bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of whole‐body 18F‐fluorodeoxyglucose positron emission tomography on therapeutic management of non‐small cell lung cancer
Authors: HEO Eun Young , YANG Seock‐Chul , YOO Chul‐Gyu , HAN Sung Koo , SHIM Young‐Soo , KIM Young Whan
Published: June 2010

Background and objective:  Accurate staging at the time of diagnosis is very important in deciding on the appropriate treatment for cancer patients. FDG PET indicates metabolic changes in cancer cells, enabling the early detection of lesions. This has the advantage of allowing more accurate staging than is possible with conventional staging tools, and has led to the incorporation of FDG PET in the initial work‐up protocols for lung cancer patients. In this study, we evaluated the clinical impact of FDG PET as an initial staging tool, on the therapeutic management of patients with non‐small cell lung cancer (NSCLC).

Methods:  Patients diagnosed with NSCLC by histopathology were retrospectively identified and both chest CT and FDG PET were performed for initial staging. Information was collected regarding the results of conventional versus FDG PET staging, and any resulting modifications of treatment were evaluated.

Results:  Among the 537 patients who were evaluated FDG PET resulted in upstaging of the tumour in 91 (17%) and downstaging of the tumour in 68 (13%). Consequently, therapeutic management was modified in 118 patients (22%). Furthermore, use of FDG PET resulted in the detection of a second primary cancer in six patients.

Conclusions:  This study confirms that FDG PET has a considerable impact on the initial staging and therapeutic management of patients with NSCLC.
Occult nodal metastasis in patients with non‐small cell lung cancer at clinical stage IA by PET/CT
Authors: PARK Hye Kyeong , JEON Kyeongman , KOH Won‐Jung , SUH Gee Young , KIM Hojoong , KWON O Jung , CHUNG Man Pyo , LEE Kyung Soo , SHIM Young Mog , HAN Joungho , UM Sang‐Won
Published: June 2010

Background and objective:  The introduction of 18F‐FDG PET/CT has enhanced the diagnostic accuracy of nodal staging for non‐small cell lung cancer (NSCLC). We analysed risk factors for occult nodal metastasis in patients with clinical stage IA NSCLC as determined by 18F‐FDG PET/CT.

Methods:  Data for 147 patients diagnosed as clinical stage IA NSCLC by PET/CT from 2005 to 2007 were retrospectively reviewed. All study patients underwent 18F‐FDG PET/CT for lung cancer staging. They also underwent cervical mediastinoscopy or systematic lymph node dissection.

Results:  Cervical mediastinoscopy was performed in 78 patients (53.1%), and N2 involvement was detected in 3.8% (3/78) of these patients. Thoracotomy with systematic lymph node dissection was done in 144 patients. Four patients (2.8%, 4/144) were diagnosed with N2 disease after systematic lymph node dissection. Total N2 involvement was 4.8% (7/147). As 9.5% (14/147) of study patients had N1 disease, 14.3% (21/147) of patients had occult nodal (N1 or N2) metastasis. In univariate analyses, larger tumour size and a higher primary tumour maximum standardized uptake value >7.3 (SUVmax) were associated with occult nodal metastasis. Multivariate analysis demonstrated that a primary tumour SUVmax >7.3 was an independent predictor of occult nodal metastasis (odds ratio: 7.574; P = 0.001).

Conclusions:  Preoperative PET/CT scans contribute to reduce the frequency of occult nodal metastasis compared with those reported in the pre‐PET/CT era. The higher SUVmax in primary tumour was an independent predictor of occult nodal metastasis in patients with clinical stage IA NSCLC by PET/CT.
Five‐year outcome in COPD patients after their first episode of acute exacerbation treated with non‐invasive ventilation
Authors: CHUNG Li Ping , WINSHIP Peta , PHUNG Scott , LAKE Fiona , WATERER Grant
Published: June 2010

Background and objective:  Little is known about long‐term survival of patients surviving the first episode of type II respiratory failure requiring non‐invasive ventilation (NIV). We aimed to determine the 1‐, 2‐ and 5‐year survival, cause of death and potential prognostic indicators in this patient cohort.

Methods:  We retrospectively identified 100 sequential COPD patients (mean age 70, mean FEV1 37% predicted) treated with NIV for the first time. Mortality and data on hospital morbidity and potential prognostic factors were collected from patient records and a State Health Data Linkage Service.

Results:  Survival at 1, 2 and 5 years was 72%, 52% and 26%, respectively. Respiratory failure secondary to COPD was the commonest cause of death (56.8%), followed by cardiovascular events (25.7%). Readmission rate at 1 year was 60% for those who survived 2 years or more and 52% for those deceased within 2 years. Recurrent respiratory failure requiring NIV was observed in 31% of the cohort. Only advance age (P = 0.04), BMI (P = 0.014) and prior domiciliary oxygen use (P = 0.03) correlated with death within 5 years. Severity of respiratory failure did not correlate with mortality.

Conclusions:  The 2‐ and 5‐year mortality rates for patients with COPD surviving their first episode of respiratory failure requiring NIV are high. Physiological measures of the severity of respiratory failure at presentation do not predict subsequent survival and nor does the time interval between first and second admissions requiring NIV. Age, BMI and prior need for domiciliary oxygen are the main predictors of mortality at 5 years.
EXPERIENCES OF BILIARY INTERVENTIONS USING SHORT DOUBLE‐BALLOON ENTEROSCOPY IN PATIENTS WITH ROUX‐EN‐Y ANASTOMOSIS OR HEPATICOJEJUNOSTOMY
Authors: Tsujino Takeshi , Yamada Atsuo , Isayama Hiroyuki , Kogure Hirofumi , Sasahira Naoki , Hirano Kenji , Tada Minoru , Kawabe Takao , Omata Masao
Published: June 2010

Background:  The efficacy of double‐balloon enteroscopy (DBE) for biliary interventions has been shown in patients with surgical anatomy. However, the use of available endoscopic retrograde cholangiography accessories during this procedure is limited because of the length of the conventional instrument (200 cm). The aim of this study was to evaluate the feasibility of short DBE for managing biliary disorders in patients with a Roux‐en‐Y gastrectomy or hepaticojejunostomy (HJ).

Patients and Methods:  Using a short enteroscope (152 cm) and commercially available endoscopic retrograde cholangiography accessories, biliary interventions were performed in six patients with Roux‐en‐Y reconstruction or HJ anastomosis.

Results:  A total of 12 biliary interventions were performed; balloon dilations of the HJ anastomosis or intrahepatic ducts (four patients), nasobiliary drainages (three patients), bile duct stone removal after endoscopic papillary large balloon dilation with or without small sphincterotomy (two patients), and a biliary stent placement (one patient). One patient showed retroperitoneal air following endoscopic papillary large balloon dilation, but recovered conservatively.

Conclusions:  Biliary interventions via DBE using a short enteroscope are feasible in patients with surgical anatomy.
MANAGEMENT OF OBSCURE GASTROINTESTINAL BLEEDING BASED ON THE CLASSIFICATION OF CAPSULE ENDOSCOPIC BLEEDING FINDINGS
Authors: Maeda Mitsunori , Kanke Kazunari , Terano Akira , Hiraishi Hideyuki
Published: June 2010

Background:  Double‐balloon endoscopy (DBE) and capsule endoscopy (CE) have been useful in managing obscure gastrointestinal bleeding (OGIB). However, DBE is invasive, complex and time‐consuming, therefore indications should probably be selective. The aim of this study was to evaluate the usefulness of the classification of the CE bleeding findings for determining the indications and timing of DBE in patients with OGIB.

Methods:  From February 2003 to January 2009, 123 patients with OGIB who underwent CE were included in this study. These CE findings were classified based on the bleeding source. Type CE‐I, II, III, IV and 0 indicate active bleeding, previous bleeding, lesions without active bleeding, a lesion outside of the small bowel, and no findings, respectively. We compared diagnostic yield and outcome between the classification and the findings of DBE or enteroclysis.

Results:  Comparisons of the positive findings rate with DBE or enteroclysis, the treatment rate and the rebleeding rate with the classification showed: CE‐Ia, 100% (6/6), 50% (3/6), 33.3% (2/6); Ib, 66.7% (4/6), 0% (0/6), 16.7% (1/6); IIa, 33.3% (1/3), 33.3% (1/3), 33.3% (1/3); IIb, 53.8% (7/13),15.4% (2/13), 30.8% (4/13); III, 100% (84/84), 9.5% (8/84), 8.3% (7/84); IV, 100% (2/2), 50% (1/2), 0% (0/2); and 0, 0% (0/9), 0% (0/9), 0% (0/9), respectively.

Conclusions:  The proportion of patients requiring treatment, the positive findings rate with DBE or enteroclysis and the rebleeding rates tended to be higher in the higher ranked classification types (CE‐I > II > III > IV > 0). These findings suggest that the classification can provide useful information on determining the indications and timing of DBE.
Recent vegetation changes at the high‐latitude tree line ecotone are controlled by geomorphological disturbance, productivity and diversity
Authors: Virtanen Risto , Luoto Miska , Rämä Teppo , Mikkola Kari , Hjort Jan , Grytnes John‐Arvid , Birks H. John B.
Published: June 2010

Aim We test how productivity, disturbance rate, plant functional composition and species richness gradients control changes in the composition of high‐latitude vegetation during recent climatic warming.

Location Northern Fennoscandia, Europe.

Methods We resampled tree line ecotone vegetation sites sampled 26 years earlier. To quantify compositional changes, we used generalized linear models to test relationships between compositional changes and environmental gradients.

Results Compositional changes in species abundances are positively related to the normalized difference vegetation index (NDVI)‐based estimate of productivity gradient and to geomorphological disturbance. Competitive species in fertile sites show the greatest changes in abundance, opposed to negligible changes in infertile sites. Change in species richness is negatively related to initial richness, whereas geomorphological disturbance has positive effects on change in richness. Few lowland species have moved towards higher elevations.

Main conclusions The sensitivity of vegetation to climate change depends on a complex interplay between productivity, physical and biotic disturbances, plant functional composition and richness. Our results suggest that vegetation on productive sites, such as herb‐rich deciduous forests at low altitudes, is more sensitive to climate warming than alpine tundra vegetation where grazing may have strong buffering effects. Geomorphological disturbance promotes vegetation change under climatic warming, whereas high diversity has a stabilizing effect.
Mathematical Models for Coinfection by Two Sexually Transmitted Agents: The Human Immunodeficiency Virus and Herpes Simplex Virus Type 2 Case
Authors: Mahiane S. Guy , Nguéma Eugène-P. Ndong , Pretorius Carel , Auvert Bertran
Published: June 2010

To study the interactions between two sexually transmitted diseases without remission of the infections, we propose to use Markovian models. One model allows the estimation of the per-partnership female-to-male transmission probabilities for each infection, and the other the per-sex-act transmission probabilities. These models take into account the essential factors for the propagation of both infections, including the variability according to age of the rates of prevalence in the population of female partners for the male individuals constituting our sample. We estimate transmission probabilities and relative risks (for circumcision, usage of condoms and the effect of one infection on the infectivity of the other) by using the maximum likelihood method. Bootstrap procedures are used to provide confidence intervals for the parameters. We illustrate the new procedures with the study of the interactions between herpes simplex virus type 2 and human immunodeficiency virus by using data from the male circumcision trial that was conducted in Orange Farm (South Africa). The study shows that the probability that a susceptible male individual acquires one of the viruses is significantly higher when he is already infected with the other. Using the Akaike information criterion, we show that the per-partnership model fits the data better than the per-sex-act model.
Cream or foam in pedal skin care: towards the ideal vehicle for urea used against dry skin
Authors: Borelli C. , Bielfeldt S. , Borelli S. , Schaller M. , Korting H. C.
Published: June 2010

Synopsis

The aim of this study was to evaluate different urea‐containing cosmetic preparations designed for foot care regarding skin occlusion. The primary aim was therefore to screen the short‐term transepidermal water loss (TEWL) as a parameter for skin barrier function and skin occlusion and to characterize the relative role of the vehicle, i.e. cream or foam in the context of cosmetics containing urea in the 2–10% range addressing the cosmetic products urea 2% cream (GEHWOL FUSSKRAFT blau), petrolatum containing cream (GEHWOL med Schrundensalbe), urea 10% cream (GEHWOL med Lipidro‐Crème), urea 10% foam (Allpresan Fuss Schaum) and vaseline (positive control) compared with an untreated area on the volar forearms of volunteers. Moreover, the short time (24 h) kinetics regarding the moisturizing effect of cream and foam formulations in diabetic patients were compared. The efficacy of a cream on reduction of skin thickness of hyperkeratotic skin in the heel region before and after a period of product application was also evaluated. In some of the trials, healthy individuals and in others, diabetic patients (type I and II) were enrolled. TEWL was determined before product application, as well as at given points of time thereafter. In this study, no excessive occlusion effects comparable with a blockage of the skin’s natural water evaporation could be observed for any of the test products. To the extent to be expected, this was found neither for the cream products nor for the foam product. Slightly lowered TEWL values after application of the 10% urea cream can be interpreted as a beneficial effect in terms of an improved barrier function. Regarding skin moisture, the urea‐containing cream formulation appeared equal or slightly superior to the foam formulation. The thickness of the horny layer was found reduced after application of 10 % urea‐containing cream. At present it looks as if cream vehicles would still be vehicles of choice in general, when it comes to the formulation of skin care preparations for not only dry skin but also in the context of pedal skin care.
Assessment of the variation of skin barrier function with anatomic site, age, gender and ethnicity
Authors: Machado M. , Hadgraft J. , Lane M. E.
Published: June 2010

Synopsis

The skin is the largest organ of the human body and its functions include protection, thermoregulation sensation and secretion. Significant advances in our understanding of how the morphology and physiology of the skin contribute to the skin’s barrier role have been achieved in recent years. The aim of this review is to summarize the principal approaches which have been used to assess variation in skin barrier function with anatomic site, age, gender, and ethnicity. The methods discussed include trans‐epidermal water loss (TEWL) measurement, assessment of corneocyte size, response to vasoactive compounds and attenuated total reflectance Fourier transform infrared (ATR‐FTIR) interrogation of skin. The utility of the various methods is considered and the most important findings in the literature to date are highlighted.
Airway response to emotion‐ and disease‐specific films in asthma, blood phobia, and health
Authors: Ritz Thomas , Wilhelm Frank H. , Meuret Alicia E. , Gerlach Alexander L. , Roth Walton t.
Published: June 2010

Earlier research found autonomic and airway reactivity in asthma patients when they were exposed to blood‐injection‐injury (BII) stimuli. We studied oscillatory resistance (Ros) in asthma and BII phobia during emotional and disease‐relevant films and examined whether muscle tension counteracts emotion‐induced airway constriction. Fifteen asthma patients, 12 BII phobia patients, and 14 healthy controls viewed one set of negative, positive, neutral, BII‐related, and asthma‐related films with leg muscle tension and a second set without. Ros, ventilation, cardiovascular activity, and skin conductance were measured continuously. Roswas higher during emotional compared to neutral films, particularly during BII material, and responses increased from healthy over asthmatic to BII phobia participants. Leg muscle tension did not abolish Rosincreases. Thus, the airways are particularly responsive to BII‐relevant stimuli, which could become risk factors for asthma patients.
Introduction: Some Questions Concerning the Productive Forces
Authors: BERNSTEIN HENRY
Published: June 2010

This introduction suggests an inherited weakness of ‘orthodox’ materialist conceptions of the development of the productive forces in capitalist agriculture, and the intellectual deficit of an uncritical and ahistorical stance that embraces such development as forever ‘progressive’. The best recent work in political ecology presents agrarian political economy with a challenge to address that intellectual deficit by interrogating and problematizing its inherited conceptions of the productive forces, both theoretically and historically. This is illustrated with reference to notions of the ‘biophysical contradictions of industrial capitalist agriculture’, a global agricultural or food ‘crisis’, and suggested alternatives, drawing on the analyses and arguments of the six papers that follow.
The Material Conditions of a Polarized Discourse: Clamours and Silences in Critical Analysis of Agricultural Water Use in India
Authors: MOLLINGA PETER P.
Published: June 2010

This paper attempts to understand why debates and controversies on agricultural water use in India have taken a bipolar form, characterized by clamours and silences, and in which, paradoxically, Indian agricultural water governance and policy has shifted very little in response to the extremely vibrant and intensive public debate and action on water resources. The paper identifies the technical features of water control systems and the institutional features of the Indian (water) governance structure as the material conditions of that polarization and the source of the deadlock. I argue that the form and content of agricultural water use debates and struggles reflect and help to reproduce their material conditions of existence rather than to transform them. The analysis presented here may help to resolve the paradox and suggest new avenues and emphases for critical analysis and public action.
Beyond Industrial Agriculture? Some Questions about Farm Size, Productivity and Sustainability
Authors: WOODHOUSE PHILIP
Published: June 2010

Although modern agriculture has increased food production faster than population growth in recent decades, there are concerns that existing models of ‘industrial agriculture’ are unsustainable due to long‐run trends towards increased fossil energy costs. This has led to suggestions that food production in future will need to be based on smaller‐scale and more labour‐intensive farming systems. This paper examines political economy arguments that large‐scale capital‐intensive agriculture has proved more productive. It counterposes these to ecological economics approaches that emphasize the low energy efficiency of capital‐intensive mechanized agriculture. The paper argues that discussion of a ‘post‐industrial’ agriculture remain polarized between visions of a more energy‐efficient mechanized agriculture on the one hand, and labour‐intensive farming by ‘new peasantries’, on the other. The paper identifies questions that are neglected by this debate, in particular those concerning the productivity of labour in food production and its implications for food prices and the livelihood basis of farming.
Material Flow Indicators in the Czech Republic in Light of the Accession to the European Union
Authors: Kovanda Jan , Weinzettel Jan , Hák Tomáš
Published: June 2010

This article deals with the economy‐wide material flows in the Czech Republic in 1990–2006. It presents in brief the overall trends of the material flow indicators in 1990–2002. The major part of the article is focused on the years 2002–2006, which immediately preceded and followed the accession of the Czech Republic to the European Union in 2004. It is shown that this accession had quite a significant impact on the volume and character of the material flows of the Czech Republic. The accession was beneficial from an economic point of view, as it allowed for an increased supply of materials needed for economic growth. Furthermore, it was accompanied by an improvement in the efficiency of material transformation into economic output. From an environmental and broader sustainability point of view, however, this accession brought about some controversial outcomes. There was a significant increase in the net export of environmental pressure, on one hand, and an increase in net additions to the physical stock of the economy, on the other. Although the former is controversial from the viewpoint of equity in sharing area and resources, the latter places an additional burden on future generations because all physical stocks will turn into waste and emissions at some point, when their life span expires.
Taking Others into Account: Self‐Interest and Fairness in Majority Decision Making
Authors: Sauermann Jan , Kaiser André
Published: June 2010

Research on the formal properties of democratic aggregation mechanisms has a long tradition in political science. Recent theoretical developments, however, show that in the discussion of normative contents of democratic decisions, the actual shape of preferences deserves just as much attention. However, our knowledge about the concrete motivations of individual behavior in democratic decisions is incomplete. Using laboratory experiments, this article examines the existence of social preferences in majority decisions. Contrary to earlier experiments of committee decision making, we develop a design that controls for the conditions of communication and the level of information between subjects. This allows us to comparatively test the predictive power of several theories. We find strong evidence that self‐interest and fairness motivate human behavior in majority decisions.
Businessman Candidates
Authors: Gehlbach Scott , Sonin Konstantin , Zhuravskaya Ekaterina
Published: June 2010

Why and when do businessmen run for public office rather than rely upon other means of influence? What are the implications of their participation for public policy? We show formally that “businessman candidacy” and public policy are jointly determined by the institutional environment. When institutions that hold elected officials accountable to voters are strong, businessmen receive little preferential treatment and are disinclined to run for office. When such institutions are weak, businessmen can subvert policy irrespective of whether they hold office, but they may run for office to avoid the cost of lobbying elected officials. Evidence from Russian gubernatorial elections supports the model's predictions. Businessman candidates emerge in regions with low media freedom and government transparency, institutions that raise the cost of reneging on campaign promises. Among regions with weaker institutions, professional politicians crowd out businessmen when the rents from office are especially large.
Arterial ReOcclusion and Persistent Distal Occlusion after Thrombus Aspiration
Authors: Zhao Limin , Rubiera Marta , Harrigan Mark R. , Alexandrov Andrei V.
Published: June 2010

BACKGROUND AND PURPOSE

Early reocclusion of intracranial arteries can lead to poor clinical outcome. We report reocclusion detection after endovascular clot aspiration, followed by administration of GPIIb‐IIIa antagonist under continuous ultrasound monitoring.

CASE DESCRIPTION

A 73‐year‐old man developed the right middle cerebral artery (MCA) occlusion with NIHSS 17 points, 6 days after aortic valve replacement. Recanalization was achieved with Penumbra™ system and reocclusion was detected with transcranial Doppler (TCD) 30 minutes postcompletion of intra‐arterial procedure. Proximal recanalization was achieved with the second thrombus aspiration while M2 MCA occlusion persisted beyond the reach of the device. Intravenous abciximab was administered under continuous TCD monitoring. Recanalization with Thrombolysis in Brain Ischemia (TIBI) flow grade 4 was observed at 60 minutes postintervention accompanied with clinical recovery to NIHSS 3 points. Abciximab was given for 12 hours with no hemorrhagic transformation on repeat CT scan. Patient was discharged home with mild left pronator drift and facial droop, and his modified ranking score was 1 at 6‐week follow‐up visit.

CONCLUSIONS

Early arterial reocclusion can occur after successful thrombus aspiration while GPIIb‐IIIa antagonist administration may lead to subsequent recanalization of persisting distal occlusions not amenable to mechanical removal.
parD toxin–antitoxin system of plasmid R1 – basic contributions, biotechnological applications and relationships with closely‐related toxin–antitoxin systems
Authors: Diago‐Navarro Elizabeth , Hernandez‐Arriaga Ana M. , López‐Villarejo Juan , Muñoz‐Gómez Ana J. , Kamphuis Monique B. , Boelens Rolf , Lemonnier Marc , Díaz‐Orejas Ramón
Published: June 2010

Toxin–antitoxin systems, as found in bacterial plasmids and their host chromosomes, play a role in the maintenance of genetic information, as well as in the response to stress. We describe the basic biology of the parD/kiskid toxin–antitoxin system of Escherichia coli plasmid R1, with an emphasis on regulation, toxin activity, potential applications in biotechnology and its relationships with related toxin–antitoxin systems. Special reference is given to the ccd toxin–antitoxin system of plasmid F because its toxin shares structural homology with the toxin of the parD system. Inter‐relations with related toxin–antitoxin systems present in the E. coli chromosome, such as the parD homologues chpA/mazEF and chpB and the relBE system, are also reviewed. The combined structural and functional information that is now available on all these systems, as well as the ongoing controversy regarding the role of the chromosomal toxin–antitoxin loci, have made this review especially timely.
The diurnal flight activity and influential factors of Frankliniella occidentalis in the greenhouse
Authors: Liang Xing‐Hui , Lei Zhong‐Ren , Wen Jin‐Zeng , Zhu Ming‐Liang
Published: June 2010

Abstract  The daily flight activity of western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae) was examined using color, yellow‐light and chemical attractant traps in a cucumber greenhouse and under controlled laboratory conditions. In the greenhouse, flying thrips were most abundant between hours 08:00–10:00, declined at mid‐day, and then slightly increased during hours 14:00–16:00; however they decreased to a very low level at 18:00. The use of light traps showed no thrip flight activity during the night. The total number of thrips that flew onto cards on rainy or cloudy days was higher than that on sunny days. We reconfirmed that traps treated with attractant attracted 4.0–9.4 times more thrip than the untreated traps. Under laboratory controlled conditions, thrip flight activity was highest under light intensity between 4 000 and 6 000 lux, air temperature of 28°C, and RH of 70%. In addition, starved thrips flew more readily than non‐starved thrips.
Allowing Innovative Stem Cell-Based Therapies outside of Clinical Trials: Ethical and Policy Challenges
Authors: Hyun Insoo
Published: June 2010

Armed with expanded federal funding for human embryonic stem cell research and new methods for deriving pluripotent stem cells, stem cell researchers in the U.S. are poised to proceed with unprecedented speed toward the development of new clinical therapies. Staring into the new dawn of regenerative medicine, many observers may assume that the only responsible route to the clinic, both scientifically and ethically, is through FDA-approved clinical trials processes. Conventional wisdom dictates that, like pharmaceutical drugs and the use of biological therapeutics, stem cell-based therapies will have to pass through a series of controlled studies — initially to assess safety and toxicity, then efficacy and comparative efficacy — before they can be justifiably administered to patients outside a clinical trials context.
Overseeing Innovative Therapy without Mistaking it for Research: A Function-Based Model Based on Old Truths, New Capacities, and Lessons from Stem Cells
Authors: Taylor Patrick L.
Published: June 2010

Innovative therapy is the name we give to novel medical interventions, radically different from the standard of care, provided in order to benefit a patient, rather than to acquire new knowledge. They are paradigmshifting, not incremental, responses to serious patient problems that standard medical care inadequately addresses. Innovative therapies are often devised by clinicians, not basic science researchers; they do not follow the linear model of basic research, to translation, to clinical research, to application. Instead, they come from thinking backwards from the patient’s circumstances, and forward from deep knowledge of how the body functions, to challenge the limits of current mechanisms for effecting cures.
Stem Cell Research as Innovation: Expanding the Ethical and Policy Conversation
Authors: Dresser Rebecca
Published: June 2010

In 1998, researchers established the first human embryonic stem cell line. Their scientific triumph triggered an ethics and policy argument that persists today. Bioethicists, religious leaders, government officials, patient advocates, and scientists continue to debate whether this research poses a promise, a threat, or a mixed ethical picture for society.

Scientists are understandably excited about the knowledge that could come from studying human embryonic stem cells. Most of them believe these cells offer a precious opportunity to learn more about why diseases develop and how they might be prevented or attacked. In their quest to gain support for stem cell research, scientists and others have claimed that the research could generate cures and treatment for everything from heart disease to cancer.
The Metamorphosis of Managed Care: Implications for Health Reform Internationally
Authors: Rodwin Marc A.
Published: June 2010

Many writers suggest that managed care had a brief life and that we are now in a post-managed care era. Yet managed care has had a long history and continues to thrive. Writers also often assume that managed care is a fixed entity, or focus on its tools, rather than the context in which it operates and the functions it performs. They overlook that managed care has evolved and neglect to examine the role that it plays in the health system.

This article argues that private actors and the state have used managed care tools to promote diverse goals. These include the following: increasing access to medical care; restricting physician entrepreneurialism; challenging professional control over the medical economy; curbing medical spending; managing medical practice and markets; furthering the growth of medical markets and private insurance; promoting for-profit medical facilities and insurers; earning bounties for reducing medical expenditures; and reducing governmental responsibility for, and oversight of, medical care. Struggles over these competing goals spurred the metamorphosis of managed care internationally.
Interpretation of the Subjects' Condition Requirement: A Legal Perspective
Authors: Shah Seema , Wendler David
Published: June 2010

Clinical research with children generates special ethical concern, raising the need for additional protections beyond those for research with competent adults. Most guidelines permit research with children when it offers a prospect of direct benefit, or poses minimal risk. Unlike many other guidelines, the U.S. federal regulations also allow institutional review boards (IRBs) to approve pediatric research that does not offer a prospect of direct benefit when the risks are no greater than a minor increase over minimal risk. To approve research in this category, IRBs must find that two additional conditions obtain:

1). The intervention or procedure presents experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social, or educational situations; and 2). The intervention or procedure is likely to yield generalizable knowledge about the subjects disorder or condition which is of vital importance for the understanding or amelioration of the subjects disorder or condition.
Reviews in Medical Ethics
Authors: Pope Thaddeus Mason , Gagne Joshua J. , Kesselheim Aaron S.
Published: June 2010

Through the Louisiana Purchase in 1803, the United States expanded its size by over 800,000 square miles. But neither President Thomas Jefferson nor Congress knew exactly what they had bought until 1806, when Meriwether Lewis and William Clark returned from their famous expedition. One of the most significant contributions of the Expedition was a better perception of the geography of the Northwest. Lewis and Clark prepared approximately 140 maps and filled in the main outlines of the previously blank map of the northwestern United States. Robert I. Field has done much the same for the vast territory of U.S. health care regulation.

On the front cover of Fields new book, Health Care Regulation in America: Complexity, Confrontation, and Compromise, is a picture of a giant three-dimensional labyrinth. Rarely is cover art so perfectly appropriate.
IN THIS ISSUE – July 2010
Authors: Jackson AE
Published: June 2010

Presence of Mycobacterium avium subsp. paratuberculosis in raw milk · Profiling of Haemophilus parasuis in live pigs · Cysticercus bovis in Australian cattle · Thoracoscopy for lung lobectomy in the dog · Common bile duct cyst in a cat · Caecal intussusceptions in horses in New Zealand · Improving access to the oral cavity of the wombat · Mycobacterium in a Tasmanian devil · Surgical treatment of osteomyelitis in an alpaca cria
Autoignition Delay Time Measurements of Methane, Ethane, and Propane Pure Fuels and Methane-Based Fuel Blends
Authors: Holton M. M. , Gokulakrishnan P. , Klassen M. S. , Roby R. J. , Jackson G. S.
Published: June 2010

Autoignition delay experiments in air have been performed in an atmospheric flow reactor using typical natural gas components, namely, methane, ethane, and propane. Autoignition delay measurements were also made for binary fuel mixtures of methane/ethane and methane/propane, and ternary mixtures of methane/ethane/propane. The effect of CO2 addition to the methane-based fuel blends on autoignition delay times was also investigated. Equivalence ratios for the experiments ranged between 0.5 and 1.25, and temperatures ranged from 930 K to 1140 K. Consistent with past studies, increasing equivalence ratio and increasing inlet temperatures over these ranges decreased autoignition delay times. Furthermore, addition of 5–10% ethane or propane decreased autoignition delay time of the binary methane-based fuel by 30–50%. Further addition of either ethane or propane showed less significant reduction of autoignition delays. Addition of 5–10% CO2 slightly decreased the autoignition delay times of methane fuel mixtures. Arrhenius correlations were used to derive activation energies for the ignition of the pure fuels and their mixtures. Results show a reduction in activation energies at the higher temperatures studied, which suggests a change in ignition chemistry at very high temperatures. Measurements show relatively good agreement with predictions from a detailed kinetics mechanism, specifically developed to model ignition chemistry of C1-C3 alkanes.
Effect of Injection Strategy on the Combustion and Exhaust Emission Characteristics of a Biodiesel-Ethanol Blend in a DI Diesel Engine
Authors: Yoon Seung Hyun , Hwang Jin Woo , Lee Chang Sik
Published: June 2010

An experimental investigation was performed on the effect of injection strategy on the combustion, exhaust emission characteristics and the particle size distribution in a small direct-injection (DI) compression ignition engine fueled with a biodiesel-ethanol blended fuel. The results obtained from the experiment of the particle distributions for the blended fuel are compared with that of diesel fuel. In addition to the distribution of the particles, exhaust emissions, such as oxides of nitrogen (NOx), hydrocarbon (HC), and carbon monoxide (CO) emissions, and combustion characteristics under different injection parameters were investigated. The injection parameters in terms of first injection mass and second injection mass were varied to investigate the combustion and emission reduction in the biodiesel and ethanol blended fuel. The results show that the first combustion and heat release generated from the first injection, and then the second injected fuel rapidly combusted with an extremely short ignition delay. The maximum combustion pressures and heat releases of a biodiesel-ethanol blend are generally higher than those of the ultra-low sulfur diesel (ULSD) in all cases, regardless if an equal quantity of fuel is injected. The soot and NOx emissions for a blend are relatively lower than the ULSD at all test ranges. In addition, HC and CO emissions for a blend also indicated relatively low levels compared with those of the ULSD. Double injection cases for biodiesel-ethanol blend, the number concentrations of larger size particles which are closely related to the weight of smoke emissions mass were significantly reduced.
LIFE SCIENCE TECHNOLOGIES: Sights Unseen: Microscopy Advances Bring the Cell Into Focus
Authors: Perkel Jeffrey M.
Published: June 2010

As the eminently quotable Yankees ballplayer, Yogi Berra, famously said, "You can observe a lot just by watching." What's true of baseball is true also of biology, and today, biologists are watching quite a bit--just check the pages of your favorite journal. Armed with increasingly sophisticated instruments and software, researchers are probing the inner lives of cells more comprehensively than ever. Many of their advances have been commercialized by the likes of Nikon, Leica, Olympus, and Zeiss; others remain confined to the labs that devised them. For the optically creative researcher, it's an exciting time to be a microscopist.
Functional Roles of Aggregation-Promoting-Like Factor in Stress Tolerance and Adherence of
Lactobacillus acidophilus
NCFM
Authors: Goh Yong Jun , Klaenhammer Todd R.
Published: June 2010

Aggregation-promoting factors (Apf) are secreted proteins that have been associated with a diverse number of functional roles in lactobacilli, including self-aggregation, the bridging of conjugal pairs, coaggregation with other commensal or pathogenic bacteria, and maintenance of cell shape.
In silico
genome analysis of
Lactobacillus acidophilus
NCFM identified LBA0493 as a 696-bp
apf
gene that encodes a putative 21-kDa Apf protein. Transcriptional studies of NCFM during growth in milk showed
apf
to be one of the most highly upregulated genes in the genome. In the present study, reverse transcriptase-quantitative PCR (RT-QPCR) analysis revealed that the
apf
gene was highly induced during the stationary phase compared to that during the logarithmic phase. To investigate the functional role of Apf in NCFM, an Δ
apf
deletion mutant was constructed. The resulting Δ
apf
mutant, NCK2033, did not show a significant difference in cell morphology or growth compared to that of the NCFMΔ
upp
reference strain, NCK1909. The autoaggregation phenotype of NCK2033 in planktonic culture was unaffected. Additional phenotypic assays revealed that NCK2033 was more susceptible to treatments with oxgall bile and sodium dodecyl sulfate (SDS). Survival rates of NCK2033 decreased when stationary-phase cells were exposed to simulated small-intestinal and gastric juices. Furthermore, NCK2033 in the stationary phase showed a reduction of
in vitro
adherence to Caco-2 intestinal epithelial cells, mucin glycoproteins, and fibronectin. The data suggest that the Apf-like proteins may contribute to the survival of
L. acidophilus
during transit through the digestive tract and, potentially, participate in the interactions with the host intestinal mucosa.
Cyclic di-GMP Signaling Regulates Invasion by
Ehrlichia chaffeensis
of Human Monocytes
Authors: Kumagai Yumi , Matsuo Junji , Hayakawa Yoshihiro , Rikihisa Yasuko
Published: June 2010

Cyclic di-GMP (c-di-GMP) is a bacterial second messenger produced by GGDEF domain-containing proteins. The genome of
Ehrlichia chaffeensis
, an obligatory intracellular bacterium that causes human monocytic ehrlichiosis, encodes a single protein that contains a GGDEF domain, called PleD. In this study, we investigated the effects of c-di-GMP signaling on
E. chaffeensis
infection of the human monocytic cell line THP-1. Recombinant
E. chaffeensis
PleD showed diguanylate cyclase activity as it generated c-di-GMP
in vitro
. Because c-di-GMP is not cell permeable, the c-di-GMP hydrophobic analog 2′-
O
-di(
tert
-butyldimethylsilyl)-c-di-GMP (CDGA) was used to examine intracellular c-di-GMP signaling. CDGA activity was first tested with
Salmonella enterica
serovar Typhimurium. CDGA inhibited well-defined c-di-GMP-regulated phenomena, including cellulose synthesis, clumping, and upregulation of
csgD
and
adrA
mRNA, indicating that CDGA acts as an antagonist in c-di-GMP signaling. [
32
P]c-di-GMP bound several
E. chaffeensis
native proteins and two
E. chaffeensis
recombinant I-site proteins, and this binding was blocked by CDGA. Although pretreatment of
E. chaffeensis
with CDGA did not reduce bacterial binding to THP-1 cells, bacterial internalization was reduced. CDGA facilitated protease-dependent degradation of particular, but not all, bacterial surface-exposed proteins, including TRP120, which is associated with bacterial internalization. Indeed, the serine protease HtrA was detected on the surface of
E. chaffeensis
, and TRP120 was degraded by treatment of
E. chaffeensis
with recombinant
E. chaffeensis
HtrA. Furthermore, anti-HtrA inhibited CDGA-induced TRP120 degradation. Our results suggest that
E. chaffeensis
invasion is regulated by c-di-GMP signaling, which stabilizes some bacterial surface-exposed proteins against proteases.
Kinetic Evidence for the Presence of Putative Germination Receptors in
C
lostridium difficile
Spores
Authors: Ramirez Norma , Liggins Marc , Abel-Santos Ernesto
Published: June 2010

Clostridium difficile
is a spore-forming bacterium that causes
Clostridium difficile
-associated disease (CDAD). Intestinal microflora keeps
C. difficile
in the spore state and prevents colonization. Following antimicrobial treatment, the microflora is disrupted, and
C. difficile
spores germinate in the intestines. The resulting vegetative cells are believed to fill empty niches left by the depleted microbial community and establish infection. Thus, germination of
C. difficile
spores is the first required step in CDAD. Interestingly,
C. difficile
genes encode most known spore-specific protein necessary for germination, except for germination (Ger) receptors. Even though
C. difficile
Ger receptors have not been identified, taurocholate (a bile salt) and glycine (an amino acid) have been shown to be required for spore germination. Furthermore, chenodeoxycholate, another bile salt, can inhibit taurocholate-induced
C. difficile
spore germination. In the present study, we examined
C. difficile
spore germination kinetics to determine whether taurocholate acts as a specific germinant that activates unknown germination receptors or acts nonspecifically by disrupting spores' membranes. Kinetic analysis of
C. difficile
spore germination suggested the presence of distinct receptors for taurocholate and glycine. Furthermore, taurocholate, glycine, and chenodeoxycholate seem to bind to
C. difficile
spores through a complex mechanism, where both receptor homo- and heterocomplexes are formed. The kinetic data also point to an ordered sequential progression of binding where taurocholate must be recognized first before detection of glycine can take place. Finally, comparing calculated kinetic parameters with intestinal concentrations of the two germinants suggests a mechanism for the preferential germination of
C. difficile
spores in antibiotic-treated individuals.
Portraits of care: medical research through portraiture
Authors: Aita Virginia A , Lydiatt William M , Gilbert Mark A
Published: June 2010

The Portraits of Care study used portraiture to investigate ideas about care and care giving at the intersection of art and medicine. The study employed mixed methods involving both qualitative and quantitative research techniques. All aspects of the study were approved by the Institutional Review Board. The study included 26 patient and 20 caregiver subjects. Patient subjects were drawn from across the lifespan and included healthy and ill patients. Caregiver subjects included professional and familial caregivers. All subjects gave their informed consent for the study and the subsequent exhibition of artwork. The artist drew or painted 100 portraits during the 2-year study. A multi-disciplinary analysis team carried out the initial analysis of portraits and subject data. Findings from their qualitative analysis were used to develop a quantitative survey and qualitative journal tool that the public used to give feedback at the subsequent exhibition. Exhibition data confirmed the initial findings. Study results showed the introspection of subjects that revealed their sense of identity and psychological status. Patients appear as ‘whole people’, not fragmented by diagnosis. Caregivers' portraits reveal their commitment to care. There is also a sense of mutuality and fluidity in the background stories of subjects. Many patient subjects have been caregivers and, at times, caregivers are also patients. Public data emphasised the identity transformation of subjects, the centrality of the idea of mortality, the presence of hope despite adversity, and the importance of empathy and compassion in care.
Duke Ferdinand: patient or possessed? The reflection of contemporary medical discourse in John Webster'sThe Duchess of Malfi
Authors: Tullo Ellen
Published: June 2010

The Duchess of Malfi, a tragedy written by John Webster, makes frequent reference to contemporary Jacobean concerns about health and disease for dramatic effect. Most notably Webster chooses to highlight lycanthropy through the evolution of the condition in the character of Duke Ferdinand. This paper examines Webster's knowledge of contemporary medical, religious and political texts and explores the reflection of both a natural humoral understanding of lycanthropy as a disease, and the concurrent importance of supernatural concerns prevalent at the time. Although Webster's choice to associate Duke Ferdinand with lycanthropy primarily serves a dramatic purpose, it is proposed that fictional works such asThe Duchess of Malfican be considered as important sources for the history of medicine since authors often reflect the contemporary understanding of health and disease from the world around them.
FLOW FIELD AND TOPOLOGICAL ANALYSIS OF HEMISPHERICAL PARACHUTE IN LOW ANGLES OF ATTACK
Authors: CAO YIHUA , SONG QIANFU , WU ZHUO , SHERIDAN JOHN
Published: June 2010

For analyzing the flow field and topological structure of hemispherical parachute in low angles of attack, a fluid-structure interaction (FSI) simulation technique is established to decide the shape of the hemispherical parachute during terminal descent. In the fluid simulation, the semi-implicit method for pressure-linked equations consistent (SIMPLEC) algorithm is introduced to solve shear stress transport (SST) k–ω turbulence Navier–Stokes (N–S) Equations. This method is proved to be efficient and stable by the experiment and corresponding numerical simulation. After obtaining the stable shape of the canopy, the parachute in different angles and velocities are considered.