRACT A 79-year-old man with lymph node recurrence of malignant melanoma received nivolumab, an anti-programmed death 1 (PD-1) monoclonal antibody. He had pre-existing ocular myasthenia gravis (MG) and a continued small amount of corticosteroid. Grade 3 creatine phosphokinase elevation appeared after two doses of nivolumab, and the treatment was postponed until it improved to grade 1. After three doses of nivolumab, he experienced diplopia and facial muscle weakness which were consistent with an acute exacerbation of MG, and the symptoms relieved without additional treatment for MG. He achieved shrinkage of metastasis after ten doses of nivolumab. Although a case who died due to MG after administration of nivolumab was reported recently, pre-existing MG is considered not to be always a contraindication of nivolumab. PMID:27019533

  2. Discrete modeling of hydraulic fracturing processes in a complex pre-existing fracture network

    NASA Astrophysics Data System (ADS)

    Kim, K.; Rutqvist, J.; Nakagawa, S.; Houseworth, J. E.; Birkholzer, J. T.

    2015-12-01

    Hydraulic fracturing and stimulation of fracture networks are widely used by the energy industry (e.g., shale gas extraction, enhanced geothermal systems) to increase permeability of geological formations. Numerous analytical and numerical models have been developed to help understand and predict the behavior of hydraulically induced fractures. However, many existing models assume simple fracturing scenarios with highly idealized fracture geometries (e.g., propagation of a single fracture with assumed shapes in a homogeneous medium). Modeling hydraulic fracture propagation in the presence of natural fractures and homogeneities can be very challenging because of the complex interactions between fluid, rock matrix, and rock interfaces, as well as the interactions between propagating fractures and pre-existing natural fractures. In this study, the TOUGH-RBSN code for coupled hydro-mechanical modeling is utilized to simulate hydraulic fracture propagation and its interaction with pre-existing fracture networks. The simulation tool combines TOUGH2, a simulator of subsurface multiphase flow and mass transport based on the finite volume approach, with the implementation of a lattice modeling approach for geomechanical and fracture-damage behavior, named Rigid-Body-Spring Network (RBSN). The discrete fracture network (DFN) approach is facilitated in the Voronoi discretization via a fully automated modeling procedure. The numerical program is verified through a simple simulation for single fracture propagation, in which the resulting fracture geometry is compared to an analytical solution for given fracture length and aperture. Subsequently, predictive simulations are conducted for planned laboratory experiments using rock-analogue (soda-lime glass) samples containing a designed, pre-existing fracture network. The results of a preliminary simulation demonstrate selective fracturing and fluid infiltration along the pre-existing fractures, with additional fracturing in part

  3. Numerical Modelling of Extended Leak-Off Test with a Pre-Existing Fracture

    NASA Astrophysics Data System (ADS)

    Lavrov, A.; Larsen, I.; Bauer, A.

    2016-04-01

    Extended leak-off test (XLOT) is one of the few techniques available for stress measurements in oil and gas wells. Interpretation of the test is often difficult since the results depend on a multitude of factors, including the presence of natural or drilling-induced fractures in the near-well area. Coupled numerical modelling of XLOT has been performed to investigate the pressure behaviour during the flowback phase as well as the effect of a pre-existing fracture on the test results in a low-permeability formation. Essential features of XLOT known from field measurements are captured by the model, including the saw-tooth shape of the pressure vs injected volume curve, and the change of slope in the pressure vs time curve during flowback used by operators as an indicator of the bottomhole pressure reaching the minimum in situ stress. Simulations with a pre-existing fracture running from the borehole wall in the radial direction have revealed that the results of XLOT are quite sensitive to the orientation of the pre-existing fracture. In particular, the fracture initiation pressure and the formation breakdown pressure increase steadily with decreasing angle between the fracture and the minimum in situ stress. Our findings seem to invalidate the use of the fracture initiation pressure and the formation breakdown pressure for stress measurements or rock strength evaluation purposes.

  4. Inheritance of pre-existing weakness in continental breakup: 3D numerical modeling

    NASA Astrophysics Data System (ADS)

    Liao, Jie; Gerya, Taras

    2013-04-01

    The whole process of continental rifting to seafloor spreading is one of the most important plate tectonics on the earth. There are many questions remained related to this process, most of which are poorly understood, such as how continental rifting transformed into seafloor spreading? How the curved oceanic ridge developed from a single straight continental rift? How the pre-existing weakness in either crust or lithospheric mantle individually influences the continental rifting and oceanic spreading? By employing the state-of-the-art three-dimensional thermomechanical-coupled numerical code (using Eulerian-Lagrangian finite-difference method and marker-in-cell technic) (Gerya and Yuen, 2007), which can model long-term plate extension and large strains, we studied the whole process of continental rifting to seafloor spreading based on the following question: How the pre-existing lithospheric weak zone influences the continental breakup? Continental rifts do not occur randomly, but like to follow the pre-existing weakness (such as fault zones, suture zones, failed rifts, and other tectonic boundaries) in the lithosphere, for instance, the western branch of East African Rift formed in the relatively weak mobile belts along the curved western border of Tanzanian craton (Corti et al., 2007; Nyblade and Brazier, 2002), the Main Ethiopian Rift developed within the Proterozoic mobile belt which is believed to represent a continental collision zone (Keranen and Klemperer, 2008),the Baikal rift formed along the suture between Siberian craton and Sayan-Baikal folded belt (Chemenda et al., 2002). The early stage formed rift can be a template for the future rift development and continental breakup (Keranen and Klemperer, 2008). Lithospheric weakness can either reduce the crustal strength or mantle strength, and leads to the crustal or mantle necking (Dunbar and Sawyer, 1988), which plays an important role on controlling the continental breakup patterns, such as controlling the

  5. A historical pyroclastic flow emplaced within a pre-existing Pleistocene lava tube: Silidong, Tianchi Volcano, Changbaishan, northeastern China

    NASA Astrophysics Data System (ADS)

    Chen, Zhengquan; Wei, Haiquan; Liu, Yongshun; Tilling, Robert I.; Xu, Jiandong; Wu, Chengzhi; Nie, Baofeng

    2015-06-01

    Pyroclastic flow deposits recently found within a pre-existing lava tube at Tianchi Volcano represent, to the best of our knowledge, the only such reported occurrence worldwide. In this case, pyroclastic flow of Tianchi's "Millennium eruption" (~1 ka) traveled about 18 km from the summit eruptive source and poured successively into the ~560-m-long accessible segment of Silidong lava tube. Mapping of tube morphology, combined with detailed characterization of the features associated with the pumice flow deposits (e.g., adhering of pyroclastic materials on tube walls, fumarole pipes, rootless vents, and flow fronts of the deposit surface) has enabled plausible inferences regarding the original within-tube conditions and dynamic flow regime during emplacement. We propose a model of an aggrading pyroclastic flow which locally varies its sedimentation rate. The pyroclastic deposit is thicker in locations of reduced flow mobility, and the resultant variations in deposit thickness appear to control the distribution of fumarole pipes and rootless vents.

  6. Strain Accommodation and its Relationship to Pre-existing Structures along the Karonga Fault, Malawi

    NASA Astrophysics Data System (ADS)

    Dawson, S.; Laó-Dávila, D. A.; Atekwana, E. A.; Clappe, B.; Johnson, T.; Hull, C. D.; Nyalugwe, V.; Abdelsalam, M. G.; Chindandali, P. R. N.; Salima, J.

    2015-12-01

    The Livingstone border fault, with its 7 km of total displacement, accommodates most of the strain in the northern portion of the Malawi Rift. Its hanging wall is also breaking up, as suggested by the 2009 earthquake sequence in Karonga. This hanging wall block is underlain in part by the NW- and N-striking Mughese Shear Zone. The superposition of new faults on the pre-existing structures makes this area an ideal location to study the effect of the orientation of pre-existing structures on the accommodation of strain in the hanging wall in the western flank of the northern Malawi Rift. We used gravity and aeromagnetic data and remote sensing to map the Precambrian macro-scale structural fabric of the greater Karonga region. Moreover, we mapped mesostructures within the Precambrian and younger rocks. In the northern portion of the Karonga fault, a single east-dipping fault zone with a mean strike of 32° and a 59° dip cuts the Precambrian foliation that has a mean strike of 301° and 79° dip, accommodating the majority of strain in this region. South of the city of Karonga, the Precambrian foliation assumes a NNW average strike that is steeply dipping. Here the Karonga fault disperses from a single fault with a 2 km damage zone to several distinct east- and west-dipping faults over 6 km that strike in the same overall direction as the foliation planes from the Mughese Shear Zone. Karoo rift structures (horsts and grabens) and their associated rock formations could also be reactivated in this area. These relationships suggest that within the Malawi Rift, strain can be accommodated differently based on the nature and orientation of pre-existing structures. The structural fabric surrounding the southern portion of the Karonga fault seems to favor reactivation and strain distribution, whereas strain is localized in the northern portion of the fault zone.

  7. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Monitoring for Pre-existing Discharges at Remining Operations B Appendix B to Part 434 Protection of.... B Appendix B to Part 434—Baseline Determination and Compliance Monitoring for Pre-existing... per year. d. Accommodating Data Below the Maximum Daily Limit at subpart C of this part. In the...

  8. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Monitoring for Pre-existing Discharges at Remining Operations B Appendix B to Part 434 Protection of... to Part 434—Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining... Maximum Daily Limit at subpart C of this part. In the event that a pollutant concentration in the...

  9. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Monitoring for Pre-existing Discharges at Remining Operations B Appendix B to Part 434 Protection of.... B Appendix B to Part 434—Baseline Determination and Compliance Monitoring for Pre-existing... per year. d. Accommodating Data Below the Maximum Daily Limit at subpart C of this part. In the...

  10. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Monitoring for Pre-existing Discharges at Remining Operations B Appendix B to Part 434 Protection of.... B Appendix B to Part 434—Baseline Determination and Compliance Monitoring for Pre-existing... per year. d. Accommodating Data Below the Maximum Daily Limit at subpart C of this part. In the...

  11. 28 CFR 79.34 - Proof of medical condition.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of medical condition. 79.34 Section... COMPENSATION ACT Eligibility Criteria for Claims by Onsite Participants § 79.34 Proof of medical condition. Proof of medical condition under this subpart will be made in the same manner and according to the...

  12. 28 CFR 79.34 - Proof of medical condition.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of medical condition. 79.34 Section... COMPENSATION ACT Eligibility Criteria for Claims by Onsite Participants § 79.34 Proof of medical condition. Proof of medical condition under this subpart will be made in the same manner and according to the...

  13. Albumin-binding adenoviruses circumvent pre-existing neutralizing antibodies upon systemic delivery.

    PubMed

    Rojas, Luis Alfonso; Condezo, Gabriela N; Moreno, Rafael; Fajardo, Carlos Alberto; Arias-Badia, Marcel; San Martín, Carmen; Alemany, Ramon

    2016-09-10

    Recombinant adenoviruses are used as vaccines, gene therapy vectors, and oncolytic viruses. However, the efficacy of such therapies is limited by pre-existing neutralizing antibodies (NAbs), especially when the virus is administered systemically for a wider biodistribution or to reach multiple metastases. To protect adenovirus against NAbs we inserted an albumin-binding domain (ABD) in the main adenovirus capsid protein, the hexon. This domain binds serum albumin to shield the virus upon systemic administration. The ABD-modified adenoviruses bind human and mouse albumin and maintain the infectivity and replication capacity in presence of NAbs. In pre-immunized mice non-modified viruses are completely neutralized, whereas ABD-modified viruses preserve the ability to transduce target organs, induce oncolysis, or generate immune responses to expressed proteins. Our results indicate that albumin coating of the virus capsid represents an effective approach to evade pre-existing NAbs. This strategy has translational relevance in the use of adenovirus for gene therapy, cancer virotherapy, and vaccination. PMID:27388756

  14. Bortezomib reduces pre-existing antibodies to recombinant immunotoxins in mice.

    PubMed

    Manning, Michael L; Mason-Osann, Emily; Onda, Masanori; Pastan, Ira

    2015-02-15

    Recombinant immunotoxin (RIT) therapy is limited in patients by neutralizing Ab responses. Ninety percent of patients with normal immune systems make neutralizing Abs after one cycle of RIT, preventing repeated dosing. Furthermore, some patients have pre-existing Abs from environmental exposure to Pseudomonas exotoxin, the component of the RIT that elicits the neutralizing Ab response. Bortezomib is an U.S. Food and Drug Administration-approved proteasome inhibitor that selectively targets and kills plasma cells that are necessary for the neutralizing Ab response. We hypothesized that bortezomib may abrogate neutralizing Ab levels, making dosing of RIT possible in mice already immune to RIT. We immunized BALB/c mice with multiple doses of SS1P, a RIT whose Ab portion targets mesothelin. Mice with elevated Ab levels were separated into groups to receive saline, bortezomib, the pentostatin/cyclophosphamide (PC) regimen, or the bortezomib/PC (BPC) combination regimen. Four weeks after finishing therapy, plasma Ab levels were assayed, and bone marrow was harvested. The bortezomib and PC regimens significantly reduced Ab levels, and we observed fewer plasma cells in the bone marrow of bortezomib-treated mice but not in PC-treated mice. The BPC combination regimen almost completely eliminated Abs and further reduced plasma cells in the bone marrow. This regimen is more effective than individual regimens and may reduce Ab levels in patients with pre-existing neutralizing Abs to Pseudomonas exotoxin, allowing RIT treatment. PMID:25560410

  15. Ionization-induced annealing of pre-existing defects in silicon carbide.

    PubMed

    Zhang, Yanwen; Sachan, Ritesh; Pakarinen, Olli H; Chisholm, Matthew F; Liu, Peng; Xue, Haizhou; Weber, William J

    2015-01-01

    A long-standing objective in materials research is to effectively heal fabrication defects or to remove pre-existing or environmentally induced damage in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power and high-frequency applications. Its high corrosion and radiation resistance makes it a key refractory/structural material with great potential for extremely harsh radiation environments. Here we show that the energy transferred to the electron system of SiC by energetic ions via inelastic ionization can effectively anneal pre-existing defects and restore the structural order. The threshold determined for this recovery process reveals that it can be activated by 750 and 850 keV Si and C self-ions, respectively. The results conveyed here can contribute to SiC-based device fabrication by providing a room-temperature approach to repair atomic lattice structures, and to SiC performance prediction as either a functional material for device applications or a structural material for high-radiation environments. PMID:26264864

  16. Ionization-induced annealing of pre-existing defects in silicon carbide

    NASA Astrophysics Data System (ADS)

    Zhang, Yanwen; Sachan, Ritesh; Pakarinen, Olli H.; Chisholm, Matthew F.; Liu, Peng; Xue, Haizhou; Weber, William J.

    2015-08-01

    A long-standing objective in materials research is to effectively heal fabrication defects or to remove pre-existing or environmentally induced damage in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power and high-frequency applications. Its high corrosion and radiation resistance makes it a key refractory/structural material with great potential for extremely harsh radiation environments. Here we show that the energy transferred to the electron system of SiC by energetic ions via inelastic ionization can effectively anneal pre-existing defects and restore the structural order. The threshold determined for this recovery process reveals that it can be activated by 750 and 850 keV Si and C self-ions, respectively. The results conveyed here can contribute to SiC-based device fabrication by providing a room-temperature approach to repair atomic lattice structures, and to SiC performance prediction as either a functional material for device applications or a structural material for high-radiation environments.

  17. Ionization-induced annealing of pre-existing defects in silicon carbide

    PubMed Central

    Zhang, Yanwen; Sachan, Ritesh; Pakarinen, Olli H.; Chisholm, Matthew F.; Liu, Peng; Xue, Haizhou; Weber, William J.

    2015-01-01

    A long-standing objective in materials research is to effectively heal fabrication defects or to remove pre-existing or environmentally induced damage in materials. Silicon carbide (SiC) is a fascinating wide-band gap semiconductor for high-temperature, high-power and high-frequency applications. Its high corrosion and radiation resistance makes it a key refractory/structural material with great potential for extremely harsh radiation environments. Here we show that the energy transferred to the electron system of SiC by energetic ions via inelastic ionization can effectively anneal pre-existing defects and restore the structural order. The threshold determined for this recovery process reveals that it can be activated by 750 and 850 keV Si and C self-ions, respectively. The results conveyed here can contribute to SiC-based device fabrication by providing a room-temperature approach to repair atomic lattice structures, and to SiC performance prediction as either a functional material for device applications or a structural material for high-radiation environments. PMID:26264864

  18. Pre-existing sensory biases in the spectral domain in frogs: empirical results and methodological considerations.

    PubMed

    Gerhardt, H C; Humfeld, Sarah C

    2013-02-01

    In many species of anurans, advertisement calls excite only one of the two inner-ear organs. One prediction of the pre-existing bias hypothesis is that signal innovations that additionally excite the "untapped" organ will be more behaviorally effective than normal calls. However, recent studies have shown that females of three species with single-peaked calls that stimulate only the basilar papilla (BP) preferred single-peaked synthetic calls with a frequency typical of conspecific calls to two-peaked calls that also stimulated the amphibian papilla (AP). We report that in spring peepers (Pseudacris crucifer) that also produce single-peaked calls, females did not show a preference in choices between single-peaked and two-peaked synthetic calls. Thus, the addition of energy exciting the AP had a neutral effect on signal attractiveness. Together, these results are unsupportive of the pre-existing bias hypothesis. An alternative hypothesis is that positive fitness consequences of responding to sounds providing extraordinary spectral stimulation are required for a novel call to become established as a mate-attracting signal. Testing these ideas requires a taxonomically broader examination of responses to sounds with novel spectral complexity, and attention to some methodological details will improve the comparability of such studies. PMID:23160797

  19. Numerical modeling of the seismic response of a large pre-existing landslide in the Marmara region

    NASA Astrophysics Data System (ADS)

    Bourdeau, Céline; Lenti, Luca; Martino, Salvatore

    2015-04-01

    Turkey is one of the geologically most active regions of Europe prone to natural hazards in particular earthquakes and landslides. Detailed seismological studies show that a catastrophic event is now expected in the Marmara region along the North Anatolian Fault Zone (NAFZ). On the shores of the Marmara sea, about 30km East of Istanbul and 15km North from the NAFZ, urbanization is fastly growing despite the presence of pre-existing large landslides. Whether such landslides could be reactivated under seismic shaking is a key question. In the framework of the MARsite European project, we selected one of the most critical landslides namely the Büyükçekmece landslide in order to assess its local seismic response. Based on detailed geophysical and geotechnical field investigations, a high-resolution engineering-geological model of the landslide slope was reconstructed. A numerical modeling was carried out on a longitudinal cross section of this landslide with a 2D finite difference code FLAC in order to assess the local seismic response of the slope and to evaluate the consistency of conditions suitable for the earthquake-induced reactivation of the landslide. The obtained ground-motion amplification pattern along the slope surface is very complex and is strongly influenced by properties changes between the pre-existing landslide mass and the surrounding material. Further comparisons of 2D versus 1D ground-motion amplifications on the one hand and 2D versus topographic site effects on the other hand will shed light on the parameters controlling the spatial variations of ground-motion amplifications along the slope surface.

  20. Effects of Pre-Existing Target Structure on the Formation of Large Craters

    NASA Technical Reports Server (NTRS)

    Barnouin-Jha, O. S.; Cintala, M. J.; Crawford, D. A.

    2003-01-01

    The shapes of large-scale craters and the mechanics responsible for melt generation are influenced by broad and small-scale structures present in a target prior to impact. For example, well-developed systems of fractures often create craters that appear square in outline, good examples being Meteor Crater, AZ and the square craters of 433 Eros. Pre-broken target material also affects melt generation. Kieffer has shown how the shock wave generated in Coconino sandstone at Meteor crater created reverberations which, in combination with the natural target heterogeneity present, created peaks and troughs in pressure and compressed density as individual grains collided to produce a range of shock mineralogies and melts within neighboring samples. In this study, we further explore how pre-existing target structure influences various aspects of the cratering process. We combine experimental and numerical techniques to explore the connection between the scales of the impact generated shock wave and the pre-existing target structure. We focus on the propagation of shock waves in coarse, granular media, emphasizing its consequences on excavation, crater growth, ejecta production, cratering efficiency, melt generation, and crater shape. As a baseline, we present a first series of results for idealized targets where the particles are all identical in size and possess the same shock impedance. We will also present a few results, whereby we increase the complexities of the target properties by varying the grain size, strength, impedance and frictional properties. In addition, we investigate the origin and implications of reverberations that are created by the presence of physical and chemical heterogeneity in a target.

  1. Numerical Study on Coalescence of Pre-Existing Flaw Pairs in Rock-Like Material

    NASA Astrophysics Data System (ADS)

    Li, Huan-Qiang; Wong, Louis Ngai Yuen

    2014-11-01

    The present numerical study, which is an extension of our previous numerical analysis on cracking processes of a single pre-existing flaw, focuses on the coalescence of two pre-existing parallel open flaws in rock subjected to a uniaxial compressive loading. To facilitate a systematic investigation, the arrangements of the flaw pair are classified into 11 categories. Simulations engaging AUTODYN are conducted on each category. The numerical results are compared with some published physical experimental test results. Eleven typical coalescence patterns are obtained, which are in good agreement with the experimental results, which include two coalescence patterns obtained in flaw pair arrangements (II) and (VIII″) not being reported in previous studies. The information gathered in the simulations helps identify the type (tensile/shear) of each crack segment involved in the coalescence. Most of the coalescence cracks initiate at or around the flaw tips, except those in flaw pair arrangements (II) and (IX') with a very short ligament length, in which the coalescence cracks initiate on the flaw surfaces away from the flaw tip regions. Based on the numerical simulation results, the properties of the 11 coalescence patterns are obtained. Except those in flaw pair arrangements (II) and (IX'), the other coalescence patterns can be interpreted with respect to the basic crack types—tensile wing crack, horsetail crack and anti-wing crack. In addition, based on the type of crack segments involved in coalescence, namely tensile and shear, the coalescence can be classified into T mode (tensile mode), S mode (shear mode) and TS mode (mixed tensile-shear mode).

  2. Gene Therapy for Mucopolysaccharidosis Type VI Is Effective in Cats Without Pre-Existing Immunity to AAV8

    PubMed Central

    Ferla, Rita; O'Malley, Thomas; Calcedo, Roberto; O'Donnell, Patricia; Wang, Ping; Cotugno, Gabriella; Claudiani, Pamela; Wilson, James M.; Haskins, Mark

    2013-01-01

    Abstract Liver gene transfer with adeno-associated viral (AAV) 2/8 vectors is being considered for therapy of systemic diseases like mucopolysaccharidosis type VI (MPS VI), a lysosomal storage disease due to deficiency of arylsulfatase B (ARSB). We have previously reported that liver gene transfer with AAV2/8 results in sustained yet variable expression of ARSB. We hypothesized that the variability we observed could be due to pre-existing immunity to wild-type AAV8. To test this, we compared the levels of AAV2/8-mediated transduction in MPS VI cats with and without pre-existing immunity to AAV8. In addition, since levels of lysosomal enzymes as low as 5% of normal are expected to be therapeutic, we evaluated the impact of pre-existing immunity on MPS VI phenotypic rescue. AAV2/8 administration to MPS VI cats without pre-existing neutralizing antibodies to AAV8 resulted in consistent and dose-dependent expression of ARSB, urinary glycosaminoglycan (GAG) reduction, and femur length amelioration. Conversely, animals with pre-existing immunity to AAV8 showed low levels of ARSB expression and limited phenotypic improvement. Our data support the use of AAV2/8-mediated gene transfer for MPS VI and other systemic diseases, and highlight that pre-existing immunity to AAV8 should be considered in determining subject eligibility for therapy. PMID:23194248

  3. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion

    PubMed Central

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth. PMID:26934465

  4. Medical Conditions and Medication Use in Adults with Down Syndrome: A Descriptive Analysis

    ERIC Educational Resources Information Center

    Kerins, Gerard; Petrovic, Kimberly; Bruder, Mary Beth; Gruman, Cynthia

    2008-01-01

    Background: We examined the presence of medical conditions and medication use within a sample of adults with Down syndrome. Methods: Retrospective chart review using a sample of 141 adults with Down syndrome and age range of 30 to 65 years. Results: We identify 23 categories of commonly occurring medical conditions and 24 categories of medications…

  5. 28 CFR 79.16 - Proof of medical condition.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Program to contact the appropriate state cancer or tumor registry. The Program will accept as proof of medical condition verification from the state cancer or tumor registry that it possesses medical records... Cancer Institute can make a diagnosis of leukemia to a reasonable degree of medical certainty: (i)...

  6. 28 CFR 79.16 - Proof of medical condition.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Program to contact the appropriate state cancer or tumor registry. The Program will accept as proof of medical condition verification from the state cancer or tumor registry that it possesses medical records... Cancer Institute can make a diagnosis of leukemia to a reasonable degree of medical certainty: (i)...

  7. A Model for Subglacial Flooding Along a Pre-Existing Hydrological Network during the Rapid Drainage of Supraglacial Lakes

    NASA Astrophysics Data System (ADS)

    Adhikari, S.; Tsai, V. C.

    2014-12-01

    Increasingly large numbers of supraglacial lakes form and drain every summer on the Greenland Ice Sheet. Presently, about 15% of the lakes drain rapidly within the timescale of a few hours, and the vertical discharge of water during these events may find a pre-existing subglacial hydrological network, particularly late in the melt season. Here, we present a model for subglacial flooding applied specifically to such circumstances. Given the short timescale of events, we treat ice and bed as purely elastic and assume that the fluid flow in the subglacial conduit is fully turbulent. We evaluate the effect of initial conduit opening, wi, on the rate of flood propagation and along-flow profiles of field variables. We find that floods propagate much faster, particularly in early times, for larger wi. For wi = 10 and 1 cm, for example, floods travel about 68% and 50% farther than in the fully coupled ice/bed scenario after 2 hours of drainage, respectively. Irrespective of the magnitude of wi, we also find that there exists a region of positive pressure gradient. This reversal of pressure gradient draws water in from the farfield and causes the conduit to narrow, respecting mass continuity. While the general shape of the profiles appears similar, greater conduit opening is found for larger wi. For wi = 10 and 1 cm, for example, the elastostatic conduit opening at the point of injection is about 1.39 and 1.26 times that of the fully coupled ice/bed scenario after 2 hours of drainage. The hypothesis of a pre-existing thin film of water is consistent with the spirit of contemporary state-of-the-art continuum models for subglacial hydrology. This also results in avoiding the pressure singularity, which is inherent in classical hydro-fracture models applied to fully coupled ice/bed scenarios, thus opening an avenue for integrating the likes of our model within continuum hydrological models. Furthermore, we foresee that the theory presented can be used to potentially infer

  8. The Influence of Pre-existing Deformation on GMA Welding Distortion in Thin Steel Plates

    NASA Astrophysics Data System (ADS)

    Davies, C. M.; Ahn, J.; Tsunori, M.; Dye, D.; Nikbin, K. M.

    2015-01-01

    Weld distortion is particularly problematic for large thin structures that are used in the assembly of ships. The drive toward lighter ships and thinner plate is restricted by the significant increase in distortion as the plate thickness decreases. The influence of pre-existing deformation in the plates to be joined on the resultant distortion in gas metal arc welded structure has been studied. DH-36 steel plate surface profiles were measured before and after the butt welding of two plates 1000 × 500 × 4 mm in size. Three dimensional finite element models that incorporate the initial plate profile have been created to simulate the welding process and to examine the relationship between the final welded plate profiles and the initial deformation present in the plates. Both symmetric and asymmetric models were considered. A significant variation in the unwelded base plates' initial distortion was observed. Generally, it has been found that if an out-of-plane deformation exists in a plate prior to welding, the level of distortion further increases in the same direction following welding. The final distortions are strongly related to the initial plate profiles. The residual stress distributions in the plates are also to some extent affected by the level of distortion initially present.

  9. EVIDENCE FOR PRE-EXISTING DUST IN THE BRIGHT TYPE IIn SN 2010jl

    SciTech Connect

    Andrews, J. E.; Clayton, Geoffrey C.; Clem, J.; Landolt, A. E-mail: landolt@phys.lsu.edu E-mail: jclem@phys.lsu.edu

    2011-08-15

    SN 2010jl was an extremely bright, Type IIn supernova (SN) which showed a significant infrared (IR) excess no later than 90 days after explosion. We have obtained Spitzer 3.6 and 4.5 {mu}m and JHK observations of SN 2010jl {approx}90 days post-explosion. Little to no reddening in the host galaxy indicated that the circumstellar material lost from the progenitor must lie in a torus inclined out of the plane of the sky. The likely cause of the high mid-IR flux is the reprocessing of the initial flash of the SN by pre-existing circumstellar dust. Using a three-dimensional Monte Carlo radiative-transfer code, we have estimated that between 0.03 and 0.35 M{sub sun} of dust exists in a circumstellar torus around the SN located 6 x 10{sup 17} cm away from the SN and inclined between 60 deg. and 80 deg. to the plane of the sky. On day 90, we are only seeing the illumination of approximately 5% of this torus, and expect to see an elevated IR flux from this material up until day {approx} 450. It is likely this dust was created in a luminous blue variable (LBV) like mass-loss event of more than 3 M{sub sun}, which is large but consistent with other LBV progenitors such as {eta} Carinae.

  10. TCR Microclusters pre-exist and contain molecules necessary for TCR signal transduction.

    PubMed

    Crites, Travis J; Padhan, Kartika; Muller, James; Krogsgaard, Michelle; Gudla, Prabhakar R; Lockett, Stephen J; Varma, Rajat

    2014-07-01

    TCR-dependent signaling events have been observed to occur in TCR microclusters. We found that some TCR microclusters are present in unstimulated murine T cells, indicating that the mechanisms leading to microcluster formation do not require ligand binding. These pre-existing microclusters increase in absolute number following engagement by low-potency ligands. This increase is accompanied by an increase in cell spreading, with the result that the density of TCR microclusters on the surface of the T cell is not a strong function of ligand potency. In characterizing their composition, we observed a constant number of TCRs in a microcluster, constitutive exclusion of the phosphatase CD45, and preassociation with the signaling adapters linker for activation of T cells and growth factor receptor-bound protein 2. The existence of TCR microclusters prior to ligand binding in a state that is conducive for the initiation of downstream signaling could explain, in part, the rapid kinetics with which TCR signal transduction occurs. PMID:24860189

  11. Plasticity induced by pre-existing defects during high strain-rate loading

    NASA Astrophysics Data System (ADS)

    Bringa, Eduardo

    2014-03-01

    High strain-rate deformation of metals has been typically studied for perfect monocrystals. Computational advances now allow more realistic simulations of materials including defects, which lower the Hugoniot Elastic Limit, and lead to microstructures differing from the ones from perfect monocrystals. As pre-existing defects one can consider vacancy clusters, dislocation loops, grain boundaries, etc. New analysis tools allow analysis of dislocation densities and twin fractions, for both f.c.c. and b.c.c. metals. Recent results for defective single crystal Ta [Tramontina et al.., High Energy Den. Phys. 10, 9 (2014), and Ruestes et al., Scripta Mat. 68, 818 (2013)], and for polycrystalline b.c.c metals [Tang et al., Mat. Sci. Eng. A 580, 414 (2013), and Gunkelmann et al., Phys. Rev. B 86, 144111 (2012)] will be highlighted, alongside new results for nanocrystalline Cu, Ta, Fe, and Zr [Ruestes et al., Scripta Mat. 71, 9 (2014)]. This work has been carried out in collaboration with D. Tramontina, C. Ruestes, E. Millan, J. Rodriguez-Nieva, M.A. Meyers, Y. Tang, H. Urbassek, N. Gunkelmann, A. Stukowski, M. Ruda, G. Bertolino, D. Farkas, A. Caro, J. Hawreliak, B. Remington, R. Rudd, P. Erhart, R. Ravelo, T. Germann, N. Park, M. Suggit, S. Michalik, A. Higginbotham and J. Wark. Funding by PICT2008-1325 and SeCTyP U.N. Cuyo.

  12. Interactions between X-ray induced transient defects and pre-existing damage precursors in DKDP crystals

    SciTech Connect

    Negres, R A; Saw, C K; Demos, S G

    2008-10-24

    Large-aperture laser systems, currently designed to achieve high energy densities at the target location (exceeding {approx} 10{sup 11} J/m{sup 3}), will enable studies of the physics of matter and radiation under extreme conditions. As a result, their optical components, such as the frequency conversion crystals (KDP/DKDP), may be exposed to X-rays and other ionizing radiation. This in turn may lead to a change in the damage performance of these materials as they may be affected by radiation-induced effects by either forming new damage initiation centers or interacting with the pre-existing damage initiating defects (so-called damage precursors). We present an experimental study on the laser-induced bulk damage performance at 355-nm of DKDP crystals following X-ray irradiation at room temperature. Results indicate that the damage performance of the material is affected by exposure to X-rays. We attribute this behavior to a change in the physical properties of the precursors which, in turn, affect their individual damage threshold.

  13. Discovery of a pre-existing molecular filament associated with supernova remnant G127.1+0.5

    SciTech Connect

    Zhou, Xin; Yang, Ji; Fang, Min; Su, Yang

    2014-08-20

    We performed millimeter observations in CO lines toward the supernova remnant (SNR) G127.1+0.5. We found a molecular filament at 4-13 km s{sup –1} consisting of two distinct parts: a straight part coming out of the remnant region and a curved part in the remnant region. The curved part is coincides well with the bright SNR shell detected in 1420 MHz radio continuum and mid-infrared observations in the northeastern region. In addition, redshifted line wing broadening is found only in the curved part of the molecular filament, which indicates a physical interaction. These provide strong evidences, for the first time, to confirm the association between an SNR and a pre-existing long molecular filament. Multi-band observations in the northeastern remnant shell could be explained by the interaction between the remnant shock and the dense molecular filament. RADEX radiative transfer modeling of the quiet and shocked components yield physical conditions consistent with the passage of a non-dissociative J-type shock. We argue that the curved part of the filament is fully engulfed by the remnant's forward shock. A spatial correlation between aggregated young stellar objects (YSOs) and the adjacent molecular filament close to the SNR is also found, which could be related to the progenitor's activity.

  14. Endoscopic skull base training using 3D printed models with pre-existing pathology.

    PubMed

    Narayanan, Vairavan; Narayanan, Prepageran; Rajagopalan, Raman; Karuppiah, Ravindran; Rahman, Zainal Ariff Abdul; Wormald, Peter-John; Van Hasselt, Charles Andrew; Waran, Vicknes

    2015-03-01

    Endoscopic base of skull surgery has been growing in acceptance in the recent past due to improvements in visualisation and micro instrumentation as well as the surgical maturing of early endoscopic skull base practitioners. Unfortunately, these demanding procedures have a steep learning curve. A physical simulation that is able to reproduce the complex anatomy of the anterior skull base provides very useful means of learning the necessary skills in a safe and effective environment. This paper aims to assess the ease of learning endoscopic skull base exposure and drilling techniques using an anatomically accurate physical model with a pre-existing pathology (i.e., basilar invagination) created from actual patient data. Five models of a patient with platy-basia and basilar invagination were created from the original MRI and CT imaging data of a patient. The models were used as part of a training workshop for ENT surgeons with varying degrees of experience in endoscopic base of skull surgery, from trainees to experienced consultants. The surgeons were given a list of key steps to achieve in exposing and drilling the skull base using the simulation model. They were then asked to list the level of difficulty of learning these steps using the model. The participants found the models suitable for learning registration, navigation and skull base drilling techniques. All participants also found the deep structures to be accurately represented spatially as confirmed by the navigation system. These models allow structured simulation to be conducted in a workshop environment where surgeons and trainees can practice to perform complex procedures in a controlled fashion under the supervision of experts. PMID:25294050

  15. Caring for Kids With Medical Conditions

    MedlinePlus

    ... becomes dizzy, call the parents immediately. previous continue Cerebral Palsy Cerebral palsy (CP) is a long-term condition involving brain damage and muscle problems. CP can cause limitations in moving, learning, hearing, seeing, ...

  16. Differentiation of pre-existing trapped methane from thermogenic methane in an igneous-intruded coal by hydrous pyrolysis

    USGS Publications Warehouse

    Dias, Robert F.; Lewan, Michael D.; Birdwell, Justin E.; Kotarba, Maciej J.

    2014-01-01

    So as to better understand how the gas generation potential of coal changes with increasing rank, same-seam samples of bituminous coal from the Illinois Basin that were naturally matured to varying degrees by the intrusion of an igneous dike were subjected to hydrous pyrolysis (HP) conditions of 360 °C for 72 h. The accumulated methane in the reactor headspace was analyzed for δ13C and δ2H, and mol percent composition. Maximum methane production (9.7 mg/g TOC) occurred in the most immature samples (0.5 %Ro), waning to minimal methane values at 2.44 %Ro (0.67 mg/g TOC), and rebounding to 3.6 mg/g TOC methane in the most mature sample (6.76 %Ro). Methane from coal with the highest initial thermal maturity (6.76 %Ro) shows no isotopic dependence on the reactor water and has a microbial δ13C value of −61‰. However, methane from coal of minimal initial thermal maturity (0.5 %Ro) shows hydrogen isotopic dependence on the reaction water and has a δ13C value of −37‰. The gas released from coals under hydrous pyrolysis conditions represents a quantifiable mixture of ancient (270 Ma) methane (likely microbial) that was generated in situ and trapped within the rock during the rapid heating by the dike, and modern (laboratory) thermogenic methane that was generated from the indigenous organic matter due to thermal maturation induced by hydrous pyrolysis conditions. These findings provide an analytical framework for better assessment of natural gas sources and for differentiating generated gas from pre-existing trapped gas in coals of various ranks.

  17. Detection and Management of Pre-Existing Cognitive Impairment and Associated Behavioral Symptoms in the Intensive Care Unit

    PubMed Central

    Lee, Hochang B.; DeLoatch, Candyce J.; Cho, SeongJin; Rosenberg, Paul; Mears, Simon C.; Sieber, Frederick E.

    2008-01-01

    Recent increase in both the elderly population and associated incidence of dementia are of critical importance to patient care in intensive care units (ICU) in the United States. Identification of pre-existing cognitive impairment such as mild cognitive impairment and dementia could prevent delirium and associated morbidity and mortality in ICU. Additionally, non-cognitive behavioral symptoms such as depression, psychosis, agitation, and catastrophic reactions are common in patients with pre-existing cognitive impairment. Detection and management of non-cognitive behavioral symptoms associated with demented elderly patients in ICU leads to improved delivery of life-saving critical care. PMID:18929940

  18. Detection and management of pre-existing cognitive impairment and associated behavioral symptoms in the Intensive Care Unit.

    PubMed

    Lee, Hochang B; DeLoatch, Candyce J; Cho, SeongJin; Rosenberg, Paul; Mears, Simon C; Sieber, Frederick E

    2008-10-01

    Recent increase in both the elderly population and associated incidence of dementia are of critical importance to patient care in ICUs in the United States. Identification of pre-existing cognitive impairment, such as mild cognitive impairment and dementia, could prevent delirium and associated morbidity and mortality in the ICU. Additionally, noncognitive behavioral symptoms, such as depression, psychosis, agitation, and catastrophic reactions, are common in patients with pre-existing cognitive impairment. Detection and management of noncognitive behavioral symptoms associated with MRI and dementia in ICU leads to improved delivery of life-saving critical care. PMID:18929940

  19. [Whiplash injury of the cervical spine--on the role of pre-existing degenerative diseases].

    PubMed

    Meenen, N M; Katzer, A; Dihlmann, S W; Held, S; Fyfe, I; Jungbluth, K H

    1994-06-01

    Radiological investigations contribute little in differentiating the problems of patients with whiplash injuries. Nevertheless the more prolonged cases of whiplash injuries must not be attributed to preexisting degenerative disease, despite radiologically-proven medicolegal opinion. In this study, 60 patients who were seen for whiplash injuries in the Department for Trauma and Reconstructive Surgery at the University Hospital Hamburg-Eppendorf for clinical and radiological evaluation, an average of 5.7 years post injury, were divided into two groups (n = 30) depending on radiologically-proven preexisting degenerative changes of the cervical spine. On average the patients with degenerative changes were 11.2 years older than those with healthy vertebral columns and also demonstrated an increase in acute symptoms in the lower cervical spine (cervicobrachial syndrome). The chronicity of individual symptoms such as neck-pain, dizziness, nausea and psychological illness was also observed in both groups. Problems such as paresthesias as well as pain in the shoulder-arm-area appeared to increase in subsequent check-ups, irrespective of the earlier degenerative changes. Patients with typical posterior headaches recovered faster when they had radiologically normal spines. Presenting late, there was a significant accumulation of patients with pre-existing degenerative changes complaining merely of tinnitus. The earlier changes in any individual motion segment do not determine the clinical course of whiplash injuries, but merely represent an area of increased vulnerability to trauma. On the other hand, trauma has not been proven to influence the development or aggravation of degenerative changes in normal or diseased spines. We are not able to differentiate the posttraumatic course from the natural history of the degenerative process, either clinically or radiologically. Considering the involvement of sensitive neurological structures the classical objective organic diagnosis

  20. Reactivation of pre-existing structures during Palaeogene to recent tectonics - the Southern Upper Rhine Graben

    NASA Astrophysics Data System (ADS)

    Ustaszewski, K.; Schumacher, M.; Schmid, S. M.

    2003-04-01

    Contour maps of the top-basement surface were established for part of the southernmost Upper Rhine Graben and the adjacent Jura Mountains based on seismic reflection profiles. Combined with surface data, they emphasise the importance of pre-existing Palaeozoic faults for the Palaeogene to recent structural evolution of the southern Upper Rhine Graben, an area of increased seismicity. The contemporaneous opening of the Palaeogene Upper Rhine Graben and Bresse Graben systems was kinematically linked by the Rhine-Bresse transform zone (RBTZ). The RBTZ formed along ENE-oriented crustal discontinuities, inherited from post-Variscan transtension. This Palaeogene rifting initiated in Late Priabonian times and encompassed sinistral transtensive reactivation of ENE-oriented basement faults and normal faulting along NNE-striking faults during ESE-WNW-directed extension. In the Mesozoic sedimentary cover these movements were accommodated by the formation of ENE-oriented flexures and NNE-striking half-grabens with hanging-wall growth faults. Mio- to Pliocene thin-skinned folding and thrusting of the Jura Mountains encountered a rift-related structural pattern, which had disrupted the Triassic basal décollement. This inherited pattern controlled the nucleation of thrusts and folds, as well as transfer zones, in the detached sedimentary cover, as is evidenced in the high semblance of subsurface faults and surface structures. Horizontal transport directions of the detached sediments (reconstructed by fault plane inversion) reveal NW- to NNE-directed fan-shaped trajectories, which indicate divergent displacements at the thin-skinned Jura front. On the other hand, increasing transpressional shortening of the frontal thrust sheet towards W with a maximum in the proximity of NNE-striking basement faults suggests a clockwise rotation of the detached sediments. Post-2.9Ma shortening of the sedimentary cover is evidenced in an array of ENE- to NE-trending syn- and anticlines, deforming

  1. 28 CFR 79.34 - Proof of medical condition.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of medical condition. 79.34 Section 79.34 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CLAIMS UNDER THE RADIATION EXPOSURE COMPENSATION ACT Eligibility Criteria for Claims by Onsite Participants § 79.34 Proof of medical...

  2. 28 CFR 79.34 - Proof of medical condition.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of medical condition. 79.34 Section 79.34 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CLAIMS UNDER THE RADIATION EXPOSURE COMPENSATION ACT Eligibility Criteria for Claims by Onsite Participants § 79.34 Proof of medical...

  3. 28 CFR 79.34 - Proof of medical condition.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of medical condition. 79.34 Section 79.34 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) CLAIMS UNDER THE RADIATION EXPOSURE COMPENSATION ACT Eligibility Criteria for Claims by Onsite Participants § 79.34 Proof of medical...

  4. Increased Susceptibility to Chemical Toxicity with (Pre-existing) Diseases: Case Studies with Particulate Matter, Cadmium, Mercury, Trichloroethylene and Dioxin

    EPA Science Inventory

    Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increas...

  5. Diagnosis and Management of Drug-Induced Liver Injury (DILI) in Patients with Pre-Existing Liver Disease.

    PubMed

    Teschke, Rolf; Danan, Gaby

    2016-08-01

    The relationship between drugs and pre-existing liver disease is complex, particularly when increased liver tests (LTs) or new symptoms emerge in patients with pre-existing liver disease during drug therapy. This requires two strategies to assess whether these changes are due to drug-induced liver injury (DILI) as a new event or due to flares of the underlying liver disease. Lacking a valid diagnostic biomarker, DILI is a diagnosis of exclusion and requires causality assessment by RUCAM, the Roussel Uclaf Causality Assessment Method, to establish an individual causality grading of the suspected drug(s). Flares of pre-existing liver disease can reliably be assessed in some hepatotropic virus infections by polymerase chain reaction (PCR) and antibody titers at the beginning and in the clinical course to ascertain flares during the natural course of the disease. Unfortunately, flares cannot be verified in many other liver diseases such as alcoholic liver disease, since specific tests are unavailable. However, such a diagnostic approach using RUCAM applied to suspected DILI cases includes clinical and biological markers of pre-existing liver diseases and would determine whether drugs or underlying liver diseases caused the LT abnormalities or the new symptoms. More importantly, a clear diagnosis is essential to ensure effective disease management by drug cessation or specific treatment of the flare up due to the underlying disease. PMID:27091053

  6. 40 CFR Appendix B to Part 434 - Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Baseline Determination and Compliance Monitoring for Pre-existing Discharges at Remining Operations B Appendix B to Part 434 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS COAL MINING...

  7. Increased Susceptibility to Chemical Toxicity with Pre-existing Diseases: Case Studies with Particulate Matter, Cadmium, Mercury, Trichloroethylene and Dioxin

    EPA Science Inventory

    Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increase...

  8. Parasitic folds with wrong vergence: How pre-existing geometrical asymmetries can be inherited during multilayer buckle folding

    NASA Astrophysics Data System (ADS)

    Frehner, Marcel; Schmid, Timothy

    2016-06-01

    Parasitic folds are typical structures in geological multilayer folds; they are characterized by a small wavelength and are situated within folds with larger wavelength. Parasitic folds exhibit a characteristic asymmetry (or vergence) reflecting their structural relationship to the larger-scale fold. Here we investigate if a pre-existing geometrical asymmetry (e.g., from sedimentary structures or folds from a previous tectonic event) can be inherited during buckle folding to form parasitic folds with wrong vergence. We conduct 2D finite-element simulations of multilayer folding using Newtonian materials. The applied model setup comprises a thin layer exhibiting the pre-existing geometrical asymmetry sandwiched between two thicker layers, all intercalated with a lower-viscosity matrix and subjected to layer-parallel shortening. When the two outer thick layers buckle and amplify, two processes work against the asymmetry: layer-perpendicular flattening between the two thick layers and the rotational component of flexural flow folding. Both processes promote de-amplification and unfolding of the pre-existing asymmetry. We discuss how the efficiency of de-amplification is controlled by the larger-scale fold amplification and conclude that pre-existing asymmetries that are open and/or exhibit low amplitude are prone to de-amplification and may disappear during buckling of the multilayer system. Large-amplitude and/or tight to isoclinal folds may be inherited and develop type 3 fold interference patterns.

  9. Medical conditions in Ashkenazi schizophrenic pedigrees.

    PubMed

    Goodman, A B

    1994-01-01

    To limit the genetic heterogeneity of schizophrenia, this study focused on the widely extended pedigrees of Ashkenazi Jewish schizophrenia probands. The hypothesis posed is that the increased prevalence among the Ashkenazim of the rare lysosomal enzyme disorders, Tay Sachs disease (TDS), caused by low levels of hexosaminidase A, and Gaucher's disease (GD), caused by low levels of glucocerebrosidase, might contribute to the demonstrated increased vulnerability to schizophrenia in this ethnic group. Signs and symptoms characterizing the candidate illnesses were systematically queried by the family history method. Rates and relative risks for symptoms characterizing these disorders and for several nonautosomal illnesses associated with TSD and/or GD (i.e., amyotrophic lateral sclerosis and Hodgkin's disease, leukemia and lymphoma) are significantly elevated in the schizophrenia pedigrees, compared to controls. The conditions with elevated rates and risks have been associated with chromosomal regions 1q21 and 15q23-q24. These areas are suggested as candidate regions for future targeted deoxyribonucleic acid (DNA) research in schizophrenia. PMID:7973467

  10. Avoiding the requirement for pre-existing optical contact during picosecond laser glass-to-glass welding.

    PubMed

    Chen, Jianyong; Carter, Richard M; Thomson, Robert R; Hand, Duncan P

    2015-07-13

    Previous reports of ultrafast laser welding of glass-to-glass have indicated that a pre-existing optical contact (or very close to) between the parts to be joined is essential. In this paper, the capability of picosecond laser welding to bridge micron-scale gaps is investigated, and successful welding, without cracking, of two glasses with a pre-existing gap of 3 µm is demonstrated. It is shown that the maximum gap that can be welded is not significantly affected by welding speeds, but is strongly dependent on the laser power and focal position relative to the interface between the materials. Five distinct types of material modification were observed over a range of different powers and surface separations, and a mechanism is proposed to explain the observations. PMID:26191923

  11. The experience of altered states of consciousness in shamanic ritual: the role of pre-existing beliefs and affective factors.

    PubMed

    Polito, Vince; Langdon, Robyn; Brown, Jac

    2010-12-01

    Much attention has been paid recently to the role of anomalous experiences in the aetiology of certain types of psychopathology, e.g. in the formation of delusions. We examine, instead, the top-down influence of pre-existing beliefs and affective factors in shaping an individual's characterisation of anomalous sensory experiences. Specifically we investigated the effects of paranormal beliefs and alexithymia in determining the intensity and quality of an altered state of consciousness (ASC). Fifty five participants took part in a sweat lodge ceremony, a traditional shamanic ritual which was unfamiliar to them. Participants reported significant alterations in their state of consciousness, quantified using the 'APZ' questionnaire, a standardized measure of ASC experience. Participants endorsing paranormal beliefs compatible with shamanic mythology, and those showing difficulty identifying feelings scored higher on positive dimensions of ASC experience. Our findings demonstrate that variation in an individual's characterisation of anomalous experiences is nuanced by pre-existing beliefs and affective factors. PMID:20558090

  12. Phenotypic T Cell Exhaustion in a Murine Model of Bacterial Infection in the Setting of Pre-Existing Malignancy

    PubMed Central

    Mittal, Rohit; Wagener, Maylene; Breed, Elise R.; Liang, Zhe; Yoseph, Benyam P.; Burd, Eileen M.; Farris, Alton B.

    2014-01-01

    While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation. PMID:24796533

  13. Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.

    PubMed

    Mittal, Rohit; Wagener, Maylene; Breed, Elise R; Liang, Zhe; Yoseph, Benyam P; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M; Ford, Mandy L

    2014-01-01

    While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation. PMID:24796533

  14. 28 CFR 79.16 - Proof of medical condition.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... COMPENSATION ACT Eligibility Criteria for Claims Relating to Leukemia § 79.16 Proof of medical condition. (a... leukemia. Proof that the claimant contracted leukemia must be made either by using the procedure outlined... section. (b) If a claimant was diagnosed as having leukemia in Arizona, Colorado, Nevada, New Mexico,...

  15. 28 CFR 79.16 - Proof of medical condition.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... COMPENSATION ACT Eligibility Criteria for Claims Relating to Leukemia § 79.16 Proof of medical condition. (a... leukemia. Proof that the claimant contracted leukemia must be made either by using the procedure outlined... section. (b) If a claimant was diagnosed as having leukemia in Arizona, Colorado, Nevada, New Mexico,...

  16. 28 CFR 79.16 - Proof of medical condition.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... COMPENSATION ACT Eligibility Criteria for Claims Relating to Leukemia § 79.16 Proof of medical condition. (a... leukemia. Proof that the claimant contracted leukemia must be made either by using the procedure outlined... section. (b) If a claimant was diagnosed as having leukemia in Arizona, Colorado, Nevada, New Mexico,...

  17. 42 CFR 494.170 - Condition: Medical records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Standard: Record retention and preservation. In accordance with 45 CFR § 164.530(j)(2), all patient records... Administration § 494.170 Condition: Medical records. The dialysis facility must maintain complete, accurate, and accessible records on all patients, including home patients who elect to receive dialysis supplies...

  18. 28 CFR 79.26 - Proof of medical condition.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... required in paragraph (c) of this section. (For claims relating to primary cancer of the liver, the... diagnosis, that authorizes the Program to contact the appropriate state cancer or tumor registry. The Program will accept as proof of medical condition verification from the state cancer or tumor...

  19. 28 CFR 79.26 - Proof of medical condition.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... required in paragraph (c) of this section. (For claims relating to primary cancer of the liver, the... diagnosis, that authorizes the Program to contact the appropriate state cancer or tumor registry. The Program will accept as proof of medical condition verification from the state cancer or tumor...

  20. 42 CFR 494.170 - Condition: Medical records.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Standard: Record retention and preservation. In accordance with 45 CFR § 164.530(j)(2), all patient records... Administration § 494.170 Condition: Medical records. The dialysis facility must maintain complete, accurate, and accessible records on all patients, including home patients who elect to receive dialysis supplies...

  1. 42 CFR 494.170 - Condition: Medical records.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Standard: Record retention and preservation. In accordance with 45 CFR § 164.530(j)(2), all patient records... Administration § 494.170 Condition: Medical records. The dialysis facility must maintain complete, accurate, and accessible records on all patients, including home patients who elect to receive dialysis supplies...

  2. 42 CFR 494.170 - Condition: Medical records.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Standard: Record retention and preservation. In accordance with 45 CFR § 164.530(j)(2), all patient records... Administration § 494.170 Condition: Medical records. The dialysis facility must maintain complete, accurate, and accessible records on all patients, including home patients who elect to receive dialysis supplies...

  3. 42 CFR 494.170 - Condition: Medical records.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Standard: Record retention and preservation. In accordance with 45 CFR § 164.530(j)(2), all patient records... Administration § 494.170 Condition: Medical records. The dialysis facility must maintain complete, accurate, and accessible records on all patients, including home patients who elect to receive dialysis supplies...

  4. Pre-existing oral contrast from lanthanum carbonate: a confounding factor in CT mesenteric angiography

    PubMed Central

    Bull, M D; Shrimanker, R; Thomas, M R M; Mulgrew, C J

    2012-01-01

    A 69-year-old male was referred from the renal unit to radiology for investigation of bleeding per rectum. A CT mesenteric angiogram was performed. However, it was noted on the pre-contrast images that the large bowel contained positive oral contrast media. The procedure was abandoned as it would have been difficult to see extravasation of intravenous contrast from a bleeding point in the large bowel. The initial belief was that either the patient had been given oral contrast by ward staff on the assumption that it would be needed, or had had a recent radiological study requiring contrast, which was still present. Neither was the case; it emerged that the patient was taking Fosrenol (Shire Pharmaceuticals, Wayne, PA), a lanthanum carbonate medication used in the treatment of hyperphosphataemia. Lanthanum is densely radio-opaque and appears as positive bowel contrast on CT and plain radiography studies. When considering radiological studies specifically requiring the absence of oral contrast, it is important to be aware of the patient's drug history to avoid non-diagnostic scans with the associated radiation exposure. PMID:22457410

  5. Pharmacotherapeutics knowledge of some nonemergency and emergency conditions among medical undergraduates in an Indian medical college

    PubMed Central

    Khan, Sarfaraz Alam; Siddiqui, Nazeem Ishrat

    2016-01-01

    Objectives: To assess pharmacotherapeutics (PT) knowledge of second professional medical undergraduates. Materials and Methods: It is a questionnaire-based cross-sectional study. The questionnaire was designed to objectively assess the current level of knowledge of PT acquired by the second MBBS students in a medical college in India. Thirty Type-A multiple choice questions (MCQs) related with the PT of common and important medical conditions and some emergency conditions were administered to 125 participants. Grading of knowledge was also done as poor, average, and good both subjectively and objectively. Descriptive statistics were used to analyze responses. Association of PT knowledge with respect to mode of admission in a medical college was analyzed with Chi-square test. Results: MCQs related with PT of nonemergency conditions were responded correctly by 9.8–77.7% of participants. MCQs related with PT of some emergency conditions were responded correctly by 17–66.1% of participants. No statistically significant association was observed in PT knowledge with respect to mode of admission. Conclusion: Gross deficiency in the PT knowledge can potentially and adversely affect future rational prescribing skills. PT knowledge about common medical conditions should be emphasized during undergraduate training program. PMID:27298493

  6. Medical and Orthopaedic Conditions in Special Olympics Athletes

    PubMed Central

    2001-01-01

    Objective: Many Special Olympics athletes experience hypokinetic diseases and comorbid conditions that may predispose them to serious injuries during physical activity. A clear understanding of these conditions and diseases may assist health care professionals in preventing further distress and managing the injuries sustained by these athletes. Such diseases and conditions include overweight and obesity, diabetes, vision problems, seizure disorders, and Down syndrome, which is often associated with atlantoaxial instability. Data Sources: MEDLINE, SPORT Discus, and Special Olympics information sources for the years 1990–2000 using the key terms Special Olympics, mental retardation, comorbidity, Down syndrome, hypokinetic diseases, and physical activity were searched. Data Synthesis: A basic review of hypokinetic diseases and comorbid conditions prepares health care professionals for working with people with mental retardation. Conclusions and Recommendations: Health care volunteers at Special Olympics events treat athletes with mental retardation who may also have some of the comorbid conditions and hypokinetic diseases observed commonly in this population. Moreover, many of these conditions and diseases are typical in athletes without mental retardation. Athletic trainers should be familiar with these conditions and diseases but should review the unique conditions and prescription medications commonly found in the Special Olympics population before providing medical services for these athletes. PMID:16404438

  7. Block-based conditional entropy coding for medical image compression

    NASA Astrophysics Data System (ADS)

    Bharath Kumar, Sriperumbudur V.; Nagaraj, Nithin; Mukhopadhyay, Sudipta; Xu, Xiaofeng

    2003-05-01

    In this paper, we propose a block-based conditional entropy coding scheme for medical image compression using the 2-D integer Haar wavelet transform. The main motivation to pursue conditional entropy coding is that the first-order conditional entropy is always theoretically lesser than the first and second-order entropies. We propose a sub-optimal scan order and an optimum block size to perform conditional entropy coding for various modalities. We also propose that a similar scheme can be used to obtain a sub-optimal scan order and an optimum block size for other wavelets. The proposed approach is motivated by a desire to perform better than JPEG2000 in terms of compression ratio. We hint towards developing a block-based conditional entropy coder, which has the potential to perform better than JPEG2000. Though we don't indicate a method to achieve the first-order conditional entropy coder, the use of conditional adaptive arithmetic coder would achieve arbitrarily close to the theoretical conditional entropy. All the results in this paper are based on the medical image data set of various bit-depths and various modalities.

  8. 45 CFR 155.345 - Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... procedures established in accordance with 45 CFR 152.45 to transition PCIP enrollees to the Exchange to... information or through other coverage groups. For an applicant who is not eligible for Medicaid based on the...) of the Code, is less than 100 percent of the FPL for the benefit year for which coverage is...

  9. 45 CFR 155.345 - Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... individuals potentially eligible for Medicaid based on other information or through other coverage groups. For... filer's household income, as defined in 26 CFR 1.36B-1(e), is less than 100 percent of the FPL for the benefit year for which coverage is requested, determines that the tax filer is not eligible for...

  10. 45 CFR 155.345 - Coordination with Medicaid, CHIP, the Basic Health Program, and the Pre-existing Condition...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... individuals potentially eligible for Medicaid based on other information or through other coverage groups. For... filer's household income, as defined in 26 CFR 1.36B-1(e), is less than 100 percent of the FPL for the benefit year for which coverage is requested, determines that the tax filer is not eligible for...

  11. Indium-111-labeled white blood cells in the detection of osteomyelitis complicated by a pre-existing condition

    SciTech Connect

    McCarthy, K.; Velchik, M.G.; Alavi, A.; Mandell, G.A.; Esterhai, J.L.; Goll, S.

    1988-06-01

    Forty-six patients (23M, 23F) ranging in age from 19 to 79 yr with a clinical history of a nonunion fracture, surgery, diabetes or a soft-tissue infection were studied with (/sup 111/In)oxine WBCs to detect osteomyelitis. There were 27 true-positive, nine true-negative, two false-positive and one false-negative. The false-positives and the false-negative occurred in patients with soft-tissue infections overlying the area of interest. All diagnoses were confirmed by intraoperative bone biopsies and cultures. Bone biopsy and scan were performed within 2 days of each other in 39 patients. The overall sensitivity was 97% (27/28), specificity, 82% (9/11) and the diagnostic accuracy, 92% (36/39). The remaining seven patients had negative (/sup 111/In)WBC scans several months after positive bone biopsies and definite antibiotic treatment. This suggests that (In)WBC scans become negative after appropriate therapy is undertaken. Interobserver data was obtained from four nuclear physicians of varying experience blinded to clinical information. A high degree of agreement was found in over 90% of the cases. This study demonstrates the utility of (/sup 111/In)WBC scans in the diagnosis and follow-up of complicated osteomyelitis and a high level of interobserver agreement in scan interpretation.

  12. Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats.

    PubMed

    Vollbrecht, Peter J; Nobile, Cameron W; Chadderdon, Aaron M; Jutkiewicz, Emily M; Ferrario, Carrie R

    2015-12-01

    Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel "junk-food" diet on the development of obesity and metabolic dysfunction, 2) over-consumption of "junk-food" in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, "junk-food" diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals. PMID:26423787

  13. Using Pre-existing Microarray Datasets to Increase Experimental Power: Application to Insulin Resistance

    PubMed Central

    Daigle, Bernie J.; Deng, Alicia; McLaughlin, Tracey; Cushman, Samuel W.; Cam, Margaret C.; Reaven, Gerald; Tsao, Philip S.; Altman, Russ B.

    2010-01-01

    Although they have become a widely used experimental technique for identifying differentially expressed (DE) genes, DNA microarrays are notorious for generating noisy data. A common strategy for mitigating the effects of noise is to perform many experimental replicates. This approach is often costly and sometimes impossible given limited resources; thus, analytical methods are needed which increase accuracy at no additional cost. One inexpensive source of microarray replicates comes from prior work: to date, data from hundreds of thousands of microarray experiments are in the public domain. Although these data assay a wide range of conditions, they cannot be used directly to inform any particular experiment and are thus ignored by most DE gene methods. We present the SVD Augmented Gene expression Analysis Tool (SAGAT), a mathematically principled, data-driven approach for identifying DE genes. SAGAT increases the power of a microarray experiment by using observed coexpression relationships from publicly available microarray datasets to reduce uncertainty in individual genes' expression measurements. We tested the method on three well-replicated human microarray datasets and demonstrate that use of SAGAT increased effective sample sizes by as many as 2.72 arrays. We applied SAGAT to unpublished data from a microarray study investigating transcriptional responses to insulin resistance, resulting in a 50% increase in the number of significant genes detected. We evaluated 11 (58%) of these genes experimentally using qPCR, confirming the directions of expression change for all 11 and statistical significance for three. Use of SAGAT revealed coherent biological changes in three pathways: inflammation, differentiation, and fatty acid synthesis, furthering our molecular understanding of a type 2 diabetes risk factor. We envision SAGAT as a means to maximize the potential for biological discovery from subtle transcriptional responses, and we provide it as a freely available

  14. Medical Transport of Children with Complex Chronic Conditions

    PubMed Central

    Lerner, Carlos F.; Kelly, Robert B.; Hamilton, Leslie J.; Klitzner, Thomas S.

    2012-01-01

    One of the most notable trends in child health has been the increase in the number of children with special health care needs, including those with complex chronic conditions. Care of these children accounts for a growing fraction of health care resources. We examine recent developments in health care, especially with regard to medical transport and prehospital care, that have emerged to adapt to this remarkable demographic trend. One such development is the focus on care coordination, including the dissemination of the patient-centered medical home concept. In the prehospital setting, the need for greater coordination has catalyzed the development of the emergency information form. Training programs for prehospital providers now incorporate specific modules for children with complex conditions. Another notable trend is the shift to a family-centered model of care. We explore efforts toward regionalization of care, including the development of specialized pediatric transport teams, and conclude with recommendations for a research agenda. PMID:22315689

  15. Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice.

    PubMed

    Annoni, Andrea; Cantore, Alessio; Della Valle, Patrizia; Goudy, Kevin; Akbarpour, Mahzad; Russo, Fabio; Bartolaccini, Sara; D'Angelo, Armando; Roncarolo, Maria Grazia; Naldini, Luigi

    2013-11-01

    A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to 50-100% of normal. The treatment was effective in 75% of treated mice. FIX-specific plasma cells (PCs) and memory B cells were reduced, likely because of memory B-cell depletion in response to constant exposure to high doses of FIX. Regulatory T cells displaying FIX-specific suppressive capacity were induced in gene therapy treated mice and controlled FIX-specific T helper cells. Gene therapy proved safer than a regimen mimicking immune tolerance induction (ITI) by repeated high-dose FIX protein administration, which induced severe anaphylactoid reactions in inhibitors-positive haemophilia B mice. Liver gene therapy can thus reverse pre-existing immunity, induce active tolerance to FIX and establish sustained FIX activity at therapeutic levels. These data position gene therapy as an attractive treatment option for inhibitors-positive haemophilic patients. PMID:24106222

  16. Impact of Pre-Existing Immunity on Gene Transfer to Nonhuman Primate Liver with Adeno-Associated Virus 8 Vectors

    PubMed Central

    Wang, Lili; Calcedo, Roberto; Bell, Peter; Lin, Jianping; Grant, Rebecca L; Siegel, Don L

    2011-01-01

    Abstract Vectors based on the primate-derived adeno-associated virus serotype 8 (AAV8) are being evaluated in preclinical and clinical models. Natural infections with related AAVs activate memory B cells that produce antibodies capable of modulating the efficacy and safety of the vector. We have evaluated the biology of AAV8 gene transfer in macaque liver, with a focus on assessing the impact of pre-existing humoral immunity. Twenty-one macaques with various levels of AAV neutralizing antibody (NAb) were injected intravenously with AAV8 vector expressing green fluorescent protein. Pre-existing antibody titers in excess of 1:10 substantially diminished hepatocyte transduction that, in the absence of NAbs, was highly efficient. Vector-specific NAb diminished liver deposition of genomes and unexpectedly increased genome distribution to the spleen. The majority of animals showed high-level and stable sequestration of vector capsid protein by follicular dendritic cells of splenic germinal centers. These studies illustrate how natural immunity to a virus that is related to a vector can impact the efficacy and potential safety of in vivo gene therapy. We propose to use the in vitro transduction inhibition assay to evaluate research subjects before gene therapy and to preclude from systemic AAV8 trials those that have titers in excess of 1:10. PMID:21476868

  17. The Prescribed Pediatric Center: A Medical Day Treatment Program for Children with Complex Medical Conditions.

    ERIC Educational Resources Information Center

    Ruppert, Elizabeth S.; Karst, Thomas O.; Brogan, Mark G.

    1998-01-01

    The Prescribed Pediatric Center (Toledo, Ohio) is a community-based, multidisciplinary program for infants and children with chronic, complex medical conditions. This article describes program beginnings; the planning process; and the program's growth, development, and components. Initial program evaluation indicates positive effects on some…

  18. Pre-existing Pulmonary Diseases and Survival in Patients With Stage-dependent Lung Adenocarcinoma: A STROBE-compliant Article.

    PubMed

    Jian, Zhi-Hong; Huang, Jing-Yang; Nfor, Oswald Ndi; Jhang, Kai-Ming; Ku, Wen-Yuan; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Wu, Ming-Fang; Liaw, Yung-Po

    2016-03-01

    Asthma, chronic obstructive pulmonary disease (COPD), and pulmonary tuberculosis (TB) are common lung diseases associated with lung cancer mortality. This study evaluated sex disparities in pre-existing pulmonary diseases and stage-dependent lung adenocarcinoma survival.Patients newly diagnosed with lung adenocarcinoma between 2003 and 2008 were identified using the National Health Insurance Research Database and Cancer Registry. Cases with lung adenocarcinoma were followed until the end of 2010. Survival curves were estimated by the Kaplan-Meier method. Cox proportional-hazard regression was used to calculate the hazard ratio (HR) of pre-existing asthma, COPD, and/or TB, and to estimate all-cause mortality risk in patients with different stages of lung adenocarcinoma.A total of 14,518 cases were identified with lung adenocarcinoma. Specifically, among men, the HRs for TB were 1.69 (95% confidence interval [CI], 1.10-2.58), 1.48 (95% CI, 1.14-1.93), and 1.27 (95% CI, 1.08-1.49) for individuals with stage I + II, III, and IV diseases, respectively. The HRs for asthma were 1.41 (95% CI, 1.00-1.99) in women with stage I + II and 1.14 (95% CI, 1.04-1.26) in men with stage IV disease. For pulmonary disease combinations in men, the HRs were 1.45 (95% CI, 1.12-1.89) for asthma + COPD + TB, 1.35 (95% CI, 1.12-1.63) for COPD + TB, 1.28 (95% CI, 1.01-1.63) for TB, and 1.15 (95%CI, 1.04-1.27) for asthma + COPD, respectively. For women with stage I + II disease, the HR was 6.94 (95% CI, 2.72-17.71) for asthma + COPD + TB.Coexistence of pre-existing pulmonary diseases increased mortality risk in men with adenocarcinoma. TB is at elevated risk of mortality among men with different stages of adenocarcinoma. Asthmatic women with early-stage adenocarcinoma had increased risk of mortality. PMID:26962806

  19. CHARGE syndrome: relations between behavioral characteristics and medical conditions.

    PubMed

    Vervloed, Mathijs P J; Hoevenaars-van den Boom, Marella A A; Knoors, Harry; van Ravenswaaij, Conny M A; Admiraal, Ronald J C

    2006-04-15

    The behaviors and medical problems in 27 persons with CHARGE syndrome were studied, because it was hypothesized that their behavior might be partly dependent on the heterogeneous medical status. With the exception of more tics, cardiac surgery was associated with positive behaviors: less withdrawn behavior, better mood, and a more easy temperament. Tube feeding was also related to positive behavior, since participants with a history of tube feeding showed less intense behavior. Cerebral deficits were associated with three problem behaviors: more intense and withdrawn behavior and a worse mood. Deaf-blindness was associated with developmental delays in expressive and overall communication level, and recurrent middle ear infections correlated with delays in written language. Of all medical conditions, only the presence or absence of heart defects and cardiac surgery could differentiate between the participants with regard to the number of behavioral problems. Participants with heart surgery especially, had less behavior problems. The number of operations and hospitalizations was not associated with behavior, but the total length of the hospitalizations was. Long hospital stays were associated with less problem behavior, especially internalizing behaviors. Cerebral and heart problems did not result in longer hospital stays, whereas esophageal reflux did. Age effects were reflected in older participants, who showed more internalizing problems. Heart surgery and hospitalization may be protective factors, but the protection might not be the actual surgery or hospital stay, as there may be other variables that are the actual cause, such as reduced vitality or altered parent child interactions after heart surgery. The study could not confirm a significant association between medical conditions and autism found in previous studies. PMID:16532469

  20. Basaloid Squamous Cell Carcinoma of Scalp From A Pre-Existing Cylindroma Metastasising To Brain: A Rare Case Report

    PubMed Central

    Srinivas, Teerthanath; Kolakebail, Jayaram Shetty; Shetty, Jayaprakash; Kukreja, Prachi

    2016-01-01

    Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer and accounts for 90% of head and neck malignancies. Intracranial metastases of SCC are extremely rare. We are reporting a case of 55-year-old female with history of recurrent swelling over right side of forehead which was previously reported as cylindroma. CT scan of head revealed irregular lytic areas in right frontal bone suggestive of erosion. There were multiple small, rim enhancing lesions in bilateral parietal regions. Clinically it was diagnosed as malignant adnexal tumour. Wide excision of the lesion revealed features of invasive basaloid squamous cell carcinoma, probably a malignant transformation of the pre-existing cylindroma. PMID:27437239

  1. A possible role of pre-existing IgM/IgG antibodies in determining immune response type.

    PubMed

    Seledtsov, V I; Seledtsova, G V

    1997-04-01

    On the basis of the data indicating the existence of two types of immuno-protection, namely macrophage-mediated and mast cell-basophil-mediated, it is argued that by reacting with potential pathogens, pre-existing IgM and IgG antibodies (both natural and induced by environmental microflora) might promote involvement of macrophages in the presentation process, favouring the generation of pathogen-specific T helper 1 (Th1), but not Th2, responses. Alternatively, the failure of these antibodies to effectively recognize pathogens might be associated with active involvement of pathogen-specific B cells in presenting Ag and, as a consequence, with the predominant development of Th2, rather than Th1, responses. PMID:9107571

  2. Pre-existing Minority Drug-Resistant HIV-1 Variants, Adherence, and Risk of Antiretroviral Treatment Failure

    PubMed Central

    Paredes, Roger; Lalama, Christina M.; Ribaudo, Heather J.; Schackman, Bruce R.; Shikuma, Cecilia; Giguel, Francoise; Meyer, William A.; Johnson, Victoria A.; Fiscus, Susan A.; D’Aquila, Richard T.; Gulick, Roy M.; Kuritzkes, Daniel R.

    2009-01-01

    Background The clinical relevance of detecting minority drug-resistant HIV-1 variants is uncertain. Methods To determine the effect of pre-existing minority non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant variants on the risk of virologic failure (VF), we reanalyzed a case-cohort substudy of efavirenz recipients in ACTG A5095. Minority K103N or Y181C populations were determined by allele-specific PCR (ASPCR) in subjects without NNRTI resistance by population sequencing. Weighted Cox proportional hazards models adjusted for recent adherence estimated the relative risk of VF in the presence of NNRTI-resistant minority variants. Results The evaluable case-cohort sample included 195 subjects from the randomly selected subcohort (51 with VF, 144 without failure [NF]), plus 127 of the remaining subjects with VF. Presence of minority K103N or Y181C mutations, or both, was detected in 8 (4.4%), 54 (29.5%) and 11 (6%), respectively, of 183 evaluable subjects in the random subcohort. Detection of minority Y181C mutants was associated with an increased risk of VF in the setting of recent adherence (HR=3.45, CI=1.90, 6.26), but not in non-adherent subjects (HR=1.39, CI=0.58, 3.29). Of note, 70% of subjects with minority Y181C achieved long-term viral suppression. Conclusions In adherent patients, pre-existing minority Y181C mutants more than tripled the risk of VF of first-line efavirenz-based ART. PMID:20102271

  3. The Association between Pre-existing Diabetes Mellitus and Pressure Ulcers in Patients Following Surgery: A Meta-analysis

    PubMed Central

    Kang, Zhou-Qing; Zhai, Xiao-Jie

    2015-01-01

    Uncertainty exists about the role of diabetes in the development of surgery-related pressure ulcers. Therefore, we conducted a meta-analysis to explore the association between pre-existing diabetes mellitus and pressure ulcers among patients after surgery. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random effects models. Thirteen eligible studies of 2367 patients in total and 12053 controls were included in the final analysis. Compared with patients without diabetes, the pooled odds ratio (OR) of the incidence of pressure ulcers in diabetic patients was 1.74 [95% confidence interval (CI) = 1.40–2.15, I2 = 51.1%]. Estimates by type of surgery suggested similar results in cardiac surgery [OR = 2.00, 95% CI = 1.42–2.82, I2 = 0%], in general surgery [OR = 1.75, 95% CI = 1.42–2.15, I2 = 0%], and in major lower limb amputations [OR = 1.65, 95% CI = 1.01–2.68, I2 = 0%] for diabetic patients versus non-diabetic controls. We did not find an increased incidence of pressure ulcers in diabetic patients undergoing hip surgery compared with non-diabetic controls [OR = 1.46, 95% CI = 0.62–3.47, I2 = 93.1%]. The excess risk of pressure ulcers associated with pre-existing diabetes was significantly higher in patients undergoing surgery, specifically in patients receiving cardiac surgery. Further studies should be conducted to examine these associations in other types of surgery. PMID:26260124

  4. 42 CFR 418.102 - Condition of participation: Medical director.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) Standard: Medical director contract. (1) A hospice may contract with either of the following— (i) A self... objective medical findings; (4) Current medication and treatment orders; and (5) Information about...

  5. 42 CFR 418.102 - Condition of participation: Medical director.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Standard: Medical director contract. (1) A hospice may contract with either of the following— (i) A self... objective medical findings; (4) Current medication and treatment orders; and (5) Information about...

  6. The role of pre-existing tectonic structures and magma chamber shape on the geometry of resurgent blocks: Analogue models

    NASA Astrophysics Data System (ADS)

    Marotta, Enrica; de Vita, Sandro

    2014-02-01

    A set of analogue models has been carried out to understand the role of an asymmetric magma chamber on the resurgence-related deformation of a previously deformed crustal sector. The results are then compared with those of similar experiments, previously performed using a symmetric magma chamber. Two lines of experiments were performed to simulate resurgence in an area with a simple graben-like structure and resurgence in a caldera that collapsed within the previously generated graben-like structure. On the basis of commonly accepted scaling laws, we used dry-quartz sand to simulate the brittle behaviour of the crust and Newtonian silicone to simulate the ductile behaviour of the intruding magma. An asymmetric shape of the magma chamber was simulated by moulding the upper surface of the silicone. The resulting empty space was then filled with sand. The results of the asymmetric-resurgence experiments are similar to those obtained with symmetrically shaped silicone. In the sample with a simple graben-like structure, resurgence occurs through the formation of a discrete number of differentially displaced blocks. The most uplifted portion of the deformed depression floor is affected by newly formed, high-angle, inward-dipping reverse ring-faults. The least uplifted portion of the caldera is affected by normal faults with similar orientation, either newly formed or resulting from reactivation of the pre-existing graben faults. This asymmetric block resurgence is also observed in experiments performed with a previous caldera collapse. In this case, the caldera-collapse-related reverse ring-fault is completely erased along the shortened side, and enhances the effect of the extensional faults on the opposite side, so facilitating the intrusion of the silicone. The most uplifted sector, due to an asymmetrically shaped intrusion, is always in correspondence of the thickest overburden. These results suggest that the stress field induced by resurgence is likely dictated by

  7. Medical Signal-Conditioning and Data-Interface System

    NASA Technical Reports Server (NTRS)

    Braun, Jeffrey; Jacobus, charles; Booth, Scott; Suarez, Michael; Smith, Derek; Hartnagle, Jeffrey; LePrell, Glenn

    2006-01-01

    A general-purpose portable, wearable electronic signal-conditioning and data-interface system is being developed for medical applications. The system can acquire multiple physiological signals (e.g., electrocardiographic, electroencephalographic, and electromyographic signals) from sensors on the wearer s body, digitize those signals that are received in analog form, preprocess the resulting data, and transmit the data to one or more remote location(s) via a radiocommunication link and/or the Internet. The system includes a computer running data-object-oriented software that can be programmed to configure the system to accept almost any analog or digital input signals from medical devices. The computing hardware and software implement a general-purpose data-routing-and-encapsulation architecture that supports tagging of input data and routing the data in a standardized way through the Internet and other modern packet-switching networks to one or more computer(s) for review by physicians. The architecture supports multiple-site buffering of data for redundancy and reliability, and supports both real-time and slower-than-real-time collection, routing, and viewing of signal data. Routing and viewing stations support insertion of automated analysis routines to aid in encoding, analysis, viewing, and diagnosis.

  8. The effect of pre-existing pulmonary vascular disease on the response to mechanical ventilation with PEEP following open-heart surgery.

    PubMed

    Trichet, B; Falke, K; Togut, A; Laver, M B

    1975-01-01

    hypertension was more pronounded in the MVR than in the AVR group, there was no significant difference between the postoperative values for Qs/Qt (Fio2 = 1.0), a condition probably fostered by marked differences in pre-existing V/Q. PMID:234211

  9. Cross-reactive and pre-existing antibodies to therapeutic antibodies—Effects on treatment and immunogenicity

    PubMed Central

    van Schie, Karin A; Wolbink, Gerrit-Jan; Rispens, Theo

    2015-01-01

    The potential for immunogenicity is an ever-present concern during the development of biopharmaceuticals. Therapeutic antibodies occasionally elicit an antibody response in patients, which can result in loss of response or adverse effects. However, antibodies that bind a drug are sometimes found in pre-treatment serum samples, with the amount depending on drug, assay, and patient population. This review summarizes published data on pre-existing antibodies to therapeutic antibodies, including rheumatoid factors, anti-allotype antibodies, anti-hinge antibodies, and anti-glycan antibodies. Unlike anti-idiotype antibodies elicited by the drug, pre-formed antibodies in general appear to have little consequences during treatment. In the few cases where (potential) clinical consequences were encountered, antibodies were characterized and found to bind a distinct, unusual epitope of the therapeutic. Immunogenicity testing strategies should therefore always include a proper level of antibody characterization, especially when pre-formed antibodies are present. This minimizes false-positives, particularly due to rheumatoid factors, and helps to judge the potential threat in case a genuine pre-dose antibody reactivity is identified. PMID:25962087

  10. Influence of pre-existing topography on downflow lava discharge rates estimated from thermal infrared airborne data

    NASA Astrophysics Data System (ADS)

    Lombardo, V.

    2016-04-01

    Remote sensing thermal data of active lava flows allow the evaluation of effusion rates. This is made possible by a simple formula relating the lava effusion rate to the heat flux radiated per unit time from the surface of the flow. Due to the assumptions of the model, this formula implies that heat flux, surface temperature and lava temperature vary as a function of the flow thickness. These relationships, never verified or validated before, have been used by several authors as a proof of the weakness of the model. Here, multispectral infrared and visible imaging spectrometer (MIVIS) high spatial resolution (5-10 m) thermal data acquired during Etna's 2001 eruption were used to investigate downflow heat flux variations in the lava flow emitted from a vent located at 2100 m a.s.l. A high correlation between the downflow heat flux and the lava flow thickness (measured from a pre-existing digital elevation model) was found. Topography beneath the flow appears to play an important role both in lava emplacement mechanisms and flow dynamics. MIVIS-derived downflow effusion rates are consistent with the law of conservation of mass assessing the reliability of remote sensing techniques.

  11. Characteristics of Memory B Cells Elicited by a Highly Efficacious HPV Vaccine in Subjects with No Pre-existing Immunity

    PubMed Central

    Scherer, Erin M.; Smith, Robin A.; Simonich, Cassandra A.; Niyonzima, Nixon; Carter, Joseph J.; Galloway, Denise A.

    2014-01-01

    Licensed human papillomavirus (HPV) vaccines provide near complete protection against the types of HPV that most commonly cause anogenital and oropharyngeal cancers (HPV 16 and 18) when administered to individuals naive to these types. These vaccines, like most other prophylactic vaccines, appear to protect by generating antibodies. However, almost nothing is known about the immunological memory that forms following HPV vaccination, which is required for long-term immunity. Here, we have identified and isolated HPV 16-specific memory B cells from female adolescents and young women who received the quadrivalent HPV vaccine in the absence of pre-existing immunity, using fluorescently conjugated HPV 16 pseudoviruses to label antigen receptors on the surface of memory B cells. Antibodies cloned and expressed from these singly sorted HPV 16-pseudovirus labeled memory B cells were predominantly IgG (>IgA>IgM), utilized diverse variable genes, and potently neutralized HPV 16 pseudoviruses in vitro despite possessing only average levels of somatic mutation. These findings suggest that the quadrivalent HPV vaccine provides an excellent model for studying the development of B cell memory; and, in the context of what is known about memory B cells elicited by influenza vaccination/infection, HIV-1 infection, or tetanus toxoid vaccination, indicates that extensive somatic hypermutation is not required to achieve potent vaccine-specific neutralizing antibody responses. PMID:25330199

  12. Combinatorial RNA Interference Therapy Prevents Selection of Pre-existing HBV Variants in Human Liver Chimeric Mice

    PubMed Central

    Shih, Yao-Ming; Sun, Cheng-Pu; Chou, Hui-Hsien; Wu, Tzu-Hui; Chen, Chun-Chi; Wu, Ping-Yi; Enya Chen, Yu-Chen; Bissig, Karl-Dimiter; Tao, Mi-Hua

    2015-01-01

    Selection of escape mutants with mutations within the target sequence could abolish the antiviral RNA interference activity. Here, we investigated the impact of a pre-existing shRNA-resistant HBV variant on the efficacy of shRNA therapy. We previously identified a highly potent shRNA, S1, which, when delivered by an adeno-associated viral vector, effectively inhibits HBV replication in HBV transgenic mice. We applied the “PICKY” software to systemically screen the HBV genome, then used hydrodynamic transfection and HBV transgenic mice to identify additional six highly potent shRNAs. Human liver chimeric mice were infected with a mixture of wild-type and T472C HBV, a S1-resistant HBV variant, and then treated with a single or combined shRNAs. The presence of T472C mutant compromised the therapeutic efficacy of S1 and resulted in replacement of serum wild-type HBV by T472C HBV. In contrast, combinatorial therapy using S1 and P28, one of six potent shRNAs, markedly reduced titers for both wild-type and T472C HBV. Interestingly, treatment with P28 alone led to the emergence of escape mutants with mutations in the P28 target region. Our results demonstrate that combinatorial RNAi therapy can minimize the escape of resistant viral mutants in chronic HBV patients. PMID:26482836

  13. Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer

    PubMed Central

    Kristian, Sascha A.; Hwang, John H.; Hall, Bradley; Leire, Emma; Iacomini, John; Old, Robert; Galili, Uri; Roberts, Charles; Mullis, Kary B.; Westby, Mike; Nizet, Victor

    2015-01-01

    The ever-increasing threat of multi-drug resistant bacterial infections has spurred renewed interest in alternative approaches to classical antibiotic therapy. In contrast to other mammals, humans do not express the galactose-α-1,3-galactosyl-β-1,4-N-acetyl-glucosamine (α-Gal) epitope. As a result of exposure of humans to α-Gal in the environment, a large proportion of circulating antibodies are specific for the trisaccharide. In this study, we examine whether these anti-Gal antibodies can be recruited and redirected to exert anti-bacterial activity. We show that a specific DNA aptamer conjugated to an α-Gal epitope at its 5′ end, herein termed an alphamer, can bind to group A Streptococcus (GAS) bacteria by recognition of a conserved region of the surface-anchored M protein. The anti-GAS alphamer was shown to recruit anti-Gal antibodies to the streptococcal surface in an α-Gal-specific manner, elicit uptake and killing of the bacteria by human phagocytes, and slow growth of invasive GAS in human whole blood. These studies provide a first in vitro proof of concept that alphamers have the potential to redirect pre-existing antibodies to bacteria in a specific manner and trigger an immediate antibacterial immune response. Further validation of this novel therapeutic approach of applying α-Gal technology in in vivo models of bacterial infection is warranted. PMID:25940316

  14. The role of pre-existing disturbances in the effect of marine reserves on coastal ecosystems: a modelling approach.

    PubMed

    Savina, Marie; Condie, Scott A; Fulton, Elizabeth A

    2013-01-01

    We have used an end-to-end ecosystem model to explore responses over 30 years to coastal no-take reserves covering up to 6% of the fifty thousand square kilometres of continental shelf and slope off the coast of New South Wales (Australia). The model is based on the Atlantis framework, which includes a deterministic, spatially resolved three-dimensional biophysical model that tracks nutrient flows through key biological groups, as well as extraction by a range of fisheries. The model results support previous empirical studies in finding clear benefits of reserves to top predators such as sharks and rays throughout the region, while also showing how many of their major prey groups (including commercial species) experienced significant declines. It was found that the net impact of marine reserves was dependent on the pre-existing levels of disturbance (i.e. fishing pressure), and to a lesser extent on the size of the marine reserves. The high fishing scenario resulted in a strongly perturbed system, where the introduction of marine reserves had clear and mostly direct effects on biomass and functional biodiversity. However, under the lower fishing pressure scenario, the introduction of marine reserves caused both direct positive effects, mainly on shark groups, and indirect negative effects through trophic cascades. Our study illustrates the need to carefully align the design and implementation of marine reserves with policy and management objectives. Trade-offs may exist not only between fisheries and conservation objectives, but also among conservation objectives. PMID:23593432

  15. Multi-epitope Models Explain How Pre-existing Antibodies Affect the Generation of Broadly Protective Responses to Influenza

    PubMed Central

    Zarnitsyna, Veronika I.; Lavine, Jennie; Ellebedy, Ali; Ahmed, Rafi; Antia, Rustom

    2016-01-01

    The development of next-generation influenza vaccines that elicit strain-transcendent immunity against both seasonal and pandemic viruses is a key public health goal. Targeting the evolutionarily conserved epitopes on the stem of influenza’s major surface molecule, hemagglutinin, is an appealing prospect, and novel vaccine formulations show promising results in animal model systems. However, studies in humans indicate that natural infection and vaccination result in limited boosting of antibodies to the stem of HA, and the level of stem-specific antibody elicited is insufficient to provide broad strain-transcendent immunity. Here, we use mathematical models of the humoral immune response to explore how pre-existing immunity affects the ability of vaccines to boost antibodies to the head and stem of HA in humans, and, in particular, how it leads to the apparent lack of boosting of broadly cross-reactive antibodies to the stem epitopes. We consider hypotheses where binding of antibody to an epitope: (i) results in more rapid clearance of the antigen; (ii) leads to the formation of antigen-antibody complexes which inhibit B cell activation through Fcγ receptor-mediated mechanism; and (iii) masks the epitope and prevents the stimulation and proliferation of specific B cells. We find that only epitope masking but not the former two mechanisms to be key in recapitulating patterns in data. We discuss the ramifications of our findings for the development of vaccines against both seasonal and pandemic influenza. PMID:27336297

  16. Evolution of a fold-thrust belt deforming a unit with pre-existing linear asperities: Insights from analog models

    NASA Astrophysics Data System (ADS)

    Burberry, Caroline M.; Swiatlowski, Jerlyn L.

    2016-06-01

    Heterogeneity, whether geometric or rheologic, in crustal material undergoing compression affects the geometry of the structures produced. This study documents the thrust fault geometries produced when discrete linear asperities are introduced into an analog model, scaled to represent bulk upper crustal properties, and compressed. Varying obliquities of the asperities are used, relative to the imposed compression, and the resultant development of thrust fault traces and branch lines in map view is tracked. Once the model runs are completed, cross-sections are created and analyzed. The models show that asperities confined to the base layer promote the clustering of branch lines in the surface thrusts. Strong clustering in branch lines is also noted where several asperities are in close proximity or cross. Slight reverse-sense reactivation of asperities cut through the sedimentary sequence is noted in cross-section, where the asperity and the subsequent thrust belt interact. The model results are comparable to the situation in the Dinaric Alps, where pre-existing faults to the SW of the NE Adriatic Fault Zone contribute to the clustering of branch lines developed in the surface fold-thrust belt. These results can therefore be used to evaluate the evolution of other basement-involved fold-thrust belts worldwide.

  17. The Role of Pre-Existing Disturbances in the Effect of Marine Reserves on Coastal Ecosystems: A Modelling Approach

    PubMed Central

    Savina, Marie; Condie, Scott A.; Fulton, Elizabeth A.

    2013-01-01

    We have used an end-to-end ecosystem model to explore responses over 30 years to coastal no-take reserves covering up to 6% of the fifty thousand square kilometres of continental shelf and slope off the coast of New South Wales (Australia). The model is based on the Atlantis framework, which includes a deterministic, spatially resolved three-dimensional biophysical model that tracks nutrient flows through key biological groups, as well as extraction by a range of fisheries. The model results support previous empirical studies in finding clear benefits of reserves to top predators such as sharks and rays throughout the region, while also showing how many of their major prey groups (including commercial species) experienced significant declines. It was found that the net impact of marine reserves was dependent on the pre-existing levels of disturbance (i.e. fishing pressure), and to a lesser extent on the size of the marine reserves. The high fishing scenario resulted in a strongly perturbed system, where the introduction of marine reserves had clear and mostly direct effects on biomass and functional biodiversity. However, under the lower fishing pressure scenario, the introduction of marine reserves caused both direct positive effects, mainly on shark groups, and indirect negative effects through trophic cascades. Our study illustrates the need to carefully align the design and implementation of marine reserves with policy and management objectives. Trade-offs may exist not only between fisheries and conservation objectives, but also among conservation objectives. PMID:23593432

  18. An Analytical Model for Assessing Stability of Pre-Existing Faults in Caprock Caused by Fluid Injection and Extraction in a Reservoir

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Bai, Bing; Li, Xiaochun; Liu, Mingze; Wu, Haiqing; Hu, Shaobin

    2016-07-01

    Induced seismicity and fault reactivation associated with fluid injection and depletion were reported in hydrocarbon, geothermal, and waste fluid injection fields worldwide. Here, we establish an analytical model to assess fault reactivation surrounding a reservoir during fluid injection and extraction that considers the stress concentrations at the fault tips and the effects of fault length. In this model, induced stress analysis in a full-space under the plane strain condition is implemented based on Eshelby's theory of inclusions in terms of a homogeneous, isotropic, and poroelastic medium. The stress intensity factor concept in linear elastic fracture mechanics is adopted as an instability criterion for pre-existing faults in surrounding rocks. To characterize the fault reactivation caused by fluid injection and extraction, we define a new index, the "fault reactivation factor" η, which can be interpreted as an index of fault stability in response to fluid pressure changes per unit within a reservoir resulting from injection or extraction. The critical fluid pressure change within a reservoir is also determined by the superposition principle using the in situ stress surrounding a fault. Our parameter sensitivity analyses show that the fault reactivation tendency is strongly sensitive to fault location, fault length, fault dip angle, and Poisson's ratio of the surrounding rock. Our case study demonstrates that the proposed model focuses on the mechanical behavior of the whole fault, unlike the conventional methodologies. The proposed method can be applied to engineering cases related to injection and depletion within a reservoir owing to its efficient computational codes implementation.

  19. 42 CFR 418.106 - Condition of participation: Drugs and biologicals, medical supplies, and durable medical equipment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Condition of participation: Drugs and biologicals, medical supplies, and durable medical equipment. 418.106 Section 418.106 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) HOSPICE CARE Conditions of...

  20. The effect of pre-existing affect on the sexual responses of women with and without a history of childhood sexual abuse.

    PubMed

    Rellini, Alessandra H; Elinson, Samantha; Janssen, Erick; Meston, Cindy M

    2012-04-01

    Women with a history of childhood sexual abuse (CSA) are at greater risk for experiencing sexual problems in their adult lives. Yet, little is known about the possible role of cognitive and affective mechanisms in the development of sexual arousal difficulties in this population. This study investigated the role of pre-existing affect (affect prior to exposure to sexual stimuli) on genital responses, subjective sexual arousal, and affect elicited during the presentation of erotic film excerpts in a community sample of 25 women with and 25 women without a history of CSA. The CSA group showed greater pre-existing negative affect and smaller genital responses to the erotic film stimuli compared to the NSA group. Findings support a moderating effect of CSA, in that pre-existing negative affect was associated with strength of genital responses in the NSA but not in the CSA group. The results did not support a mediation model of pre-existing negative affect as an explanation for smaller physiological sexual responses in the CSA group. Taken together, the findings suggest that pre-existing affect may be more relevant for women with no history of CSA and call for more research on factors implicated in impaired sexual responses in women with a history of CSA. PMID:21667233

  1. Towards ethical guidelines for dealing with unsolicited patient emails and giving teleadvice in the absence of a pre-existing patient-physician relationship — systematic review and expert survey

    PubMed Central

    2000-01-01

    Background Many health information providers on the Internet and doctors with email accounts are confronted with the phenomenon of receiving unsolicited emails from patients asking for medical advice. Also, a growing number of websites offer "ask-the-doctor" services, where patients can ask questions to health professionals via email or other means of telecommunication. It is unclear whether these types of interactions constitute medical practice, and whether physicians have the ethical obligation to respond to unsolicited patient emails. Objective To improve the quality of online communication between patients and health professionals (physicians, experts) in the absence of a pre-existing patient-physician relationship or face-to-face communication, by preparing a set of guiding ethical principles applicable to this kind of interaction. Methods Systematic review of the literature, professional, and ethical codes; and consultation with experts. Results Two different types of patient-physician encounters have to be distinguished. "Traditional" clinical encounters or telemedicine applications are called "Type B" interactions here (Bona fide relationship). In comparison, online interactions lack many of the characteristics of bona fide interactions; most notably there is no pre-existing relationship and the information available to the physician is limited if, for example, a physician responds to the email of a patient who he has never seen before. I call these "Type A" consultations (Absence of pre-existing patient-physician relationship). While guidelines for Type B interactions on the Internet exist (Kane, 1998), this is not the case for Type A interactions. The following principles are suggested: Physicians responding to patients' requests on the Internet should act within the limitations of telecommunication services and keep the global nature of the Internet in mind; not every aspect of medicine requires face-to-face communication; requests for help, including

  2. Dioxins from medical waste incineration: Normal operation and transient conditions.

    PubMed

    Chen, Tong; Zhan, Ming-xiu; Yan, Mi; Fu, Jian-ying; Lu, Sheng-yong; Li, Xiao-dong; Yan, Jian-hua; Buekens, Alfons

    2015-07-01

    Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are key pollutants in waste incineration. At present, incinerator managers and official supervisors focus only on emissions evolving during steady-state operation. Yet, these emissions may considerably be raised during periods of poor combustion, plant shutdown, and especially when starting-up from cold. Until now there were no data on transient emissions from medical (or hospital) waste incineration (MWI). However, MWI is reputed to engender higher emissions than those from municipal solid waste incineration (MSWI). The emission levels in this study recorded for shutdown and start-up, however, were significantly higher: 483 ± 184 ng Nm(-3) (1.47 ± 0.17 ng I-TEQ Nm(-3)) for shutdown and 735 ng Nm(-3) (7.73 ng I-TEQ Nm(-3)) for start-up conditions, respectively. Thus, the average (I-TEQ) concentration during shutdown is 2.6 (3.8) times higher than the average concentration during normal operation, and the average (I-TEQ) concentration during start-up is 4.0 (almost 20) times higher. So monitoring should cover the entire incineration cycle, including start-up, operation and shutdown, rather than optimised operation only. This suggestion is important for medical waste incinerators, as these facilities frequently start up and shut down, because of their small size, or of lacking waste supply. Forthcoming operation should shift towards much longer operating cycles, i.e., a single weekly start-up and shutdown. PMID:26159561

  3. Modification of Ad5 Hexon Hypervariable Regions Circumvents Pre-Existing Ad5 Neutralizing Antibodies and Induces Protective Immune Responses

    PubMed Central

    Bruder, Joseph T.; Semenova, Elena; Chen, Ping; Limbach, Keith; Patterson, Noelle B.; Stefaniak, Maureen E.; Konovalova, Svetlana; Thomas, Charlie; Hamilton, Melissa; King, C. Richter; Richie, Thomas L.; Doolan, Denise L.

    2012-01-01

    The development of an effective malaria vaccine is a high global health priority. Vaccine vectors based on adenovirus type 5 are capable of generating robust and protective T cell and antibody responses in animal models and are currently being evaluated in clinical trials for HIV and malaria. They appear to be more effective in terms of inducing antigen-specific immune responses as compared with non-Ad5 serotype vectors. However, the high prevalence of neutralizing antibodies to Ad5 in the human population, particularly in the developing world, has the potential to limit the effectiveness of Ad5-based vaccines. We have generated novel Ad5-based vectors that precisely replace the hexon hypervariable regions with those derived from Ad43, a subgroup D serotype with low prevalence of neutralizing antibody in humans. We have demonstrated that these hexon-modified adenovectors are not neutralized efficiently by Ad5 neutralizing antibodies in vitro using sera from mice, rabbits and human volunteers. We have also generated hexon-modified adenovectors that express a rodent malaria parasite antigen, PyCSP, and demonstrated that they are as immunogenic as an unmodified vector. Furthermore, in contrast to the unmodified vector, the hexon-modified adenovectors induced robust T cell responses in mice with high levels of Ad5 neutralizing antibody. We also show that the hexon-modified vector can be combined with unmodified Ad5 vector in prime-boost regimens to induce protective responses in mice. Our data establish that these hexon-modified vectors are highly immunogenic even in the presence of pre-existing anti-adenovirus antibodies. These hexon-modified adenovectors may have advantages in sub-Saharan Africa where there is a high prevalence of Ad5 neutralizing antibody in the population. PMID:22496772

  4. Programmed death ligand 1 as an indicator of pre-existing adaptive immune responses in human hepatocellular carcinoma.

    PubMed

    Xie, Qian-Kun; Zhao, Yu-Jie; Pan, Tao; Lyu, Ning; Mu, Lu-Wen; Li, Shao-Long; Shi, Mu-De; Zhang, Zhen-Feng; Zhou, Peng-Hui; Zhao, Ming

    2016-07-01

    It is well known that the aberrant expression of programmed death ligand 1 (PD-L1) on tumor cells impairs antitumor immunity. To date, in hepatocellular carcinoma (HCC), the relationship between PD-L1 expression and host-tumor immunity is not well defined. Here, the expression levels of PD-L1 and CD8(+) T cell infiltration were analyzed by immunohistochemistry (IHC) in formalin fixed paraffin embedded (FFPE) specimens from 167 HCC patients undergoing resection. A significant positive association was found between PD-L1 expression and the presence of CD8(+) T cell (p < 0.0001). Moreover, constitutive PD-L1 protein expression was not detected by western blot in HepG2, Hep3B, and 7402 HCC cancer cell lines; but co-cultured these cell lines with INFγ, a cytokine produced by activated CD8(+) T cells, remarkably upregulated PD-L1 expression. In fresh frozen HCC specimens, INFγ was found to be significantly correlated with PD-L1 and CD8(+) gene expression, as evaluated by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). These findings indicate that increased PD-L1 level may represent an adaptive immune resistance mechanism exerted by tumor cells in response to endogenous antitumor activity. Both increased intratumoral PD-L1 and CD8(+) were significantly associated with superior DFS (CD8(+): p = 0.03; PD-L1: p = 0.023) and OS (CD8(+): p = 0.001 and PD-L1: p = 0.059), but PD-L1 expression was not independently prognostic. In conclusions, PD-L1 upregulation is mainly induced by activated CD8(+) cytotoxic T cells pre-existing in HCC milieu rather than be constitutively expressed by the tumor cells, and it is a favorable prognostic factor for HCC. PMID:27622038

  5. Recrystallization fabrics of sheared quartz veins with a strong pre-existing crystallographic preferred orientation from a seismogenic shear zone

    NASA Astrophysics Data System (ADS)

    Price, Nancy A.; Song, Won Joon; Johnson, Scott E.; Gerbi, Christopher C.; Beane, Rachel J.; West, David P.

    2016-07-01

    Microstructural investigations were carried out on quartz veins in schist, protomylonite, and mylonite samples from an ancient seismogenic strike-slip shear zone (Sandhill Corner shear zone, Norumbega fault system, Maine, USA). We interpret complexities in the microstructural record to show that: (1) pre-existing crystallographic preferred orientations (CPO) in the host rock may persist in the new CPO patterns of the shear zone and (2) the inner and outer parts of the shear zone followed diverging paths of fabric development. The host rocks bounding the shear zone contain asymmetrically-folded quartz veins with a strong CPO. These veins are increasingly deformed and recrystallized with proximity to the shear zone core. Matrix-accommodated rotation and recrystallization may position an inherited c-axis maximum in an orientation coincident with rhomb < a > or basal < a > slip. This inherited CPO likely persists in the shear zone fabric as a higher concentration of poles in one hemisphere of the c-axis pole figure, leading to asymmetric crossed girdle or paired maxima c-axis patterns about the foliation plane. Three observed quartz grain types indicate a general trend of localization with decreasing temperature: (1) large (> 100 μm), low aspect ratio (<~5) and (2) high aspect ratio (~ 5-20) grains overprinted by (3) smaller (<~80 μm), low aspect ratio (<~4) grains through subgrain rotation-dominated recrystallization. In the outer shear zone, subgrain rotation recrystallization led to a well-developed c-axis crossed girdle pattern. In the inner shear zone, the larger grains are completely overprinted by smaller grains, but the CPO patterns are relatively poorly developed and are associated with distinctively different misorientation angle histogram profiles ("flat" neighbor-pair profile with similar number fraction for angles from 10 to 90°). This may reflect the preferential activation of grain size sensitive deformation processes in the inner-most part of the

  6. The pressor effect of NO synthase inhibition correlates to pre-existing systolic BP in the rat.

    PubMed

    Elayan, Hamzeh H; Kennedy, Brian P; Ziegler, Michael G

    2002-01-10

    A number of studies have found that the vasopressor effect of nitric oxide (NO) synthase inhibition is small following treatment with hypotensive agents but is enhanced after hypertensive agents, and have implicated NO in the mechanism of action of these drugs. We investigated the hypothesis that the rate of vascular NO synthesis is directly related to blood pressure. The vasopressor effect of 10 mg/kg of L-nitro-L-arginine methyl ester (L-NAME) was studied in relation to changes in BP induced by a variety of treatments in both pentobarbital sodium anesthetized and pithed rats. BP reductions were induced by blood withdrawal, surgery and pithing. BP increases were made by injecting 10 and 15 microg/kg boluses of phenylephrine or by injecting 5% albumin solution. Pithing decreased baseline BP and attenuated the vasopressor effect of L-NAME while phenylephrine increased both BP levels and the hypertensive effect of L-NAME. Volume expansion with 5% albumin solution increased both BP and the vasopressor effect of L-NAME. Both surgery (abdominal incision) and withdrawal of 1 ml blood reduced BP and attenuated the pressor effect of L-NAME. When the results of all these studies were combined, systolic BP was found to correlate strongly with the vasopressor effect of L-NAME (R2 = 0.73, P < 0.0001). Diastolic BP correlated less well with L-NAME (R2 = 0.36, P < 0.0003). The results suggest that shear stress generated by blood flow during the systole releases NO, and lowers BP. The pressor effect of NO synthase inhibition is closely related to pre-existing systolic BP. PMID:11871783

  7. Pre-existing adversity, level of child protection involvement, and school attendance predict educational outcomes in a longitudinal study.

    PubMed

    Maclean, Miriam J; Taylor, Catherine L; O'Donnell, Melissa

    2016-01-01

    Maltreatment largely occurs in a multiple-risk context. The few large studies adjusting for confounding factors have raised doubts about whether low educational achievement results from maltreatment or co-occurring risk factors. This study examined prevalence, risk and protective factors for low educational achievement among children involved with the child protection system compared to other children. We conducted a population-based record-linkage study of children born in Western Australia who sat national Year 3 reading achievement tests between 2008 and 2010 (N=46,838). The longitudinal study linked data from the Western Australian Department of Education, Department of Child Protection and Family Support, Department of Health, and the Disability Services Commission. Children with histories of child protection involvement (unsubstantiated maltreatment reports, substantiations or out-of-home care placement) were at three-fold increased risk of low reading scores. Adjusting for socio-demographic adversity partially attenuated the increased risk, however risk remained elevated overall and for substantiated (OR=1.68) and unsubstantiated maltreatment (OR=1.55). Risk of low reading scores in the out-of-home care group was fully attenuated after adjusting for socio-demographic adversity (OR=1.16). Attendance was significantly higher in the out-of-home care group and served a protective role. Neglect, sexual abuse, and physical abuse were associated with low reading scores. Pre-existing adversity was also significantly associated with achievement. Results support policies and practices to engage children and families in regular school attendance, and highlight a need for further strategies to prevent maltreatment and disadvantage from restricting children's opportunities for success. PMID:26626345

  8. 41 CFR 105-64.208 - What special conditions apply to release of medical records?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... apply to release of medical records? 105-64.208 Section 105-64.208 Public Contracts and Property....208 What special conditions apply to release of medical records? Medical records containing... writing by you, or by your guardian or conservator. Medical records in an Official Personnel Folder...

  9. 41 CFR 105-64.208 - What special conditions apply to release of medical records?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... apply to release of medical records? 105-64.208 Section 105-64.208 Public Contracts and Property....208 What special conditions apply to release of medical records? Medical records containing... writing by you, or by your guardian or conservator. Medical records in an Official Personnel Folder...

  10. 41 CFR 105-64.208 - What special conditions apply to release of medical records?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... apply to release of medical records? 105-64.208 Section 105-64.208 Public Contracts and Property....208 What special conditions apply to release of medical records? Medical records containing... writing by you, or by your guardian or conservator. Medical records in an Official Personnel Folder...

  11. 41 CFR 105-64.208 - What special conditions apply to release of medical records?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... apply to release of medical records? 105-64.208 Section 105-64.208 Public Contracts and Property....208 What special conditions apply to release of medical records? Medical records containing... writing by you, or by your guardian or conservator. Medical records in an Official Personnel Folder...

  12. 41 CFR 105-64.208 - What special conditions apply to release of medical records?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... apply to release of medical records? 105-64.208 Section 105-64.208 Public Contracts and Property....208 What special conditions apply to release of medical records? Medical records containing... writing by you, or by your guardian or conservator. Medical records in an Official Personnel Folder...

  13. 42 CFR 410.38 - Durable medical equipment: Scope and conditions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... supporting documentation, including pertinent parts of the beneficiary's medical record (for example, history... 42 Public Health 2 2010-10-01 2010-10-01 false Durable medical equipment: Scope and conditions... HUMAN SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other...

  14. 42 CFR 484.34 - Condition of participation: Medical social services.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition of participation: Medical social services....34 Condition of participation: Medical social services. If the agency furnishes medical social services, those services are given by a qualified social worker or by a qualified social work...

  15. 42 CFR 484.34 - Condition of participation: Medical social services.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition of participation: Medical social services....34 Condition of participation: Medical social services. If the agency furnishes medical social services, those services are given by a qualified social worker or by a qualified social work...

  16. 42 CFR 484.34 - Condition of participation: Medical social services.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition of participation: Medical social services....34 Condition of participation: Medical social services. If the agency furnishes medical social services, those services are given by a qualified social worker or by a qualified social work...

  17. 42 CFR 416.47 - Condition for coverage-Medical records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Condition for coverage-Medical records. 416.47....47 Condition for coverage—Medical records. The ASC must maintain complete, comprehensive, and accurate medical records to ensure adequate patient care. (a) Standard: Organization. The ASC must...

  18. 42 CFR 416.47 - Condition for coverage-Medical records.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Condition for coverage-Medical records. 416.47... Coverage § 416.47 Condition for coverage—Medical records. The ASC must maintain complete, comprehensive, and accurate medical records to ensure adequate patient care. (a) Standard: Organization. The ASC...

  19. 42 CFR 484.34 - Condition of participation: Medical social services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Medical social services....34 Condition of participation: Medical social services. If the agency furnishes medical social services, those services are given by a qualified social worker or by a qualified social work...

  20. The role of pre-existing Precambrian structures in rift evolution: The Albertine and Rhino grabens, Uganda

    NASA Astrophysics Data System (ADS)

    Katumwehe, Andrew B.; Abdelsalam, Mohamed G.; Atekwana, Estella A.

    2015-04-01

    We integrated Shuttle Radar Topography Mission (SRTM) Digital Elevation Models (DEM), airborne magnetic, radiometric and three-dimensional Full Tensor Gravity Gradiometry (3D-FTG) data to investigate the role of Precambrian structures in the evolution of the largely amagmatic Miocene-Recent aged Albertine and Rhino grabens in Uganda. These grabens represent the northern segment of the Western Branch of the East African Rift System (EARS). The two NE-trending grabens are connected by a right-stepping transfer zone and they extend within the Archean-Paleoproterozoic Northeast Congo block which represents the northeastern extension of the Congo craton. Our results show the following and highlight the importance of pre-existing structures in the evolution of continental rift systems: (1) The NE-extent of the Albertine full-graben is controlled by NE-trending Precambrian fabric and the graben terminates at its northeastern end when it encounters a multiply folded Precambrian basement terrain with poorly-developed NW-trending structural grain. Additionally, the northeastern termination of the Albertine graben coincides with the presence of NW-trending right-stepping high-density bodies within the Precambrian terrain. (2) The transfer zone between the Albertine and Rhino grabens is controlled by NE-trending Precambrian structures which might have facilitated the development of relay ramp faults. (3) Strain localization within the better-developed southeastern border fault of the Rhino half-graben is facilitated by the presence of Precambrian structures better aligned in a NE-direction in the southeastern part of the basin compared to its northwestern part. (4) Further to the northeast, the Rhino graben is segmented and transitions into a narrower ENE-trending half-graben with a better-developed border fault on its northwestern side. This segmentation coincides with the presence of N-trending Precambrian structures. (5) The Rhino graben terminates farther northeast against

  1. Effects of Mining-Induced Stress Perturbations on Pre-Existing Faults Near a Deep South African Gold Mine

    NASA Astrophysics Data System (ADS)

    Lucier, A. M.; Heesakkers, V.; Zoback, M. D.; Reches, Z.

    2007-12-01

    For over a century, mining-induced earthquakes have been recorded in the deep underground mining region of Witwatersrand Basin in South Africa. The TauTona gold mine experiences an appreciable number of mining- induced earthquakes and is the site of the Natural Earthquake Laboratory in South African Mines (NELSAM) project. In this work, we constrain the virgin (i.e. unperturbed) state of stress near the TauTona gold mine using an iterative forward modeling approach that combines observations of drilling induced borehole failures in borehole images, boundary element modeling of the mining-induced stress perturbations, and forward modeling of borehole failures based on the results of the boundary element modeling. We find that the state of stress is a normal faulting regime with principal stress orientations that are slightly deviated from vertical and horizontal and therefore denoted with a (*). The maximum principal stress, Sv*, is deviated 0° to 20° from vertical towards the NNW and has a magnitude gradient of 27 ± 0.3 MPa/km. The intermediate principal stress, SHmax*, is inclined 0° to 20° from horizontal with an azimuth of 145° to 168° and has a magnitude gradient of 21.5 to 26 MPa/km. The least principal stress, Shmin*, is inclined 0° to 10° from horizontal with an azimuth of 235° to 258° and has a magnitude gradient of 13 to 15.5 MPa/km. Using this constrained stress state, we investigate the likelihood of faulting to occur both on pre-existing fault planes that are optimally-oriented to the virgin stress state and on faults affected by the mining-perturbed stress field, the latter of which is calculated with boundary element modeling. The far-field stress state indicates that the crust is in a state of frictional faulting equilibrium, such that normal faulting is likely to occur on faults striking SSE and NNW and have a dip angle of approximately 45° to 80°. The mining-induced stress perturbation affects faults relatively closer to the mining

  2. The impact of pre-existing antibody on subsequent immune responses to meningococcal A-containing vaccines.

    PubMed

    Idoko, Olubukola T; Okolo, Seline N; Plikaytis, Brian; Akinsola, Adebayo; Viviani, Simonetta; Borrow, Ray; Carlone, George; Findlow, Helen; Elie, Cheryl; Kulkarni, Prasad S; Preziosi, Marie-Pierre; Ota, Martin; Kampmann, Beate

    2014-07-16

    -vaccination titers attained ≥4-fold responses as compared to 76% with high titers where study vaccine was received. Our data confirm the presence of high pre-vaccination Men A antibody concentrations/titers within the African meningitis belt, with significantly higher concentrations in older individuals. Although all participants had significant increase in antibody levels following vaccination, the four-fold or greater response in antibody titers were significantly higher in individuals with lower pre-existing antibody titers, especially after receiving PsA-TT. This finding may have some implications for vaccination strategies adopted in the future. PMID:24863486

  3. Influence of pre-existing inflammation on the outcome of acute coronary syndrome: a cross-sectional study

    PubMed Central

    Odeberg, Jacob; Freitag, Michael; Forssell, Henrik; Vaara, Ivar; Persson, Marie-Louise; Odeberg, Håkan; Halling, Anders; Råstam, Lennart; Lindblad, Ulf

    2016-01-01

    Objectives Inflammation is a well-established risk factor for the development of coronary artery disease (CAD) and acute coronary syndrome (ACS). However, less is known about its influence on the outcome of ACS. The aim of this study was to determine if blood biomarkers of inflammation were associated specifically with acute myocardial infarction (MI) or unstable angina (UA) in patients with ACS. Design Cross-sectional study. Setting Patients admitted to the coronary care unit, via the emergency room, at a central county hospital over a 4-year period (1992–1996). Participants In a substudy of Carlscrona Heart Attack Prognosis Study (CHAPS) of 5292 patients admitted to the coronary care unit, we identified 908 patients aged 30–74 years, who at discharge had received the diagnosis of either MI (527) or UA (381). Main outcome measures MI or UA, based on the diagnosis set at discharge from hospital. Results When adjusted for smoking, age, sex and duration of chest pain, concentrations of plasma biomarkers of inflammation (high-sensitivity C reactive protein>2 mg/L (OR=1.40 (1.00 to 1.96) and fibrinogen (p for trend=0.035)) analysed at admission were found to be associated with MI over UA, in an event of ACS. A strong significant association with MI over UA was found for blood cell markers of inflammation, that is, counts of neutrophils (p for trend<0.001), monocytes (p for trend<0.001) and thrombocytes (p for trend=0.021), while lymphocyte count showed no association. Interestingly, eosinophil count (p for trend=0.003) was found to be significantly lower in patients with MI compared to those with UA. Conclusions Our results show that, in patients with ACS, the blood cell profile and degree of inflammation at admission was associated with the outcome. Furthermore, our data suggest that a pre-existing low-grade inflammation may dispose towards MI over UA. PMID:26758266

  4. 42 CFR 482.22 - Condition of participation: Medical staff.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... medical staff must be composed of doctors of medicine or osteopathy and, in accordance with State law, may... the committee must be doctors of medicine or osteopathy. (3) The responsibility for organization and conduct of the medical staff must be assigned only to an individual doctor of medicine or osteopathy...

  5. 42 CFR 482.22 - Condition of participation: Medical staff.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... to medical staff. The medical staff must include doctors of medicine or osteopathy. In accordance... majority of the members of the committee must be doctors of medicine or osteopathy. (3) The responsibility...) An individual doctor of medicine or osteopathy. (ii) A doctor of dental surgery or dental...

  6. 42 CFR 482.22 - Condition of participation: Medical staff.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... appointment to medical staff. The medical staff must be composed of doctors of medicine or osteopathy. In... the committee must be doctors of medicine or osteopathy. (3) The responsibility for organization and... medicine or osteopathy. (ii) A doctor of dental surgery or dental medicine, when permitted by State law...

  7. 14 CFR 67.213 - General medical condition.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other... exercise the privileges of the airman certificate applied for or held; or (2) May reasonably be expected... unable to perform those duties or exercise those privileges. (c) No medication or other treatment...

  8. 14 CFR 67.113 - General medical condition.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other... exercise the privileges of the airman certificate applied for or held; or (2) May reasonably be expected... unable to perform those duties or exercise those privileges. (c) No medication or other treatment...

  9. 14 CFR 67.313 - General medical condition.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... established medical history or clinical diagnosis of diabetes mellitus that requires insulin or any other... exercise the privileges of the airman certificate applied for or held; or (2) May reasonably be expected... unable to perform those duties or exercise those privileges. (c) No medication or other treatment...

  10. Influence of pre-existing invasive aspergillosis on allo-HSCT outcome: a retrospective EBMT analysis by the Infectious Diseases and Acute Leukemia Working Parties.

    PubMed

    Penack, O; Tridello, G; Hoek, J; Socié, G; Blaise, D; Passweg, J; Chevallier, P; Craddock, C; Milpied, N; Veelken, H; Maertens, J; Ljungman, P; Cornelissen, J; Thiebaut-Bertrand, A; Lioure, B; Michallet, M; Iacobelli, S; Nagler, A; Mohty, M; Cesaro, S

    2016-03-01

    Historically, invasive aspergillosis (IA) has been a major barrier for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The influence of invasive IA on long-term survival and on transplant-related complications has not been investigated in a larger patient cohort under current conditions. Our aim was to analyze the long-term outcome of patients undergoing allo-HSCT with a history of prior IA. We used European Society for Blood and Marrow Transplantation database data of first allo-HSCTs performed between 2005 and 2010 in patients with acute leukemia. One thousand one hundred and fifty patients with data on IA before allo-HSCT were included in the analysis. The median follow-up time was 52.1 months. We found no significant impact of IA on major transplant outcome variables such as overall survival, relapse-free survival, non-relapse mortality, cumulative incidence of acute GvHD grade II-IV, chronic GvHD, pulmonary complications and leukemia relapse. However, we found a trend toward lower overall survival (P=0.078, hazard ratio (HR) (95% confidence interval (CI)): 1.16 (0.98, 1.36)) and higher non-relapse mortality (P=0.150, HR (95% CI): 1.19 (0.94, 1.50)) in allo-HSCT recipients with pre-existing IA. Our data suggest that a history of IA should not generally be a contraindication when considering the performance of allo-HSCT in patients with acute leukemia. PMID:26501769

  11. Effect of the pre-existing carbides on the grain boundary network during grain boundary engineering in a nickel based alloy

    SciTech Connect

    Liu, Tingguang; Xia, Shuang; Li, Hui; Zhou, Bangxin; Bai, Qin

    2014-05-01

    Grain boundary engineering was carried out on an aging-treated nickel based Alloy 690, which has precipitated carbides at grain boundaries. Electron backscatter diffraction technique was used to investigate the grain boundary networks. Results show that, compared with the solution-annealed samples, the aging-treated samples with pre-existing carbides at grain boundaries need longer duration or higher temperature during annealing after low-strain tensile deformation for forming high proportion of low-Σ coincidence site lattice grain boundaries (more than 75%). The reason is that the primary recrystallization is inhibited or retarded owing to that the pre-existing carbides are barriers to grain boundaries migration. - Highlights: • Study of GBE as function of pre-existing GB carbides, tensile strain and annealing • Recrystallization of GBE is inhibited or retarded by the pre-existing carbides. • Retained carbides after annealing show the original GB positions. • More than 80% of special GBs were formed after the modification of GBE processing. • Multiple twinning during recrystallization is the key process of GBE.

  12. 43 CFR 404.53 - Does this rule provide authority for the transfer of pre-existing facilities from Federal to...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Does this rule provide authority for the transfer of pre-existing facilities from Federal to private ownership, or from private to Federal ownership? 404.53 Section 404.53 Public Lands: Interior Regulations Relating to Public Lands BUREAU...

  13. 43 CFR 404.53 - Does this rule provide authority for the transfer of pre-existing facilities from Federal to...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Does this rule provide authority for the transfer of pre-existing facilities from Federal to private ownership, or from private to Federal ownership? 404.53 Section 404.53 Public Lands: Interior Regulations Relating to Public Lands BUREAU...

  14. 43 CFR 404.53 - Does this rule provide authority for the transfer of pre-existing facilities from Federal to...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Does this rule provide authority for the transfer of pre-existing facilities from Federal to private ownership, or from private to Federal ownership? 404.53 Section 404.53 Public Lands: Interior Regulations Relating to Public Lands BUREAU...

  15. 43 CFR 404.53 - Does this rule provide authority for the transfer of pre-existing facilities from Federal to...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Does this rule provide authority for the transfer of pre-existing facilities from Federal to private ownership, or from private to Federal ownership? 404.53 Section 404.53 Public Lands: Interior Regulations Relating to Public Lands BUREAU...

  16. A dairy-based high calcium diet improves glucose homeostasis and reduces steatosis in the context of pre-existing obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High dietary calcium (Ca) in the context of a dairy food matrix has been shown to reduce obesity development and associated inflammation in diet-induced obese (DIO) rodents. The influence of Ca and dairy on these phenotypes in the context of pre-existing obesity is not known. Furthermore, interpre...

  17. An immunoinhibition approach to overcome the impact of pre-existing antibodies on cut point establishment for immunogenicity assessment of moxetumomab pasudotox.

    PubMed

    Schneider, Amy K; Vainshtein, Inna; Roskos, Lorin K; Chavez, Carlos; Sun, Bo; Liang, Meina

    2016-08-01

    Immunogenicity can impact PK, PD, efficacy and safety of biopharmaceuticals, and is often evaluated as a secondary objective in clinical studies. Methods to detect anti-drug antibodies (ADA) and neutralizing ADA (NAb) are semi-quantitative and utilize cut points to determine positive or negative samples. Assay cut points are established by the statistical analysis of treatment-naïve subject specimens that are assumed ADA and NAb-negative. Pre-existing antibodies to various biopharmaceuticals have been observed in treatment-naïve subjects and may artificially elevate the cut point, resulting in compromised assay sensitivities, inaccuracy in immunogenicity reporting and ultimately misleading assessment of the impact of immunogenicity on clinical outcomes. Although several approaches such as removal of pre-existing antibody samples or increasing the sample dilution could be used for cut point establishment to mitigate impact of pre-existing antibodies, they each have limitations, especially when a high prevalence of pre-existing antibodies is observed. Here we describe an innovative approach used to establish cut points for ADA and NAb assays of moxetumomab pasudotox (moxetumomab), a recombinant anti-CD22 immunotoxin, to which a high prevalence of pre-existing antibodies was observed. In order to overcome the challenges associated with this high prevalence and prevent establishment of an artificially elevated cut point, we developed an immunoinhibition approach that allowed generation of pseudo ADA and NAb-negative populations for cut point determination. Immunoinhibition was performed by adding excess moxetumomab (for ADA) or a non-CD22 binding PE38-containing immunotoxin, CAT-5001 (for NAb), to treatment-naive samples prior to evaluating samples for cut point establishment. This approach successfully eliminated pre-existing antibody activity in treatment-naive samples, enabling establishment of more accurate ADA and NAb assay cut points. A comparative analysis of

  18. Medical issues associated with commercial flights.

    PubMed

    Silverman, Danielle; Gendreau, Mark

    2009-06-13

    Almost 2 billion people travel aboard commercial airlines every year. Health-care providers and travellers need to be aware of the potential health risks associated with air travel. Environmental and physiological changes that occur during routine commercial flights lead to mild hypoxia and gas expansion, which can exacerbate chronic medical conditions or incite acute in-flight medical events. The association between venous thromboembolism and long-haul flights, cosmic-radiation exposure, jet lag, and cabin-air quality are growing health-care issues associated with air travel. In-flight medical events are increasingly frequent because a growing number of individuals with pre-existing medical conditions travel by air. Resources including basic and advanced medical kits, automated external defibrillators, and telemedical ground support are available onboard to assist flight crew and volunteering physicians in the management of in-flight medical emergencies. PMID:19232708

  19. Quantifying remobilization of pre-existing nitrogen from cuttings to new growth of woody plants using 15N at natural abundance

    PubMed Central

    2013-01-01

    Background For measurements of nitrogen isotope composition at natural abundance, carry-over of pre-existing nitrogen remobilized to new plant growth can cause deviation of measured isotope composition (δ15N) from the δ15Nof newly acquired nitrogen. To account for this problem, a two-step approach was proposed to quantify and correct for remobilized nitrogen from vegetative cuttings of Populus balsamifera L. grown with either nitrate (δ15N = 58.5‰) or ammonium (δ15N = −0.96‰). First, the fraction of carry-over nitrogen remaining in the cutting was estimated by isotope mass balance. Then measured δ15N values were adjusted for the fraction of pre-existing nitrogen remobilized to the plant. Results Mean plant δ15N prior to correction was 49‰ and −5.8‰ under nitrate and ammonium, respectively. Plant δ15N was non-linearly correlated to biomass (r2 = 0.331 and 0.249 for nitrate and ammonium, respectively; P < 0.05) where the δ15N of plants with low biomass approached the δ15N of the pre-existing nitrogen. Approximately 50% of cutting nitrogen was not remobilized, irrespective of size. The proportion of carry-over nitrogen in new growth was not different between sources but ranged from less than 1% to 21% and was dependent on plant biomass and, to a lesser degree, the size of the cutting. The δ15N of newly acquired nitrogen averaged 52.7‰ and −6.4‰ for nitrate and ammonium-grown plants, respectively; both lower than their source values, as expected. Since there was a greater difference in δ15N between the carried-over pre-existing and newly assimilated nitrogen where nitrate was the source, the difference between measured δ15N and adjusted δ15N was also greater. There was no significant relationship between biomass and plant δ15N with either ammonium or nitrate after adjusting for carry-over nitrogen. Conclusion Here, we provide evidence of remobilized pre-existing nitrogen influencing δ15N of new growth of P. balsamifera L

  20. The Role of Pre-Existing Diabetes Mellitus on Hepatocellular Carcinoma Occurrence and Prognosis: A Meta-Analysis of Prospective Cohort Studies

    PubMed Central

    Bray, Freddie; Gao, Shan; Gao, Jing; Li, Hong-Lan; Xiang, Yong-Bing

    2011-01-01

    Background The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis. Methods We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models. Results The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15–2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39–2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13–1.48) risk of death from all-causes and 91% increased (95%CI: 1.41–2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12–3.33) compared with non-diabetic patients. Conclusion The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes

  1. 42 CFR 482.22 - Condition of participation: Medical staff.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Section 482.22 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... staff that operates under bylaws approved by the governing body and is responsible for the quality of... also be composed of other practitioners appointed by the governing body. (1) The medical staff...

  2. Archean tonalites are not derived by melting of hot subducted slabs: They are produced by differentiation of mafic, hydrous magmas and melting of pre-existing crust

    NASA Astrophysics Data System (ADS)

    Grove, T. L.; Bowring, S. A.

    2001-05-01

    Slab melting in a subduction zone has been called upon to produce high-MgO, high- silica magmas known as adakites (EOS, 2001, 82: 65-69). Adakites are rare, volumetrically minor in subduction zone settings, and appear to be associated with subduction of young, "hot" oceanic crust which is inferred to be easier to melt. These conditions are often hypothesized to have been more common in the Archean, resulting in the gregarious tonalite-trondjhemite-granite (TTG) suites thought to characterize Archean cratons. There are at least two difficulties with this hypothesis. 1) Most Archean TTGs are not compositionally similar to adakites. Although the Archean TTGs share some trace element characteristics (e.g. high Sr and low Y), they do not have the high magnesium contents that are a distinctive hallmark of adakites. The important major element characteristics of Archean TTGs are strikingly similar to modern silica-rich igneous rocks that formed through a combination of complex petrologic processes that include: fractionation of more mafic subduction-related basalts, re-melting of underplated basalt in the lower crust (+/- garnet-bearing amphibolites), and melting and assimilation of pre-existing crustal rocks. In arc settings, these processes all occur within the overriding plate, not in the subducted slab. 2) Adakites are not produced by hot slab melting, but by wet slab fluid loss or low extents of water-saturated melting. Experimental calibration of the melting conditions that formed primitive adakite magmas at Mt. Shasta, California indicate that mantle melting occurs when a water-rich fluid component released from the cooler slab encounters hotter overlying mantle at the base of the mantle wedge and melts at the vapor-saturated solidus. Melting continues as the hydrous mantle melts ascends into hotter, shallower mantle wedge, and a cool, hydrous magma is separated at the top of the wedge and delivered to the crust. Thus, the major element and trace-element signatures

  3. Medical conditions affecting well-accommodated travelers in Lebanon.

    PubMed

    Saab, Bassem; Musharrafieh, Umayya

    2005-01-01

    There are no data on the prevalence of common diseases affecting travelers to Lebanon. Between 2001 and 2002, one among nine physicians was consulted on guests who needed medical attention in a five-star Beirut hotel. Physicians were consulted 114 times. The mean age of the patients was 36.6 years. Gastroenteritis (50.9%) followed by respiratory problems (25.4%) were the leading causes for consultation. PMID:15996447

  4. The 3D Numerical Simulation for the Propagation Process of Multiple Pre-existing Flaws in Rock-Like Materials Subjected to Biaxial Compressive Loads

    NASA Astrophysics Data System (ADS)

    Bi, J.; Zhou, X. P.; Qian, Q. H.

    2016-05-01

    General particle dynamics (GPD), which is a novel meshless numerical method, is proposed to simulate the initiation, propagation and coalescence of 3D pre-existing penetrating and embedded flaws under biaxial compression. The failure process for rock-like materials subjected to biaxial compressive loads is investigated using the numerical code GPD3D. Moreover, internal crack evolution processes are successfully simulated using GPD3D. With increasing lateral stress, the secondary cracks keep growing in the samples, while the growth of the wing cracks is restrained. The samples are mainly split into fragments in a shear failure mode under biaxial compression, which is different from the splitting failure of the samples subjected to uniaxial compression. For specimens with macroscopic pre-existing flaws, the simulated types of cracks, the simulated coalescence types and the simulated failure modes are in good agreement with the experimental results.

  5. Chronic medical conditions among jail detainees in residential psychiatric treatment: a latent class analysis.

    PubMed

    Swartz, James A

    2011-08-01

    Studies of incarcerates with serious mental illnesses have found elevated rates of chronic medical conditions such as asthma and diabetes, and of infectious diseases such as tuberculosis compared with general population rates. This study explored the pattern of chronic medical conditions in a sample of adult detainees in psychiatric treatment in a large urban jail to develop a clinical profile encompassing the full range of medical conditions. A total of 431 male and female detainees were sampled with certainty from admissions to a residential psychiatric treatment program (overall recruitment rate = 67%). Interviews used the World Mental Health version of the Composite International Diagnostic Interview to assess psychiatric and substance use disorders per DSM-IV criteria and chronic medical conditions. Latent class analysis was conducted using 17 medical conditions as class indicators, yielding a 3-class model composed of: a latent class with a high to intermediate probability of multiple medical conditions (HMC; 12.5% of the sample); an intermediate class with a lower probability of having a smaller number of medical conditions (MMC; 43.2%); and a class with a low probability of any medical condition (44.3%). Those in the HMC class were more likely to report respiratory problems, severe headaches, musculoskeletal pain, hypertension, and arthritis, have greater functional impairment, and have a higher number of co-occurring psychiatric disorders. Being older (50+ years) and female were associated with higher odds of being in the HMC or MMC classes. The policy implications for providing medical care to incarcerates with complex mixtures of medical conditions and psychiatric disorders are considered. PMID:21394659

  6. Adherence to medication regimens among low-income patients with multiple comorbid chronic conditions.

    PubMed

    Mishra, Shiraz I; Gioia, Deborah; Childress, Saltanat; Barnet, Beth; Webster, Ramothea L

    2011-11-01

    This qualitative study sought to explore facilitators and barriers to adherence to multiple medications among low-income patients with comorbid chronic physical and mental health conditions. The 50 focus group participants identified personal/contextual and health system factors as major impediments to adherence to multiple medications. These factors included medication side effects, fear of harm from medication, fear of dependence on medication, complex instructions, suboptimal communications with doctor, suspicion about doctors' and pharmaceutical companies' motives in prescribing medication, and the high cost ofmedications. Participants also identified motivators, both internal (self-initiated) and external (initiated by family, doctor, support groups),to ensure adherence to multiple medications. These motivators included self-discipline, sense of personal responsibility, faith, support from family members and doctors, and focused health education and self-management support. Three themes emerged that enhanced understanding of the complexity of adherence to multiple medications: (1) reaching one's own threshold for medication adherence, (2) lack of shared information and decision making, and (3) taking less than the prescribed medication. Further analysis of the data revealed that the patients perceived a lack of shared decision making in the management of their comorbid chronic conditions and their medication regimen. PMID:22308877

  7. A Comparison of Expedition Medical Condition List Treatment Directives with Integrated Medical Model Simulation Data Presentation and Briefing Report

    NASA Technical Reports Server (NTRS)

    Lewis, Robert

    2013-01-01

    This aerospace medicine clerkship project is under the direction of Dr. Sharmila Watkins and is in cooperation with Dr. Eric Kerstman and Dr. Ronak Shah. The questions of the research project are: 1. What are the main drivers of evacuation and loss of crew life (LOCL) on three Design Reference Missions (DRMs): Near Earth Asteroid (NEA), Lunar Sortie and Lunar Outpost using an inexhaustible International Space Station medical kit 2. What are the treatment designations for these driving medical conditions as listed in Expedition Medical Condition List (EMCL) 3. Do the drivers make sense in the context of the given Design Reference Mission (DRM) 4. Do any EMCL treatment designations need re-assessing.

  8. Tests and Medical Conditions Associated with Dementia Diagnosis

    ERIC Educational Resources Information Center

    Burt, Diana B.; Primeaux-Hart, Sharon; Loveland, Katherine A.; Cleveland, Lynne A.; Lewis, Kay R.; Lesser, Jary; Pearson, Pamela L.

    2005-01-01

    Diagnosis of dementia in adults with intellectual disabilities requires documentation of clinically significant declines in memory and other cognitive skills, as well as changes in everyday and emotional functioning. To improve diagnostic accuracy in adults with Down syndrome, the authors examined conditions often associated with dementia, as well…

  9. The Prevalence of Medical Conditions Among U.S. Chinese Community-Dwelling Older Adults

    PubMed Central

    Chen, Ruijia; Simon, Melissa A.

    2014-01-01

    Background. The burden of medical conditions is increasing among U.S. older adults, yet we have very limited knowledge about medical conditions among Chinese older adults in the United States. This study aimed to examine the prevalence of medical conditions and its sociodemographic and health-related correlates within the context of a population-based cohort study of U.S. Chinese older adults. Method. Using a community-based participatory research approach, community-dwelling Chinese older adults aged 60 years and older in the Greater Chicago area were interviewed between 2011 and 2013. Results. Of the 3,159 participants interviewed, 58.9% were female and the mean age was 72.8 years. In total, 84.3% of older adults had one or more medical condition, 24.6% reported two conditions, 19.5% had three conditions, and 17.0% reported four or more conditions. A sizeable percentage of older adults had never been screened for dyslipidemia (24.4%) or had never been screened for diabetes mellitus (35.7%).For those who reported high cholesterol, 73.0% were taking medications when compared with 76.1% of those who reported having diabetes and 88.3% of those who reported having high blood pressure. Various sociodemographic and health-related characteristics were correlated with medical conditions. Conclusion. Medical conditions were common among U.S. Chinese older adults, yet screening and treatment rates were fairly low. Future longitudinal studies should be conducted to better understand the risk and protective factors associated with medical conditions. PMID:25378445

  10. Advancing medical-surgical nursing practice: improving management of the changing patient condition.

    PubMed

    Monroe, Heidi; Plylar, Peggy; Krugman, Mary

    2014-01-01

    Higher patient acuities and more novice nurses on medical-surgical units have Educators focused on achieving positive outcomes with changes in patient condition. An educational program was developed to enhance nurses' knowledge, skill, and confidence in assessing hemodynamics, recognizing early signs of instability, and administering vasoactive medications. The program was successful with significant knowledge improvement as well as an increased use of the Medical Emergency Team while maintaining a low number of code calls. PMID:25407973

  11. Simultaneous Bilateral Tibial Tubercle Avulsion Fracture in a case of Pre-Existing Osgood-Schlatter Disease (OSD)

    PubMed Central

    Narayana Gowda, BS; Mohan Kumar, J

    2012-01-01

    Introduction: Osgood-Schlatter disease (OSD) is a well known condition, characterized by pain over the tibial tubercle with subsequent tubercle prominence. Avulsion fracture following OSD is a rare complication. We report an unusual case of simultaneous bilateral tibial tubercle avulsion fracture in a 16 year old boy who was a known case of OSD. Case presentation: A 16 year old boy a known case of OSD presented to the outpatient department with history of jumping from the school compound wall (two feet height) while playing, followed by severe pain around anterior aspect of both knees and difficulty in walking. Radiographs showed bilateral tibial tubercle avulsion fracture. He was treated successfully with open reduction and internal fixation with tension band wiring. At the end of 22 months the patient was symptomatically relieved and both the tuberosities were united with the main bone. Conclusion: Even though bilateral Osgood-Schlatter disease (OSD) is a well known condition, one should always keep in mind the risk of tibial tubercle avulsion fractures while treating a case of OSD. Patient should be advised not to involve in strenuous activities till the disease subsides radiologically or till skeletal maturity.

  12. The Impact of Medical Conditions on the Support of Children with Profound Intellectual and Multiple Disabilities

    ERIC Educational Resources Information Center

    Zijlstra, H. P.; Vlaskamp, C.

    2005-01-01

    Background: The aim of this study was to analyse the impact of medical conditions of children with profound intellectual and multiple disabilities on the professional support they receive in centres for special education. Method: The medical files, the daily records and daily communication records between parents and professionals were reviewed…

  13. Adherence to Medication Regimens among Low-Income Patients with Multiple Comorbid Chronic Conditions

    ERIC Educational Resources Information Center

    Mishra, Shiraz I.; Gioia, Deborah; Childress, Saltanat; Barnet, Beth; Webster, Ramothea L.

    2011-01-01

    This qualitative study sought to explore facilitators and barriers to adherence to multiple medications among low-income patients with comorbid chronic physical and mental health conditions. The 50 focus group participants identified personal/contextual and health system factors as major impediments to adherence to multiple medications. These…

  14. Investigating the Influence of Pre-Existing Basement Structures on the Propagation of the Malawi Rift using SRTM, RADARSAT, and Aeromagnetic Data

    NASA Astrophysics Data System (ADS)

    Robertson, K.; Atekwana, E. A.; Abdelsalam, M. G.; Laó-Dávila, D. A.

    2015-12-01

    The Malawi rift is a Neogene, amagmatic rift located where the Western Branch of the East Africa Rift System (EARS) terminates. In more mature rifts, magmatism is frequently recognized as a driving factor in rift propagation; however, the amagmatic nature of the Malawi rift permits investigation into the relationship between pre-existing structures and current rift propagation, without the influence of magmatism. To map surface structures, we used Shuttle Radar Topography Mission (SRTM) Digital Elevation Model (DEM) and RADARSAT imagery over southern Malawi. To process the SRTM data, we applied edge enhancing filters and derivatives, and extracted topographic profiles to examine scarp height and minimum vertical exposed displacement. We mapped morphologically-defined structures by filtering the RADARSAT imagery using an enhanced lee filter to reduce noise and a Laplacian filter for edge enhancement. To examine Precambrian basement structures, we filtered aeromagnetic data using vertical and horizontal derivatives, tilt derivative, and analytic signal to create magnetic anomaly maps. Surface mapping indicated three primary trends in the southern Malawi rift: NW-SE (dominant), NE-SW, both of which are most likely the remnants of Mesozoic Karoo rifting, and a NNE-SSW trend seen in Neogene rifting. The Precambrian basement structural mapping also reveals three primary trends: WNW-ESE, NE-SW, and NW-SE. Ductile deformation causes the dominant basement fabric to change, switching polarity as the rift propagated southward from NE-SW orientation to NW-SE and WNW-ESE orientations, and back to a NE-SW orientation. In general, the surficial structures follow this trend. In some areas, however, the more recent rifting cut across pre-existing basement structures, possibly due to rheological heterogeneities or selective strain partitioning. Nonetheless, pre-existing basement structures played a critical role in strain localization and fault propagation in Malawi. However

  15. Pre-existing Epithelial Diversity in Normal Human Livers: A Tissue-tethered Cytometric Analysis in Portal/Periportal Epithelial Cells

    PubMed Central

    Isse, Kumiko; Lesniak, Andrew; Grama, Kedar; Maier, John; Specht, Susan; Castillo-Rama, Marcela; Lunz, John; Roysam, Badrinath; Michalopoulos, George; Demetris, Anthony J.

    2012-01-01

    Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BEC). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte-BEC hybrid cells appear. This has been attributed to activation and differentiation of putative hepatic progenitor cells (HPC) residing in the Canals of Hering and/or metaplasia of pre-existing mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high resolution whole slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes pre-existed in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. “Virtually digested” WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g. scatter plots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically-associated with mature epithelial forms (HNF4α for hepatocytes, CK19 and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. Results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bi-potential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC to hepatocytes, and vice versa. Conclusion Novel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable pre-existent hybrid epithelial diversity in normal human liver. This computationally-enabled tissue analysis approach offers much broader potential beyond the results presented here. PMID:23150208

  16. 42 CFR 416.47 - Condition for coverage-Medical records.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Condition for coverage-Medical records. 416.47 Section 416.47 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) AMBULATORY SURGICAL SERVICES Specific Conditions for Coverage § 416.47 Condition for...

  17. The social phobia and anxiety inventory: problem of underlying medical conditions.

    PubMed

    Klieger, Douglas M; Johnson, Heather K

    2007-12-01

    The study investigated the possibility of score inflation in the Social Phobia and Anxiety Inventory due to underlying medical conditions in respondents. The Diagnostic and Statistical Manual of Mental Disorders provides an exclusionary rule disallowing a diagnosis of social phobia when the fear is based on the presence of a medical condition. A computer-administered procedure, designed to simulate visually this paper-and-pencil inventory was created and compared to the original in a pilot study with r of .94 between the two procedures. Analysis indicates such medically based responding is common among college men and women (N= 127, M age = 19.0). Specifically, 50% of respondents reported 0 or 1 medical condition(s), while those in the fourth quartile averaged 43 medical bases for their responses. The most frequent self-reports of medical conditions were stuttering (2.8%), acne (2.4%), dry mouth (2.1%), obesity (.9%), and scars (.9%). Several possible solutions were discussed in view of the overall conclusion of a substantive basis for medical responding on this inventory. PMID:18232422

  18. Group invariant solution for a pre-existing fracture driven by a power-law fluid in impermeable rock

    NASA Astrophysics Data System (ADS)

    Fareo, A. G.; Mason, D. P.

    2013-12-01

    The effect of power-law rheology on hydraulic fracturing is investigated. The evolution of a two-dimensional fracture with non-zero initial length and driven by a power-law fluid is analyzed. Only fluid injection into the fracture is considered. The surrounding rock mass is impermeable. With the aid of lubrication theory and the PKN approximation a partial differential equation for the fracture half-width is derived. Using a linear combination of the Lie-point symmetry generators of the partial differential equation, the group invariant solution is obtained and the problem is reduced to a boundary value problem for an ordinary differential equation. Exact analytical solutions are derived for hydraulic fractures with constant volume and with constant propagation speed. The asymptotic solution near the fracture tip is found. The numerical solution for general working conditions is obtained by transforming the boundary value problem to a pair of initial value problems. Throughout the paper, hydraulic fracturing with shear thinning, Newtonian and shear thickening fluids are compared.

  19. DNase I and proteinase K impair Listeria monocytogenes biofilm formation and induce dispersal of pre-existing biofilms.

    PubMed

    Nguyen, Uyen T; Burrows, Lori L

    2014-09-18

    Current sanitation methods in the food industry are not always sufficient for prevention or dispersal of Listeria monocytogenes biofilms. Here, we determined if prevention of adherence or dispersal of existing biofilms could occur if biofilm matrix components were disrupted enzymatically. Addition of DNase during biofilm formation reduced attachment (<50% of control) to polystyrene. Treatment of established 72h biofilms with 100μg/ml of DNase for 24h induced incomplete biofilm dispersal, with <25% biofilm remaining compared to control. In contrast, addition of proteinase K completely inhibited biofilm formation, and 72h biofilms-including those grown under stimulatory conditions-were completely dispersed with 100μg/ml proteinase K. Generally-regarded-as-safe proteases bromelain and papain were less effective dispersants than proteinase K. In a time course assay, complete dispersal of L. monocytogenes biofilms from both polystyrene and type 304H food-grade stainless steel occurred within 5min at proteinase K concentrations above 25μg/ml. These data confirm that both DNA and proteins are required for L. monocytogenes biofilm development and maintenance, and that these components of the biofilm matrix can be targeted for effective prevention and removal of biofilms. PMID:25043896

  20. Phenological asynchrony between herbivorous insects and their hosts: signal of climate change or pre-existing adaptive strategy?

    PubMed Central

    Singer, Michael C.; Parmesan, Camille

    2010-01-01

    Climate change alters phenological relations between interacting species. We might expect the historical baseline, or starting-point, for such effects to be precise synchrony between the season at which a consumer most requires food and the time when its resources are most available. We synthesize evidence that synchrony was not the historical condition in two insect–plant interactions involving Edith's checkerspot butterfly (Euphydryas editha), the winter moth (Operophtera brumata) and their host plants. Initial observations of phenological mismatch in both systems were made prior to the onset of anthropogenically driven climate change. Neither species can detect the phenology of its host plants with precision. In both species, evolution of life history has involved compromise between maximizing fecundity and minimizing mortality, with the outcome being superficially maladaptive strategies in which many, or even most, individuals die of starvation through poor synchrony with their host plants. Where phenological asynchrony or mismatch with resources forms the starting point for effects of anthropogenic global warming, consumers are particularly vulnerable to impacts that exacerbate the mismatch. This vulnerability likely contributed to extinction of a well-studied metapopulation of Edith's checkerspot, and to the skewed geographical pattern of population extinctions underlying a northward and upward range shift in this species. PMID:20819810

  1. Lipoprotein (a): impact by ethnicity and environmental and medical conditions.

    PubMed

    Enkhmaa, Byambaa; Anuurad, Erdembileg; Berglund, Lars

    2016-07-01

    Levels of lipoprotein (a) [Lp(a)], a complex between an LDL-like lipid moiety containing one copy of apoB, and apo(a), a plasminogen-derived carbohydrate-rich hydrophilic protein, are primarily genetically regulated. Although stable intra-individually, Lp(a) levels have a skewed distribution inter-individually and are strongly impacted by a size polymorphism of the LPA gene, resulting in a variable number of kringle IV (KIV) units, a key motif of apo(a). The variation in KIV units is a strong predictor of plasma Lp(a) levels resulting in stable plasma levels across the lifespan. Studies have demonstrated pronounced differences across ethnicities with regard to Lp(a) levels and some of this difference, but not all of it, can be explained by genetic variations across ethnic groups. Increasing evidence suggests that age, sex, and hormonal impact may have a modest modulatory influence on Lp(a) levels. Among clinical conditions, Lp(a) levels are reported to be affected by kidney and liver diseases. PMID:26637279

  2. C/EBPα Activates Pre-existing and De Novo Macrophage Enhancers during Induced Pre-B Cell Transdifferentiation and Myelopoiesis.

    PubMed

    van Oevelen, Chris; Collombet, Samuel; Vicent, Guillermo; Hoogenkamp, Maarten; Lepoivre, Cyrille; Badeaux, Aimee; Bussmann, Lars; Sardina, Jose Luis; Thieffry, Denis; Beato, Miguel; Shi, Yang; Bonifer, Constanze; Graf, Thomas

    2015-08-11

    Transcription-factor-induced somatic cell conversions are highly relevant for both basic and clinical research yet their mechanism is not fully understood and it is unclear whether they reflect normal differentiation processes. Here we show that during pre-B-cell-to-macrophage transdifferentiation, C/EBPα binds to two types of myeloid enhancers in B cells: pre-existing enhancers that are bound by PU.1, providing a platform for incoming C/EBPα; and de novo enhancers that are targeted by C/EBPα, acting as a pioneer factor for subsequent binding by PU.1. The order of factor binding dictates the upregulation kinetics of nearby genes. Pre-existing enhancers are broadly active throughout the hematopoietic lineage tree, including B cells. In contrast, de novo enhancers are silent in most cell types except in myeloid cells where they become activated by C/EBP factors. Our data suggest that C/EBPα recapitulates physiological developmental processes by short-circuiting two macrophage enhancer pathways in pre-B cells. PMID:26235892

  3. Pre-existing CD19-independent GL7(-) Breg cells are expanded during inflammation and in mice with lupus-like disease.

    PubMed

    Wang, Xiaoqian; Wei, Yinxiang; Xiao, He; Liu, Xiaoling; Zhang, Yu; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Zhang, Li; Ma, Ning; Shen, Beifen; Li, Yan; Egwuagu, Charles E; Wang, Renxi

    2016-03-01

    Interleukin 10 (IL-10)-producing regulatory B-cells (Bregs) suppress inflammatory responses that mediate autoimmune diseases. However, it is unknown whether Bregs derive from a pre-existing dedicated B-cell lineage or if any B-cell can differentiate into Bregs in response to BCR or TLR activation. GL7(+) B-cells are antigen-experienced differentiated B-cells while GL7(-/lo) are at an early stage of B-cell differentiation. While both GL7(-/lo) and GL7(+) B cells can produce IL-10, differentiation of GL7(-) B-cells into Bregs does not require CD19- or Bcl6-induced signals, suggesting that BCR-induced proliferation or Ig class-switching is not necessary for generation of Breg cells. Of particular importance, we show that GL7(-) Breg cells are dramatically expanded in lupus-like mice and GL7(-) Bregs suppressed inflammatory responses in lupus-like mice by inducing expansion of Foxp3(+)Treg cells. Taken together, these results suggest that pre-existing GL7(-)IL-10(+) cells are expanded during inflammation, differentiate into GL7(+) Bregs and contribute to immune-regulation in lupus-like mice. PMID:26852110

  4. Lack of efficacy of pre bronchoscopy inhaled salbutamol on symptoms and lung functions in patients with pre-existing airway obstruction

    PubMed Central

    Mohan, Anant; Momin, Indrajit; Poulose, Rosemary; Mohan, Charu; Madan, Karan; Hadda, Vijay; Guleria, Randeep; Pandey, RM

    2016-01-01

    Background: Fiberoptic bronchoscopy (FOB) may exaggerate symptoms and lung functions in patients with pre-existing airway obstruction. Interventions which can alleviate or minimize this procedure-related bronchospasm, especially in this high-risk group are, therefore, required. Methods: A double-blinded randomized controlled trial was conducted to evaluate the efficacy of 400 μg of inhaled salbutamol on patients with spirometric evidence of airflow obstruction planned for FOB. Patient's dyspnea, procedure tolerability, and change in spirometry were assessed before and after the procedure. Results: A total of 50 patients were enrolled (78% males), with a mean (standard deviation) age of 49.8 (6.2) years. There was a significant fall in % predicted FEV1 within each group compared to their respective pre-bronchoscopy values. However, no significant difference in the % predicted or absolute FEV1 level was observed between the two groups. Similarly, although both groups experienced increased dyspnea immediately following FOB, this difference was not significant between the two groups either on the Borg or visual analog scale scales. Pre-FOB anxiety levels and the tolerability of the procedure as assessed by the bronchoscopist were similar in both groups. Conclusion: FOB in patients with pre-existing airway obstruction aggravates cough and dyspnea, with a concomitant decline in FEV1 and FVC. The administration of pre-FOB inhaled salbutamol does not have any significant beneficial effect on procedure-related outcomes. PMID:27578926

  5. Reduction in Noise-Induced Functional Loss of the Cochleae in Mice with Pre-Existing Cochlear Dysfunction Due to Genetic Interference of Prestin

    PubMed Central

    Cai, Qunfeng; Wang, Bo; Coling, Donald; Zuo, Jian; Fang, Jie; Yang, Shiming; Vera, Krystal; Hu, Bo Hua

    2014-01-01

    Various cochlear pathologies, such as acoustic trauma, ototoxicity and age-related degeneration, cause hearing loss. These pre-existing hearing losses can alter cochlear responses to subsequent acoustic overstimulation. So far, the knowledge on the impacts of pre-existing hearing loss caused by genetic alteration of cochlear genes is limited. Prestin is the motor protein expressed exclusively in outer hair cells in the mammalian cochlea. This motor protein contributes to outer hair cell motility. At present, it is not clear how the interference of prestin function affects cochlear responses to acoustic overstimulation. To address this question, a genetic model of prestin dysfunction in mice was created by inserting an internal ribosome entry site (IRES)-CreERT2-FRT-Neo-FRT cassette into the prestin locus after the stop codon. Homozygous mice exhibit a threshold elevation of auditory brainstem responses with large individual variation. These mice also display a threshold elevation and a shift of the input/output function of the distortion product otoacoustic emission, suggesting a reduction in outer hair cell function. The disruption of prestin function reduces the threshold shifts caused by exposure to a loud noise at 120 dB (sound pressure level) for 1 h. This reduction is positively correlated with the level of pre-noise cochlear dysfunction and is accompanied by a reduced change in Cdh1 expression, suggesting a reduction in molecular responses to the acoustic overstimulation. Together, these results suggest that prestin interference reduces cochlear stress responses to acoustic overstimulation. PMID:25486270

  6. Pre-existing oblique transfer zones and transfer/transform relationships in continental margins: New insights from the southeastern Gulf of Aden, Socotra Island, Yemen

    NASA Astrophysics Data System (ADS)

    Bellahsen, N.; Leroy, S.; Autin, J.; Razin, P.; d'Acremont, E.; Sloan, H.; Pik, R.; Ahmed, A.; Khanbari, K.

    2013-11-01

    Transfer zones are ubiquitous features in continental rifts and margins, as are transform faults in oceanic lithosphere. Here, we present a structural study of the Hadibo Transfer Zone (HTZ), located in Socotra Island (Yemen) in the southeastern Gulf of Aden. There, we interpret this continental transfer fault zone to represent a reactivated pre-existing structure. Its trend is oblique to the direction of divergence and it has been active from the early up to the latest stages of rifting. One of the main oceanic fracture zones (FZ), the Hadibo-Sharbithat FZ, is aligned with and appears to be an extension of the HTZ and is probably genetically linked to it. Comparing this setting with observations from other Afro-Arabian rifts as well as with passive margins worldwide, it appears that many continental transfer zones are reactivated pre-existing structures, oblique to divergence. We therefore establish a classification system for oceanic FZ based upon their relationship with syn-rift structures. Type 1 FZ form at syn-rift structures and are late syn-rift to early syn-OCT. Type 2 FZ form during the OCT formation and Type 3 FZ form within the oceanic domain, after the oceanic spreading onset. The latter are controlled by far-field forces, magmatic processes, spreading rates, and oceanic crust rheology.

  7. 42 CFR 482.24 - Condition of participation: Medical record services.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Medical record services. 482.24 Section 482.24 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS OF PARTICIPATION FOR HOSPITALS...

  8. 42 CFR 482.61 - Condition of participation: Special medical record requirements for psychiatric hospitals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition of participation: Special medical record requirements for psychiatric hospitals. 482.61 Section 482.61 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS...

  9. 42 CFR 482.61 - Condition of participation: Special medical record requirements for psychiatric hospitals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition of participation: Special medical record requirements for psychiatric hospitals. 482.61 Section 482.61 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS...

  10. 42 CFR 482.61 - Condition of participation: Special medical record requirements for psychiatric hospitals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition of participation: Special medical record requirements for psychiatric hospitals. 482.61 Section 482.61 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS OF PARTICIPATION FOR...

  11. 42 CFR 482.61 - Condition of participation: Special medical record requirements for psychiatric hospitals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition of participation: Special medical record requirements for psychiatric hospitals. 482.61 Section 482.61 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS...

  12. If You Pop Over There: A Corpus-based Study of Conditionals in Medical Discourse.

    ERIC Educational Resources Information Center

    Ferguson, Gibson

    2001-01-01

    Focuses on if conditionals in medical discourse. Three genres are examined: research articles, journal editorials, and doctor-patient consultations. Analyzes a variety of formal, semantic, and pragmatic aspects of conditionals across genres. Concludes with brief reflections on pedagogic implications. (Author/VWL)

  13. 76 FR 15798 - Special Conditions: Boeing 747-468, Installation of a Medical Lift

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ...These special conditions are issued for the Boeing 747-468 airplane. This airplane, as modified by Jet Aviation, will have a novel or unusual design feature associated with the installation of a medical lift. The applicable airworthiness regulations do not contain adequate or appropriate safety standards for this design feature. These special conditions contain the additional safety standards......

  14. 42 CFR 482.61 - Condition of participation: Special medical record requirements for psychiatric hospitals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition of participation: Special medical record... PARTICIPATION FOR HOSPITALS Requirements for Specialty Hospitals § 482.61 Condition of participation: Special... stated by the patient and/or others significantly involved. (4) The social service records,...

  15. Efficacy of Suvaxyn CSF Marker (CP7_E2alf) in the presence of pre-existing antibodies against Bovine viral diarrhea virus type 1.

    PubMed

    Dräger, Carolin; Schröder, Charlotte; König, Patricia; Tegtmeyer, Birthe; Beer, Martin; Blome, Sandra

    2016-09-01

    Classical swine fever (CSF) is still one of the most important viral diseases of pigs worldwide and outbreaks are notifiable to the OIE. The different control options also include (emergency) vaccination, preferably with a vaccine that allows differentiation of infected from vaccinated animals (DIVA principle). Recently, the chimeric pestivirus "CP7_E2alf" (Suvaxyn® CSF Marker, Zoetis) was licensed as live attenuated marker vaccine by the European Medicines Agency (EMA). In the context of risk assessments for an emergency vaccination scenario, the question has been raised whether pre-existing anti-pestivirus antibodies, especially against the vaccine backbone Bovine viral diarrhea virus type 1 (BVDV-1), would interfere with "CP7_E2alf" vaccination and the accompanying DIVA diagnostics. To answer this question, a vaccination-challenge-trial was conducted with Suvaxyn® CSF Marker and the "gold-standard" of live-modified CSF vaccines C-strain (RIEMSER® Schweinepestvakzine) as comparator. Pre-existing antibodies against BVDV-1 were provoked in a subset of animals through intramuscular inoculation of a recent field isolate from Germany (two injections with an interval of 2weeks). Twenty-seven days after the first injection, intramuscular vaccination of pre-exposed and naïve animals with either "CP7_E2alf" or C-strain "Riems" was performed. Seven days later, all vaccinated animals and two additional controls were oro-nasally challenged with highly virulent CSF virus (CSFV) strain Koslov. It was demonstrated that pre-existing BVDV-1 antibodies do not impact on the efficacy of live attenuated vaccines against CSF. Both C-strain "Riems" and marker vaccine "CP7_E2alf" were able to confer full protection against highly virulent challenge seven days after vaccination. However, slight interference was seen with serological DIVA diagnostics accompanying the vaccination with CP7_E2alf. Amended sample preparation and combination of test systems was able to resolve most cases

  16. Effects of pre-existing ice crystals on cirrus clouds and comparison between different ice nucleation parameterizations with the Community Atmosphere Model (CAM5)

    NASA Astrophysics Data System (ADS)

    Shi, X.; Liu, X.; Zhang, K.

    2015-02-01

    In order to improve the treatment of ice nucleation in a more realistic manner in the Community Atmosphere Model version 5.3 (CAM5.3), the effects of pre-existing ice crystals on ice nucleation in cirrus clouds are considered. In addition, by considering the in-cloud variability in ice saturation ratio, homogeneous nucleation takes place spatially only in a portion of the cirrus cloud rather than in the whole area of the cirrus cloud. Compared to observations, the ice number concentrations and the probability distributions of ice number concentration are both improved with the updated treatment. The pre-existing ice crystals significantly reduce ice number concentrations in cirrus clouds, especially at mid- to high latitudes in the upper troposphere (by a factor of ~10). Furthermore, the contribution of heterogeneous ice nucleation to cirrus ice crystal number increases considerably. Besides the default ice nucleation parameterization of Liu and Penner (2005, hereafter LP) in CAM5.3, two other ice nucleation parameterizations of Barahona and Nenes (2009, hereafter BN) and Kärcher et al. (2006, hereafter KL) are implemented in CAM5.3 for the comparison. In-cloud ice crystal number concentration, percentage contribution from heterogeneous ice nucleation to total ice crystal number, and pre-existing ice effects simulated by the three ice nucleation parameterizations have similar patterns in the simulations with present-day aerosol emissions. However, the change (present-day minus pre-industrial times) in global annual mean column ice number concentration from the KL parameterization (3.24 × 106 m-2) is less than that from the LP (8.46 × 106 m-2) and BN (5.62 × 106 m-2) parameterizations. As a result, the experiment using the KL parameterization predicts a much smaller anthropogenic aerosol long-wave indirect forcing (0.24 W m-2) than that using the LP (0.46 W m-2) and BN (0.39 W m-2) parameterizations.

  17. Factors associated with a patient-centered medical home among children with behavioral health conditions.

    PubMed

    Knapp, Caprice; Woodworth, Lindsey; Fernandez-Baca, Daniel; Baron-Lee, Jacqueline; Thompson, Lindsay; Hinojosa, Melanie

    2013-11-01

    At some point in their lives, nearly one-half of all American children will have a behavioral health condition. Many will not receive the care they need from a fragmented health delivery system. The patient-centered medical home is a promising model to improve their care; however, little evidence exists. Our study aim was to examine the association between several behavioral health indicators and having a patient-centered medical home. 91,642 children's parents or guardians completed the 2007 National Survey of Children's Health. An indicator for patient-centered medical home was included in the dataset. Descriptive statistics, bivariate tests, and multivariate regression models were used in the analyses. Children in the sample were mostly Male (52 %), White (78 %), non-Hispanic (87 %), and did not have a special health care need (80 %). 6.2 % of the sample had at least one behavioral health condition. Conditions ranged from ADHD (6 %) to Autism Spectrum Disorder (ASD) (1 %). Frequency of having a patient-centered medical home also varied for children with a behavioral health condition (49 % of children with ADHD and 33 % of children with ASD). Frequency of having a patient-centered medical home decreased with multiple behavioral health conditions. Higher severity of depression, anxiety, and conduct disorder were associated with a decreased likelihood of a patient-centered medical home. Results from our study can be used to target patient-centered medical home interventions toward children with one or more behavioral health conditions and consider that children with depression, anxiety, and conduct disorder are more vulnerable to these disparities. PMID:23108741

  18. Self-Medication of Somatic and Psychiatric Conditions Using Botanical Marijuana.

    PubMed

    Osborn, Lawrence A; Lauritsen, Kirstin J; Cross, Nicole; Davis, Alan K; Rosenberg, Harold; Bonadio, Francis; Lang, Brent

    2015-01-01

    As a complement to research evaluating botanical marijuana as a medical therapy for various somatic and psychiatric conditions, there is a growing body of research assessing marijuana users' self-reports of the symptoms and conditions for which they use marijuana without a physician's recommendation. As part of two larger web-based surveys and one in-situ survey at an outdoor marijuana festival, we asked regular marijuana users if they consumed the drug without a physician's recommendation and, if so, to describe (or select from a checklist) the conditions for which they used marijuana as a medication. Participants reported using marijuana to self-medicate a wide variety of both somatic conditions (such as pain, diabetes, and irritable bowel syndrome) and psychiatric conditions (such as depression, anxiety, and insomnia). Because fewer than half of the American states, and only a few countries, allow physicians to recommend medicinal marijuana, these findings may be of interest to clinicians as they treat patients, to lawmakers and policymakers as they consider legislation allowing physicians to recommend botanical marijuana for somatic and psychiatric conditions, and to researchers evaluating conditions that individuals elect to self-medicate using botanical marijuana. PMID:26595140

  19. [The main ways of improvement of medical support of the Air Forces in modern conditions].

    PubMed

    Blaginin, A A; Grebeniuk, A N; Lizogub, I N

    2014-02-01

    Blaginin A.A., Grebenyuk A.N., Lizogub LN. - The main ways of improvement of medical support of the Air Forces in modern conditions. Aircrew conducting active hostilities suffers from the whole spectrum of factors and conditions of the combat situation. The main task for the medical service of the Air Force is to carry out preventive and curative action for aviation specialists who are responsible for the combat capability of aircraft formations. The medical service of the Air Force must have forces and facilities for planning, organization and implementation of the treatment of lightly wounded and sick aviation professionals with short periods of recovery, medical rehabilitation of aircrew qfter suffering injuries, diseases, sanatorium therapy of aircrew with partial failure of health, outpatient and inpatient medical examination aircrew - flight commissions, preventive rest of aviation specialists with symptoms of chronic fatigue. Should be trained aviation physicians, including both basic military medical education and in-depth study of the medical aspects of various fields of personnel of the Air Force. PMID:25046924

  20. Pre-existing caverns in salt formations could be the major cause of sinkhole hazards along the coast of the Dead Sea

    NASA Astrophysics Data System (ADS)

    Legchenko, A.; Ezersky, M.; Boucher, M.; Camerlynck, C.; Al-Zoubi, A.; Chalikakis, K.

    2008-10-01

    Since 1990 hundreds of sinkholes have appeared along the coast of the Dead Sea. In the literature the rapid development of sinkholes is explained as a result of a drop in the level of the Dead Sea. This model assumes very fast dissolution of large volumes of salt and the creation of new caverns that cause sinkholes in 10 to 20 years. However, the results of our geophysical study do not confirm the fast dissolution assumption. To explain the available field observations, we propose the following model: (1) slow dissolution of salt (much longer than 20 years) with the creation of caverns without development of sinkholes; (2) sinkhole development is triggered by the lowering of the groundwater level because the rocks overlying the salt formation become unsaturated; (3) the time of sinkhole appearance is controlled by the mechanical properties of the rocks that overlie pre-existing caverns.

  1. Bovine adenoviral vector-based H5N1 influenza vaccine overcomes exceptionally high levels of pre-existing immunity against human adenovirus.

    PubMed

    Singh, Neetu; Pandey, Aseem; Jayashankar, Lakshmi; Mittal, Suresh K

    2008-05-01

    Because of the high prevalence of adenovirus (Ad) infections in humans, it is believed that pre-existing Ad-neutralizing antibodies (vector immunity) may negatively impact the immune response to vaccine antigens when delivered by human Ad (HAd) vectors. In order to evaluate whether bovine Ad subtype 3 (BAd3), a non-HAd vector, can effectively elude high levels of pre-existing vector immunity, naïve and HAd serotype 5 (HAd)-primed mice were immunized with BAd-H5HA [BAd3 vector expressing the hemagglutinin (HA) gene from H5N1 influenza virus]. Even in the presence of very high levels of HAd-specific neutralizing antibody, no significant reductions in HA-specific humoral and cell-mediated immune (CMI) responses were observed in HAd-primed mice immunized with BAd-H5HA. In naïve mice immunized with HAd-H5HA (HAd5 vector expressing H5N1 HA) and boosted with BAd-H5HA, the humoral responses elicited were significantly higher (P < 0.01) than with either HAd-H5HA or BAd-H5HA alone, while the CMI responses were comparable in the groups. This finding underlines the importance of a heterologous prime-boost approach for achieving an enhanced immune response. The immunization of naïve or HAd-primed mice with BAd-H5HA bestowed full protection from morbidity and mortality following a potentially lethal challenge with A/Hong Kong/483/97. These results demonstrate the importance of BAd vectors as an alternate or supplement to HAd vectors for influenza pandemic preparedness. PMID:18301400

  2. Enhancing the performance of multi-crystalline silicon photovoltaic module by encapsulating high efficient Eu3+ complex into its pre-existing EVA layer

    NASA Astrophysics Data System (ADS)

    Wang, Tongxin; Yu, Bo; Hu, Zhijia; Wang, Xin; Zou, Gang; Zhang, Qijin

    2013-03-01

    Luminescent down shifting (LDS) technique is one effective way to improve the poor response of multi-crystalline silicon (mc-Si) photovoltaic (PV) modules at short wavelength less than 400 nm. Eu3+ complexes are effective LDS species for PV modules due to their large stokes' shift and high luminescent quantum efficiency (LQE). Although Eu3+ complexes have been utilized in PV modules as LDS species widely, they have not been encapsulated into the pre-existing poly-ethylene vinyl acetate (EVA) layer of modules between glass and solar cell by now. The aim of our work is to enhance the performance of mc-Si PV modules by encapsulating high efficient Eu3+ complexes into their pre-existing EVA layers which would not modify the well-established manufacturing process for PV modules. In this work, two Eu3+ complexes with different absorption spectrum were encapsulated into the commercial EVA layer by soaking method for the first time and used in the encapsulation of mc-Si PV modules. Hereinto, Eu(TTA)3(TPPO)2 (TTA = 2-thenoyltrifluoroacetonate, TPPO = triphenylphosphine oxide) (EuTT) with absorption spectrum less than 400 nm and high LQE (0.73) improves the external quantum efficiency of mc-Si PV module from 0.05 to 0.20, which produces a 0.42% increases in its power conversion efficiency. In addition, it is found that the enhancement brought by Eu(TTA)3(TPPO)2 can reduce cost of power generated by mc-Si devices from US1/Wp to US0.98/Wp according to the calculation. Therefore, Eu(TTA)3(TPPO)2 as LDS species with high LQE and low cost is promising for enhancing the performance of mc-Si PV modules in practical application.

  3. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses.

    PubMed

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes; Bassi, Maria Rosaria; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2012-01-01

    Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii). To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity. PMID:22514686

  4. Early colonoscopy confers survival benefits on colon cancer patients with pre-existing iron deficiency anemia: a nationwide population-based study.

    PubMed

    Teng, Chieh-Lin Jerry; Yu, Jui-Ting; Chen, Yi-Huei; Lin, Ching-Heng; Hwang, Wen-Li

    2014-01-01

    This study aimed to examine the prognostic significance of pre-existing iron deficiency anemia (IDA) and the benefits of early colonoscopy in patients with colon cancer, since these have not been clearly established to date. Using the Taiwanese National Health Insurance Research Database, we retrieved and retrospectively reviewed the records of patients aged ≥ 55 years who were diagnosed with colon cancer between 2000 and 2005. The patient cohort was divided into two groups: patients with (n = 1,260) or without (n = 15,912) an IDA diagnosis during ≤ 18 months preceding the date of colon cancer diagnosis. We found that diabetes (27.9% vs. 20.3%, p<0.0001), cardiovascular disease (61.6% vs. 54.7%, p<0.001), and chronic kidney disease (4.6% vs. 2.2%, p<0.0001) were more common among patients with IDA than among those without IDA. The median overall survival times for patients with IDA and those without IDA were 4.6 and 5.7 years, respectively (p = 0.002). Patients who underwent colonoscopy ≤ 30 days, 31-90, and ≥ 91 days after IDA diagnosis showed median overall survival times of 5.79, 4.43, and 4.04 years, respectively (p = 0.003). Delayed colonoscopy was an independent factor associated with poor overall survival (adjusted hazard ratio, 1.28; 95% confidence interval, 1.07-1.53; p = 0.01). In conclusion, colon cancer patients with IDA were more likely to experience comorbidities than were those without IDA. Pre-existing IDA was a poor prognostic factor in adult men and postmenopausal women who had colon cancer. Early colonoscopy could improve overall survival possibly by facilitating early diagnosis and treatment. PMID:24466209

  5. Effects of pre-existing anti-carrier immunity and antigenic element multiplicity on efficacy of a modular virus-like particle vaccine.

    PubMed

    Chuan, Yap P; Rivera-Hernandez, Tania; Wibowo, Nani; Connors, Natalie K; Wu, Yang; Hughes, Fiona K; Lua, Linda H L; Middelberg, Anton P J

    2013-09-01

    Modularization of a peptide antigen for presentation on a microbially synthesized murine polyomavirus (MuPyV) virus-like particle (VLP) offers a new alternative for rapid and low-cost vaccine delivery at a global scale. In this approach, heterologous modules containing peptide antigenic elements are fused to and displayed on the VLP carrier, allowing enhancement of peptide immunogenicity via ordered and densely repeated presentation of the modules. This study addresses two key engineering questions pertaining to this platform, exploring the effects of (i) pre-existing carrier-specific immunity on modular VLP vaccine effectiveness and (ii) increase in the antigenic element number per VLP on peptide-specific immune response. These effects were studied in a mouse model and with modular MuPyV VLPs presenting a group A streptococcus (GAS) peptide antigen, J8i. The data presented here demonstrate that immunization with a modular VLP could induce high levels of J8i-specific antibodies despite a strong pre-existing anti-carrier immune response. Doubling of the J8i antigenic element number per VLP did not enhance J8i immunogenicity at a constant peptide dose. However, the strategy, when used in conjunction with increased VLP dose, could effectively increase the peptide dose up to 10-fold, leading to a significantly higher J8i-specific antibody titer. This study further supports feasibility of the MuPyV modular VLP vaccine platform by showing that, in the absence of adjuvant, modularized GAS antigenic peptide at a dose as low as 150 ng was sufficient to raise a high level of peptide-specific IgGs indicative of bactericidal activity. PMID:23532896

  6. Fitness Conferred by BCR-ABL Kinase Domain Mutations Determines the Risk of Pre-Existing Resistance in Chronic Myeloid Leukemia

    PubMed Central

    Skaggs, Brian; Gorre, Mercedes; Sawyers, Charles L.; Michor, Franziska

    2011-01-01

    Chronic myeloid leukemia (CML) is the first human malignancy to be successfully treated with a small molecule inhibitor, imatinib, targeting a mutant oncoprotein (BCR-ABL). Despite its successes, acquired resistance to imatinib leads to reduced drug efficacy and frequent progression of disease. Understanding the characteristics of pre-existing resistant cells is important for evaluating the benefits of first-line combination therapy with second generation inhibitors. However, due to limitations of assay sensitivity, determining the existence and characteristics of resistant cell clones at the start of therapy is difficult. Here we combined a mathematical modeling approach using branching processes with experimental data on the fitness changes (i.e., changes in net reproductive rate) conferred by BCR-ABL kinase domain mutations to investigate the likelihood, composition, and diversity of pre-existing resistance. Furthermore, we studied the impact of these factors on the response to tyrosine kinase inhibitors. Our approach predicts that in most patients, there is at most one resistant clone present at the time of diagnosis of their disease. Interestingly, patients are no more likely to harbor the most aggressive, pan-resistant T315I mutation than any other resistance mutation; however, T315I cells on average establish larger-sized clones at the time of diagnosis. We established that for patients diagnosed late, the relative benefit of combination therapy over monotherapy with imatinib is significant, while this benefit is modest for patients with a typically early diagnosis time. These findings, after pre-clinical validation, will have implications for the clinical management of CML: we recommend that patients with advanced-phase disease be treated with combination therapy with at least two tyrosine kinase inhibitors. PMID:22140458

  7. A distinct pre-existing inflammatory tumour microenvironment is associated with chemotherapy resistance in high-grade serous epithelial ovarian cancer

    PubMed Central

    Koti, M; Siu, A; Clément, I; Bidarimath, M; Turashvili, G; Edwards, A; Rahimi, K; Masson, A-M M; Squire, J A

    2015-01-01

    Background: Chemotherapy resistance is a major determinant of poor overall survival rates in high-grade serous ovarian cancer (HGSC). We have previously shown that gene expression alterations affecting the NF-κB pathway characterise chemotherapy resistance in HGSC, suggesting that the regulation of an immune response may be associated with this phenotype. Methods: Given that intrinsic drug resistance pre-exists and is governed by both tumour and host factors, the current study was performed to examine the cross-talk between tumour inflammatory microenvironment and cancer cells, and their roles in mediating differential chemotherapy response in HGSC patients. Expression profiling of a panel of 184 inflammation-related genes was performed in 15 chemoresistant and 19 chemosensitive HGSC tumours using the NanoString nCounter platform. Results: A total of 11 significantly differentially expressed genes were found to distinguish the two groups. As STAT1 was the most significantly differentially expressed gene (P=0.003), we validated the expression of STAT1 protein by immunohistochemistry using an independent cohort of 183 (52 resistant and 131 sensitive) HGSC cases on a primary tumour tissue microarray. Relative expression levels were subjected to Kaplan–Meier survival analysis and Cox proportional hazard regression models. Conclusions: This study confirms that higher STAT1 expression is significantly associated with increased progression-free survival and that this protein together with other mediators of tumour–host microenvironment can be applied as a novel response predictive biomarker in HGSC. Furthermore, an overall underactive immune microenvironment suggests that the pre-existing state of the tumour immune microenvironment could determine response to chemotherapy in HGSC. PMID:25826225

  8. Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity

    PubMed Central

    Brestoff, Jonathan R.; Brodsky, Tim; Sosinsky, Alexandra Z.; McLoughlin, Ryan; Stansky, Elena; Fussell, Leila; Sheppard, Aaron; DiSanto-Rose, Maria; Kershaw, Erin E.; Reynolds, Thomas H.

    2015-01-01

    The superoxide dismutase mimetic manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin (MnTBAP) is a potent antioxidant compound that has been shown to limit weight gain during short-term high fat feeding without preventing insulin resistance. However, whether MnTBAP has therapeutic potential to treat pre-existing obesity and insulin resistance remains unknown. To investigate this, mice were treated with MnTBAP or vehicle during the last five weeks of a 24-week high fat diet (HFD) regimen. MnTBAP treatment significantly decreased body weight and reduced white adipose tissue (WAT) mass in mice fed a HFD and a low fat diet (LFD). The reduction in adiposity was associated with decreased caloric intake without significantly altering energy expenditure, indicating that MnTBAP decreases adiposity in part by modulating energy balance. MnTBAP treatment also improved insulin action in HFD-fed mice, a physiologic response that was associated with increased protein kinase B (PKB) phosphorylation and expression in muscle and WAT. Since MnTBAP is a metalloporphyrin molecule, we hypothesized that its ability to promote weight loss and improve insulin sensitivity was regulated by heme oxygenase-1 (HO-1), in a similar fashion as cobalt protoporphyrins. Despite MnTBAP treatment increasing HO-1 expression, administration of the potent HO-1 inhibitor tin mesoporphyrin (SnMP) did not block the ability of MnTBAP to alter caloric intake, adiposity, or insulin action, suggesting that MnTBAP influences these metabolic processes independent of HO-1. These data demonstrate that MnTBAP can ameliorate pre-existing obesity and improve insulin action by reducing caloric intake and increasing PKB phosphorylation and expression. PMID:26397111

  9. Manganese [III] Tetrakis [5,10,15,20]-Benzoic Acid Porphyrin Reduces Adiposity and Improves Insulin Action in Mice with Pre-Existing Obesity.

    PubMed

    Brestoff, Jonathan R; Brodsky, Tim; Sosinsky, Alexandra Z; McLoughlin, Ryan; Stansky, Elena; Fussell, Leila; Sheppard, Aaron; DiSanto-Rose, Maria; Kershaw, Erin E; Reynolds, Thomas H

    2015-01-01

    The superoxide dismutase mimetic manganese [III] tetrakis [5,10,15,20]-benzoic acid porphyrin (MnTBAP) is a potent antioxidant compound that has been shown to limit weight gain during short-term high fat feeding without preventing insulin resistance. However, whether MnTBAP has therapeutic potential to treat pre-existing obesity and insulin resistance remains unknown. To investigate this, mice were treated with MnTBAP or vehicle during the last five weeks of a 24-week high fat diet (HFD) regimen. MnTBAP treatment significantly decreased body weight and reduced white adipose tissue (WAT) mass in mice fed a HFD and a low fat diet (LFD). The reduction in adiposity was associated with decreased caloric intake without significantly altering energy expenditure, indicating that MnTBAP decreases adiposity in part by modulating energy balance. MnTBAP treatment also improved insulin action in HFD-fed mice, a physiologic response that was associated with increased protein kinase B (PKB) phosphorylation and expression in muscle and WAT. Since MnTBAP is a metalloporphyrin molecule, we hypothesized that its ability to promote weight loss and improve insulin sensitivity was regulated by heme oxygenase-1 (HO-1), in a similar fashion as cobalt protoporphyrins. Despite MnTBAP treatment increasing HO-1 expression, administration of the potent HO-1 inhibitor tin mesoporphyrin (SnMP) did not block the ability of MnTBAP to alter caloric intake, adiposity, or insulin action, suggesting that MnTBAP influences these metabolic processes independent of HO-1. These data demonstrate that MnTBAP can ameliorate pre-existing obesity and improve insulin action by reducing caloric intake and increasing PKB phosphorylation and expression. PMID:26397111

  10. Modelling Estimates of Norovirus Disease in Patients with Chronic Medical Conditions

    PubMed Central

    Verstraeten, Thomas; Jiang, Baoguo; Weil, John G.; Lin, Jennifer H.

    2016-01-01

    Background The burden of disease due to norovirus infection has been well described in the general United States population, but studies of norovirus occurrence among persons with chronic medical conditions have been limited mostly to the immunocompromised. We assessed the impact of norovirus gastroenteritis on health care utilization in US subjects with a range of chronic medical conditions. Methods We performed a retrospective cohort study using MarketScan data from July 2002 to December 2013, comparing the rates of emergency department visits, outpatient visits and hospitalizations among patients with chronic conditions (renal, cardiovascular, respiratory, immunocompromising, gastrointestinal, hepatic/pancreatic and neurological conditions and diabetes) with those in a healthy population. We estimated the rates of these outcomes due to norovirus gastroenteritis using an indirect modelling approach whereby cases of gastroenteritis of unknown cause and not attributed to a range of other causes were assumed to be due to norovirus. Results Hospitalization rates for norovirus gastroenteritis were higher in all of the risk groups analyzed compared with data in otherwise healthy subjects, ranging from 3.2 per 10,000 person-years in persons with chronic respiratory conditions, to 23.1 per 10,000 person-years in persons with chronic renal conditions, compared to 2.1 per 10,000 among persons without chronic conditions. Over 51% of all norovirus hospitalizations occurred in the 37% of the population with some form of chronic medical condition. Outpatient visits for norovirus gastroenteritis were also increased in persons with chronic gastrointestinal or immunocompromising conditions. Conclusion Norovirus gastroenteritis leads to significantly higher rates of healthcare utilization in patients with a chronic medical condition compared to patients without any such condition. PMID:27438335