bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population-Based Analysis of Incidence and Outcome of Transformed Non-Hodgkin's Lymphoma
Authors: Al-Tourah Abdulwahab J. , Gill Karamjit K. , Chhanabhai Mukesh , Hoskins Paul J. , Klasa Richard J. , Savage Kerry J. , Sehn Laurie H. , Shenkier Tamara N. , Gascoyne Randy D. , Connors Joseph M. 
Published: October 2008

Purpose To assess the incidence and predictive factors for development of transformed lymphoma in a population-based series of patients with follicular lymphoma (FL). Patients and Methods The Lymphoid Cancer Database was used to identify patients with FL diagnosed and treated in the province of British Columbia, Canada. Transformed lymphoma was defined as the development of aggressive non-Hodgkin's lymphoma (NHL) in patients with FL. Factors present at the time of initial diagnosis of indolent NHL and at transformation were analyzed for their impact on risk of transformation and subsequent outcome. Results Between 1986 and 2001, 600 patients with newly diagnosed FL met the inclusion criteria. With a median follow-up of 109 months (range, 10 to 244), 170 (28%) developed transformation, 107 (63%) based on biopsy confirmation. The annual risk of transformation was 3% continuously through 15 years. A multivariate analysis of clinical factors at diagnosis identified advanced stage as the only predictor of future transformation. The median post-transformation survival was 1.7 years. The 5-year survival was superior for patients with limited extent transformation compared with those with advanced cases (66% v 19%, P < .0001). Patients with transformation based on clinical versus histological criteria had an identical median survival of 1.8 years (P = .2). Conclusion The annual risk of transformation of FL is 3% continuing without plateau beyond 15 years. Advanced stage at diagnosis is predictive of future transformation. Clinically diagnosed transformation has an equal impact on outcome as biopsy proven transformation.
Immunoembolization of Malignant Liver Tumors, Including Uveal Melanoma, Using Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Sato Takami , Eschelman David J. , Gonsalves Carin F. , Terai Mizue , Chervoneva Inna , McCue Peter A. , Shields Jerry A. , Shields Carol L. , Yamamoto Akira , Berd David , Mastrangelo Michael J. , Sullivan Kevin L. 
Published: October 2008

Purpose We conducted a phase I study to investigate the feasibility and safety of immunoembolization with granulocyte-macrophage colony-stimulating factor (GM-CSF; sargramostim) for malignant liver tumors, predominantly hepatic metastases from patients with primary uveal melanoma. Patients and Methods Thirty-nine patients with surgically unresectable malignant liver tumors, including 34 patients with primary uveal melanoma, were enrolled. Hepatic artery embolization accompanied an infusion of dose-escalated GM-CSF (25 to 2,000 μg) given every 4 weeks. Primary end points included dose-limiting toxicity and maximum tolerated dose (MTD). Patients who completed two cycles of treatments were monitored for hepatic antitumor response. Survival rates of patients were also monitored. Results MTD was not reached up to the dose level of 2,000 μg, and there were no treatment-related deaths. Thirty-one assessable patients with uveal melanoma demonstrated two complete responses, eight partial responses, and 10 occurrences of stable disease in their hepatic metastases. The median overall survival of intent-to-treat patients who had metastatic uveal melanoma was 14.4 months. Multivariate analyses indicated that female sex, high doses of GM-CSF (≥ 1,500 μg), and regression of hepatic metastases (complete and partial responses) were correlated to longer overall survival. Moreover, high doses of GM-CSF were associated with prolonged progression-free survival in extrahepatic sites. Conclusion Immunoembolization with GM-CSF is safe and feasible in patients with hepatic metastasis from primary uveal melanoma. Encouraging preliminary efficacy and safety results warrant additional clinical study in metastatic uveal melanoma.
Prevalence of Lymphedema in Women With Breast Cancer 5 Years After Sentinel Lymph Node Biopsy or Axillary Dissection: Objective Measurements
Authors: McLaughlin Sarah A. , Wright Mary J. , Morris Katherine T. , Giron Gladys L. , Sampson Michelle R. , Brockway Julia P. , Hurley Karen E. , Riedel Elyn R. , Van Zee Kimberly J. 
Published: October 2008

PurposeSentinel lymph node biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. The aim of this study was to determine the long-term prevalence of lymphedema after SLN biopsy (SLNB) alone and after SLNB followed by axillary lymph node dissection (SLNB/ALND).Patients and MethodsAt median follow-up of 5 years, lymphedema was assessed in 936 women with clinically node-negative breast cancer who underwent SLNB alone or SLNB/ALND. Standardized ipsilateral and contralateral measurements at baseline and follow-up were used to determine change in ipsilateral upper extremity circumference and to control for baseline asymmetry and weight change. Associations between lymphedema and potential risk factors were examined.ResultsOf the 936 women, 600 women (64%) underwent SLNB alone and 336 women (36%) underwent SLNB/ALND. Patients having SLNB alone were older than those having SLNB/ALND (56 v 52 years; P < .0001). Baseline body mass index (BMI) was similar in both groups. Arm circumference measurements documented lymphedema in 5% of SLNB alone patients, compared with 16% of SLNB/ALND patients (P < .0001). Risk factors associated with measured lymphedema were greater body weight (P < .0001), higher BMI (P < .0001), and infection (P < .0001) or injury (P = .02) in the ipsilateral arm since surgery.ConclusionWhen compared with SLNB/ALND, SLNB alone results in a significantly lower rate of lymphedema 5 years postoperatively. However, even after SLNB alone, there remains a clinically relevant risk of lymphedema. Higher body weight, infection, and injury are significant risk factors for developing lymphedema.
Anti–Cytotoxic T-Lymphocyte Antigen-4 Antibody: The First in an Emerging Class of Immunomodulatory Antibodies for Cancer Treatment
Authors: Fong Lawrence , Small Eric J. 
Published: October 2008

PurposeTo evaluate the emerging role of immunomodulatory antibodies in cancer treatment. Antibodies (ipilimumab and tremelimumab) targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), an inhibitory molecule on T cells, represent the vanguard of these new drugs.DesignWe performed a systematic review of the clinical studies examining the clinical activity of anti–CTLA-4 antibodies. We also review the potential mechanisms and toxicities associated with these treatments.ResultsClinical activity with anti–CTLA-4 monoclonal antibodies (mAbs) has paved the way for additional T-cell immunomodulatory monoclonal antibody (mAb) approaches for the treatment of cancer to be investigated. Because anti–CTLA-4 mAbs target the immune system and not the tumor, they may provide significant potential advantages over traditional antitumor mAbs, chemotherapies, and immunotherapies (ie, vaccines and cytokines). Other antibodies, such as CD137 agonists, CD40 agonists, and PD-1 antagonists, are currently in various stages of preclinical and clinical development.ConclusionAvailable clinical data suggest that anti–CTLA-4 mAbs are very different from traditional mAbs, chemotherapies, and immunotherapies in terms of patterns of response, duration of response, and adverse event profile. Ongoing clinical studies aim to establish the efficacy and safety of anti–CTLA-4 mAbs as monotherapy or in combination with other drugs for the treatment of metastatic melanoma and a variety of other cancer types.
Ontogenetic changes in the structural stiffness of the tailstock of bottlenose dolphins (Tursiops truncatus)
Authors: Etnier S. A. , McLellan W. A. , Blum J. , Pabst D. A. 
Published: October 2008

SUMMARYLate-term fetal bottlenose dolphins (Tursiops truncatus) are bent ventrolaterally en utero, requiring extreme flexibility of the axial skeleton and associated soft tissues. At birth, neonatal dolphins must immediately swim to the surface to breath, yet the dorsoventral oscillations used during locomotion may be compromised by the lateral flexibility evident in the fetus. The unique fetal position of dolphins, coupled with their need to swim at birth, places conflicting mechanical demands on the tailstock. Our previous research demonstrated that neonatal dolphins possess laterally placed, axial muscles that are functionally specialized to actively maintain the straightened posture of the tailstock. Here, we investigated the development of passive lateral stability in the tailstock of bottlenose dolphins by performing whole-body bending tests on an ontogenetic series of stranded dolphin specimens (N=15), including fetuses, neonates and juveniles (total length 58–171 cm). Structural stiffness increased,while overall body curvature decreased, with increasing body length. Scaling analyses suggest that increased structural stiffness is due to increases in size and probably changes in the passive material properties of the tailstock through ontogeny. The neutral zone was approximately constant with increasing size, while the relative neutral zone (neutral zone/total length) decreased. The lateral stability of the tailstock appears to be controlled by a combination of active and passive systems and the role of these systems varies through ontogeny. While neonates use active, muscular mechanisms to limit lateral deformations of the tailstock, the stability of the maturing tailstock is due primarily to its passive tissue properties.
Scaling the duration of activity relative to body mass results in similar locomotor performance and metabolic costs in lizards
Authors: Donovan E. R. , Gleeson T. T. 
Published: October 2008

SUMMARYThis study examines the physiological response to locomotion in lizards following bouts of activity scaled to body mass. We evaluate this method as a way to compare locomotor energetics among animals of varying body mass. Because most of the costs of brief activity in reptiles are repaid during recovery we focus on the magnitude and duration of the excess post-exercise oxygen consumption (EPOC). Lizards ranging from 3 g to 2400 g were run on a treadmill for durations determined by scaling the run time of each animal to the 1/4 power of body mass and allowing each animal to run at its maximum speed for that duration. This protocol resulted in each species traveling the same number of body lengths and incurring similar factorial increases in V̇O2. Following activity, EPOC volume (ml O2) and the cost of activity per body length traveled (ml O2 per body length) scaled linearly with body mass. This study shows that the mass-specific costs of activity over an equivalent number of body lengths are similar across a broad range of body mass and does not show the typical patterns of allometric scaling seen when cost of locomotion are expressed on a per meter basis. Under field conditions larger animals are likely to travel greater absolute distances in a given bout of activity than smaller animals but may travel a similar number of body lengths. This study suggests that if locomotor costs are measured on a relative scale (ml O2 per body length traveled), which reflects these differences in daily movement distances, that locomotor efficiency is similar across a wide range of body mass.
Running biomechanics: shorter heels, better economy
Authors: Scholz M. N. , Bobbert M. F. , van Soest A. J. , Clark J. R. , van Heerden J. 
Published: October 2008

SUMMARY
Better running economy (i.e. a lower rate of energy consumption at a given speed) is correlated with superior distance running performance. There is substantial variation in running economy, even among elite runners. This variation might be due to variation in the storage and reutilization of elastic energy in tendons. Using a simple musculoskeletal model, it was predicted that the amount of energy stored in a tendon during a given movement depends more critically on moment arm than on mechanical properties of the tendon, with the amount of stored energy increasing as the moment arm gets smaller. Assuming a link between elastic energy reutilization and overall metabolic cost of running, a smaller moment arm should therefore be associated with superior running economy. This prediction was confirmed experimentally in a group of 15 highly trained runners. The moment arm of the Achilles tendon was determined from standardized photographs of the ankle, using the position of anatomical landmarks. Running economy was measured as the rate of metabolic energy consumption during level treadmill running at a speed of 16 km h–1. A strong correlation was found between the moment arm of the Achilles tendon and running economy. Smaller muscle moment arms correlated with lower rates of metabolic energy consumption (r2=0.75, P&lt;0.001).
The mechanism of flight guidance in honeybee swarms: subtle guides or streaker bees?
Authors: Schultz Kevin M. , Passino Kevin M. , Seeley Thomas D. 
Published: October 2008

SUMMARYWhen a honeybee swarm takes off to fly to its new home site, less than 5%of the bees in the swarm have visited the site and thereby know in what direction the swarm must fly. How does the small minority of informed bees indicate the swarm's flight direction to the large majority of uninformed bees? Previous simulation studies have suggested two possible mechanisms of visual flight guidance: the informed bees guide by flying in the preferred direction but without an elevated speed (subtle guide hypothesis) or they guide by flying in the preferred direction and with an elevated speed(streaker bee hypothesis). We tested these hypotheses by performing a video analysis that enabled us to measure the flight directions and flight speeds of individual bees in a flying swarm. The distributions of flight speed as a function of flight direction have conspicuous peaks for bees flying toward the swarm's new home, especially for bees in the top of the swarm. This is strong support for the streaker bee hypothesis.
Differential recovery from exercise and hypoxia exposure measured using 31P- and 1H-NMR in white muscle of the common carpCyprinus carpio
Authors: Hallman Troy M. , Rojas-Vargas Anibal C. , Jones David R. , Richards Jeffrey G. 
Published: October 2008

SUMMARYPhosphocreatine (PCr) was reduced to equivalent levels in carp white muscle by high-intensity exhaustive exercise and exposure to hypoxia at 15°C and 25°C in order to assess the influence of intracellular pH(pHi), temperature and lactate levels on PCr recovery in vivo. High-intensity exercise resulted in a significantly lower pHi compared with hypoxia exposure and the rate of PCr depletion and tissue acidification during hypoxia exposure was significantly higher in carp held at 25°C compared with those at 15°C. During recovery, PCr and pHi returned towards normoxia/resting levels at a faster rate following hypoxia exposure than after exercise. The lower pHi in exercised carp caused a greater perturbation to cellular energy status(assessed as the free energy of ATP hydrolysis; ΔfG′) and resulted in a higher [ATP]/[ADPfree] ratio, which may limit mitochondrial ATP production and contribute to the slower recovery from exercise compared with recovery from hypoxia exposure. Rates of recovery from exercise and hypoxia exposure were not affected by acclimation temperature (15 and 25°C), suggesting that the processes involved in acclimation compensate for the Q10 effects of temperature on metabolic processes. Finally, using a dual 31P-NMR and 1H-NMR analysis technique, we demonstrated that the greater tissue acidification observed after high-intensity exercise compared with hypoxia exposure occurred at similar white muscle lactate concentrations.
The effects of CO2 and external buffering on ammonia excretion and Rhesus glycoprotein mRNA expression in rainbow trout
Authors: Nawata C. Michele , Wood Chris M. 
Published: October 2008

SUMMARYRhesus (Rh) proteins were recently characterized as ammonia gas(NH3) channels. Studies indicate, however, that Rh proteins also facilitate CO2 transport in a green alga and in human erythrocytes. Previously, we reported that Rh mRNA expression in various rainbow trout tissues responded to high environmental ammonia. To determine whether or not Rh proteins may also be involved in CO2 transport in rainbow trout,we examined the effects of a 12 h exposure to external hypercapnia (1%CO2 in air) on Rh mRNA expression in the gill, skin and erythrocytes. External hypercapnic conditions lowered the water pH and facilitated ammonia excretion; therefore, we also studied the effects of hypercapnia and normocapnia in the presence of 10 mmol l–1Hepes-buffered water. Hepes treatment prevented water acidification, but resulted in elevated plasma ammonia levels and reduced ammonia excretion rates. Hypercapnia exposure without buffering did not elicit changes in Rh mRNA expression in the gill or skin. However, Rhcg2 mRNA expression was downregulated in the gills and upregulated in the skin of both normocapnia- and hypercapnia-exposed fish in Hepes-buffered water. mRNA expression of a newly cloned Rhbg2 cDNA was downregulated in the skin of fish exposed to buffered water, and Rhag mRNA expression in erythrocytes was decreased with exposure to normocapnia in buffered water but not with hypercapnia exposure in either buffered or unbuffered water. With the aid of Hepes buffering, we were able to observe the effects of both CO2 and ammonia on Rh mRNA expression. Overall, we conclude that high CO2 did not directly elicit changes in Rh mRNA transcription levels in the gill and skin, and that the changes observed probably reflect responses to high plasma ammonia, mirroring those in trout exposed to high environmental ammonia. Therefore a dual function for gill and skin Rh proteins in CO2 and ammonia transport is not evident from these results. Rhag expression, however, responded differentially to high CO2 and high ammonia, suggesting a possible dual role in the erythrocytes.
Thermal tolerance in bottlenose dolphins (Tursiops truncatus)
Authors: Yeates Laura C. , Houser Dorian S. 
Published: October 2008

SUMMARYWater and air temperature are potentially limiting factors to the pole-ward distributions of coastal bottlenose dolphins. This study assessed the lower critical temperature of captive bottlenose dolphins to air temperature(LCTa) and water temperature (LCTw) through the use of open flow respirometry. Five dolphins, ranging from 14 to 33 years of age and acclimated to the waters of the southern California coast(14.2–22.5°C), were subjected to water temperatures ranging from 0.2 to 18.0°C. Two of the animals were additionally subjected to air temperatures ranging from –2.4 to 17.8°C while maintaining water temperature approximately 3°C above their individual LCTw. The LCTw ranged from 5.5 to 10.6°C and generally decreased with increasing animal mass; for dolphins in excess of 187 kg, the LCTwranged from 5.5 to 5.7°C. No LCTa could be determined across the range of air temperatures tested. Core body temperature remained within the limits of normal body temperatures reported for dolphins but demonstrated a direct relationship to water temperature in three subjects and varied across a range of 1.5°C. Air and water temperature had a minimal synergistic effect on dolphin thermoregulation, i.e. water temperature exerted the predominant impact on thermoregulation. For dolphins in excess of 187 kg,water temperature alone would appear to be insufficient to limit the use of habitat north of current bottlenose dolphin ranges along the coastal United States. However, thermal impacts to smaller dolphins, in particular adolescents, neonates and accompanying females, may work in concert with other factors (e.g. prey distribution, predator avoidance, social interactions) to influence coastal residency patterns and population structure.
Comparison of smooth and hairy attachment pads in insects: friction,adhesion and mechanisms for direction-dependence
Authors: Bullock James M. R. , Drechsler Patrick , Federle Walter 
Published: October 2008

SUMMARY
Adhesive pads on the legs of animals can be classified as either `smooth'or `hairy' (fibrillar). It has been proposed that the hairy design conveys superior and controllable adhesion. However, no study has yet compared the basic performance of both systems. As such, we measured single-pad friction and adhesion forces in sample hairy (Gastrophysa viridula) and smooth(Carausius morosus) pads and simultaneously recorded contact area. Adhesion and friction forces per unit pad area were very similar in smooth and hairy systems. Insect pads of both types adhere via a thin film of liquid secretion. As found previously for the smooth system, forces in the fibrillar system strongly decreased with larger amounts of fluid secretion present, suggesting that the fluid mainly serves to maximize contact on rough substrates. One essential prerequisite for the control of surface attachment during locomotion is the direction-dependence of adhesive pads. We compared the mechanisms of direction-dependence in smooth and hairy systems by performing proximal and distal slides. Both types of pad exhibited a large drop in friction when moved away from the body, although this effect was more extreme for the hairy system. Direction-dependence is explained in both smooth and fibrillar systems by the instability of the tarsal chain, causing the whole pad to peel off. In the fibrillar pads, anisotropy additionally arises from the direction-dependence of individual setae.
Control of discontinuous gas exchange inSamia cynthia: effects of atmospheric oxygen, carbon dioxide and moisture
Authors: Terblanche John S. , Marais Elrike , Hetz Stefan K. , Chown Steven L. 
Published: October 2008

SUMMARYThe evolution of discontinuous gas exchange (DGE) in insects is highly controversial. Adaptive hypotheses which have obtained experimental support include a water savings mechanism for living in dry environments (hygric hypothesis), a reduction in oxidative damage due to a high-performance oxygen delivery system (oxidative damage hypothesis), and the need for steep intratracheal partial pressure gradients to exchange gases under the hypercapnic and/or hypoxic conditions potentially encountered in subterranean environments (chthonic hypothesis). However, few experimental studies have simultaneously assessed multiple competing hypotheses within a strong inference framework. Here, we present such a study at the species level for a diapausing moth pupa, Samia cynthia. Switching gas conditions from controlled normoxic, normocapnic and intermediate humidity to either high or low oxygen, high or low moisture, elevated carbon dioxide, or some combination of these, revealed that DGE was abandoned under all conditions except high oxygen, and high or low gas moisture levels. Thus, support is found for the oxidative damage hypothesis when scored as maintenance of DGE. Modulation of DGE under either dry or hyperoxic conditions suggested strong support for the oxidative damage hypothesis and some limited support for the hygric hypothesis. Therefore, this study demonstrates that the DGE can be maintained and modulated in response to several environmental variables. Further investigation is required using a strong-inference, experimental approach across a range of species from different habitats to determine how widespread the support for the oxidative damage hypothesis might be.