bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjoint Sensitivity and Predictability of Tropical Cyclogenesis
Authors: Doyle James D. , Reynolds Carolyn A. , Amerault Clark , Moskaitis Jonathan
Published: August 2012

The sensitivity of tropical cyclogenesis and subsequent intensification is explored by applying small perturbations to the initial state in the presence of organized mesoscale convection and synoptic-scale forcing using the adjoint and tangent linear models for the Coupled Ocean–Atmosphere Mesoscale Prediction System (COAMPS). The forward, adjoint, and tangent linear models are used to compare and contrast predictability characteristics for the disturbance that became Typhoon Nuri and a nondeveloping organized convective cluster in the western Pacific during The Observing System Research and Predictability Experiment (THORPEX) Pacific Asian Regional Campaign (T-PARC) and the Tropical Cyclone Structure-2008 (TCS-08) experiments.

The adjoint diagnostics indicate that the intensity (e.g., maximum surface wind speed, minimum surface pressure) of a tropical disturbance is very sensitive to perturbations in the moisture and temperature fields and to a lesser degree the wind fields. The highest-resolution adjoint simulations (grid increment of 13 km) indicate that the most efficient intensification is through moistening in the lower and middle levels and heating in banded regions that are coincident with vorticity maxima in the initial state. Optimal adjoint perturbations exhibit rapid growth for the Nuri case and only modest growth for the nondeveloping system. The adjoint results suggest that Nuri was near the threshold for development, indicative of low predictability. The low-level sensitivity maximum and tendency for optimal perturbation growth to extend vertically through the troposphere are consistent with a “bottom up” development process of TC genesis, although a secondary midlevel sensitivity maximum is present as well. Growth originates at small scales and projects onto the scale of the vortex, a manifestation of perturbations that project onto organized convection embedded in regions of cyclonic vorticity.
On the Rapid Intensification of Hurricane Wilma (2005). Part II: Convective Bursts and the Upper-Level Warm Core
Authors: Chen Hua , Zhang Da-Lin
Published: August 2012

Previous studies have focused mostly on the roles of environmental factors in the rapid intensification (RI) of tropical cyclones (TCs) because of the lack of high-resolution data in inner-core regions. In this study, the RI of TCs is examined by analyzing the relationship between an upper-level warm core, convective bursts (CBs), sea surface temperature (SST), and surface pressure falls from 72-h cloud-permitting predictions of Hurricane Wilma (2005) with the finest grid size of 1 km. Results show that both the upper-level inertial stability increases and static stability decreases sharply 2–3 h prior to RI, and that the formation of an upper-level warm core, from the subsidence of stratospheric air associated with the detrainment of CBs, coincides with the onset of RI. It is found that the development of CBs precedes RI, but most subsidence warming radiates away by gravity waves and storm-relative flows. In contrast, many fewer CBs occur during RI, but more subsidence warming contributes to the balanced upper-level cyclonic circulation in the warm-core (as intense as 20°C) region. Furthermore, considerable CB activity can still take place in the outer eyewall as the storm weakens during its eyewall replacement. A sensitivity simulation, in which SSTs are reduced by 1°C, shows pronounced reductions in the upper-level warm-core intensity and CB activity. It is concluded that significant CB activity in the inner-core regions is an important ingredient in generating the upper-level warm core that is hydrostatically more efficient for the RI of TCs, given all of the other favorable environmental conditions.
A New Type of the Indian Ocean Dipole since the Mid-1970s
Authors: Du Yan , Cai Wenju , Wu Yanling
Published: August 2012

The tropical Indian Ocean dipole/zonal mode (IOD) is phase locked with the austral winter and spring seasons. This study describes three types of the IOD in terms of their peak time and duration. In particular, the authors focus on a new type that develops in May–June and matures in July–August, which is distinctively different from the canonical IOD, which may develop later and peak in September–November or persist from June to November. Such “unseasonable” IOD events are only observed since the mid-1970s, a period after which the tropical Indian Ocean has a closer relationship with the Pacific Ocean. The unseasonable IOD is an intrinsic mode of the Indian Ocean and occurs without an ensuing El Niño. A change in winds along the equator is identified as a major forcing. The wind change is in turn related to a weakening Walker circulation in the Indian Ocean sector in austral winter, which is in part forced by the rapid Indian Ocean warming. Thus, although the occurrence of the unseasonable IOD may be partially influenced by oceanic variability, the authors’ results suggest an influence from the Indian Ocean warming. This suggestion, however, awaits further investigation using fully coupled climate models.
Incubator City
Authors: Bickers Robert
Published: August 2012

Shanghai’s peculiar status between 1842 and 1943, its sovereignty degraded in key ways, meant that it gave sanctuary to, and spawned, a wide range of nationalist activity and counteractivity. This essay examines five different layers of activity that the city hosted, and spawned, and explores how they interacted, and touches also on their legacies. It outlines the three key factors that gave shape to the city and to its overt and covert political communities: space, law, and time (or the calendar). The essay explores the interplay of the physical and administrative realms that cut across the city, the restrictions they imposed, and the opportunities they opened up, and shows vividly how nationalism and the urban intersected in this site of multinational imperial power.
Divine Attributes in the Book of Joel
Authors: Watson Douglas
Published: August 2012

Disagreement about the substance of the book of Joel is due, in part, to the complexity of and inconsistency in the book's portrait of the deity. This article seeks to unpack four divine attributes that undergird the complicated presentation of Yhwh in the book of Joel's interpretation of disaster: divine abandonment, divine aggression, divine compassion, and divine judgment. In each case, the portrait of the deity that emerges is rooted in the literature of Israelite laments. The importance of Israelite laments in shaping the themes, motifs, and metaphors of the book of Joel offers clues about the religious tradition from which the text emerged.
Measuring Emotional Intelligence in Early Adolescence With the MSCEIT-YV
Authors: Rivers Susan E. , Brackett Marc A. , Reyes Maria R. , Mayer John D. , Caruso David R. , Salovey Peter
Published: August 2012

Emotional intelligence (EI) theory provides a framework to study the role of emotion skills in social, personal, and academic functioning. Reporting data validating the importance of EI among youth have been limited due to a dearth of measurement instruments. In two studies, the authors examined the reliability and validity of the Mayer–Salovey–Caruso Emotional Intelligence Test—Youth Version (MSCEIT-YV), a performance test of EI. Study 1 examined psychometric attributes of the MSCEIT-YV in a large sample of fifth- to eighth-grade students ( N = 756). Study 2 examined the relationship of the MSCEIT to student and teacher reports of academic, social, and personal functioning among fifth- and sixth-grade students ( N = 273). The authors report that EI can be measured reliably with the MSCEIT-YV and that higher scores on the test are related to healthier psychological functioning and greater social competence based on both teacher and student ratings, as well as to academic performance in English language arts.
The Measurement Invariance of the Wong and Law Emotional Intelligence Scale (WLEIS) Across Three Chinese University Student Groups From Canada and China
Authors: Li Tongwei , Saklofske Donald H. , Bowden Stephen C. , Yan Gonggu , Fung Tak Shing
Published: August 2012

The current study assessed the measurement equivalence of the Wong & Law Emotional Intelligence Scale (WLEIS) with three groups of Chinese university students. Two research sessions were conducted—one in Beijing, China with university students ( N = 680), and the other in Calgary, Canada where two groups of Chinese students were administered the WLEIS in either Chinese ( N = 151) or English ( N = 151). The WLEIS had satisfactory reliability, the four-factor structure was replicated, and metric invariance was supported across the three groups. The present study provided empirical support to the growing emotional intelligence measurement invariance literature and demonstrated the robustness of both the English and Chinese versions of the WLEIS.
Raphael, Azariah and Jesus of Nazareth: Tobit's Significance for Early Christology
Authors: Muñoa Phillip
Published: August 2012

This article demonstrates that the apocryphal text of Tobit sheds important light on notions of deliverance that were emerging in Second Temple Judaism. Raphael, the angel-deliverer of Tobit, depicts a stage in the development of angelic mediation that stands apart from angelic deliverers in previous Jewish texts, and can be significantly associated with early Christianity's view of Jesus. Here, for the first time, is a heavenly being who appears as a nondescript Israelite and brings news of hope, healing and demonic liberation to suffering Israelites of little account. Raphael offers a precedent for Christian accounts that the historical Jesus was a preexistent savior who lived as a simple Israelite.
Joseph and Aseneth: Loyalty, Traitors, Antiquity and Diasporan Identity
Authors: Hacham Noah
Published: August 2012

The final part of Joseph and Aseneth (chs. 23–29) tells a story that seems unconnected to the main part of the book. It recounts an attempt by Pharaoh's son to kill Joseph and Aseneth, his death and Joseph's 48-year rule over Egypt. Scholarly research barely relates to this story, probably since it inhabits the margins of the love story of Joseph and Aseneth. Neither does this story contribute any valuable commentary on the biblical Genesis narrative. It is suggested that this part of the book underscores the unbroken Jewish loyalty to the Ptolemaic-Egyptian regime in the unique circumstances of deep-rooted Jewish participation in that regime alongside adversarial elites, as well as the need to exhibit and emphasize Jewish loyalty while also depicting an internecine struggle within the royal family. The probable date of the book is therefore the last decade of the second century or the first two decades of the first century BCE.
Extreme fasting among Daoist priestesses of the Tang Dynasty: an old Chinese variant of anorexia nervosa?
Authors: Lo Ann L , Hsu LK George , Vandereycken Walter
Published: August 2012

Austere and prolonged fasting among Shangqing Daoist priestesses ( Daogu) of the Tang Dynasty (618–907) occurred as part of a lifestyle practice to achieve a mystical state of afterlife existence, body immortality and residence in the Shangqing heavenly kingdom. These fasting practices were conducted exclusively for religious reasons and cannot be reconceptualized as a form of an eating disorder without radically altering their original purpose and meaning.
The nature of King James VI/I’s medical conditions: new approaches to the diagnosis
Authors: Peters Timothy , Garrard Peter , Ganesan Vijeya , Stephenson John
Published: August 2012

It has been claimed that King James VI/I, an antecedent of King George III, suffered from acute porphyria, and that the disease was passed on to George III through his grand-daughter Sophie, mother of George I. The life of James is reviewed and previously-proposed diagnoses are considered. James’s medical history is discussed in detail and, where possible, examined with validated symptom scales. Using an online database of neurological diseases, the authors show that James’s symptomatology is compatible with a diagnosis of Attenuated (mild) Lesch-Nyhan disease; no evidence was found to support a diagnosis of acute porphyria. In addition, there is evidence of associated Asperger traits which may explain some of the King’s unusual behavioural and psycho-social features.
Freemasonry and psychiatry in Poland
Authors: Nasierowski Tadeusz , Britmann Jonathan
Published: August 2012

The history of Freemasonry in Poland is linked with the national independence movement. Masonic organizations supported its ideas, even though they were not always compliant with Masonic ethics. Polish Freemasonry was reborn in 1920, with an important role played by three psychiatrists: Rafał Radziwiłłowicz, Witold Łuniewski and Jan Mazurkiewicz, who were Grand Masters of the Grand National Lodge of Poland. Some of the ethical problems discussed at the lodge sessions were later reflected in their academic and social work. Mazurkiewicz’s work was most crucial to the development of Polish psychiatry. His presentation of the clinical picture of schizophrenia, formulated in the 1930s, was identical with the concept proposed by Andreasen and Crow in the 1980s.
‘De la non-existence de la monomanie’, by Jean-Pierre Falret (1854)
Authors: Lepoutre Thomas , Dening Tom
Published: August 2012

In 1854 Jean-Pierre Falret published an essay arguing against the concept of monomania, a nosological form which structured most French classifications of insanity until the middle of the nineteenth century. The historical importance of the text is already well known, since it marks the beginning of the decline of the monomanias. But the aim of this Classic Text was twofold: not only to cast doubt on the existence of the particular form, but also to reveal some misleading ‘tendencies’ or implicit ‘principles’ inherent to the Esquirolian nosology, in order to shine a new light on the conceptual apprehension of madness. Falret emphasized the importance of thorough clinical observations and the perspective of the whole patient, rejecting the partial attention given to isolated symptoms, and in this respect his work represents a turning point away from the more traditional alienism.
Sandbagging
Authors: Kräkel Matthias
Published: August 2012

Participants of dynamic contests sometimes play with the rules of the game by withholding effort in the beginning. Such behavior is referred to as sandbagging. I consider a two-period contest between heterogeneous players and analyze potential sandbagging of high-ability participants in period one. This sandbagging can be beneficial to avoid second-period matches against other high-ability opponents. I characterize the conditions under which sandbagging leads to a coordination problem, similar to that of the battle of the sexes. Moreover, if players' abilities have a stronger impact on the outcome of the first-period contest than effort choices, mutual sandbagging by all high-ability players can arise.
Survival Function Estimates for Champions Tour Golfers
Authors: Coate Douglas , Schwenkenberg Julia
Published: August 2012

In this article, the authors present survival function estimates for elite professional golfers who have participated on the Champions professional golf tour. Kaplan–Meier survivor function estimates for these golfers show median survival of 89 years and mean life expectancy of 85 years. The authors find comparable results for winners of the U. S. Professional Golf Association (PGA) Senior Open championship, which is also restricted to players 50 years of age and over. Champions tour golfer life expectancies are high in comparison to the general male population of the United States and at the high end of the life expectancy advantages estimated for other elite athletes.
Alternative Approaches to Measuring MRP
Authors: Lane Erin , Nagel Juan , Netz Janet S.
Published: August 2012

College men’s basketball players have alleged that the National Collegiate Athletic Association’s (NCAA) cap on athletic scholarships is illegal and leads to lower scholarships than would prevail in a free market. Recently, the NCAA increased the limit on athletic scholarships. The authors compare the marginal revenue product (MRP) of men’s basketball players to athletic scholarship caps. The authors estimate MRPs using players’ playing statistics; information on the distribution of pro salaries; and players’ future draft status. The authors find that players’ MRPs are greater than the athletic scholarship caps for about 60% of men’s basketball players, not just the star players.
Examining the support needs of ageing family carers in developing future plans for a relative with an intellectual disability
Authors: Taggart Laurence , Truesdale-Kennedy Maria , Ryan Assumpta , McConkey Roy
Published: August 2012

Background:

Planning for the future care of adults with an intellectual disability after the main family carer ceases their care, continues to be a sensitive and difficult time posing challenges for service providers internationally. Limited research has been undertaken on this topic because until recently, people with intellectual disability usually pre-deceased their parents. This study examined ageing carers’ preferences for future care and the support systems required to make such future plans.

Methods:

The study was conducted in one region of the United Kingdom with a high proportion of family carers. A mixed methods design was employed. In Stage 1, a structured questionnaire was used to collate information on the health, caregiving demands and future planning preferences of 112 parent and sibling carers; aged 60–94 years. In Stage 2, 19 in-depth semistructured interviews were undertaken with a sample of carers to explore a range of issues around future planning.

Findings:

Over half of the carers were lone carers, mainly female, with many reporting a wide range of health problems. A third of these carers reported that their caregiving resulted in high levels of anxiety. The main preference of the carers was for the person to remain in the family home, with either the family and/or paid staff to support them. A minority of parent carers preferred the person to move into the home of a sibling, although some favoured the person moving to a residential facility with other people with intellectual disabilities. The majority of carers did not want their relative to move into an older people’s residential/nursing facility. In the qualitative data, four main themes were identified around future planning: unremitting apprehension, the extent of planning, obstacles encountered and solutions for future planning. Avoidance, lack of guidance and a lack of appropriate residential provision were cited as obstacles to making future plans compounded by the emotional upset experienced by carers in thinking about the future.

Conclusion:

Findings of this study clearly identify the emotional, informational and practical supports required by these ageing family carers. These findings have national and international relevance in influencing how governments and service providers support parent and sibling carers to proactively plan for the future, and in the development of both in-home and out-of-home options when a family carer can no longer provide care. This is more urgent than ever given the growing numbers of older persons with intellectual disabilities in future decades.
A humanized single-chain antibody against beta 3 integrin inhibits pulmonary metastasis by preferentially fragmenting activated platelets in the tumor microenvironment
Authors: Zhang Wei , Dang Suying , Hong Tao , Tang Jian , Fan Jing , Bu Dawei , Sun Yanjie , Wang Zhugang , Wisniewski Thomas
Published: August 2012

Platelets play a supportive role in tumor metastasis. Impairment of platelet function within the tumor microenvironment may provide a clinically useful approach to inhibit metastasis. We developed a novel humanized single-chain antibody (scFv Ab) against integrin GPIIIa49-66 (named A11) capable of lysing activated platelets. In this study, we investigate the effect of A11 on the development of pulmonary metastases. In the Lewis lung carcinoma (LLC) metastatic model, A11 decreases the mean number of surface nodules and mean volume of pulmonary nodules. It protects against lung metastases in a time window that extended 4 hours before and 4 hours after the IV injection of LLCs. Coinjection of GPIIIa49-66 albumin reverses the antimetastatic activity of A11 in the B16 melanoma model, consistent with the pathophysiologic relevance of the platelet GPIIIa49-66 epitope. Significantly, A11 had no effect on angiogenesis using both in vitro and in vivo assays. The underlying molecular mechanisms are a combination of inhibition of each of the following interactions: between activated platelets and tumor cells, platelets and endothelial cells, and platelets and monocytes, as well as disaggregation of an existing platelet/tumor thrombus. Our observations may provide a novel antimetastatic strategy through lysing activated platelets in the tumor microenvironment using humanized anti–GPIIIa49-66 scFv Ab.
Effect of muscle load tasks with maximal isometric contractions on oxygenation of the trapezius muscle and sympathetic nervous activity in females with chronic neck and shoulder pain
Authors: Shiro Yukiko , Arai Young-Chang P , Matsubara Takako , Isogai Shunsuke , Ushida Takahiro
Published: August 2012

Background

Sympathetic nervous activity contributes to the maintenance of muscle oxygenation. However, patients with chronic pain may suffer from autonomic dysfunction. Furthermore, insufficient muscle oxygenation is observed among workers with chronic neck and shoulder pain. The aim of our study was to investigate how muscle load tasks affect sympathetic nervous activity and changes in oxygenation of the trapezius muscles in subjects with chronic neck and shoulder pain.

Methods

Thirty females were assigned to two groups: a pain group consisting of subjects with chronic neck and shoulder pain and a control group consisting of asymptomatic subjects. The participants performed three sets of isometric exercise in an upright position; they contracted their trapezius muscles with maximum effort and let the muscles relax (Relax). Autonomic nervous activity and oxygenation of the trapezius muscles were measured by heart rate variability (HRV) and Near-Infrared Spectroscopy.

Results

Oxyhemoglobin and total hemoglobin of the trapezius muscles in the pain group were lower during the Relax period compared with the control group. In addition, the low frequency / high frequency (LF/HF) ratio of HRV significantly increased during isometric exercise in the control group, whereas there were no significant changes in the pain group.

Conclusions

Subjects with neck and shoulder pain showed lower oxygenation and blood flow of the trapezius muscles responding to isometric exercise, compared with asymptomatic subjects. Subjects with neck and shoulder pain also showed no significant changes in the LF/HF ratio of HRV responding to isometric exercise, which would imply a reduction in sympathetic nervous activity.
Essential oil of the leaves of Ricinus communis L.: In vitro cytotoxicity and antimicrobial properties
Authors: Zarai Zied , Chobba Ines Ben , Mansour Riadh Ben , Békir Ahmed , Gharsallah Néji , Kadri Adel
Published: August 2012

Background

The aim of the present study was to appraise the antimicrobial activity of Ricinus communis L. essential oil against different pathogenic microorganisms and the cytotoxic activity against HeLa cell lines.

Methods

The agar disk diffusion method was used to study the antibacterial activity of Ricinus communis L. essential oil against 12 bacterial and 4 fungi strains. The disc diameters of zone of inhibition (DD), the minimum inhibitory concentrations (MIC) and the concentration inhibiting 50% (IC50) were investigated to characterize the antimicrobial activities of this essential oil. The in vitro cytotoxicity of Ricinus communis L. essential oil was examined using a modified MTT assay; the viability and the IC50 were used to evaluate this test.

Results

The essential oil from the leaves of Ricinus communis L. was analyzed by GC–MS and bioassays were carried out. Five constituents of the oil were identified by GC–MS. The antimicrobial activity of the oil was investigated in order to evaluate its efficacy against twelve bacteria and four fungi species, using disc diffusion and minimum inhibitory concentration methods. The essential oil showed strong antimicrobial activity against all microorganisms tested with higher sensitivity for Bacillus subtilis, Staphylococcus aureus and Enterobacter cloacae. The cytotoxic and apoptotic effects of the essential oil on HeLa cell lines were examined by MTT assay. The cytotoxicity of the oil was quite strong with IC50 values less than 2.63 mg/ml for both cell lines.

Conclusion

The present study showed the potential antimicrobial and anticarcinogenic properties of the essential oil of Ricinus communis L., indicating the possibilities of its potential use in the formula of natural remedies for the topical treatment of infections.
The orosomucoid 1 protein (α1 acid glycoprotein) is overexpressed in odontogenic myxoma
Authors: García-Muñoz Alejandro , Rodríguez Mario A , Bologna-Molina Ronell , Cázares-Raga Febe E , Hernández-Hernández Fidel C , Farfán-Morales J Eduardo , Trujillo Juan J , Licéaga-Escalera Carlos , Mendoza-Hernández Guillermo
Published: August 2012

Background

Odontogenic myxoma (OM) is a benign, but locally invasive, neoplasm occurring in the jaws. However, the molecules implicated in its development are unknown. OM as well as Dental Follicle (DF), an odontogenic tissue surrounding the enamel organ, is derived from ectomesenchymal/mesencyhmal elements. To identify some protein that could participate in the development of this neoplasm, total proteins from OM were separated by two-dimensional electrophoresis and the profiles were compared with those obtained from DF, used as a control.

Results

We identified eight proteins with differential expression; two of them were downregulated and six upregulated in OM. A spot consistently overexpressed in odontogenic myxoma, with a molecular weight of 44-kDa and apIof 3.5 was identified as the orosomucoid 1 protein. Western blot experiments confirmed the overexpression of this protein in odontogenic myxoma and immunohistochemical assays showed that this protein was mainly located in the cytoplasm of stellate and spindle-shaped cells of this neoplasm.

Conclusion

Orosomucoid 1, which belongs to a group of acute-phase proteins, may play a role in the modulation of the immune system and possibly it influences the development of OM.
MicroRNA-124 as a novel treatment for persistent hyperalgesia
Authors: Willemen Hanneke LDM , Huo Xiao-Jiao , Mao-Ying Qi-Liang , Zijlstra Jitske , Heijnen Cobi J , Kavelaars Annemieke
Published: August 2012

Background

Chronic pain is often associated with microglia activation in the spinal cord. We recently showed that microglial levels of the kinase G protein–coupled receptor kinase (GRK)2 are reduced in models of chronic pain. We also found that mice with a cell-specific reduction of around 50% in GRK2 level in microglia/macrophages (LysM-GRK2+/− mice) develop prolonged inflammatory hyperalgesia concomitantly with ongoing spinal microglia/macrophage activation. The microRNA miR-124 is thought to keep microglia/macrophages in brain and spinal cord in a quiescent state. In the present study, we investigated the contribution of miR-124 to regulation of hyperalgesia and microglia/macrophage activation in GRK2-deficient mice. In addition, we investigated the effect of miR-124 on chronic inflammatory and neuropathic pain in wild-type (WT) mice.

Methods

Hyperalgesia was induced by intraplantar IL-1β in WT and LysM-GRK2+/− mice. We determined spinal cord microglia/macrophage miR-124 expression and levels of pro-inflammatory M1 and anti-inflammatory M2 activation markers. The effect of intrathecal miR-124 treatment on IL-1β-induced hyperalgesia and spinal M1/M2 phenotype, and on carrageenan-induced and spared nerve injury-induced chronic hyperalgesia in WT mice was analyzed.

Results

Transition from acute to persistent hyperalgesia in LysM-GRK2+/− mice is associated with reduced spinal cord microglia miR-124 levels. In our LysM-GRK2+/− mice, there was a switch towards a pro-inflammatory M1 phenotype together with increased pro-inflammatory cytokine production. Intrathecal administration of miR-124 completely prevented the transition to persistent pain in response to IL-1β in LysM-GRK2+/− mice. The miR-124 treatment also normalized expression of spinal M1/M2 markers of LysM-GRK2+/− mice. Moreover, intrathecal miR-124 treatment reversed the persistent hyperalgesia induced by carrageenan in WT mice and prevented development of mechanical allodynia in the spared nerve injury model of chronic neuropathic pain in WT mice.

Conclusions

We present the first evidence that intrathecal miR-124 treatment can be used to prevent and treat persistent inflammatory and neuropathic pain. In addition, we show for the first time that persistent hyperalgesia in GRK2-deficient mice is associated with an increased ratio of M1/M2 type markers in spinal cord microglia/macrophages, which is restored by miR-124 treatment. We propose that intrathecal miR-124 treatment might be a powerful novel treatment for pathological chronic pain with persistent microglia activation.
Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin® litigation
Authors: Vedula S Swaroop , Goldman Palko S , Rona Ilyas J , Greene Thomas M , Dickersin Kay
Published: August 2012

Background

Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin®, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain.

Methods

We included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf for the Court’s findings).

We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom.

Results

We present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or published; how publication of study results was delayed; and the role of ghost authorship.

Conclusions

Taken together, the extracts we present from internal company documents illustrate implementation of a strategy at odds with unbiased study conduct and dissemination. Our findings suggest that Pfizer and Parke-Davis’s publication strategy had the potential to distort the scientific literature, and thus misinform healthcare decision-makers.
Epigallocatechin gallate incorporation into lignin enhances the alkaline delignification and enzymatic saccharification of cell walls
Authors: Elumalai Sasikumar , Tobimatsu Yuki , Grabber John H , Pan Xuejun , Ralph John
Published: August 2012

Background

Lignin is an integral component of the plant cell wall matrix but impedes the conversion of biomass into biofuels. The plasticity of lignin biosynthesis should permit the inclusion of new compatible phenolic monomers such as flavonoids into cell wall lignins that are consequently less recalcitrant to biomass processing. In the present study, epigallocatechin gallate (EGCG) was evaluated as a potential lignin bioengineering target for rendering biomass more amenable to processing for biofuel production.

Results

In vitro peroxidase-catalyzed polymerization experiments revealed that both gallate and pyrogallyl (B-ring) moieties in EGCG underwent radical cross-coupling with monolignols mainly by β–O–4-type cross-coupling, producing benzodioxane units following rearomatization reactions. Biomimetic lignification of maize cell walls with a 3:1 molar ratio of monolignols and EGCG permitted extensive alkaline delignification of cell walls (72 to 92%) that far exceeded that for lignified controls (44 to 62%). Alkali-insoluble residues from EGCG-lignified walls yielded up to 34% more glucose and total sugars following enzymatic saccharification than lignified controls.

Conclusions

It was found that EGCG readily copolymerized with monolignols to become integrally cross-coupled into cell wall lignins, where it greatly enhanced alkaline delignification and subsequent enzymatic saccharification. Improved delignification may be attributed to internal trapping of quinone-methide intermediates to prevent benzyl ether cross-linking of lignin to structural polysaccharides during lignification, and to the cleavage of ester intra-unit linkages within EGCG during pretreatment. Overall, our results suggest that apoplastic deposition of EGCG for incorporation into lignin would be a promising plant genetic engineering target for improving the delignification and saccharification of biomass crops.
Lung function monitoring in patients with duchenne muscular dystrophy on steroid therapy
Authors: Machado Darlene L , Silva Elaine C , Resende Maria B D , Carvalho Celso R F , Zanoteli Edmar , Reed Umbertina C
Published: August 2012

Background

Duchenne muscular dystrophy (DMD) is a sex-linked inherited muscle disease characterized by a progressive loss in muscle strength and respiratory muscle involvement. After 12 years of age, lung function declines at a rate of 6 % to 10.7 % per year in patients with DMD. Steroid therapy has been proposed to delay the loss of motor function and also the respiratory involvement.

Method

In 21 patients with DMD aged between seven and 16 years, the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1) were evaluated at three different times during a period of two years.

Results

We observed in this period of evaluation the maintenance of the FVC and the FEV1 in this group of patients independently of chronological age, age at onset of steroid therapy, and walking capacity.

Conclusion

The steroid therapy has the potential to stabilize or delay the loss of lung function in DMD patients even if they are non-ambulant or older than 10 years, and in those in whom the medication was started after 7 years of age.
The effect of different depths of medial heel skive on plantar pressures
Authors: Bonanno Daniel R , Zhang Cheryl Y , Farrugia Rose C , Bull Matthew G , Raspovic Anita M , Bird Adam R , Landorf Karl B
Published: August 2012

Background

Foot orthoses are often used to treat lower limb injuries associated with excessive pronation. There are many orthotic modifications available for this purpose, with one being the medial heel skive. However, empirical evidence for the mechanical effects of the medial heel skive modification is limited. This study aimed to evaluate the effect that different depths of medial heel skive have on plantar pressures.

Methods

Thirty healthy adults (mean age 24 years, range 18–46) with a flat‐arched or pronated foot posture and no current foot pain or deformity participated in this study. Using the in‐shoe pedar‐X® system, plantar pressure data were collected for the rearfoot, midfoot and forefoot while participants walked along an 8 metre walkway wearing a standardised shoe. Experimental conditions included a customised foot orthosis with the following 4 orthotic modifications: (i) no medial heel skive, (ii) a 2 mm medial heel skive, (iii) a 4 mm medial heel skive and (iv) a 6 mm medial heel skive.

Results

Compared to the foot orthosis with no medial heel skive, statistically significant increases in peak pressure were observed at the medial rearfoot – there was a 15% increase (p = 0.001) with the 4 mm skive and a 29% increase (p < 0.001) with the 6 mm skive. No significant change was observed with the 2 mm medial heel skive. With respect to the midfoot and forefoot, there were no significant differences between the orthoses.

Conclusions

This study found that a medial heel skive of 4 mm or 6 mm increases peak pressure under the medial rearfoot in asymptomatic adults with a flat‐arched or pronated foot posture. Plantar pressures at the midfoot and forefoot were not altered by a medial heel skive of 2, 4 or 6 mm. These findings provide some evidence for the effects of the medial heel skive orthotic modification.
Glucocorticoid receptor gene polymorphisms and disease activity during pregnancy and the postpartum period in rheumatoid arthritis
Authors: Quax Rogier AM , de Man Yaël A , Koper Jan W , van Rossum Elisabeth FC , Willemsen Sten P , Lamberts Steven WJ , Hazes Johanna MW , Dolhain Radboud JEM , Feelders Richard A
Published: August 2012

Introduction

The mechanism underlying the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and the subsequent postpartum flare is incompletely understood, and the disease course varies widely between pregnant RA patients. In pregnancy, total and free levels of cortisol increase gradually, followed by a postpartum decrease to prepregnancy values. The glucocorticoid receptor (GR) polymorphisms BclI and N363S are associated with relatively increased glucocorticoid (GC) sensitivity, whereas the 9β and ER22/23EK polymorphisms of the GR gene are associated with a relatively decreased GC sensitivity. We examined the relation between the presence of these GR polymorphisms and level of disease activity and disease course of RA during pregnancy and postpartum.

Methods

We studied 147 participants of the PARA study (Pregnancy-Induced Amelioration of Rheumatoid Arthritis study), a prospective study investigating the natural improvement during pregnancy and the postpartum flare in women with RA. Patients were visited, preferably before pregnancy, at each trimester and at three postpartum time points. On all occasions, disease activity was scored by using DAS28. All patients were genotyped for the GR polymorphisms BclI, N363S, 9β, and ER22/23EK and divided in groups harboring either polymorphisms conferring increased GC sensitivity (BclI and N363S; GC-S patients) or polymorphisms conferring decreased GC sensitivity (9β or 9β + ER22/23EK; GC-I patients). Data were analyzed by using a mixed linear model, comparing GC-S patients with GC-I patients with respect to improvement during pregnancy and the postpartum flare. The cumulative disease activity was calculated by using time-integrated values (area under the curve, AUC) of DAS28 in GC-I patients versus GC-S patients. Separate analyses were performed according to the state of GC use.

Results

GC-S patients treated with GC had a significantly lower AUC of DAS28 in the postpartum period than did GC-I patients. This difference was not observed in patients who were not treated with GCs. During pregnancy, GC-S and GC-I patients had comparable levels of disease activity and course of disease.

Conclusions

Differences in relative GC sensitivity, as determined by GR polymorphisms, are associated with the level of disease activity in the postpartum period in GC-treated patients, but they do not seem to influence the course of the disease per se.
Distribution of Prolyl Oligopeptidase in Human Peripheral Tissues and in Ovarian and Colorectal Tumors
Authors: Myöhänen Timo T. , Pyykkö Elisa , Männistö Pekka T. , Carpen Olli
Published: August 2012

Prolyl oligopeptidase (PREP) is a serine protease that hydrolyzes peptides shorter than 30-mer, and it has been connected with multiple physiological and pathological conditions. PREP has been mostly studied in the brain, but significant PREP activities have been measured in peripheral tissues. Moreover, increased PREP activities have been found in tumors. In this study, the authors studied the immunohistochemical distribution of PREP protein in human peripheral tissues and in ovarian and colorectal tumors. PREP was found to be widely distributed in human peripheral tissues and specifically in certain cells. The most intense PREP expression was seen in the testis, ovaries, liver, and some parts of the skin. At the cellular level, high PREP levels were seen as a rule in secreting epithelial cells and cells involved in reproduction. Increased PREP expression was seen in most of the tumors studied. PREP expression was higher in malignant than benign tumors, and in ovarian epithelial cancers, there was a trend for increased PREP staining with increased malignancy grade. Results suggest that PREP may be associated with secretory processes as well as in reproduction. A more abundant expression of PREP in malignant than benign tumors suggests that PREP may be associated with expansion and metastasis of tumors.
The Effects of Traditional and Social Earned Media on Sales: A Study of a Microlending Marketplace
Authors: Stephen Andrew T. , Galak Jeff
Published: August 2012

Marketers distinguish three types of media: paid (e.g., advertising), owned (e.g., company website), and earned (e.g., publicity). The effects of paid media on sales have been extensively covered in the marketing literature. The effects of earned media, however, have received limited attention. The authors examine how two types of earned media, traditional (e.g., publicity and press mentions) and social (e.g., blog and online community posts), affect sales and activity in each other. They analyze 14 months of daily sales and media activity data from a microlending marketplace website using a multivariate autoregressive time-series model. They find that (1) both traditional and social earned media affect sales; (2) the per-event sales impact of traditional earned media activity is larger than for social earned media; (3) because of the greater frequency of social earned media activity, after adjusting for event frequency, social earned media's sales elasticity is significantly greater than traditional earned media's; and (4) social earned media appears to play an important role in driving traditional earned media activity.
Contribuição da ultra-sonografia na orientação do tratamento cirúrgico do empiema pleural em crianças
Authors: Cirino Luís Marcelo Inaco , Otoch José Pinhata , Garcia Antonio Escamila , Pereira Paulo Roberto Bueno , Margarido Nelson Fontana , Tolosa Erasmo Magalhães Castro de
Published: August 2012

Os autores utilizam a ultra-sonografia para orientar a escolha da alternativa cirúrgica para o tratamento do empiema pleural em crianças. Comparam os achados ultra-sonográficos pré-operatórios com os achados cirúrgicos de 77 crianças com empiema pleural parapneumônico tratadas no Hospital Universitário da Universidade de São Paulo de novembro de 1986 a novembro de 1996. Propõem classificação numérica desses achados e os correlacionam com a fase anatomo-patológica do empiema e a evolução clínica pós-operatória dos pacientes, baseados na necessidade de mais de uma intervenção cirúrgica para a cura definitiva. Concluem que a ultra-sonografia é método fidedigno para revelar o estágio evolutivo do empiema pleural e orientar a racionalização da escolha da terapêutica cirúrgica.
Piomiosite tropical
Authors: Siqueira Nilton Ghiotti de , Siqueira Cláudia Maria Villar Maziero de
Published: August 2012

A piomiosite tropical, apesar de ser uma patologia reconhecida em nosso meio há mais de cem anos, ainda é pouco divulgada no Brasil, e pode-se perder tempo e dinheiro em exames para afastar a possibilidade de tumores ou tratar sua incidência vem aumentando em regiões de clima temperado, devido à disseminação do Vírus da lmunodeticiência Humana e aos tratamentos imúnossupressivos. Apesar de realizado em instituições que muitas vezes não apresentam recursos diagnósticos de primeira linha, demonstramos que o tratamento pode ser adequado se houver experiência clínica e bom senso. São descritos quarenta casos de piomiosite tropical, atendidos consecutivamente por um mesmo cirurgião; a idade média dos pacientes foi de 16 anos e o sexo predominante o masculino. O diagnóstico foi clínico em 73% dos casos e o tratamento realizado foi drenagem por incisão direta sobre a massa, deixando dreno tubular, usado para irrigação do abscesso. O tempo médio de permanência do dreno no local foi de cinco dias, e a média de permanência hospitalar, sete dias. Dois casos (5%) evoluíram para osteomielite e um caso foi a óbito. A evolução foi satisfatória em 93% dos pacientes.
Achados tomográficos das alterações abdominais pós-operatórias dos pacientes submetidos ao derivação gastrojejunal em Y-de-Roux sem anel
Authors: Ribas Fernanda Marcondes , Nassif Paulo Afonso Nunes , Ribas Carmen Paredes Marcondes , Dietz Ulrich Andreas , Tuon Felipe , Wendler Eduardo , Enokawa Marcelo Seiki , Ferri Kellen Regina
Published: August 2012

OBJETIVO: Avaliar por exame de tomografia computadorizada de pacientes submetidos à derivação gastrojejunal em Y-de-Roux, sem anel, para tratamento de obesidade mórbida. MÉTODOS: Estudaram-se 40 pacientes, encaminhados ao serviço de tomografia do Hospital Universitário Evangélico de Curitiba para avaliação diagnóstica. Encontravam-se em pós-operatório de cirurgia bariátrica tendo sido operados no mesmo hospital. Foram incluídos pacientes submetidos à operação laparoscópica com sintomas que necessitavam de avaliação tomográfica diagnóstica. Excluíram-se pacientes que tinham sido submetidos à cirurgia bariátrica por outras técnicas cirúrgicas; que tinham sido operados por outra equipe; que não concordassem com a administração de contraste iodado por via oral ou endovenosa; e que excediam o limite de peso da mesa de exame. Para análise estatística utilizou-se a média das variáveis. RESULTADOS: Os pacientes apresentaram-se com idade entre 23 a 70 anos e eram 11 homens e 29 mulheres. Não houve alterações extra-abdominais detectáveis pela tomografia de abdômen total; dos 40 pacientes avaliados, 30 apresentavam achados tomográficos dentro do limite da normalidade. A presença de estenose na anastomose gastrojejunal foi encontrada em um paciente; hérnia interna ocorreu em cinco; fístula anastomótica em um e abcesso em três dos pacientes estudados. CONCLUSÃO: A tomografia de abdome total não conseguiu informar a causa dos sintomas dos pacientes operados em 87,5% dos pacientes que procuraram re-avaliação médica por sintomas pós-operatórios da cirurgia bariátrica.