bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Estradiol on the Thermoneutral Zone and Core Temperature in Ovariectomized Rats
Authors: Dacks Penny A. , Rance Naomi E.
Published: January 2010

Hot flushes represent a disorder of central thermoregulation characterized by the episodic activation of heat loss mechanisms. Although flushes are associated with estrogen withdrawal, there is little understanding of the effects of estrogen on thermoregulation in any species. It has been proposed that hormone withdrawal increases the sensitivity of hypothalamic neural pathways that control heat dissipation effectors. If so, we predicted that ovariectomized rats without estradiol treatment would activate tail skin vasodilatation (a major heat loss effector) at lower ambient temperatures and thereby lower the thermoneutral zone. The thermoneutral zone, defined as the range of ambient temperatures in which thermoregulation is achieved only by sensible (dry) heat loss, was evaluated based on properties of skin vasomotion. Core and tail skin temperatures were recorded in ovariectomized rats (with and without estradiol-17β) exposed to ambient temperatures from 13 to 34 C in an environmental chamber. Rats without estradiol exhibited increased skin vasodilatation and a shift in the thermoneutral zone to lower ambient temperatures. Moreover, the ambient temperature threshold for skin vasodilatation was significantly lower in rats without estradiol treatment. At most ambient temperatures, average core temperature was unaffected by estradiol. However, at ambient temperatures of 32.5 C and above, untreated ovariectomized rats exhibited higher core temperatures compared with estradiol-treated rats. Thus, estradiol-17β treatment enhanced the maintenance of core temperature during heat exposure. These findings support the hypothesis that estrogen withdrawal increases the sensitivity of thermoregulatory neural pathways and modifies the activation of heat loss mechanisms.
Certolizumab Pegol: A TNF-α Antagonist for the Treatment of Moderate-to-Severe Crohn's Disease
Authors: Smith Lisa S , Nelson Michael , Dolder Christian R
Published: January 2010

Objective:

To review certolizumab pegol for the treatment of moderate-to-severe Crohn's disease (CD).

Data Sources:

Clinical studies were identified through MEDLINE (1966–October 1, 2009), bibliographies of articles, International Pharmaceutical Abstracts, clinicaltrials.gov, fda.gov, and New Drug Approval documents ( www.accessdata.fda.gov ). Search terms were CDP 870, certolizumab pegol, Cimzia, Crohn's disease, and inflammatory bowel disease.

Study Selection and Data Extraction:

Human studies describing pharmacology, pharmacokinetics, efficacy, and safety of certolizumab pegol were identified. Phase 2 and Phase 3 randomized controlled trials and observational studies were reviewed, with emphasis given to Phase 2 and Phase 3 trials.

Data Synthesis:

Certolizumab pegol is a tumor necrosis factor-alfa (TNF-α) antagonist, approved for the treatment of moderate-to-severe CD that is failing conventional therapy. It is an antigen-binding fragment (Fab') portion of an immunoglobulin G antibody attached to a polyethylene glycol moiety. In 2 Phase 3 randomized, placebo-controlled trials, certolizumab pegol was effective in inducing clinical response compared with placebo. Common adverse effects during clinical trials were upper respiratory tract infection, urinary tract infection, and arthralgia. Serious infection occurred in 3% of patients. The 4 published controlled trials for the use of certolizumab pegol in the treatment of CD share similar limitations with other studies of TNF-α antagonists including high placebo response, natural course of disease fluctuation, and the use of Crohn's Disease Activity Index to assess outcomes. However, certolizumab pegol is an effective agent for adults with moderate-to-severe CD with less than optimal response to conventional therapy. Long-term efficacy and safety data are unavailable. Certolizumab pegol and adalimumab, unlike infliximab, can be self-administered.

Conclusions:

With similarity in cost and the lack of head-to-head comparisons, patient and physician preference may determine choice of TNF-α antagonist.
Update on Pressure Ulcer Management and Deep Tissue Injury
Authors: Mao Cindy L , Rivet Amanda J , Sidora Tara , Pasko Mary T
Published: January 2010

Objective:

To review recent literature regarding therapeutic management of pressure ulcers and to discuss the potential implications of the newly recognized entity, deep tissue injury (DTI).

Data Sources:

A MEDLINE search was conducted of pressure ulcer therapy published between January 2001 and October 2009. Key search terms included pressure ulcers, deep tissue injury, nutrition, antibiotics, and therapy.

Study Selection and Data Extraction:

Comparative clinical trials involving pharmacologic agents in the treatment of pressure ulcers and DTI were evaluated. Included trials were those with defined interventions and outcome parameters for wound healing.

Data Synthesis:

Pressure ulcers remain an important issue in the care of elderly and immobilized patients. DTI has been recently added by the National Pressure Ulcer Advisory Panel as a separate category in the staging of pressure ulcers. There is currently a lack of consensus on how to identify and treat DTI. but preventive measures typically employed in the management of all pressure ulcers have been recommended. Recent studies on topical phenytoin, silver preparations, and growth factors report benefit in the management of pressure ulcers. However, studies evaluating these treatment approaches often lack the sample size necessary to adequately support recommendations.

Conclusions:

Determining the extent of tissue damage in DTI is currently not possible. Therefore, management recommendations focus on limiting extension of the ulcer stage through preventive strategies. Routine use of topical phenytoin, silver preparations, or growth factors in therapy of pressure ulcers cannot be recommended until more data from rigorously designed studies are available.
Safety of Subcutaneous Octreotide in Patients with Sulfonylurea-Induced Hypoglycemia and Congestive Heart Failure
Authors: Vallurupalli Srikanth
Published: January 2010

Objective:

To report the safe use of subcutaneous octreotide in the treatment of sulfonylurea-induced hypoglycemia in 2 patients with severe congestive heart failure.

Case Summary:

Two patients with congestive heart failure with systolic dysfunction presented with severe hypoglycemia (blood glucose level: patient 1, 31 mg/dL; patient 2, 36 mg/dL) secondary to sulfonylurea agents. The mechanism of hypoglycemia was poor oral intake and prolonged half-life of the drugs due to renal failure. Hypoglycemia was refractory to glucose supplementation. Patient 1 received 2 doses of octreotide 50 μg subcutaneously 12 hours apart, with resolution of hypoglycemia (blood glucose level: <33 mg/dL before administration of octreotide, 62 mg/dL after first dose, 121 mg/dL after second dose). Patient 2 received an initial dose of octreotide 25 μg subcutaneously; hypoglycemia persisted after this dose, and the patient was given 2 doses of 50 μg subcutaneously 12 hours apart, leading to resolution of hypoglycemia (blood glucose level: 57 mg/dL before administration of octreotide, 80 mg/dL after first dose, 85 mg/dL after second dose, 146 mg/dL after third dose). Resolution of hypoglycemia with octreotide treatment obviated the need for prolonged intravenous dextrose infusions. No local or systemic adverse effects, especially cardiac adverse events, were noted during the course of treatment.

Discussion:

Octreotide is considered the antidote for sulfonylurea-induced hypoglycemia. It may be especially useful in patients with congestive heart failure who may not tolerate intravenous infusions of dextrose. The package insert cautions of the occurrence of cardiac adverse effects such as bradycardia, heart block, and worsening heart failure. Patients with heart failure may theoretically be at a higher risk of these adverse effects due to the concurrent use of atrioventricular blocking agents. However, a review of current literature reveals that the adverse effect profile depends on the route, dose, and formulation of the octreotide used along with the clinical indication. These adverse effects may not be clinically significant with the doses used for treatment of sulfonylurea-induced hypoglycemia and the benefits of the drug may outweigh the risks.

Conclusions:

In these cases, octreotide was safely and effectively used in the treatment of sulfonylurea-induced hypoglycemia in patients with congestive heart failure by adhering to dosing guidelines and close monitoring.
Evaluating the effects of implementation intention and self‐concordance on behaviour
Authors: Chatzisarantis Nikos L. D. , Hagger Martin S. , Wang John C. K.
Published: January 2010

The purpose of the present study was to investigate effects of implementation intentions on taking one multivitamin tablet, everyday, for 2 weeks, among individuals who endorsed self‐concordant and self‐discordant forms of motivation. A 2 (implementation intentions: yes, no)×3(motivation: self‐concordance, self‐discordance, control) experimental design was adopted with university students being exposed to manipulations of implementation intentions, self‐concordance, and self‐discordance (male=110, female=120, M age=23.50 years, SD=7.21). Results of the study indicated that while implementation intentions increased multivitamin intake for individuals who endorsed self‐concordant and self‐discordant forms of motivation, the combination of self‐concordance and implementation intentions produced particularly enhanced levels of compliance on multivitamin intake. The implications of results of the present study to theory development and practice are discussed.
Implicit Visuomotor Processing for Quick Online Reactions Is Robust against Aging
Authors: Kadota Koji , Gomi Hiroaki
Published: January 2010

It is well established that humans can react more quickly to a visual stimulus in the visual field center than to one in the visual periphery and that the reaction to a stimulus in the visual periphery markedly deteriorates with aging. These tendencies are true in conventional discrimination-reaction tasks. Surprisingly, however, we found that they are entirely different when reactions are induced by the same visual stimuli during reaching movements. The reaction time for a stimulus in the visual periphery was significantly faster than in the central vision, and age-related slowing of reactions to the stimulus in the visual periphery were quite small, compared to that observed in the conventional reaction tasks. This inconsistent slowing of reactions in different motor conditions underscores a distinctive visuomotor pathway for online control, which is more robust against age-related deterioration.
Norrin Promotes Vascular Regrowth after Oxygen-Induced Retinal Vessel Loss and Suppresses Retinopathy in Mice
Authors: Ohlmann Andreas , Seitz Roswitha , Braunger Barbara , Seitz David , Bösl Michael R. , Tamm Ernst R.
Published: January 2010

Norrin is a secreted protein that is involved in retinal angiogenesis and activates the Wnt-signaling pathway. We studied the role of Norrin in microvascular endothelial cellsin vitro, and in a mouse model of retinopathy characterized by oxygen-induced vascular loss followed by hypoxia-induced pathological neovascularization. Recombinant Norrin significantly increased proliferation, viability, migration, and tube formationin vitro. Two independent transgenic mouse strains with ectopic overexpression of Norrin from the lens (βB1-Crystallin-Norrin), or the retinal pigment epithelium (Rpe65-Norrin) were generated and exposed to high oxygen. Following oxygen treatment, vascular loss was significantly smaller in retinae of transgenic mice from both strains as compared to wild-type littermates. In addition, the anatomical correct regrowth of vessels was significantly increased, while pathological neovascularization was suppressed.In vitroandin vivoeffects of Norrin could be blocked by adding DKK (Dickkopf)-1, an inhibitor of Wnt/β-catenin signaling. Treatment of microvascular endothelial cells with Norrin caused a substantial increase in the expression of angiopoietin-2 (Ang-2). When inhibitory antibodies against Ang-2 were added to Norrin, the proliferative effects of Norrin were significantly suppressed. We conclude that Norrin is a potent factor to induce angiogenesis in microvascular endothelial cells, which has the distinct potential to suppress the damaging effects of oxygen-induced retinopathyin vivo. The effects of Norrin appear to be mediated, at least partially, via the induction of Ang-2.
Mechanisms of Spatial Attention Control in Frontal and Parietal Cortex
Authors: Szczepanski Sara M. , Konen Christina S. , Kastner Sabine
Published: January 2010

Theories of spatial attentional control have been largely based upon studies of patients suffering from visuospatial neglect, resulting from circumscribed lesions of frontal and posterior parietal cortex. In the intact brain, the control of spatial attention has been related to a distributed frontoparietal attention network. Little is known about the nature of the control mechanisms exerted by this network. Here, we used a novel region-of-interest approach to relate activations of the attention network to recently described topographic areas in frontal cortex [frontal eye field (FEF), PreCC/IFS (precentral cortex/inferior frontal sulcus)] and parietal cortex [intraparietal sulcus areas (IPS1–IPS5) and an area in the superior parietal lobule (SPL1)] to examine their spatial attention signals. We found that attention signals in most topographic areas were spatially specific, with stronger responses when attention was directed to the contralateral than to the ipsilateral visual field. Importantly, two hemispheric asymmetries were found. First, a region in only right, but not left SPL1 carried spatial attention signals. Second, left FEF and left posterior parietal cortex (IPS1/2) generated stronger contralateral biasing signals than their counterparts in the right hemisphere. These findings are the first to characterize spatial attention signals in topographic frontal and parietal cortex and provide a neural basis in support of an interhemispheric competition account of spatial attentional control.
Selective T-Type Calcium Channel Block in Thalamic Neurons Reveals Channel Redundancy and Physiological Impact ofITwindow
Authors: Dreyfus Fanny M. , Tscherter Anne , Errington Adam C. , Renger John J. , Shin Hee-Sup , Uebele Victor N. , Crunelli Vincenzo , Lambert Régis C. , Leresche Nathalie
Published: January 2010

Although it is well established that low-voltage-activated T-type Ca2+channels play a key role in many neurophysiological functions and pathological states, the lack of selective and potent antagonists has so far hampered a detailed analysis of the full impact these channels might have on single-cell and neuronal network excitability as well as on Ca2+homeostasis. Recently, a novel series of piperidine-based molecules has been shown to selectively block recombinant T-type but not high-voltage-activated (HVA) Ca2+channels and to affect a number of physiological and pathological T-type channel-dependent behaviors. Here we directly show that one of these compounds, 3,5-dichloro-N-[1-(2,2-dimethyl-tetrahydro-pyran-4-ylmethyl)-4-fluoro-piperidin-4-ylmethyl]-benzamide (TTA-P2), exerts a specific, potent (IC50= 22 nm), and reversible inhibition of T-type Ca2+currents of thalamocortical and reticular thalamic neurons, without any action on HVA Ca2+currents, Na+currents, action potentials, and glutamatergic and GABAergic synaptic currents. Thus, under current-clamp conditions, the low-threshold Ca2+potential (LTCP)-dependent high-frequency burst firing of thalamic neurons is abolished by TTA-P2, whereas tonic firing remains unaltered. Using TTA-P2, we provide the first direct demonstration of the presence of a window component of Ca2+channels in neurons and its contribution to the resting membrane potential of thalamic neurons and to the Up state of their intrinsically generated slow (<1 Hz) oscillation. Moreover, we demonstrate that activation of only a small fraction of the T-type channel population is required to generate robust LTCPs, suggesting that LTCP-driven bursts of action potentials can be evoked at depolarized potentials where the vast majority of T-type channels are inactivated.
Firing and Cellular Properties of V2a Interneurons in the Rodent Spinal Cord
Authors: Dougherty Kimberly J. , Kiehn Ole
Published: January 2010

Previous studies have shown that a group of ventrally located neurons, designated V2a interneurons, play a key role in maintaining locomotor rhythmicity and in ensuring appropriate left–right alternation during locomotion (Crone et al., 2008, 2009). These V2a interneurons express the transcription factor Chx10. The aim of the present study was to characterize the locomotor-related activity of individual V2a interneurons, their cellular properties, and their detailed anatomical attributes in Chx10-GFP mice. A dorsal horn-removed preparation was developed to allow for visual whole-cell patch recordings from V2a interneurons along the entire lumbar spinal cord while at the same time leaving enough of the spinal cord intact to generate fictive locomotion. During drug-evoked locomotor-like activity, a large proportion of Chx10 cells showed rhythmic firing or membrane potential fluctuations related to either flexor or extensor activity in every lumbar segment. Chx10 cells received predominantly rhythmic excitatory input. Chx10 neurons displayed a wide variety of firing and potential rhythmogenic properties. However, none of these properties was obviously related to the observed rhythmicity during locomotor-like activity. In dual recordings, we found no evidence of Chx10 neuron interconnectivity. Intracellular fills revealed diverse projection patterns with most Chx10 interneurons being local with projections to the central pattern generator and motor neuron regions of the spinal cord and others with long ascending and/or descending branches. These data are compatible with V2a neurons having a role in regulating segmental left–right alternation and ipsilateral motor neuron firing with little effect on rhythm generation.
Electrophysiological Characterization of V2a Interneurons and Their Locomotor-Related Activity in the Neonatal Mouse Spinal Cord
Authors: Zhong Guisheng , Droho Steven , Crone Steven A. , Dietz Shelby , Kwan Alex C. , Webb Watt W. , Sharma Kamal , Harris-Warrick Ronald M.
Published: January 2010

The V2a class of Chx10-expressing interneurons has been implicated in frequency-dependent control of left–right phase during locomotion in the mouse. We have used theChx10::CFPmouse line to further investigate the properties and locomotion-related activity of V2a interneurons in the isolated neonatal spinal cord. V2a interneurons can be divided into three classes, based on their tonic, phasic, or delayed-onset responses to step depolarization. Electrical coupling is found only between neurons of same class and helps to synchronize neuronal activity within the class. Serotonin (5-HT) excites isolated tonic V2a interneurons by depolarizing the neurons and increasing their membrane input resistance, with no significant effects on action potential properties, a mechanism distinct from 5-HT excitation of commissural interneurons. During NMDA-/5-HT-induced locomotor-like activity, patch-clamp recordings and two-photon calcium imaging experiments show that approximately half of V2a interneurons fire rhythmically with ventral root-recorded motor activity; the rhythmic V2a interneurons fired during one half of the cycle, in phase with either the ipsilateral or the contralateral L2 ventral root bursts. The percentage of rhythmically firing V2a interneurons increases during higher-frequency fictive locomotion, and they become significantly more rhythmic in their firing during the locomotor cycle; this may help to explain the frequency-dependent shift in left–right coupling inChx10::DTAmice, which lack these neurons. Our results together with data from the accompanying paper (Dougherty and Kiehn, 2009) reinforce earlier proposals that the V2a interneurons are components of the hindlimb central pattern generator, helping to organize left–right locomotor coordination in the neonatal mouse spinal cord.
Botriomicose cutânea: relato de caso
Authors: Coelho Weber Soares , Diniz Lucia Martins , Souza Filho João Basílio de
Published: January 2010

Botriomicose é infecção bacteriana crônica, granulomatosa, supurativa, que afeta a pele e os tecidos subcutâneos. Caracteriza-se por lesão cutânea com múltiplas fístulas, que drena secreção purulenta, na qual se encontram grãos branco-amarelados, PAS-positivos. O principal agente etiológico é o Staphylococcus aureus, e outros germes menos frequentes são Pseudomonas aeruginosa, Escherichia coli, isolados ou associados. Os autores relatam um caso da doença, com lesões exuberantes de consistência fibrosa e múltiplos orifícios fistulosos dos quais drenavam grãos branco-amarelados, localizadas na perna direita e provocando aumento de volume do membro, que tiveram resolução com sulfametoxazol- trimetoprim.
Derolathrus cavernicolusn. sp., a Beetle Family New for North America (Coleoptera: Jacobsoniidae)
Authors: Peck Stewart B
Published: January 2010

Derolathrus cavernicolus n. sp. is the first beetle in the family Jacobsoniidae described from continental North America. It is reported from cave and forested habitats in Florida, the island of Barbados in the Lesser Antilles, and tentatively from the island of Hawaii, USA. A key to the three known New World species of Derolathrus is provided. Derofathrus atomusSharp, 1908, of Hawaii is redescribed and new records are reported from Hawaii and the United States Virgin Islands. Derolathrus sharpiGrouvelle, 1912, of Guadeloupe (Lesser Antilles) is redescribed and new records are reported from the West Indian islands of St. John and Montserrat. Some of the populations may be accidental introductions through the movement of horticultural materials and more can be expected.
Molecular Phylogenetic Placement of the Recently Described Armored Scale Insect Abgrallaspis aguacatae and Several Congeners (Hemiptera: Diaspididae)
Authors: Rugman-Jones Paul F , Andersen Jeremy C , Morse Joseph G , Normark Benjamin B , Stouthamer Richard
Published: January 2010

‘Hass’ avocado, Persea americana Miller, fruit being imported into California from Mexico are infested with high levels of a previously unknown species of armored scale insect (Hemiptera: Diaspididae). This species has recently been described and given the name Abgrallaspis aguacatae Evans, Watson & Miller. However, the validity of morphological characters used to diagnose genera within the tribe Aspidiotini (Diaspididae) is the subject of continued debate. Here, we seek to circumnavigate the inherent problems associated with interpretation of somewhat plastic phenotypic characters. We use two different nuclear gene regions (28S and Elongation Factor 1α) and three different analysis methods (maximum parsimony, maximum likelihood, and Bayesian analyses) to infer phylogeny from DNA sequence data for 35 aspidiotine species. Our analyses suggest that the new species is misplaced in the genus Abgrallaspis Balachowsky and that this genus and several closely allied genera are paraphyletic or polyphyletic. The findings of our analyses are discussed specifically in relation to the current placement of A. aguacatae and more broadly in relation to the long-recognized problem of defining generic boundaries between Abgrallaspis, Diaspidiotus Berlese, and Hemiberlesia Cockerell.
Ground Ant Diversity (Hymenoptera: Formicidae) in the Iberá Nature Reserve, the Largest Wetland of Argentina
Authors: Calcaterra Luis A , Cuezzo Fabiana , Cabrera Sonia M , Briano Juan A
Published: January 2010

The Iberá Nature Reserve in northeastern Argentina protects one of the largest freshwater wetlands and reservoirs of species in South America. However, key invertebrate groups such as the ants (Hymenoptera: Formicidae) remain almost unknown. The main objective of this work was to study the ground ant diversity in four main habitats of Iberá: grasslands, savannas, forests, and floating islands. Pitfall traps were used to characterize ground foraging ant assemblages, compare ant diversity among environments, and establish habitat associations. We also used bait traps, manual collections, and Winkler and Berlese extractors on the ground, vegetation, and litter strata to increase the species inventory. In total, 94 species in 30 genera were captured, representing the highest number of species reported from a survey of a protected area of Argentina. The richest genus was Pheidole Westwood with 23 species including three species reported for the first time in Argentina. The most common species was Solenopsis invicta Buren. Overall, the savanna was the richest and most diverse habitat with the highest number of exclusive species and functional groups. The grassland showed the highest number of rare species, but only half of the expected species were captured. The forest showed the lowest ant richness, diversity, and equitability, but one half of the species were exclusive to forest habitat. Generalized myrmicines were predominant and dominant in all habitats. Our findings indicate that habitat specialization could be an important factor determining the organization of ant assemblages in Iberá. The protection of each of these unique and threatened natural habitats of Argentina is needed to ensure the long-term preservation of their exclusive ant species.
Metabolism of Imidacloprid in Workers of Reticulitermes flavipes (Isoptera: Rhinotermitidae)
Authors: Tomalski Michael , Leimkuehler William , Schal Coby , Vargo Edward L
Published: January 2010

The chloro-nicotinyl insecticide imidacloprid is used extensively as a soil treatment against subterranean termites. We conducted the first study of the metabolic fate of imidacloprid in termites, by exposing workers of the eastern subterranean termite, Reticulitermes flavipes (Kollar) (Isoptera: Rhinotermitidae) to radiolabeled imidacloprid through topical application and ingestion. Several days after topical application, we detected up to 11 radiolabeled compounds. The parent compound, IMI, and the following six metabolites were identified by liquid chromatography/mass spectrometry: olefin-imidacloprid (major metabolite), 4/5-OH imidacloprid, 4,5-di-OH imidacloprid, des-nitro olefin imidacloprid, des-nitro imidacloprid, and a glucuronide conjugate of des-nitro imidacloprid (des-nitro IMI-glu). Over time, detoxification of imidacloprid proceeded from less polar to more polar compounds, with des-nitro IMI-glu seeming to be the ultimate, major end product in surviving termites. Degradation of imidacloprid was limited to internal tissues of the termite. Workers fed wood treated with imidacloprid or provided with a treated substrate (sand) had metabolitic profiles similar to topically treated termites. Termites fed imidacloprid or exposed to it in soil excreted detectable amounts of all of the identified metabolites. Finally, we determined that imidacloprid metabolites were less toxic to termites than imidacloprid itself. Only the olefin-imidacloprid and 5-OH imidacloprid caused morbidity in termites exposed to sand treated with these compounds, but at concentrations ≈10–20-fold higher than the parent imidacloprid. Our results shed light on the metabolic pathway used by termites to detoxify imidacloprid and show how metabolism plays a key role in determining the availability of the active ingredient and its various metabolites for transfer among workers within the colony.
Early Skin Toxicity as a Predictive Factor for Tumor Control in Hepatocellular Carcinoma Patients Treated with Sorafenib
Authors: Vincenzi Bruno , Santini Daniele , Russo Antonio , Addeo Raffaele , Giuliani Francesco , Montella Liliana , Rizzo Sergio , Venditti Olga , Frezza Anna Maria , Caraglia Michele , Colucci Giuseppe , Del Prete Salvatore , Tonini Giuseppe
Published: January 2010

Introduction.

Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients.

Materials and Methods.

All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand–foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response plus stable disease) and TTP.

Results.

Sixty-five HCC patients treated with sorafenib were included in this analysis: 47 (73.3%) received sorafenib after failure of some local treatment, whereas 18 (27.7%) received it as first-line treatment. Twenty-nine patients developed at least grade 1 skin toxicity (rash, 13; HFSR, 16). In patients who developed skin toxicity, the tumor control rate was 48.3%, versus 19.4% in patients without cutaneous side effects. The median TTP was 8.1 months in the group of patients with skin toxicity versus 4.0 months in those without skin toxicity. This difference was also statistically significant on multivariate analysis. A borderline statistically significant difference was also observed in terms of OS in patients with early skin toxicity.

Conclusions.

Skin toxicity should be closely monitored in HCC patients treated with sorafenib in relation to its potential role as a surrogate marker of efficacy.
On the Observability for a Class of Nonlinear (Bio)chemical Systems
Authors: Aguilar-López Ricardo , Mata-Machuca Juan , Martinez-Guerra Rafael
Published: January 2010

In this work the observability properties for a class of nonlinear systems is presented, by considering linear, geometric and algebraic approaches. The observability conditions for state variables, unstructured uncertainties and detectable states are considered for a class of nonlinear systems related with several (bio)-chemical reacting processes. The considered examples are related with (bio)-chemical continuous reactors and a metabolic model, where their observability properties are analyzed. A comparison of the corresponding results is done, showing the suitability of each approach.
Responding to the Challenges of "Against Intellectual Monopoly"
Authors: Vertinsky Liza S.
Published: January 2010

Most would agree that a sound patent system is one in which the social benefits of the system exceed the social costs. Many would also agree that the current patent system imposes significant social costs, and that the current proposed patent reform legislation is largely motivated by a desire to address those costs. In their book, Against Intellectual Monopoly (2008), Boldrin and Levine base their policy recommendation to abolish the patent system on the claim that the social costs of having any patent system, even an “improved” or “reformed” one, will inevitably exceed its benefits. I argue that while Against Intellectual Monopoly falls short of establishing a case for abolishing the patent system, it succeeds in making a case for rethinking the law and economics paradigm of patents that has formed the foundation for much of patent law scholarship and policy. The arguments that Boldrin and Levine offer provide compelling reasons for re-examining the core assumptions underlying the dominant models of how patents impact innovation, paying greater attention to institutional alternatives and to historical lessons about the strength of competitive markets and the costs and benefits of regulatory intervention that dampens competition. I suggest we can meet the challenges highlighted by Boldrin and Levine by providing a more central role for New Institutional Economics (NIE) in the study of patent law, refocusing our analysis on the structure of activities and transactions that drive alternative processes of innovation and the roles that institutions (including but not limited to patent, contract and competition laws, and the informal rules governing collaboration and research activities) and organizations (both public and private) play in determining transactional structures and innovation outcomes.
Watt, Again? Boldrin and Levine Still Exaggerate the Adverse Effect of Patents on the Progress of Steam Power
Authors: Selgin George , Turner John L.
Published: January 2010

In an earlier comment on Boldrin and Levine’s 2003 lecture on patents and their effect on technology, we observed that their account of James Watt’s influence on the progress of steam technology contained factual errors which tended to exaggerate the negative consequences of Watt’s patent. We concluded that it was far from obvious that a corrected account would support Boldrin and Levine’s bold conjectures. While Boldrin and Levine’s 2008 “Against Intellectual Monopoly” begins with a new version of Watt’s story that claims to take our earlier criticisms into account, here we assess that version and conclude that it shares many of the shortcomings of the original.
A Recommendation on How to Intelligently Approach Emerging Problems in Intellectual Property Systems
Authors: North Douglass C.
Published: January 2010

We currently have no framework that allows us to really understand how a political system works, and how property rights and patent systems evolved, and so we do not have a body of theory that allows us to make predictive statements that would in fact lead to improving the function of property rights and patent systems. The body of neoclassical economic theory is very elegant and very useful, but it cannot describe how a system is evolving. If we want to understand how patent systems work, we may not simply rely on understanding the economics of patent systems, there must be developed a structure of incentives that will continue to encourage people to innovate and transform solutions to solve new and different problems that evolve over time. What we would ideally like in a world that is dynamic, where change is going on both in the political system and in the economic system, is to have an adaptively efficient structure.
A Rhetorical Response to Boldrin & Levine: Against Intellectual (Property) Extremism
Authors: McManis Charles
Published: January 2010

The two sides of the contemporary debate over intellectual property agree that the law needs to “strike a balance” between providing sufficient incentive for creation and the freedom to make use of existing ideas. Michele Boldrin and David Levine, on the other hand, boldly declare in their recent work “Against Intellectual Monopoly” that they have arrived at conclusions that “are at variance with both sides.” In this commentary, I examine 1) their assertion that intellectual property should be viewed as an “intellectual monopoly”; 2) their claim to have mustered evidence and authorities showing that innovators and creators can be well protected in the absence of intellectual property law; and 3) their rhetorical practices throughout the book. I conclude that 1) their assertion that intellectual property constitutes an “intellectual monopoly” is itself a bad analogy and an example of the logical fallacy of hasty generalization; 2) the evidence and authorities they muster in support of their claim that innovators and creators can be well protected in the absence of intellectual property law are unpersuasive, as they actually tend to support the opposite conclusion; and 3) their book as a whole is an example of bad rhetorical argumentation.
Introduction: The Kauffman Foundation Conference on Intellectual Property and Innovation
Authors: De Geest Gerrit
Published: January 2010

Introduction to the special issue on the Kauffman Foundation Conference on Intellectual Property and Innovation, held at St. Louis (USA) on April 2-3, 2009. This conference was organized by the Center on Law, Innovation and Economic Growth of the Washington University School of Law, and sponsored by the Ewing Marion Kauffman Foundation and the Skandalaris Center for Entrepreneurial Studies.
Click Chemistry for the Synthesis of RGD-Containing Integrin Ligands
Authors: Colombo Matteo , Bianchi Aldo
Published: January 2010

In the last few years click chemistry reactions, and in particular coppercatalyzed cycloadditions, have been used intensively for the preparation of new bioconjugate molecules and materials applicable to biomedical and pharmaceutical areas. This review will be focused on conjugates of the tripeptide Arg-Gly-Asp formed by means of click chemistry reactions. This sequence is a well known binding motif for specific transmembrane proteins and is involved in cellular adhesion to the extracellular matrix, allowing the selective recognition of the biomolecule or polymer in which it is incorporated.
Elucidating the Structure-Activity Relationships of the Vasorelaxation and Antioxidation Properties of Thionicotinic Acid Derivatives
Authors: Prachayasittikul Supaluk , Wongsawatkul Orapin , Worachartcheewan Apilak , Nantasenamat Chanin , Ruchirawat Somsak , Prachayasittikul Virapong
Published: January 2010

Nicotinic acid, known as vitamin B3, is an effective lipid lowering drug and intense cutaneous vasodilator. This study reports the effect of 2-(1-adamantylthio)nicotinic acid (6) and its amide 7 and nitrile analog 8 on phenylephrine-induced contraction of rat thoracic aorta as well as antioxidative activity. It was found that the tested thionicotinic acid analogs 6-8 exerted maximal vasorelaxation in a dose-dependent manner, but their effects were less than acetylcholine (ACh)-induced nitric oxide (NO) vasorelaxation. The vasorelaxations were reduced, apparently, in both NG-nitro-L-arginine methyl ester (L-NAME) and indomethacin (INDO). Synergistic effects were observed in the presence of L-NAME plus INDO, leading to loss of vasorelaxation of both the ACh and the tested nicotinic acids. Complete loss of the vasorelaxation was noted under removal of endothelial cells. This infers that the vasorelaxations are mediated partially by endothelium-induced NO and prostacyclin. The thionicotinic acid analogs all exhibited antioxidant properties in both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) assays. Significantly, the thionicotinic acid 6 is the most potent vasorelaxant with ED50 of 21.3 nM and is the most potent antioxidant (as discerned from DPPH assay). Molecular modeling was also used to provide mechanistic insights into the vasorelaxant and antioxidative activities. The findings reveal that the thionicotinic acid analogs are a novel class of vasorelaxant and antioxidant compounds which have potential to be further developed as promising therapeutics.
Nanotechnology for Early Cancer Detection
Authors: Choi Young-Eun , Kwak Ju-Won , Park Joon Won
Published: January 2010

Vast numbers of studies and developments in the nanotechnology area have been conducted and many nanomaterials have been utilized to detect cancers at early stages. Nanomaterials have unique physical, optical and electrical properties that have proven to be very useful in sensing. Quantum dots, gold nanoparticles, magnetic nanoparticles, carbon nanotubes, gold nanowires and many other materials have been developed over the years, alongside the discovery of a wide range of biomarkers to lower the detection limit of cancer biomarkers. Proteins, antibody fragments, DNA fragments, and RNA fragments are the base of cancer biomarkers and have been used as targets in cancer detection and monitoring. It is highly anticipated that in the near future, we might be able to detect cancer at a very early stage, providing a much higher chance of treatment.
Decreased plasma levels of darunavir/ritonavir in a vertically infected pregnant woman carrying multiclass-resistant HIV type-1
Authors: Pinnetti Carmela , Tamburrini Enrica , Ragazzoni Enzo , De Luca Andrea , Navarra Pierluigi
Published: January 2010

We report a case of a vertically infected woman treated with darunavir/ritonavir plus a standard backbone before pregnancy. The analysis of darunavir/ritonavir concentrations in peripheral maternal plasma throughout pregnancy, as well as in umbilical cord blood at delivery, showed low levels of darunavir in the mother and limited transfer across the placenta.
Randomized trial of a computerized coronary heart disease risk assessment tool in HIV-infected patients receiving combination antiretroviral therapy
Authors:   Swiss HIV Cohort Study, Bucher Heiner C , Rickenbach Martin , Young Jim , Glass Tracy R , Vallet Yannick , Bernasconi Enos , Cavassini Matthias , Fux Christoph , Schiffer Véronique , Vernazza Pietro , Weber Rainer , Battegay Manuel
Published: January 2010

Background

Exposure to combination antiretroviral therapy (cART) can lead to important metabolic changes and increased risk of coronary heart disease (CHD). Computerized clinical decision support systems have been advocated to improve the management of patients at risk for CHD but it is unclear whether such systems reduce patients’ risk for CHD.

Methods

We conducted a cluster trial within the Swiss HIV Cohort Study (SHCS) of HIV-infected patients, aged 18 years or older, not pregnant and receiving cART for >3 months. We randomized 165 physicians to either guidelines for CHD risk factor management alone or guidelines plus CHD risk profiles. Risk profiles included the Framingham risk score, CHD drug prescriptions and CHD events based on biannual assessments, and were continuously updated by the SHCS data centre and integrated into patient charts by study nurses. Outcome measures were total cholesterol, systolic and diastolic blood pressure and Framingham risk score.

Results

A total of 3,266 patients (80% of those eligible) had a final assessment of the primary outcome at least 12 months after the start of the trial. Mean (95% confidence interval) patient differences where physicians received CHD risk profiles and guidelines, rather than guidelines alone, were total cholesterol -0.02 mmol/l (-0.09–0.06), systolic blood pressure -0.4 mmHg (-1.6– 0.8), diastolic blood pressure -0.4 mmHg (-1.5–0.7) and Framingham 10-year risk score -0.2% (-0.5–0.1).

Conclusions

Systemic computerized routine provision of CHD risk profiles in addition to guidelines does not significantly improve risk factors for CHD in patients on cART.
Modular Design of Li-Ion and Li-Polymer Batteries for Undersea Environments
Authors: White David A.
Published: January 2010

AbstractLi-Ion chemistry is ideal for undersea environments. The cells are sealed and do not outgas, and the polymer versions can withstand pressures greater than 10,000 psi. This combination results in a battery that is easier and safer to use and one that does not require
heavy, expensive pressure vessels.Recent advances in electronic control of the Li-Ion battery and new modular design concepts for construction of complex battery systems have resulted in battery systems that are more robust, more flexible, longer lived, easier to charge and maintain, and
safer than their lower density counterparts. These new Li-Ion battery systems can be designed to deliver this energy at high voltages and high currents. Electronic charge control within the battery system allows charging by direct connection to power supplies or constant power sources such
as fuel cells and solar panels.The modular design concept for Li-Ion and Li-Polymer battery systems are presented with an emphasis on construction for undersea applications. Key to the modular battery system design concept is the ability to electronically balance all the cells within the
battery system automatically without operator intervention. Two different methods are described, which show how electronic balancing of all the cells within the battery system is accomplished. Examples of production battery systems already in service are shown, and systems under development
are provided.
HADEEP: Free-Falling Landers to the Deepest Places on Earth
Authors: Jamieson Alan J. , Fujii Toyonobu , Solan Martin , Priede Imants G.
Published: January 2010

AbstractThe hadal zone, comprising mostly deep trenches that plummet to nearly 11 km deep, represents the largest poorly understood habitat on Earth. This knowledge dearth has been technology induced rather than of scientific interest. The U.K.‐Japan collaborative
project Hadal Environment and Educational Program (HADEEP) is one venture where scientists and technologists have been working to fill this knowledge gap, particularly from a biological perspective. With limited funds and even more limited time, two 12,000-m autonomous free-fall baited imaging
landers, known as hadal landers, were constructed to follow in the footsteps of the 1960 Trieste I dive; “to remotely go where two guys had gone before.” In the past 2 years, the hadal landers have been deployed in five hadal trenches in the North and South Pacific Ocean
across a depth range of 5,500‐10,000 m. This new technology has led to many new discoveries including, among others, large aggregations of fish at 7,703 m, which are the deepest video footage of fish ever taken. Here we describe the origins of the HADEEP project, the challenges in developing
the technology, and the scientific outcomes of exploring the deepest environment on Earth some 50 years after the pioneering Trieste I dive to Challenger Deep.
The Strawberry Leaf Roller, Ancylis comptana fragariae (Walsh and Riley) (Lepidoptera: Tortricidae), as a Source of Overwintered Macrocentrus ancylivorus Rohwer (Hymenoptera: Braconidae) in Ontario
Authors: Putman Wm. L.
Published: January 2010

Macrocentrus ancylivorus Rohwer overwintered in larvàe of the strawberry leaf roller, Ancylis comptana fragariae (Walsh & Riley), at the rate of from 544 to 7,623 per acre of strawberry field. Not more than 300 per acre of peach orchard, could be expected to overwinter in larvae of the Oriental fruit moth, Grapholitha molesta (Busck). About half of the larvae of M. ancylivorus in leaf rollers did not survive the winter.
The Olfactory Response of Ips confusus (LeConte) (Coleoptera: Scolytidae) to the Secondary Attraction in the Laboratory
Authors: Wood D. L. , Bushing R. W.
Published: January 2010

A highly sensitive bioassay of the olfactory response of I. confusus is described. The response of beetles to air streams carrying attractants is a chemoklinotaxis but positive orientation occurs only in moving air. There is no evidence of ameno-taxis in odorless air streams or orientation to attractants in still air. Male behavior is characterized by an “area” orientation near the attractive material, an indirect approach to the source as shown by their entering adjacent air channels, and stopping frequently in the traverse during which they make klinotactic movements. The females exhibit a “point” or “straight-line” response, crawling directly to the source, rarely deviating into adjacent channels and only occasionally interrupting their approach.

Bark-wood samples of ponderosa pine become attractive 4-6 hours after male beetles are introduced into preformed entrance tunnels, the peak attraction occurring between 18 and 144 hours. Frass is not attractive until 9-12 hours after introduction of males. The ratio of females to males responding positively during the peak attraction period was approximately 8:5. The level of attractiveness to females falls as the season progresses, the highest response being recorded in late May and June. Sexual maturity as judged by the appearance of motile sperm was not correlated with host feeding or the initiation of attraction. Frass of males boring in Douglas fir was unattractive to females.

Attraction is initiated by male feeding in the phloem-cambial tissue of a host and is delayed until the first food has passed through the gut. The attractant appears to be associated with male excrement and may be produced, at least in part, in the hindgut.