bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of Various Treatments for Posttransplant Hepatitis B Virus Recurrence
Authors: Yi Nam‐Joon , Lee Kwang‐Woong , Kong Sun‐Young , Park Kyoung‐Un , Lee Kyoung‐Bun , Hong Geun , Han Sung‐Sik , Park Sang‐Jae , Suh Kyung‐Suk
Published: January 2013

Background

Currently, no treatment guidelines are available for posttransplant hepatitis B virus (HBV) recurrence. We retrospectively evaluated the rate of clearance of hepatitis B surface antigen (HBsAg) from serum according to various treatment regimens in two large Korean liver transplantation centers.

Methods

Between 1996 and 2008, HBV recurred in 59 patients among 933 HBV liver recipients (6.3 %). Patients with HBV recurrence were divided into four groups according to their treatment: group L (lamivudine‐based therapy n = 21) and group N [new nucleos(t)ide analogue (NA)‐based therapy, n = 38]. Intravenous hepatitis B immunoglobulin (ivHBIG) had been simultaneously administered to 10 patients in group L and 26 patients in group N. The mean posttransplant follow‐up duration and time to HBV recurrence were 69 (14–152) months and 37 (3–120) months.

Results

Overall, 22 patients (37.3 %) showed seronegative conversion of HBsAg for a median 8 months after treatment (range 1–15 months). The seroclearance rate was significantly higher in group N (n = 20, 52.6 %) than in group L (n = 2, 9.5 %) (p < 0.000). The time to seroconversion did not differ between group L (7 months, range 5–16) and group N (7 months, range 1–15) (p = 0.428). Subgroup analysis showed that the HBsAg seroconversion rate was much higher for patients given combined ivHBIG and new NAs (15/26 patients, 58.0 %) than the others (p = 0.006).

Conclusions

Seroclearance of HBsAg could be achieved using new NAs in half of the patients after posttransplant HBV recurrence. Combined ivHBIG may add a synergistic effect to new NAs for clearing HBsAg.
Monetary regimes, economic stability, and EU accession: Comparing Bulgaria and Romania
Authors: Nenovsky Nikolay , Tochkov Kiril , Turcu Camelia
Published: January 2013

This paper traces the origins of the different monetary regimes adopted in Bulgaria and Romania in 1996–97 and examines their performance during the EU accession. The findings indicate that the constraints of the currency board in Bulgaria shifted economic activity towards the private sector, while the discretionary policies in Romania turned public finances into both a contributor and a response mechanism to economic imbalances. While the prospects of EU accession initially enhanced the performance of the monetary anchors, the implicit insurance of EU membership increased moral hazard and led to a rapid rise in private and public debt. The paper also explores the historical parallels between the monetary regimes of Bulgaria and Romania in 1996–97 and 1925–1940.
Law of large numbers for certain cylinder flows
Authors: CIRILO PATRÍCIA , LIMA YURI , PUJALS ENRIQUE
Published: January 2013

We construct new examples of cylinder flows, given by skew product extensions of irrational rotations on the circle, that are ergodic and rationally ergodic along a subsequence of iterates. In particular, they exhibit a law of large numbers. This is accomplished by explicitly calculating, for a subsequence of iterates, the number of visits to zero, and it is shown that such number has a Gaussian distribution.
Low-cost eWLB packaging for automotive radar MMICs in the 76–81 GHz range
Authors: Böck J. , Wojnowski M. , Wagner C. , Knapp H. , Hartner W. , Treml M. , Schmückle F. J. , Sinha S. , Lachner R.
Published: January 2013

Embedded wafer-level ball grid array (eWLB) is investigated as a low-cost plastic package for automotive radar applications in the 76–81 GHz range. Low transmission losses from chip to package and board are achieved by appropriate circuit and package design. Special measures are taken to effectively remove the heat from the package and to optimize the package process to achieve automotive quality targets. A 77 GHz radar chip set in eWLB package is developed, which can be applied on the system board using standard solder reflow assembly. These radar MMICs provide excellent radio frequency (RF) performance for the next generation automotive radar sensors. The potential for even higher system integration is shown by a radar transceiver with antennas integrated in the eWLB package. These results demonstrate that eWLB technology is an attractive candidate to realize low-cost radar systems and to enable radar safety affordable for everyone in the near future.
The International Law Commission's Draft Articles on the Effects of Armed Conflicts on Treaties: Evaluating the Applicability of Impossibility of Performance and Fundamental Change
Authors: TAN Zhi Peng Benny
Published: January 2013

The International Law Commission recently completed its work on the controversial issue of the effects of armed conflicts on treaties, culminating in the adoption of a set of eighteen draft articles and an annex. The Commission's efforts are nothing short of commendable, but this article argues that insufficient attention has been paid to the role of supervening impossibility of performance and fundamental change of circumstances in determining the effects of armed conflicts on treaties. Although both doctrines may in fact appropriately apply in the context of armed conflicts, the mere referencing of them in the adopted draft articles gives rise to several problems. In particular, the two doctrines were codified by the 1969 Vienna Convention on the Law of Treaties without their application to armed conflicts in mind. Some changes to the draft articles are proposed to address these difficulties.
Inactivation of the microRNA-183/96/182cluster results in syndromic retinal degeneration
Authors: Lumayag Stephen , Haldin Caroline E. , Corbett Nicola J. , Wahlin Karl J. , Cowan Colleen , Turturro Sanja , Larsen Peter E. , Kovacs Beatrix , Witmer P. Dane , Valle David , Zack Donald J. , Nicholson Daniel A. , Xu Shunbin
Published: January 2013

The microRNA-183/96/182cluster is highly expressed in the retina and other sensory organs. To uncover its in vivo functions in the retina, we generated a knockout mouse model, designated “miR-183CGT/GT,” using a gene-trap embryonic stem cell clone. We provide evidence that inactivation of the cluster results in early-onset and progressive synaptic defects of the photoreceptors, leading to abnormalities of scotopic and photopic electroretinograms with decreasedb-wave amplitude as the primary defect and progressive retinal degeneration. In addition, inactivation of themiR-183/96/182cluster resulted in global changes in retinal gene expression, with enrichment of genes important for synaptogenesis, synaptic transmission, photoreceptor morphogenesis, and phototransduction, suggesting that themiR-183/96/182cluster plays important roles in postnatal functional differentiation and synaptic connectivity of photoreceptors.
Endoplasmic reticulum-associated mitochondria–cortex tether functions in the distribution and inheritance of mitochondria
Authors: Lackner Laura L. , Ping Holly , Graef Martin , Murley Andrew , Nunnari Jodi
Published: January 2013

To elucidate the functional roles of mitochondrial dynamics in vivo, we identified genes that become essential in cells lacking the dynamin-related proteins Fzo1 and Dnm1, which are required for mitochondrial fusion and division, respectively. The screen identified Num1, a cortical protein implicated in mitochondrial division and distribution that also functions in nuclear migration. Our data indicate that Num1, together with Mdm36, forms a physical tether that robustly anchors mitochondria to the cell cortex but plays no direct role in mitochondrial division. Our analysis indicates that Num1-dependent anchoring is essential for distribution of the static mitochondrial network in
fzo1 dnm1
cells. Consistently, expression of a synthetic mitochondria–cortex tether rescues the viability of
fzo1 dnm1 num1
cells. We find that the cortical endoplasmic reticulum (ER) also is a constituent of the Num1 mitochondria–cortex tether, suggesting an active role for the ER in mitochondrial positioning in cells. Thus, taken together, our findings identify Num1 as a key component of a mitochondria–ER–cortex anchor, which we termed “MECA,” that functions in parallel with mitochondrial dynamics to distribute and position the essential mitochondrial network.
Depression, Anxiety, and Moods of Hospitalized Patients under Contact Precautions
Authors: Day Hannah R. , Perencevich Eli N. , Harris Anthony D. , Gruber-Baldini Ann L. , Himelhoch Seth S. , Brown Clayton H. , Morgan Daniel J.
Published: January 2013

Objective.

To determine the association between contact precautions and depression or anxiety as well as feelings of anger, sadness, worry, happiness, or confusion.

Design.

Prospective frequency-matched cohort study.

Setting.

The University of Maryland Medical Center, a 662-bed tertiary care hospital in Baltimore, Maryland.

Participants.

A total of 1,876 medical and surgical patients over the age of 18 years were approached; 528 patients were enrolled from January through November 2010, and 296 patients, frequency matched by hospital unit, completed follow-up on hospital day 3.

Results.

The primary outcome was Hospital Anxiety and Depression Scale (HADS) scores on hospital day 3, controlling for baseline HADS scores. Secondary moods were measured with visual analog mood scale diaries. Patients under contact precautions had baseline symptoms of depression 1.3 points higher (P < .01) and anxiety 0.8 points higher (P= .08) at hospital admission using HADS. Exposure to contact precautions was not associated with increased depression (P= .42) or anxiety (P= .25) on hospital day 3. On hospital day 3, patients under contact precautions were no more likely than unexposed patients to be angry (20% vs 20%;P= .99), sad (33% vs 38%;P= .45), worried (51% vs 46%;P= .41), happy (58% vs 67%;P= .14), or confused (23% vs 24%;P= .95).

Conclusions.

Patients under contact precautions have more symptoms of depression and anxiety at hospital admission but do not appear to be more likely to develop depression, anxiety, or negative moods while under contact precautions. The use of contact precautions should not be restricted by the belief that contact precautions will produce more depression or anxiety.
Composition and abstraction of logical regulatory modules: application to multicellular systems
Authors: Mendes Nuno D. , Lang Frédéric , Le Cornec Yves-Stan , Mateescu Radu , Batt Gregory , Chaouiya Claudine
Published: January 2013

Motivation: Logical (Boolean or multi-valued) modelling is widely used to study regulatory or signalling networks. Even though these discrete models constitute a coarse, yet useful, abstraction of reality, the analysis of large networks faces a classical combinatorial problem. Here, we propose to take advantage of the intrinsic modularity of inter-cellular networks to set up a compositional procedure that enables a significant reduction of the dynamics, yet preserving the reachability of stable states. To that end, we rely on process algebras, a well-established computational technique for the specification and verification of interacting systems.

Results: We develop a novel compositional approach to support the logical modelling of interconnected cellular networks. First, we formalize the concept of logical regulatory modules and their composition. Then, we make this framework operational by transposing the composition of logical modules into a process algebra framework. Importantly, the combination of incremental composition, abstraction and minimization using an appropriate equivalence relation (here the safety equivalence) yields huge reductions of the dynamics. We illustrate the potential of this approach with two case-studies: the Segment-Polarity and the Delta-Notch modules.

Availability and implementation: GINsim (http://ginsim.org) and CADP (http://cadp.inria.fr) are freely available for academic users. Files needed to reproduce our results are provided at http://compbio.igc.gulbenkian.pt/nmd/node/45.

Contact:  chaouiya@igc.gulbenkian.pt

Supplementary information:  Supplementary data are available at Bioinformatics online
Impact of Thiocyanate Salts on Physical, Thermal, and Rheological Properties of Zein Films
Authors: Selling Gordon W. , Maness Ashley , Bean Scott , Smith Brennan
Published: January 2013

A new class of zein additives was investigated, thiocyanate salts. Ammonium, potassium, guanidine (GTC), and magnesium thiocyanate salts were added to solutions of zein in with various amounts of tri(ethylene glycol) (TEG), cast as films, and then tested to determine the impact that each salt had on properties. The presence of these salts affected solution rheology and intrinsic viscosity, demonstrating that the salts interacted with the protein. It was found that these salts acted as plasticizers, as they lowered the glass transition temperature of zein when evaluated with differential scanning calorimetry. In zein films in which TEG was present, these salts increased elongation and reduced tensile strength. However, unlike traditional plasticizers (such as TEG), when the salts were used as the only additive, elongation was not increased and tensile strength was not decreased. Of the salts tested, GTC in combination with TEG was found to increase elongation the most. The impact of salts on elongation was greatly affected by the relative humidity in which the samples were stored.
VEHICLE CURRENCY*
Authors: Devereux Michael B. , Shi Shouyong
Published: January 2013

Historically, the world economy has been dominated by a single currency accepted in the exchange of goods and assets among countries. In recent decades, the U.S. dollar has played this role. The dollar acts as a “vehicle currency” in the sense that agents in nondollar economies will generally engage in currency trade indirectly using the U.S. dollar instead of using direct bilateral trade among their own currencies. A vehicle currency is desirable when there are transactions costs of exchange. This article constructs a dynamic general equilibrium model of a vehicle currency. We explore the nature of the efficiency gains arising from a vehicle currency and show how it depends on the total number of currencies in existence, the size of the vehicle currency economy, and the monetary policy followed by the vehicle currency’s government. We find that there can be significant welfare gains to a vehicle currency in a system of many independent currencies. But these gains are asymmetrically weighted toward the residents of the vehicle currency country. The survival of a vehicle currency places natural limits on the monetary policy of the vehicle currency country.
Drawings, Photos, and Performances: Using Visual Methods with Children
Authors: Johnson Ginger A. , Pfister Anne E. , Vindrola‐Padros Cecilia
Published: January 2013

Children have largely been overlooked as research participants in anthropological work. The anthropology of childhood has played an instrumental role in bringing attention to this fact, and it has highlighted important contributions children's viewpoints can make to our discipline. In this article, we present three case studies that involved children as active participants through the use of visual methodology: Vindrola‐Padros's research in Argentina used drawing techniques to document children's experiences of oncology treatment; Johnson's work in Kenya used photovoice with children living in orphanages to understand their coping strategies; and Pfister's study in Mexico City looked at how combining dance and drama encouraged participation among deaf and hearing children.
Stability Analysis and Convergence Control of Iterative Algorithms for Reliability Analysis and Design Optimization
Authors: Yang Dixiong , Xiao Hui
Published: January 2013

Iterative algorithms are widely applied in reliability analysis and design optimization. Nevertheless, phenomena of failed convergence, such as periodic oscillation, bifurcation, and chaos, are oftentimes observed in iterative procedures of solving some nonlinear problems. In the present paper, the essential causes of numerical instabilities including periodic oscillation and chaos of iterative solutions are revealed by the eigenvalue-based stability analysis of iterative schemes. To understand and control these instabilities, the stability transformation method (STM), which is capable of tackling numerical instabilities of iterative algorithms in reliability analysis and design optimization, is proposed. Finally, several benchmark examples of convergence control of PMA (performance measure approach) for probabilistic analysis and the SORA (sequential optimization and reliability assessment) for reliability-based design optimization (RBDO) are presented. The observations from the benchmark examples indicate that the STM is a promising approach to achieve convergence control for iterative algorithms in reliability analysis and design optimization.
Evolving Strategies in Mechanobiology to More Effectively Treat Damaged Musculoskeletal Tissues
Authors: Butler David L. , Dyment Nathaniel A. , Shearn Jason T. , Kinneberg Kirsten R. C. , Breidenbach Andrew P. , Lalley Andrea L. , Gilday Steven D. , Gooch Cynthia , Rao M. B. , Liu Chia-feng , Wylie Christopher
Published: January 2013

In this paper, we had four primary objectives. (1) We reviewed a brief history of the Lissner award and the individual for whom it is named, H.R. Lissner. We examined the type (musculoskeletal, cardiovascular, and other) and scale (organism to molecular) of research performed by prior Lissner awardees using a hierarchical paradigm adopted at the 2007 Biomechanics Summit of the US National Committee on Biomechanics. (2) We compared the research conducted by the Lissner award winners working in the musculoskeletal (MS) field with the evolution of our MS research and showed similar trends in scale over the past 35 years. (3) We discussed our evolving mechanobiology strategies for treating musculoskeletal injuries by accounting for clinical, biomechanical, and biological considerations. These strategies included studies to determine the function of the anterior cruciate ligament and its graft replacements as well as novel methods to enhance soft tissue healing using tissue engineering, functional tissue engineering, and, more recently, fundamental tissue engineering approaches. (4) We concluded with thoughts about future directions, suggesting grand challenges still facing bioengineers as well as the immense opportunities for young investigators working in musculoskeletal research. Hopefully, these retrospective and prospective analyses will be useful as the ASME Bioengineering Division charts future research directions.
COLOR-OCTET BOUND STATES, INDUCED BY HIGGS MECHANISM
Authors: BLADWELL S. , DMITRIEV V. F. , FLAMBAUM V. V. , KOZLOV A.
Published: January 2013

The current limits for fourth generation quarks allows to expect their mass of the order of 500 GeV. In this mass region for quark–antiquark pair the additional Yukawa-type attraction due to Higgs mechanism is expected to emerge. This Higgs-induced attraction greatly exceeds strong interaction between quarks and leads to the formation of bound states in both color-octet S(8) and singlet S(1) states. In the key of recent works on significance of color-octet channel for production of color-singlet state of fourth generation [Formula: see text] we calculated the binding energies for both octet and singlet states. Such an attraction localizes quarks in extremely small area. Hence, color-octet pair of fourth generation quarks can form the "nucleus" and, together with color neutralizing light particle that is captured by strong interaction in orbit around the nucleus, create particle with structure similar to Deuterium.
Moo1 obesity quantitative trait locus in BTBR T+ Itpr3tf/J mice increases food intake
Authors: Karunakaran Subashini , Manji Akiff , Yan Chenhua Serena , Wu Zi-Jun John , Clee Susanne M.
Published: January 2013

The rising prevalence of obesity is one of the greatest health challenges facing the world today. Discovery of genetic factors affecting obesity risk will provide important insight to its etiology that could suggest new therapeutic approaches. We have previously identified the Modifier of obese 1 ( Moo1) quantitative trait locus (QTL) in a cross between leptin-deficient BTBR T+ Itpr3tf/J (BTBR) and C57BL/6J (B6) mice. Understanding the mechanism by which this locus acts will aid in the identification of candidate genes. Here we refined the location of this QTL and sought to determine the mechanism by which Moo1 affects body weight. We found that the effects of Moo1 also alter high fat diet-induced obesity in mice having functional leptin. In detailed metabolic analyses we determined that this locus acts by increasing food intake in BTBR mice, without affecting energy expenditure. The expression levels of the main molecular mediators of food intake in the hypothalamus were not altered, suggesting this locus affects an independent pathway, consistent with its identification in mice lacking functional leptin. Finally, we show that the increased adiposity resulting from Moo1 is sufficient to affect glucose tolerance. These studies show that the Moo1 obesity QTL affects food intake, likely through a novel mechanism, and indicate that modulation of the underlying pathway may not only ameliorate obesity but also its clinical consequences.
Phenotypic Correlations between Monocytes and CD4+ T Cells in Allergic Patients
Authors: Moniuszko Marcin , Kowal Krzysztof , Jeznach Marta , Rusak Malgorzata , Dabrowska Milena , Bodzenta-Lukaszyk Anna
Published: January 2013

Despite widely acknowledged contributions of innate and adaptive immune systems to the pathogenesis of allergic diseases, mutual interactions occurring in vivo between components of those two systems have not been studied in sufficient detail. Here, we wished to investigate whether phenotypic features of monocytes and CD4+ T cells in allergic patients are reciprocally related. Therefore, we recruited 50 untreated house dust mite-sensitive allergic rhinitis patients and 29 non-atopic healthy individuals and performed comprehensive simultaneous flow cytometric analysis of mutual correlations between levels of CD14, CD16, CD163, CD206, CD124 (IL-4R), CD210 (IL-10R) and CD25, CD124, CD127 (IL-7R), CD210, ICOS expression on monocytes and CD4+ T cells, respectively. We found that CD163 monocyte expression in allergic but not healthy subjects is positively correlated with monocyte IL-10R, and, to a lesser extent, CD206, but not IL-4R expression. Levels of CD163 expression were not related to frequencies of CD14++CD16–, CD14++CD16+, and CD14+CD16++ monocyte subsets. In contrast to healthy controls, intensities of monocyte IL-10R in allergic individuals were significantly correlated with monocyte CD206 and IL-4R expression. In addition, levels of monocyte IL-4R and IL-10R monocyte expression were positively correlated to expression of IL-4R and IL-10R on CD4+ T cells in both groups of studied subjects. Interestingly, we demonstrated a significant positive correlation between levels of monocyte CD206 expression and levels of IL-10R and IL-4R expression on CD4+ T cells in allergic but not healthy individuals. In summary, we conclude that allergic rhinitis is associated with a number of phenotypic alterations of circulating monocytes and CD4+ T cells.
Different Frequencies of Tc17/Tc1 and Th17/Th1 Cells in Chronic Spontaneous Urticaria
Authors: Lopes Ana , Machado Daniel , Pedreiro Susana , Henriques Ana , Silva Isabel , Tavares Beatriz , Inácio Maria Jesus , Chieira Celso , Martinho António , Pais Maria Luísa , Pereira Celso , Paiva Artur
Published: January 2013

Background: Chronic urticaria is associated with an immune dysregulation usually mediated by T lymphocytes. Recently, Th17 and Tc17 have been implicated in autoimmune diseases; however, their role in urticaria is not clear yet. Methods: For the study we recruited 20 patients [10 of them had autoreactive chronic spontaneous urticaria (positive autologous intradermal serum test response, ASST+), and the other 10 were nonautoreactive chronic spontaneous urticaria patients (ASST–)] and 17 healthy age- and gender-matched controls (HG). The frequency and functional activity of Th17/Tc17 and Th1/Tc1 cells were evaluated by flow cytometry and type 2 cytokine mRNA by real-time PCR. Results: Our results demonstrated a significant decrease in Th17 frequency in both chronic urticaria groups compared to HG; regarding the amount of IL-17, at the single cell level, it was reduced in ASST– compared to HG. Concerning the Th1 and Th17 cells producing IFN-γ, IL-2, and TNF-α, a lower frequency was noted in chronic urticaria patients compared to HG. In contrast, a significantly increased frequency of Tc1 cells producing these cytokines was noted in ASST+ compared to HG and ASST–. Also, the frequency of Tc17 cells producing TNF-α was increased in ASST+ compared to HG; however, with respect to the amount of TNF-α, at the single cell level, we found a decrease in ASST+ compared to HG. Regarding type 2 cytokine mRNA, a higher expression was verified in ASST+ compared to HG. Conclusion: Our data suggest a probable involvement of cytotoxic T cells, mainly the Tc1 and Tc17 subsets, in chronic urticaria, particularly in the ASST+ group.
Two Cases of Mucinous Cystadenoma of the Appendix Successfully Treated by Laparoscopy
Authors: Yoshida Yuko , Sato Koichi , Tada Takashi , Maekawa Hiroshi , Sakurada Mutumi , Orita Hajime , Ito Tomoaki , Hirata Fumiko , Wada Ryo
Published: January 2013

Two cases of mucinous cystadenoma of the appendix successfully treated by laparoscopy are reported. An 81-year-old woman with lower right back pain was diagnosed with mucinous cystadenoma of the appendix or appendiceal carcinoma and underwent elective laparoscopic surgery. The other case involved a 70-year-old man with hematochezia who was diagnosed with mucinous cystadenoma. He also underwent elective laparoscopic surgery. In these two cases, gauze was folded around the tumors rather than grasping them directly. The postoperative courses were uneventful, and these patients had no recurrent disease at 2-year follow-up. In such cases, surgical excision of the tumor without rupture is of paramount importance because rupture of the lesion can cause pseudomyxoma peritonei. Though appendiceal mucinous cystadenoma has been considered a contraindication of laparoscopic resection, it was possible to achieve this by using a laparoscopic procedure with a gauze technique.
A Decorated Ivory Belt from Tilla Bulak, Southern Uzbekistan
Authors: Gruber Martin , Il’yasov Jangar , Kaniuth Kai
Published: January 2013

Abstract

The ivory belt-plate, one of two found in a burial at the site of Tilla Bulak, Uzbekistan, shows a battle scene between two groups of mounted warriors. It belongs to a small group of figural belt plates from the region and is dated iconographically to the 1st century BC / 1st century AD. The elephant tooth from which it was worked was more than 2000 years old at the time.
Blowin’ in the Wind: Short-Term Weather and Belief in Anthropogenic Climate Change
Authors: Hamilton Lawrence C. , Stampone Mary D.
Published: January 2013

A series of polls provides new tests for how weather influences public beliefs about climate change. Statewide data from 5000 random-sample telephone interviews conducted on 99 days over 2.5 yr (2010–12) are merged with temperature and precipitation indicators derived from U.S. Historical Climatology Network (USHCN) station records. The surveys carry a question designed around scientific consensus statements that climate change is happening now, caused mainly by human activities. Alternatively, respondents can state that climate change is not happening, or that it is happening but mainly for natural reasons. Belief that humans are changing the climate is predicted by temperature anomalies on the interview day and the previous day, controlling for season, survey, and individual characteristics. Temperature effects concentrate among one subgroup, however: individuals who identify themselves as independent, rather than aligned with a political party. Interviewed on unseasonably warm days, independents tend to agree with the scientific consensus regarding anthropogenic climate change. On unseasonably cool days, they tend not to agree. Although temperature effects are sharpest for just a 2-day window, positive effects are seen for longer windows as well. As future climate change shifts the distribution of anomalies and extremes, this will first affect beliefs among unaligned voters.
Platelets and whole blood coagulation
Authors: Baugh Robert F
Published: January 2013

In our early work in developing activated clotting time (ACT) assays, it became apparent that changes occurred in coagulation times as a whole blood sample aged (0-6 h). Subsequent studies showed that the coagulation parameters of plasma obtained from the samples remained stable during this time frame. These changes in whole blood clotting times during storage were eventually traced to the platelets. Several years of work demonstrated that this change was due to the removal of the blood from the vascular lining. This recalled a mechanism that was originally put forth in the 1970s with the discovery of prostacyclin. In this postulated mechanism, platelets are ‘time-bombs’. They are kept under control by prostacyclin (PGI2) secreted by the vascular lining. Without this prostacyclin, platelets ‘preactivate’. Since that time, additional substances secreted by the vascular endothelium have been identified, such as nitric oxide, that also influence platelet activity.

The ‘preactivation’ of platelets in a blood sample can be followed using an ACT. In the same donor, the preactivation is uniform and reproducible over an extended period (months). There is, however, considerable variability between donors. Some donors’ platelets preactivate dramatically, while other donors show hardly any change. Prostacyclin, added to the blood sample when it is collected, prevents this preactivation. The clinical significance of these observations has yet to be clearly established, but these observations raise a number of questions with respect to methods for improving platelet function during bypass and in evaluating the risk of platelet-mediated cardiovascular disease.
Pre-operative coagulopathy management of a neonate with complex congenital heart disease: a case study
Authors: Stammers Alfred H , Rauch Eric D , Willett Lynne D , Newberry Jamie W , Duncan Kim F
Published: January 2013

Severe coagulation defects often develop in neonates undergoing cardiac surgery, both as a result of the surgical intervention, and as pre-existing defects in the hemostatic mechanisms. The following case report describes a newborn patient with complex congenital heart disease and respiratory failure whose pre-operative coagulopathy was aggressively managed prior to surgical correction.

A 5-day-old, 2.5 kg child presented with interrupted aortic arch, ventricular septal defect, atrial septal defect, and patent ductus arteriosus. On admission, he was in respiratory arrest suffering from profound acidemia. In addition, the child was hypothermic (30.1°C), septic ( Streptococcus viridans), and coagulopathic (disseminated intravascular coagulation - DIC). The patient was immediately intubated and initial coagulation assessment revealed the following: prothrombin time (PT) 48.9 s (international normalized ratio (INR) 15.7), activated partial thromboplastin time (aPTT) •106 s, platelet count 30 000 mm3, fibrinogen 15 mg dL-1 and antithrombin III (AT-III) 10%.

Before cardiac surgery could be performed, the patient’s DIC was corrected with the administration of cryoprecipitate (15 ml), fresh frozen plasma (300 ml), and platelets (195 ml). In spite of the large transfusion of fresh frozen plasma, the AT-III activity, measured as a percentage, remained depressed at 33. Initial thromboelastographic (TEG) determination revealed an index of +2.02, and following 100 IU administration of an AT-III concentrate, declined to -2.32. Sequential TEG profiles were performed over several days, with the results used to guide both transfusion and medical therapy. The congenital heart defect correction was subsequently performed with satisfactory initial results, but the patient developed a fungal infection and expired on the 16th post-operative day.

The present case describes techniques of coagulation management for a newborn with both a severe hemostatic defect and congenital heart disease.
Plasma endotoxin concentrations during cardiac surgery may be related to atherosclerosis
Authors: Videm Vibeke , Svennevig Jan L , Fosse Erik , Mohr Brit , Aasen Ansgar O
Published: January 2013

Systemic endotoxemia develops during cardiopulmonary bypass, probably due to intestinal ischaemia. Differences in endotoxaemia among various cardiac operations and the relationship between endotoxemia and postoperative complications were studied in high-risk patients. Blood samples were obtained at termination of bypass in 136 adults undergoing elective cardiac surgery. Postoperative complications were registered prospectively. Plasma endotoxin was quantified by a kinetic limulus amebocyte lysate assay. Mean endotoxin concentrations were significantly lower in patients undergoing isolated valve replacement (89 ng/l) than in patients undergoing coronary artery bypass grafting alone (234 ng/l), or combined with valve replacement (278 ng/l) or carotid artery surgery (321 ng/l) ( p < 0.05). In multivariate linear regression, only the number of grafts (0, 1-3, 4-5) was significantly correlated to endotoxin concentrations ( p < 0.0005). Endotoxin concentrations were related to development of gastrointestinal dysfunction ( p = 0.03), but not to mortality ( p = 0.24) or other complications ( p = 0.62).
Impaired carbon dioxide transport during and after cardiopulmonary bypass
Authors: Cavaliere Franco
Published: January 2013

Changes in the CO2 carrying power of blood were evaluated during and after cardiopulmonary bypass (CPB) by calculating the equation of the whole blood CO2 dissociation curve and the ratio between the arterial-venous differences of CO2 content and CO2 tension (Ra-v). Sixteen patients undergoing normothermic CPB for coronary revascularization were studied; arterial and mixed venous blood gas analyses were performed prior to CPB, at the end of first cardioplegia infusion, 25 and 45 min after CPB commencement and 10 min after the termination of CPB. After CPB commencement, the whole blood CO2 dissociation curve became flatter and did not further change during or after CPB. Ra-v decreased from 1.06 ± 0.16 to 0.72 ± 0.12 ml/mmHg after the start of CPB and did not change significantly during CPB; it was still 0.73 ± 0.13 ml/mmHg after CPB. The data indicate that during CPB the amount of CO2 removed from tissues by 1 litre of blood decreases by about 30% and that impairment in CO2 transport persists after the restoration of physiological circulation. Impairment in CO2 transport is mainly caused by haemodilution, but it could be worsened by acidosis.
Effects of nonpulsatile left heart bypass on renal sympathetic nerve activity in rabbits
Authors: Tokunaga Shigehiko , Nakano Toshihide , Tominaga Ryuji , Imaizumi Tsutomu , Takeshita Akira , Yasui Hisataka
Published: January 2013

To determine the effects of nonpulsatile left heart bypass (LHB) on sympathetic nerve activity the renal sympathetic nerve activity (RSNA) was directly measured in rabbits. In anaesthetized rabbits ( n=6), LHB was instituted with a centrifugal pump. Before and during LHB, heart rate (HR), arterial pressure (AP), central venous pressure (CVP), left atrial pressure (LAP) and spike counts of RSNA were measured. After bilateral vagotomy (section of the afferent inputs of the cardiac reflex arc) the same parameters were measured before and during LHB. Data were obtained at the same level of mean AP before and during LHB. Mean AP and CVP were not changed by LHB before and after vagotomy. LAP was significantly decreased by LHB before and after vagotomy. RSNA and HR were not significantly changed by LHB before and after vagotomy. Our results clarify the complex baroreflex control during nonpulsatile LHB and indicate that RSNA is not altered by LHB.
Oxygen free radical generation in healthy blood donors and cardiac patients: the protective effect of allopurinol
Authors: Belboul Ali , Roberts Donald , Börjesson Richard , Johnsson Joakim
Published: January 2013

Cardiopulmonary bypass (CPB) activates the complement system, which leads to granulocyte activation and free radical production. Free radical activity during CPB has been associated with myocardial dysfunction. However, the relationship between cardiac enzymes and granulocytes to lipid peroxidation in cardiac surgery patients is unknown. Moreover, the effect of allopurinol on lipid peroxidation during mechanical trauma has to be explored.

Thirty-four patients undergoing coronary bypass surgery and 26 healthy blood donors participated in this prospective study where granulocyte counts, cardiac enzymes and malondialdehyde (MDA) were measured and related. Allopurinol was used ex vivo, as scavenger, to explore its effect on lipid peroxidation.

In the patient group, the mean preoperative MDA level (2.2 ± 0.7, nmol/ml) significantly increased after 30 min of bypass (3.3 ± 0.9 nmol/ml; p < 0.0001), and showed a second peak at aortic declamping (4.1 ± 0.9 nmol/ml). There were significant correlations between MDA and granulocyte counts ( r = 0.59, p < 0.0001) and cardiac enzymes ( r = 0.55, p < 0.0001). In an ex vivo setting, further mechanical trauma to blood significantly increased the MDA levels, both in the control ( p < 0.0001) and in the patient group ( p < 0.0001) and this effect could be reduced by allopurinol ( p < 0.0001). CPB and mechanical trauma generate oxygen free radicals. Allopurinol was found to reduce lipid peroxidation of red cells following mechanical trauma and this has to be further investigated regarding its ability to reduce morbidity in patients undergoing open heart surgery.
Effect of Carmeda® BioActive Surface coating versus Trillium™ Biopassive Surface coating of the oxygenator on circulating platelet count drop during cardiopulmonary bypass
Authors: Palanzo David A , Zarro Debra L , Manley Norman J , Montesano Ralph M , Quinn Michael , Elmore Barbara-Anne , Gustafson Patricia A , Castagna Joseph M
Published: January 2013

An investigation was conducted to evaluate the effect that surface coating of the hollow-fiber membrane oxygenator had on circulating platelet count drop during cardiopulmonary bypass (CPB). Sixty patients undergoing non-emergency myocardial revascularization for coronary artery disease were randomly divided into two groups. Group one ( n = 32) received the Carmeda®-coated Maxima- Plus PRF oxygenator while the patients in Group two ( n = 28) received the Trillium™-coated Affinity oxygenator during CPB. The net platelet count drops for the pump specimen (15-20 min after the initiation of bypass) for the Carmeda and the Trillium groups were 3.6±15.8% and 6.2±10.2%, respectively. The net platelet count drop for the warming specimen for the Carmeda and the Trillium groups were 2.9±19.4% and 0.5±11.0%, respectively. There were no statistically significant differences between the groups. The authors conclude that using either the Carmeda®-coated Maxima- Plus PRF oxygenator or the Trillium™-coated Affinity® oxygenator afford similar benefits in regards to preserving circulating platelet counts during bypass.
Leukocyte filtration in cardiac surgery: a review
Authors: Matheis G , Scholz M , Simon A , Dzemali Omer , Moritz A
Published: January 2013

Leukocyte filtration has evolved as an important technique in cardiac surgery with cardiopulmonary bypass to prevent pathogenic effector functions mediated by activated leukocytes. The underlying mechanisms that result in an improvement of laboratory variables as well as clinical outcome are not resolved yet. Moreover, the optimum strategy for the use of current filtration technology has not been systematically evaluated. This paper, therefore, reviews how activated leukocytes may lead to tissue damage, summarizes the known effects of leukocyte filtration on clinical outcome and laboratory parameters, and deals with current experimental and clinical efforts to further limit the pathogenic effects of leukocytes in cardiac surgery.
Fingertip temperature during cardiopulmonary bypass
Authors: Johnson J , Desai J B
Published: January 2013

Temperature changes in the nasopharynx, fingertip, forearm and extracorporeal circuit were continuously monitored, starting 10 min before and up to 16 min into the rewarming period of hypothermic (32°C) cardiopulmonary bypass in 14 patients operated on for coronary artery revascularization. Arterial blood temperature was the first to increase after starting rewarming, followed by the nasopharynx and the fingertip temperatures. Fingertip temperature started to increase abruptly 6.2 (2.02 SD) min after rewarming started. At this point, nasopharyngeal temperature was 34.2°C (1.42 SD) and took a further 8.3 min to reach 37°C. Assuming that increasing fingertip temperature indicates a central thermoregulatory response to warming, we suggest that nasopharyngeal temperature is a poor monitor of brain temperature. We also suggest that fingertip temperature may be used to monitor the point at which cerebral temperature reaches ‘normothermia’. Further body warming, using arterial temperatures ≥39°C, should be avoided because of the danger of brain hyperthermia.
Neurone-specific enolase and Sangtec 100 assays during cardiac surgery: part I - the effects of heparin, protamine and propofol
Authors: Gao F , Harris D NF , Sapsed-Byrne S , Sharp S
Published: January 2013

Neurone-specific enolase (NSE) and Sangtec 100 (S-100) (Sangtec Medical, Sweden) assays are designed for clotted samples, but when studying cerebral damage following cardiac surgery, perioperative samples will contain heparin and/or protamine. The lipid emulsion propofol is also frequently used during cardiac surgery and could affect the assays. We, therefore, studied the effects of heparin, protamine and propofol on the accuracy of NSE and S-100 assays in five healthy patients. Blood samples were taken and divided into four groups: normal saline was added to group A; heparin to group B; heparin followed by protamine to group C; and propofol to group D. NSE and S-100 concentrations were measured for all samples. Neither heparin, protamine nor propofol affected the accuracy of S-100 and NSE assays; therefore, samples can be taken throughout operations involving cardiopulmonary bypass without influencing the results.
Bubble generation and venous air filtration by hard-shell venous reservoirs: a comparative study
Authors: Mitchell S J , Willcox T , Gorman D F
Published: January 2013

We have previously shown significant bubble formation in Medtronic Maxima hard-shell venous reservoirs (HSVRs). In the present study, we not only investigated the mechanism of this bubble formation, but also the extent of bubble clearance by membrane oxygenators and arterial line filters. In addition, we also compared the performance of five HSVRs with respect to bubble formation and venous air filtration.

Salvaged clinical CPB circuits containing different HSVRs were studied by downstream Doppler monitoring under fixed flow - decreasing volume, fixed volume - increasing flow, and entrained venous air conditions.

Bubbles formed in the Medtronic Maxima top entry HSVR at volumes below 800 ml and flows above 3.5 l min-1, and were incompletely removed by a membrane oxygenator and arterial line filter. Decreased bubbling was seen when the reservoir atmosphere was flushed with CO2, suggesting that these bubbles formed in a fountain at the venous inflow. The Medtronic Maxima Forte HSVR formed significantly fewer bubbles at low volumes, and filtered venous air effectively. Negligible bubble formation occurred in the Sorin, Terumo, or Baxter reservoirs.

The minimum recommended operating volume for the Medtronic Maxima top entry reservoir should be reset at 600 ml and this device should always be used with an arterial filter. Bubble formation is substantially reduced in the new Medtronic Maxima Forte HSVR and this device is a good filter for venous air.
Biocompatibility of three different membrane oxygenators: effects on complement, neutrophil and monocyte activation
Authors: de Vroege R , Rutten P MMJ , Kalkman C , Out T A , Jansen P GM , Eijsman L , de Mol B JM , Wildevuur C RH
Published: January 2013

The inflammatory reaction of extracorporeal circuits can be assessed by measuring complement activation and the release of activation markers of leucocytes. The purpose of this study was to compare three commercially available membrane oxygenators with respect to complement (C3a), granulocyte (lactoferrin) and monocyte (interleukin-6, IL-6) activation. Thirty patients undergoing cardiac surgery were randomly assigned to undergo cardiopulmonary bypass (CPB) with one of the following oxygenators: a polypropylene hollow-fibre membrane (group 1; 2.2 m2), a polypropylene flat-sheet membrane (group 2; 3.1 m2) or a silicone envelope membrane (group 3; 3.5 m2). In all patients, a significant increase in C3a in plasma occurred during CPB with peak levels after the administration of protamine sulphate. In blood samples taken before aortic crossclamp release, at the end of CPB, and 20 min after protamine administration C3a was significantly lower in group 1 than in the other two groups. Lactoferrin increased significantly during CPB in all patients without a significant difference between the groups. IL-6 did not increase during CPB, but raised significantly after 4 h in the intensive care unit in all groups. Moreover, IL-6 was significant lower in group 1 than group 3. The data suggest that the polypropylene hollow-fibre membrane oxygenator, i.e. the oxygenator with the smallest surface area, is more biocompatible than the other types, probably because of a smaller contact surface area.
The effect of albumin priming solution on platelet activation during experimental long-term perfusion
Authors: Adrian Katrin , Mellgren Karin , Skogby Maria , Friberg Lars Göran , Mellgren Gösta , Wadenvik Hans
Published: January 2013

The objective of this study was to evaluate the effect of albumin priming on platelet consumption and activation during long-term perfusion. Two identical in vitro extracorporeal membrane oxygenation circuits were used; one was primed with Ringer’s solution containing human serum albumin, the other with Ringer’s solution only. Fresh heparinized human blood was pooled, divided between the two systems and circulated for 24 h at 37°C. Platelet count, plasma concentration of betathromboglobulin (BTG), platelet membrane density of glycoprotein (GP) Ib and of GPIIb/IIIa were assayed before the start and at 0.5, 1, 3, 12 and 24 h of perfusion. In total, seven experiments were performed. We found that during the first hour of perfusion, slightly higher platelet counts ( p = 0.058) and lower BTG values ( p = 0.0005) were observed in the circuits primed with albumin, compared to the control circuits. No statistically significant differences were observed for the platelet membrane expression of GPIb and GPIIb/IIIa. We conclude that albumin priming appears to transiently prevent platelet consumption and activation during long-term perfusion.