bluuebunny/crossref_metadata_2025 huggingface dataset:
Socially and temporally extended end-of-life decision-making process for dementia patients
Authors: Muramoto Osamu
Published: February 2011

There are two contrasting views on the decision-making for life-sustaining treatment in advanced stages of dementia when the patient is deemed incompetent. One is to respect the patient's precedent autonomy by adhering to advance directives or using the substituted judgement standard. The other is to use the best-interests standard, particularly if the current judgement on what is best for the incapacitated patient contradicts the instructions from the patient's precedent autonomy. In this paper, I argue that the protracted clinical course of dementia over many years requires the extended perspective of a progressive decision-making process—extended in both social space and time. The ongoing debate between these two competing views has missed this perspective by focussing on an exclusive disjunction between the competent former self and the incompetent current self. Drawing on theories of situated cognition in cognitive science, I will show that the cognition of a demented patient can be viewed as extended and embodied by her supportive social environment. As the disease progresses, the content of the mind of a demented person becomes partially constituted by such external resources along with her diminishing intrinsic mind. With this understanding, medical decision-making for a demented patient can be construed as a temporally and socially extended practice. A collective decision-making body consisting of the patient, her family and surrogates, and the clinician, should make progressive decisions as a whole over years of the disease course. Finally, I will provide a practical example of how this proposal can be applied in clinical practice.
Parental procreative obligation and the categorisation of disease: the case of cystic fibrosis
Authors: Bosslet Gabriel T
Published: February 2011

The advent of prenatal genetic diagnosis has sparked debates among ethicists and philosophers regarding parental responsibility towards potential offspring. Some have attempted to place moral obligations on parents to not bring about children with certain diseases in order to prevent harm to such children. There has been no rigorous evaluation of cystic fibrosis in this context. This paper will demonstrate cystic fibrosis to have unique properties that make it difficult to categorise among other diseases with the goal of promulgating a reproductive rule. Once this is established, it will be demonstrated that procreative rules that appeal to future health are inadequate in the era of advancing genetic knowledge. Utilising a specification of Joel Feinberg's ‘open future’ concept outlined by Matteo Mameli, it will offer an analysis of parental obligation that does not constrain parents of potential children with cystic fibrosis with a moral obligation not to bring them about.
Limitation of treatment at the end of life: an empirical-ethical analysis regarding the practices of physician members of the German Society for Palliative Medicine
Authors: Schildmann Jan , Hoetzel Julia , Baumann Anne , Mueller-Busch Christof , Vollmann Jochen
Published: February 2011

Objectives

To determine the frequencies and types of limitation of medical treatment performed by physician members of the German Society for Palliative Medicine and to analyse the findings with respect to clinical and ethical aspects of end-of-life practices.

Design

Cross-sectional postal survey.

Setting

Data collection via the secretary of the German Society for Palliative Medicine using the German language version of the EURELD survey instrument.

Subjects

All 1645 physician members of the German Society for Palliative Medicine.

Main outcome measures

Types and frequencies of limitation of treatment and possible determinants.

Results

901 physicians participated in the study (response rate 55.8%). Participants reported limitation of treatment in 69.1% of cases. These decisions most often affected artificial nutrition (19%), chemotherapy (14%), antibiotics (11%) and medication other than antibiotics (11%). In the majority of eligible cases, physicians estimated the life-shortening effect of limitation of treatment to be <7 days. However, estimations differ depending on the medical measures in question. Bivariate statistical analysis indicated that withholding of treatment was performed significantly more frequently for patients aged ≥65 years (p=0.019). In addition, there were significant associations between the incidence of limitation of treatment and the different diseases reported by respondents as the underlying cause of death.

Conclusion

The findings of this study provide information on the current state of an ethically and clinically challenging aspect of clinical practice and can serve as a starting point for further interdisciplinary research on normative and empirical aspects of treatment decision-making at the end of life.
To lie or not to lie: resident physician attitudes about the use of deception in clinical practice
Authors: Everett Jo P , Walters Clifford A , Stottlemyer Debra L , Knight Curtis A , Oppenberg Andrew A , Orr Robert D
Published: February 2011

Background

Physicians face competing values of truth-telling and beneficence when deception may be employed in patient care. The purposes of this study were to assess resident physicians' attitudes towards lying, explore lie types and reported reasons for lying.

Method

After obtaining institutional review board review (OSR# 58013) and receiving exempt status, posts written by Loma Linda University resident physicians in response to forum questions in required online courses were collected from 2002 to 2007. Responses were blinded and manually coded by two investigators using NVivo software. Qualitative and quantitative analyses of the data were performed with links to various attributes. A 95% binomial proportion CI was used to analyse the attribute data.

Results

The study found that the majority of residents (90.3%) would disclose the truth about medical errors. Similarly, many residents (55.7%) would disclose the truth regarding unanticipated events, especially if the error was serious enough to result in a malpractice suit (74.7%). However, many residents (40.9%) would not reveal a near miss event because they believe it has no impact on patient health. Some residents (47.3%) would deceive the insurance company for additional patient benefits. Of those willing to lie, only a small group (4.2%) gave self-serving reasons.

Conclusions

This study demonstrates that the ethical issues related to deception that trouble attending physicians also exist at the resident physician level. Residents primarily lie for altruistic reasons and rarely for egoistic or self-serving purposes that may or may not result in harm to patients, insurance companies and/or physicians themselves.
Superselective Wada test for ruptured spontaneous fusiform middle cerebral artery aneurysm: a technical case report
Authors: Rajpal Sharad , Moftakhar Roham , Bauer Andrew M , Turk Aquilla S , Niemann David B
Published: February 2011

Background

Spontaneous fusiform aneurysms of the middle cerebral artery (sfaMCA) are quite uncommon and tend to occur in young adults. The use of superselective angiography for ruptured and unruptured aneurysms can help delineate vital angioarchitecture and assist with perioperative planning and treatment modality. The use of superselective Wada testing (SWT) for treatment of a ruptured sfaMCA involving the dominant hemisphere, however, has never been described in the English literature. We report a case of a ruptured sfaMCA involving the dominant hemisphere where superselective angiography and SWT were utilized to predict the ability to occlude a major vessel without adverse neurological sequelae.

Case description

A healthy young patient presented with subarachnoid hemorrhage. Initial CT-angiogram of the head identified a left-sided fusiform MCA aneurysm measuring 1.3 cm by 0.5 cm in maximum dimensions. Diagnostic angiography evaluation demonstrated an irregular, fusiform aneurysm involving the central (Rolandic) trunk of the left MCA. An SWT was then performed through an SL 10 microcatheter with injection of sodium amytal. Verbal, motor and cognitive testing were performed twice and revealed no neurological defects. The patient underwent subsequent coil embolization of the aneurysm. Formal post-procedure evaluation revealed no speech, language or cognitive deficits. She was eventually discharged home and remained without neurological deficits at her follow-up appointment 12 months after her initial presentation.

Conclusion

Intraoperative SWT can be performed as part of the initial evaluation for patients with sfaMCA of the dominant cerebral hemisphere to help choose the appropriate treatment algorithm and predict post-treatment neurological deficits.
Counting 15 million more poor in India, thanks to tobacco
Authors: John Rijo M , Sung Hai-Yen , Max Wendy B , Ross Hana
Published: February 2011

Objective

To quantify the impact of tobacco use and the related medical expenditure on poverty in India.

Methods

Tobacco expenditure and associated medical expenditure attributable to tobacco use were subtracted from the household monthly consumption expenditure in order to derive an appropriate measure of household disposable income. The 2004 National Sample Survey, a nationally representative survey of Indian households, was used to estimate the true level of poverty.

Results

Our estimates indicate that accounting for direct expenditure on tobacco would increase the rural and the urban poverty rates by 1.5% (affecting 11.8 million people) and 0.72% (affecting 2.3 million people), respectively. Similarly, the out-of-pocket costs of tobacco-attributable medical care result in 0.09% higher poverty rates in rural areas (affecting 0.7 million people) and in 0.07% higher poverty rates in urban locations (affecting 0.23 million people).

Conclusions

Tobacco consumption impoverishes roughly 15 million people in India. Hence tobacco control measures would not only improve public health, but would also reduce poverty in India.
Assessing the utility of C:N ratios for predicting lipid content in fishes
Authors: Fagan Kelly-Anne , Koops Marten A. , Arts Michael T. , Power Michael
Published: February 2011

Numerous researchers have attempted to find suitable proxies for the lipid content of fishes. Owing to the high carbon content of lipids, C:N ratios have been used as a predictor of lipid content both for the purposes of quantifying condition and for stable isotope analyses. Here we examine the utility of C:N ratios for predicting the lipid content within and among populations, and to validate commonly used published percent lipid – C:N ratio models. No common percent lipid – C:N ratio model was found to apply; instead, population-specific influences on lipid content were observed. Published lipid prediction models significantly underestimated lipid content, and often had worse prediction error than the error obtained by using measured mean lipids as the prediction for all samples. Maximum prediction error by population ranged from a low of 50.7% to a high of 65.0%. Our results provide no support for the idea that there is a predictable relationship between bulk C:N ratios and lipid content. We recommend that sample-specific relationships be developed in situations where lipid prediction is needed, rather than relying on published models.
Intracohort and intercohort spatial density dependence in juvenile brown trout (Salmo trutta)
Authors: Kvingedal Eli , Einum Sigurd
Published: February 2011

An increased mobility with age can be expected for many organisms, which will reduce the potential for spatial density dependence. Here we quantify the extent of spatial density dependence for two juvenile age classes of brown trout ( Salmo trutta ) that differ in their dispersal abilities. As predicted, spatial variation in intracohort density had a strong effect on the performance of underyearlings, but not on yearlings. However, rather surprisingly, local underyearling density influenced the energetics of the older age class to the same extent as their own. Thus, yearlings do not appear to prioritize growth rate per se as a cue in movement decisions. The spatial patterns of densities and performance are consistent with older fish distributing themselves primarily according to preferred abiotic variables that also influence energetics. Such decisions would remove any relation between local density of their own age class and growth performance. However, because of competitive effects from the patchily distributed younger age class, spatial homogenization of competition intensities appears to be constrained. Variation in yearling body mass also increased with density of their own age class, indicating that even though the average effect of intracohort competition was absent, the individual response was asymmetric.
Liming restores Atlantic salmon (Salmo salar) populations in acidified Norwegian rivers
Authors: Hesthagen Trygve , Larsen Bjørn M. , Fiske Peder
Published: February 2011

Acidification has exterminated or seriously reduced Atlantic salmon ( Salmo salar ) populations in 40–45 Norwegian rivers. As this problem still exists, liming to restore salmon has been necessary, which now involves 21 of these rivers. Thirteen rivers were electrofished 1 year before liming and again 1–12 years later. There was a significant effect both of time after liming and status (e.g., formerly lost and reduced stocks) on the densities of both fry (age 0+) and parr (age ≥ 1+). However, the rate of increase in densities of young salmon in these two status categories was not significantly different in either age group. The development in parr densities suggests that more than 20 years of liming is required to restore salmon in rivers with lost native populations. Stocked rivers and rivers unaltered by hydropower developments generally had higher fry densities and faster increase in parr densities. Annual rod catches of adult salmon increased significantly after liming started, reaching about 45 t after 10 years of treatment. This is 11%–12% of the current total catch of Atlantic salmon in all Norwegian rivers. Liming thus makes an important contribution to the restoration of salmon in formerly acidified rivers.
The effect of dreissenid invasions on chlorophyll and the chlorophyll : total phosphorus ratio in north-temperate lakes
Authors: Higgins S. N. , Vander Zanden M. J. , Joppa L. N. , Vadeboncoeur Y.
Published: February 2011

We investigated the effects of dreissenid mussel ( Dreissena polymorpha and D. rostriformis bugensis ) invasions on the concentrations of chlorophyll a (Chl) and total phosphorus(TP), and the Chl:TP ratio within 27 north-temperate lakes that spanned large gradients in lake size and trophic status, using two approaches: (i) regression analysis and (ii) hierarchical modeling. Overall, Chl declined by 40%–45% after dreissenid invasion and the magnitude of effect was structured by epilimnetic volume within stratified, but not nonstratified (mixed) lakes. Declines in TP over the invasion period were significant only for stratified systems and were smaller (∼16% reduction from pre-invasion values) than for Chl. Across the complete trophic gradient (i.e., among lakes) the regression approach (analysis of covariance) indicated a significant decline in the intercept of the Chl:TP, but not the slope. In contrast, hierarchical modeling indicated a decline in the slope of Chl:TP among lakes between pre- and post-invasion periods. As with Chl, the effect of dreissenids on Chl:TP declined with increases in epilimnetic volume in stratified, but not nonstratified lakes. Dreissenid effects on Chl were prolonged, with no indication of diminishing within 7–10 years of invasion.
Geographic variation in density, demography, and life history traits of a harvested, sex-changing, temperate reef fish
Authors: Caselle Jennifer E. , Hamilton Scott L. , Schroeder Donna M. , Love Milton S. , Standish Julie D. , Rosales-Casián Jorge A. , Sosa-Nishizaki Oscar
Published: February 2011

Geographic variation in ecological and environmental factors may lead to intraspecific differences among populations. For the California sheephead ( Semicossyphus pulcher ), an important predator in kelp forests and a target of commercial and recreational fisheries, we evaluated the degree to which different populations exhibited variation in density, demography, and life history traits. We assessed biogeographic patterns of abundance through underwater visual census at 39 sites spanning a major portion of the species range (southern California, USA, to Baja California, Mexico) and made collections from seven focal sites to investigate geographic differences in demography and life histories. California sheephead densities were significantly greater in the southern part of their range and at offshore islands than along the mainland coast. At the focal sites, we found significant spatial variation in density, fecundity, size structure, growth rates, annual survivorship, and the timing of maturation and sex change. Density- and temperature-dependent effects helped to explain the intraspecific differences in these parameters. Studies such as this one will allow for demographic plasticity to be incorporated into future stock assessments. Management of temperate reef fishes may best be achieved on smaller spatial scales as we increase our understanding of geographic variation among populations.
Sea lice infection of juvenile pink salmon (Oncorhynchus gorbuscha): effects on swimming performance and postexercise ion balance
Authors: Nendick L. , Sackville M. , Tang S. , Brauner C. J. , Farrell A. P.
Published: February 2011

Sea lice ( Lepeophtheirus salmonis ) infection negatively affected swimming performance and postswim body ion concentrations of juvenile pink salmon ( Oncorhynchus gorbuscha ) at a 0.34 g average body mass but not at 1.1 g. Maximum swimming velocity (Umax) was measured on over 350 individual pink salmon (0.2–3.0 g), two-thirds of which had a sea lice infection varying in intensity (one to three sea lice per fish) and life stage (chalimus 1 to preadult). For fish averaging 0.34 g (caught in a nearby river free of sea lice and transferred to seawater before being experimentally infected), the significant reduction in Umax was dependent on sea lice life stage, not intensity, and Umax decreased only after the chalimus 2 life stage. Experimental infections also significantly elevated postswim whole body concentrations of sodium (by 23%–28%) and chloride (by 22%–32%), but independent of sea lice developmental stage or infection intensity. For fish averaging 1.1 g (captured in seawater with existing sea lice), the presence of sea lice had no significant effect on either Umax or postswim whole body ions. Thus, a single L. salmonis impacted swimming performance and postswim whole body ions of only the smallest pink salmon and with a sea louse stage of chalimus 3 or greater.
The effects of handling time, ambient light, and anaesthetic method, on the standardized measurement of fish colouration
Authors: Gray Suzanne M. , Hart Francine L. , Tremblay Maude E.M. , Lisney Thomas J. , Hawryshyn Craig W.
Published: February 2011

The effects of handling time, ambient light intensity, and anaesthetic method, on the collection of spectral reflectance data were assessed in two species of Malawi cichlids ( Melanochromis auratus and Metriaclima zebra ). Using spectrometry, colour patches were measured over 10 min, under increasing ambient light levels, and using three anaesthetic methods. As time elapsed, maximum percent reflectance (Rmax) decreased across all anaesthetic methods and species, suggesting that measurements should be taken immediately after capture and anaesthetization. With increasing light intensity, Rmaxincreased significantly, suggesting that measurements should be taken under natural ambient conditions when possible. Finally, we found that anaesthetizing fish using an ice bath produced significantly higher Rmaxthan using either MS-222 (tricaine methanesulphonate) or clove oil (eugenol). However, the highest proportion of ultraviolet (UV) colouration was recorded while fish were anaesthetized with clove oil. Our results highlight the variation involved in measuring fish colour patterns using two related species, and thus indicate the need for a standardized approach to collecting spectral reflectance data in fish.
Egg retention in relation to arrival timing and reproductive longevity in female sockeye salmon (Oncorhynchus nerka)
Authors: Hruska Kimberly A. , Hinch Scott G. , Patterson David A. , Healey Michael C.
Published: February 2011

Some female Pacific salmon ( Oncorhynchus spp.) arrive at spawning grounds but fail to complete spawning prior to death. One hypothesis regarding egg retention is that some individuals do not have sufficient time on spawning grounds for successful completion of spawning. We investigated this hypothesis by quantifying the relationships among arrival timing, reproductive longevity, and egg retention in female sockeye salmon ( Oncorhynchus nerka ) from Weaver Creek Spawning Channel (British Columbia, Canada) in 2006. 250 females were tagged over three sampling periods and followed until death. Earlier-arriving females lived longer than later-arriving females (p < 0.001), but patterns of egg retention were not different across sampling dates (p > 0.40). Complete spawners tended to establish a redd sooner after arrival than incomplete spawners (p = 0.001); there was no relationship between spawning completion and reproductive maturity or fork length (p > 0.30). Consistent with the time limitation hypothesis, females retained a lower proportion of eggs with increasing reproductive longevity. Several long-lived females (>7 days) failed to spawn completely before death, indicating that time limitation was not a factor for spawning success in all females. Further research examining the role of individual-specific behavioural physiology on egg retention in sockeye salmon is needed.
Blowin’ in the wind: reciprocal airborne carbon fluxes between lakes and land This paper is based on the J.C. Stevenson Memorial Lecture presented at the Canadian Conference for Fisheries Research (CCFFR) in Ottawa, Ontario, 9–11 January 2009.
Authors: Vander Zanden M. Jake , Gratton Claudio
Published: February 2011

Ecologists are increasingly interested in how disjunct habitats are connected through the cross-habitat movement of matter, prey, nutrients, and detritus and the implications for recipient systems. The study of lake ecosystems has been dominated by the study of pelagic (open-water) production and processes, though there is growing awareness of the role of terrestrial inputs and benthic trophic pathways. Here, we review the phenomena of airborne fluxes to and from lakes. We assemble published data on terrestrial particulate organic carbon (TPOC) deposition to lakes, insect production, and insect emergence and use these data to simulate how airborne lake-to-land and land-to-lake carbon flux is expected to scale with ecosystem size, while taking into account among-lake variability in emergence and TPOC deposition. Emergent insect flux to land increases as a function of lake size, while TPOC deposition to lakes decreases as a function of lake size. TPOC deposition exceeds insect emergence in small lakes, while in large lakes, insect emergence exceeds TPOC deposition. We present a general framework for considering directional fluxes across habitat boundaries. Furthermore, our results highlight the overarching role of ecosystem geometry in determining insect emergence, airborne carbon deposition, and net carbon flux between adjacent ecosystems.
Evaluation of static liquefaction potential of silty sand slopes
Authors: Lade Poul V. , Yamamuro Jerry A.
Published: February 2011

The mechanism of instability in granular soils is explained and its requirement as a forerunner to the liquefaction of level or sloping ground is described. Case histories support the observation that it is silty sands that liquefy under static and a majority of earthquake-induced conditions. Recent experiments show that clean sands do not behave similarly to silty sands. Tests on loose, silty sand indicate a “reverse” behavior with respect to confining pressure and this violates the basic assumption that loose, silty sands behave similarly to loose, clean sands. Strong correlations between fines content, compressibility, and liquefaction potential are often found for these soils. A procedure for the analysis and evaluation of static liquefaction of slopes of fine sand and silt, such as submarine slopes, mine tailings, and spoil heaps, is presented. It involves determination of the region of instability in stress space in which potential liquefaction may be initiated and determination of the state of stress in the slope. A method of finding the state of stress is developed to predict the zone of potential liquefaction in simple slopes. Trigger mechanisms for initiation of instability followed by soil liquefaction are reviewed and mechanisms of soil strengthening are discussed.
A photoswitchable bichromophoric oxazine with fast switching speeds and excellent fatigue resistance
Authors: Deniz Erhan , Impellizzeri Stefania , Sortino Salvatore , Raymo Françisco M.
Published: February 2011

In search of strategies to regulate the photochemical and photophysical properties of photochromic oxazines, we designed a multichromophoric compound incorporating 3H-indole, benzooxazine, and 2-(4-dimethylaminophenyl)ethynyl fragments. We synthesized this molecule in two steps in an overall yield of 51%, starting from commercial precursors. The ultraviolet irradiation of this photochrome opens a [1,3]oxazine ring in less than 6 ns to generate a zwitterionic isomer with a quantum yield of 0.10. In particular, the photoinduced ring opening generates a 4-nitrophenolate anion and a 3H-indolium cation. Additionally, this process brings the 2-(4-dimethylaminophenyl)ethynyl appendage into conjugation with the 3H-indolium cation. As a result, two distinct bands for the anionic and cationic fragments of the photogenerated zwitterion appear in the visible region of the absorption spectrum. The photogenerated isomer has a lifetime of 2 µs and switches back to the original form with first-order kinetics. Furthermore, this bichromophoric photochrome tolerates hundreds of switching cycles with no sign of degradation and can be operated within rigid polymer matrices. Thus, this particular structural design can lead to the development of a new family of bichromophoric photochromes and photoresponsive materials with microsecond switching times and excellent fatigue resistances.
Aggregation of zinc tetraphenylporphyrin characterized by ensemble and single-molecule fluorescence spectroscopy
Authors: O’Brien Jaclyn A. , Lu Yin , Hooley Emma N. , Ghiggino Kenneth P. , Steer Ronald P. , Paige Matthew F.
Published: February 2011

The aggregation of metalloporphyrins is believed to play a crucial role in the excited-state annihilation process known as triplet–triplet annihilation, which in turn has significant potential applications in photon upconversion schemes. In this work, the propensity of the water-soluble metalloporphyrin zinc (II) meso-tetra(4-sulfonatophenyl)porphine to undergo aggregation when adsorbed to glass cover slips was investigated by single-molecule fluorescence microscopy. In proof-of-principle experiments, it was demonstrated (1) that individual molecules of the metalloporphyrin can be directly visualized in spite of their very weak fluorescence emission, and (2) that at low concentrations (10−8 mol/L), the molecule has a strong tendency to form multimolecular aggregates. A subset of the multimolecular aggregates shows a significant blue-shift in fluorescence emission, though at present the precise nature of the molecular aggregates remains unclear.
Dye-sensitized solar cells made of titania nanoparticles structured into a mesoporous material
Authors: Aprile Carmela , Teruel Laura , Alvaro Mercedes , García Hermenegildo
Published: February 2011

Using cetyltrimethylammonium bromide as the structure-directing agent, titania nanoparticles (3–5 nm) were organized into a mesoporous material (8.6 nm average pore size and 99 m2/g). The textural and spatial structuring of the mesoporous material were studied by isothermal gas adsorption, X-ray diffraction, and transmission electron microscopy. Dye-sensitized solar cells using mesoporous material exhibit a one order of magnitude increase in the overall efficiency with respect to analogous cells prepared using the same nanoparticles without periodic mesoporous material. This photovoltaic enhancement is due to increased adsorption of the dye (ruthenium polypyridyl N719) to the mesoporous material arising from the larger area of this mesoporous solid with respect to the same unstructured nanoparticles.
Kinetic and mechanistic studies of the reactions of diarylgermylenes and tetraaryldigermenes with carbon tetrachloride
Authors: Huck Lawrence A. , Leigh William J.
Published: February 2011

The mechanisms of the reactions of diphenylgermylene (GePh2) with CCl4in hydrocarbon solvents and in THF solution have been studied, employing 3,4-dimethyl-1,1-diphenylgermacyclopent-3-ene (6a) and 1,1-diphenylgermacyclobutane (17) as photochemical precursors to GePh2. In hydrocarbon solvents, the reaction produces Ph2GeCl2(10) and Ph2Ge(Cl)CCl3(12) in a ratio of 10:12 ≈ 7, along with a variety of other radical-derived products and small amounts of Ph2GeH(D)Cl (11), which is formed partly by reaction of GePh2with adventitious HCl. The reaction is much cleaner in THF, where 12 is formed as the major product (10:12 ≈ 0.8); a similar product distribution is obtained in hexanes containing 0.05 mol/L THF, while 12 is the exclusive product in hexanes containing 3 mmol/L NEt3. Rate constants for the reactions of CCl4with GePh2and five ring-substituted derivatives were determined by laser flash photolysis, as well as Arrhenius parameters for reaction of the parent (GePh2), in the two solvents. The reactions of GePh2with CCl4and CHCl3have also been studied in 3-methylpentane solution at 78–90 K. Different reaction mechanisms are clearly operative in hydrocarbon and complexing solvents, but both involve modest charge donation from germanium to the substrate in the transition state for the rate-determining step. For the reaction in hydrocarbon solvents, the data are consistent with inner-sphere electron transfer following or in concert with weak Lewis acid–base complexation. A similar mechanism is proposed for the reaction in THF solution, in competition with a second involving nucleophilic attack of the germylene–THF complex at a chlorine atom of the substrate. Rate constants were also determined for reaction of CCl4with the corresponding tetraaryldigermenes at low halocarbon concentrations in hexanes, along with Arrhenius parameters for the parent (Ge2Ph4). These reactions also proceed via initial Cl-atom abstraction, based on the identity of the products formed in the reaction of CCl4with tetramesityldigermene.
Impact of CCR7 on the gastrointestinal field effect
Authors: Koscielny A. , Engel D. , Maurer J. , Hirner A. , Kurts C. , Kalff J. C.
Published: February 2011

Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune mediated. This study aimed to investigate the role of CCR7 in IM-induced FE. Since CCR7 is expressed on activated dendritic cells and T cells and is well known to control their migration, we hypothesized that lack of CCR7 reduces or abolishes FE. Small bowel muscularis and colonic muscularis from CCR7−/− and wild-type (WT) mice were obtained after IM of the jejunum or sham operation. FE was analyzed by measuring gastrointestinal transit time of orally given fluorescent dextran (geometric center), colonic transit time, infiltration of MPO-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of the inflammatory cytokine IL-6 were determined by RT-PCR. The number of dendritic cells and CD3+CD25+ T cells separately isolated from jejunum and colon was determined in mice after IM and sham operation. There was no significant difference in IL-6 mRNA upregulation in colonic muscularis between sham-operated WT and CCR7−/− mice after IM. Contractility of circular muscularis strips of the colon was significantly improved in CCR7−/− animals following IM and did not vary significantly from sham-operated animals. Additionally, inflammation of the colon determined by the number of MPO-positive cells and colonic transit time was significantly reduced in CCR7−/− mice. In contrast, jejunal contractility and jejunal inflammation of transgenic mice did not differ significantly from WT mice after IM. These data are supported by a significant increase of CD3+CD25+ T cells in the colonic muscularis of WT mice after IM, which could not be observed in CCR7−/− mice. These data demonstrate that CCR7 is required for FE and postoperative ileus. CCR7 indirectly affects FE by inhibiting migration of activated dendritic cells and of T cells from the jejunum to the colon. These findings support the critical role of the adaptive immune system in FE.
Alterations of serum proteinN-glycosylation in two mouse models of chronic liver disease are hepatocyte and not B cell driven
Authors: Blomme Bram , Van Steenkiste Christophe , Grassi Paola , Haslam Stuart M. , Dell Anne , Callewaert Nico , Van Vlierberghe Hans
Published: February 2011

N-glycosylation of immunoglobulin G (IgG) has an important impact on the modification of the total serum N-glycome in chronic liver patients. Our aim was to determine the role and magnitude of the alterations in which hepatocytes and B cells are involved in two mouse models of chronic liver disease. Common bile duct ligation (CBDL) and subcutaneous injections with CCl4were induced in B cell-deficient and wild-type (WT) mice. IgG depletion was performed with beads covered with protein A/G and the depletions were evaluated by SDS-PAGE and Western blot analysis. N-glycan analysis was performed by improved DSA-FACE technology. Structural analysis of the mouse serum N-glycans was performed by exoglycosidase digests and MALDI-TOF mass spectrometry of permethylated glycans. The alterations seen in B cell-deficient mice closely resembled the alterations in WT mice, in both the CBDL and the CCl4models. N-glycan analysis of the IgG fraction in both mouse models revealed different changes compared with humans. Overall, the impact of IgG glycosylation on total serum glycosylation was marginal. Interestingly, the amount of fibrosis present in CBDL B cell-deficient mice was significantly increased compared with CBDL WT mice, whereas the opposite was true for the CCl4model as determined by Sirius red staining. However, this had no major effect on the alteration of N-glycosylation of serum proteins. Alterations of total serum N-glycome in mouse models of chronic liver disease are hepatocyte-driven. Undergalactosylation of IgG is not present in mouse models of chronic liver disease.
Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans
Authors: Kellogg Dean L. , Zhao Joan L. , Wu Yubo , Johnson John M.
Published: February 2011

We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC). Intradermal microdialysis was used to treat one site with 1 mM ODQ in 2% DMSO and Ringer, a second site with 2% DMSO in Ringer, and a third site received Ringer. In protocol 1, after a period of normothermia, whole body heat stress was induced. In protocol 2, local heating units warmed local skin temperature from 34 to 41°C to cause local vasodilation. In protocol 1, in normothermia, CVC did not differ among sites [ODQ, 15 ± 3% maximum CVC (CVCmax); DMSO, 14 ± 3% CVCmax; Ringer, 17 ± 6% CVCmax; P > 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 ± 4% CVCmax; DMSO, 64 ± 4% CVCmax; Ringer, 63 ± 4% CVCmax; P < 0.05, ODQ vs. DMSO or Ringer). In protocol 2, at 34°C local temperature, CVC did not differ among sites (ODQ, 17 ± 2% CVCmax; DMSO, 18 ± 4% CVCmax; Ringer, 18 ± 3% CVCmax; P > 0.05). ODQ attenuated CVC increases at 41°C local temperature (ODQ, 54 ± 5% CVCmax; DMSO, 86 ± 4% CVCmax; Ringer, 90 ± 2% CVCmax; P < 0.05 ODQ vs. DMSO or Ringer). sGC participates in neurogenic active vasodilation during heat stress and in the local response to direct skin warming.
Effect of calorie restriction on the free-living physical activity levels of nonobese humans: results of three randomized trials
Authors: Martin Corby K. , Das Sai Krupa , Lindblad Lauren , Racette Susan B. , McCrory Megan A. , Weiss Edward P. , DeLany James P. , Kraus William E. ,   for the CALERIE Study Team
Published: February 2011

The objective of this study was to evaluate the influence of calorie restriction (CR) on free-living physical activity levels among humans. Data were from three CALERIE phase I site-specific protocols. Participants were nonobese (body mass index = 23.5–29.9 kg/m2) adults randomly assigned to 25% CR, low-calorie diet (LCD, 890 kcal/day supplement diet until 15% weight loss, then weight maintenance), or control at Pennington Biomedical Research Center (PBRC); 30% or 10% CR at Tufts University; and 20% CR or control at Washington University School of Medicine (WUSM). Activity was measured at months 0, 3, and 6 (PBRC) and at months 0, 3, 6, 9, and 12 (WUSM and Tufts). Total daily energy expenditure (TEE) by doubly labeled water and resting metabolic rate (RMR) were used to compute activity energy expenditure: AEE = TEE − RMR − 0.1 * TEE. Accelerometry and 7-day recall categorized activities by intensity. At Tufts, the 10% and 30% CR groups experienced significant decreases in AEE at months 6, 9, and 12. At month 6, a larger decrease in AEE was observed in the CR than the control group at WUSM. At months 3 and 6, larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC. Accelerometry and 7-day PAR did not consistently detect changes in activity categories. CR-associated changes in AEE were variable but, generally, reduced the energy deficit, which would reduce the expected rate of weight loss. Accelerometry and recall did not consistently explain reduced AEE, suggesting that increased muscle efficiency and/or decreased fidgeting accounted for decreased AEE. Inaccuracy of accelerometry and recall also likely negatively affected sensitivity.
Oxygen-dependent quenching of phosphorescence used to characterize improved myocardial oxygenation resulting from vasculogenic cytokine therapy
Authors: Hiesinger William , Vinogradov Sergei A. , Atluri Pavan , Fitzpatrick J. Raymond , Frederick John R. , Levit Rebecca D. , McCormick Ryan C. , Muenzer Jeffrey R. , Yang Elaine C. , Marotta Nicole A. , MacArthur John W. , Wilson David F. , Woo Y. Joseph
Published: February 2011

This study evaluates a therapy for infarct modulation and acute myocardial rescue and utilizes a novel technique to measure local myocardial oxygenation in vivo. Bone marrow-derived endothelial progenitor cells (EPCs) were targeted to the heart with peri-infarct intramyocardial injection of the potent EPC chemokine stromal cell-derived factor 1α (SDF). Myocardial oxygen pressure was assessed using a noninvasive, real-time optical technique for measuring oxygen pressures within microvasculature based on the oxygen-dependent quenching of the phosphorescence of Oxyphor G3. Myocardial infarction was induced in male Wistar rats ( n = 15) through left anterior descending coronary artery ligation. At the time of infarction, animals were randomized into two groups: saline control ( n = 8) and treatment with SDF ( n = 7). After 48 h, the animals underwent repeat thoracotomy and 20 μl of the phosphor Oxyphor G3 was injected into three areas (peri-infarct myocardium, myocardial scar, and remote left hindlimb muscle). Measurements of the oxygen distribution within the tissue were then made in vivo by applying the end of a light guide to the beating heart. Compared with controls, animals in the SDF group exhibited a significantly decreased percentage of hypoxic (defined as oxygen pressure ≤ 15.0 Torr) peri-infarct myocardium (9.7 ± 6.7% vs. 21.8 ± 11.9%, P = 0.017). The peak oxygen pressures in the peri-infarct region of the animals in the SDF group were significantly higher than the saline controls (39.5 ± 36.7 vs. 9.2 ± 8.6 Torr, P = 0.02). This strategy for targeting EPCs to vulnerable peri-infarct myocardium via the potent chemokine SDF-1α significantly decreased the degree of hypoxia in peri-infarct myocardium as measured in vivo by phosphorescence quenching. This effect could potentially mitigate the vicious cycle of myocyte death, myocardial fibrosis, progressive ventricular dilatation, and eventual heart failure seen after acute myocardial infarction.
Endogenous reactive oxygen species modulates voltage-gated sodium channels in dorsal root ganglia of rats
Authors: Wang Han-Jun , Li Yu-Long , Zhang Li-Bin , Zucker Irving H. , Gao Lie , Zimmerman Matthew C. , Wang Wei
Published: February 2011

We recently reported that reactive oxygen species (ROS) plays an excitatory role in modulation of the exercise pressor reflex (EPR) in normal rats. In this study, we further tested two independent hypotheses: 1) ROS interacts with EPR-related ionotropic receptors such as the purinergic receptors (P2) and transient receptor potential vanilloid 1 receptors (TRPV1) to indirectly modulate the EPR function; 2) ROS directly affects excitability of muscle afferents by modulating the voltage-gated sodium (Nav) channels. To test the first hypothesis, we performed animal experiments to investigate the effect of the SOD mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl (Tempol) on the pressor response to hindlimb intra-arterial (IA) injection of either α,β-methylene ATP (a P2X agonist) or capsaicin (a TRPV1 agonist) in decerebrate rats. To test the second hypothesis, we used the patch-clamp technique to determine the effect of ROS on Nav channels on the soma of muscle afferents. We also performed local microinjection of a sodium channel blocker, tetrodotoxin (TTX), into ipsilateral L4/L5 dorsal root ganglia (DRGs) to investigate whether the blockade of Nav channels by TTX affects the EPR function. We found that Tempol did not affect the pressor response to injection of either capsaicin or α,β-methylene ATP but significantly decreased the Nav current in small and medium-sized 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled DRG neurons. A membrane-permeant superoxide dismutase, polyethylene glycol (PEG)-SOD, had an effect on the Nav current in these neurons similar to that of Tempol. Microinjection of TTX into L4/L5 DRGs dramatically attenuated the pressor response to static contraction induced by electrical stimulation of L4/L5 ventral roots. These data suggest that ROS modulates the EPR by affecting the activity of the Nav channels on muscle afferents.
Heat-Shock Induction of Tumor-Derived Danger Signals Mediates Rapid Monocyte Differentiation into Clinically Effective Dendritic Cells
Authors: Aguilera Raquel , Saffie Carlos , Tittarelli Andrés , González Fermín E. , Ramírez Marcos , Reyes Diego , Pereda Cristián , Hevia Daniel , García Tamara , Salazar Lorena , Ferreira Arturo , Hermoso Marcela , Mendoza-Naranjo Ariadna , Ferrada Carlos , Garrido Paola , López Mercedes N. , Salazar-Onfray Flavio
Published: February 2011

Purpose: This study characterizes, biologically and clinically, a novel type of dendritic cells (DC) produced in the short term and called tumor antigen–presenting cells (TAPCells). In particular, we identified factors present in a lysate derived from heat-shocked allogeneic melanoma cells (TRIMEL) that are associated with TAPCells' enhanced capability to induce CD8+ T-cell responses in vitro and in vaccinated melanoma patients.

Experimental Design: First, extensive phenotypic and functional characterization of TAPCells was performed, followed by vaccination of 45 melanoma patients with four doses of TAPCells over a period of 2 months. Specific delayed-type hypersensitivity (DTH) reaction was analyzed posttreatment and correlated with overall survival rates. Furthermore, heat-shock (HS)-induced factors present in TRIMEL and their effects on DC activation were identified and studied.

Results: TRIMEL induced a committed, mature, DC-like phenotype in TAPCells and effectively activated melanoma-specific CD4+ and CD8+ T cells. Clinically, 64% of vaccinated patients showed positive DTH reaction against TRIMEL, and this was associated with improved overall survival. HS treatment of tumor cells increased calreticulin (CRT) plasma membrane translocation and induced the release of high-mobility group box 1 proteins (HMGB1). Both CRT and HMGB1 mobilization were associated with enhanced TAPCells' maturation and antigen (Ag) cross-presentation, respectively. DTH infiltration analysis revealed the presence of CD8+/CD45RO+ T cells, thus confirming TAPCells' ability to cross-present Ags in vivo.

Conclusions: Our results indicate that lysates derived from heat-shocked tumor cells are an optimal source of tumor-associated Ags, which are crucial for the generation of DCs with improved Ag cross-presentation capacity and clinically effective immunogenicity. Clin Cancer Res; 17(8); 2474–83. ©2011 AACR.
Splenectomy in Chronic Hepatic Disorders: Portal Vein Thrombosis and Improvement of Liver Function
Authors: Ushitora Yuichiro , Tashiro Hirotaka , Takahashi Shoichi , Amano Hironobu , Oshita Akihiko , Kobayashi Tsuyoshi , Chayama Kazuaki , Ohdan Hideki
Published: February 2011

Background: Splenectomy is gaining increasing importance for cirrhotic patients with hypersplenism. However, its safety and efficacy for patients with chronic liver disease remain unclear. Methods: We retrospectively examined the medical records of 38 consecutive cirrhotic patients who underwent splenectomy or simultaneous hepatectomy and splenectomy for hepatocellular carcinoma. Results: White blood cell and platelet counts significantly increased 3 months after splenectomy. Serum levels of total bilirubin and prothrombin time significantly improved 1 year after splenectomy. Interferon therapy was administered to 25 patients after splenectomy. A sustained viral response was achieved in 8 patients (42%). The total incidence of portal or splenic vein thrombosis (PSVT) detected by postoperative dynamic computed tomography was 13/38 (34.2%). Multivariate analysis revealed preoperative spleen volume (SV) to be the sole independent predictor of postoperative PSVT. Receiver-operator characteristic curve analysis showed that a cut-off SV of 450 ml corresponded to a sensitivity of 85% and a specificity of 56%. Conclusions: Splenectomy improved the liver function and facilitated effective interferon therapy in cirrhotic patients with hypersplenism, although preoperative SV was frequently associated with postoperative PSVT.