bluuebunny/crossref_metadata_2025 huggingface dataset:
Affective attachments and foreign policy: Israel and the 1993 Oslo Accords
Authors: Sasley Brent E.
Published: June 2010

Although the important role of emotions in decision-making has been highlighted in the psychology, neural science, and decision research literatures, this conclusion has not been widely adopted in foreign policy analysis and International Relations (IR). Of the work that has been done, much of it has been focused on public perceptions and the impact on foreign policy, but not on elites and the actual decisions of foreign policy. This article seeks to address this imbalance by examining the role of one element of emotion — affect — on key foreign policy decision-makers. It argues that the greater the emotional attachment a leader has to an object, the less flexible she is in foreign policy toward that object. The model is used to explain a critical puzzle in IR: Israel’s decision to pursue and sign the 1993 Oslo Accords.
Is global democracy possible?
Authors: Koenig-Archibugi Mathias
Published: June 2010

Scepticism about the possibility of a democratically governed global polity is often rooted in beliefs about ‘necessary conditions’. Some democracy scholars consider a transition to global democracy to be incompatible with necessary conditions for democratic governance, while some International Relations scholars consider it to be incompatible with necessary conditions for international structural change. This article assesses hypotheses and evidence about democratic transitions within states and transformations in the interaction among states and concludes that arguments based on necessary conditions are not compelling. This suggests that global democracy may be unlikely but it is not impossible.
Decreasing Birth Weight May Predispose Premature Infants to Increased Mortality From Necrotizing Enterocolitis
Authors: Drenckpohl Douglas , Knaub Lisa , Schneider Catherine , McConnell Connie , Huaping Wang  , Macwan Kamlesh
Published: June 2010

The objective of this study was to determine if there are any “risk factors” that could assist clinicians in identifying premature infants who are at greater risk for mortality when developing necrotizing enterocolitis (NEC). This was a retrospective study of infants admitted to the neonatal intensive care unit (NICU) at Children’s Hospital of Illinois, Peoria. Seventy-eight patients were diagnosed with NEC and were divided into 2 groups: NEC-survived versus NEC-died. Maternal risk factors, infant demographics, birth weight, incidence of sepsis, histamine-2 (H2) receptor blockers prescribed, temperature, anemia, and day of life when trophic feedings were begun and when enteral feedings were advanced were compared for significant differences. Univariate tests demonstrated that mothers of infants who died from NEC had a higher incidence of premature rupture of membranes. A premature infant’s decreasing birth weight significantly increased the risk for NEC-related mortality. Premature infants who received early trophic feedings had less NEC-related mortality, but this finding was not significant. Other conditions such as maternal risk factors, H2 blockers in total parenteral nutrition, enteral feedings, and temperature were not significant. Logistic regression indicated that a premature infant’s birth weight significantly increased his or her probability of dying from NEC while adjusting for other variables. A premature infant’s birth weight could be used by clinicians as a tool to identify patients at greater risk for NEC-related mortality. Although the true etiology of NEC remains unclear, early initiation of trophic feedings with colostrum may be the best defense for preventing the onset of this devastat- ing disease.
PTEN regulates collagen-induced platelet activation
Authors: Weng Zhen , Li Ding , Zhang Lin , Chen Jian , Ruan Changgeng , Chen Guoqiang , Gartner T. Kent , Liu Junling
Published: June 2010

Phosphatidylinositol 3-kinase (PI3K) has been shown to play an important role in collagen-induced platelet activation, but the role(s) of PTEN, a major regulator of the PI3K/Akt signaling pathway, has not been examined in platelets. Here, we report that Pten−/− mouse blood contains 25% more platelets than Pten+/+ blood and that PTEN deficiency significantly shortened the bleeding time, increased the sensitivity of platelets to collagen-induced activation and aggregation, and enhanced phosphorylation of Akt at Ser473 in response to collagen. Furthermore, we found that PP2, and the combination of apyrase, indomethacin + 1B5, respectively, inhibited collagen-induced aggregation in both PTEN+/+ and PTEN−/− platelets. In contrast, LY294002 (a PI3K inhibitor) prevented the aggregation of PTEN+/+, but not PTEN−/−, platelets. Therefore, PTEN apparently regulates collagen-induced platelet activation through PI3K/Akt-dependent and -independent signaling pathways.
Transcriptome sequencing and comparative analysis of cucumber flowers with different sex types
Authors: Guo Shaogui , Zheng Yi , Joung Je-Gun , Liu Shiqiang , Zhang Zhonghua , Crasta Oswald R , Sobral Bruno W , Xu Yong , Huang Sanwen , Fei Zhangjun
Published: June 2010

Background

Cucumber,Cucumis sativusL., is an economically and nutritionally important crop of theCucurbitaceaefamily and has long served as a primary model system for sex determination studies. Recently, the sequencing of its whole genome has been completed. However, transcriptome information of this species is still scarce, with a total of around 8,000 Expressed Sequence Tag (EST) and mRNA sequences currently available in GenBank. In order to gain more insights into molecular mechanisms of plant sex determination and provide the community a functional genomics resource that will facilitate cucurbit research and breeding, we performed transcriptome sequencing of cucumber flower buds of two near-isogenic lines, WI1983G, a gynoecious plant which bears only pistillate flowers, and WI1983H, a hermaphroditic plant which bears only bisexual flowers.

Result

Using Roche-454 massive parallel pyrosequencing technology, we generated a total of 353,941 high quality EST sequences with an average length of 175bp, among which 188,255 were from gynoecious flowers and 165,686 from hermaphroditic flowers. These EST sequences, together with ~5,600 high quality cucumber EST and mRNA sequences available in GenBank, were clustered and assembled into 81,401 unigenes, of which 28,452 were contigs and 52,949 were singletons. The unigenes and ESTs were further mapped to the cucumber genome and more than 500 alternative splicing events were identified in 443 cucumber genes. The unigenes were further functionally annotated by comparing their sequences to different protein and functional domain databases and assigned with Gene Ontology (GO) terms. A biochemical pathway database containing 343 predicted pathways was also created based on the annotations of the unigenes. Digital expression analysis identified ~200 differentially expressed genes between flowers of WI1983G and WI1983H and provided novel insights into molecular mechanisms of plant sex determination process. Furthermore, a set of SSR motifs and high confidence SNPs between WI1983G and WI1983H were identified from the ESTs, which provided the material basis for future genetic linkage and QTL analysis.

Conclusion

A large set of EST sequences were generated from cucumber flower buds of two different sex types. Differentially expressed genes between these two different sex-type flowers, as well as putative SSR and SNP markers, were identified. These EST sequences provide valuable information to further understand molecular mechanisms of plant sex determination process and forms a rich resource for future functional genomics analysis, marker development and cucumber breeding.
Tracking the transcriptional host response from the acute to the regenerative phase of experimental pneumococcal meningitis
Authors: Wittwer Matthias , Grandgirard Denis , Rohrbach Janine , Leib Stephen L
Published: June 2010

Background

Despite the availability of effective antibiotic therapies, pneumococcal meningitis (PM) has a case fatality rate of up to 30% and causes neurological sequelae in up to half of the surviving patients. The underlying brain damage includes apoptosis of neurons in the hippocampus and necrosis in the cortex. Therapeutic options to reduce acute injury and to improve outcome from PM are severely limited.

With the aim to develop new therapies a number of pharmacologic interventions have been evaluated. However, the often unpredictable outcome of interventional studies suggests that the current concept of the pathophysiologic events during bacterial meningitis is fragmentary. The aim of this work is to describe the transcriptomic changes underlying the complex mechanisms of the host response to pneumococcal meningitis in a temporal and spatial context using a well characterized infant rat model.

Methods

Eleven days old nursing Wistar rats were infected by direct intracisternal injection of 2 × 106cfu/ml of Streptococcus pneumoniae. Animals were sacrificed at 1, 3, 10 and 26 days after infection, the brain harvested and the cortex and hippocampus were sampled. The first two time points represent the acute and sub-acute phase of bacterial meningitis, whereas the latter represent the recovery phase of the disease.

Results

The major events in the regulation of the host response on a transcriptional level occur within the first 3 days after infection. Beyond this time, no differences in global gene expression in infected and control animals were detectable by microarray analysis. Whereas in the acute phase of the disease immunoregulatory processes prevail in the hippocampus and the cortex, we observed a strong activation of neurogenic processes in the hippocampal dentate gyrus, both by gene expression and immunohistology starting as early as 3 days after infection.

Conclusions

Here we describe the cellular pathways involved in the host response to experimental pneumococcal meningitis in specified disease states and brain regions. With these results we hope to provide the scientific basis for the development of new treatment strategies which take the temporal aspects of the disease into account.
Modelling human musculoskeletal functional movements using ultrasound imaging
Authors: Peolsson Michael , Löfstedt Tommy , Vogt Susanna , Stenlund Hans , Arndt Anton , Trygg Johan
Published: June 2010

Background

A widespread and fundamental assumption in the health sciences is that muscle functions are related to a wide variety of conditions, for example pain, ischemic and neurological disorder, exercise and injury. It is therefore highly desirable to study musculoskeletal contributions in clinical applications such as the treatment of muscle injuries, post-surgery evaluations, monitoring of progressive degeneration in neuromuscular disorders, and so on.

The spatial image resolution in ultrasound systems has improved tremendously in the last few years and nowadays provides detailed information about tissue characteristics. It is now possible to study skeletal muscles in real-time during activity.

Methods

The ultrasound images are transformed to be congruent and are effectively compressed and stacked in order to be analysed with multivariate techniques. The method is applied to a relevant clinical orthopaedic research field, namely to describe the dynamics in the Achilles tendon and the calf during real-time movements.

Results

This study introduces a novel method to medical applications that can be used to examine ultrasound image sequences and to detect, visualise and quantify skeletal muscle dynamics and functions.

Conclusions

This new objective method is a powerful tool to use when visualising tissue activity and dynamics of musculoskeletal ultrasound registrations.
"I'm the Momma": Using photo-elicitation to understand matrilineal influence on family food choice
Authors: Johnson Cassandra M , Sharkey Joseph R , McIntosh Alex W , Dean Wesley R
Published: June 2010

Background

Many complex and subtle aspects relating to mothers and food choice are not well understood. Mothers play a primary role in their children's food choices, but research has not specifically examined how matrilineal family members who do not reside in the same household, such as a mother's mother, aunt, or grandmother, influence the current family's food choices.

Methods

Seven participants were recruited from the Household Food Inventory (HFI) Study in the Bryan/College Station, Texas. All participants completed an in-depth interview, photographed food-related activities, and discussed photographs in a follow-up in-depth interview. Interviews were transcribed verbatim from audio recordings. Transcripts were analyzed using several qualitative approaches including grounded theory to identify themes and subthemes.

Results

Participants discussed the following themes relating to the influence of their mother or other female relation (Mom) on their families' food choices: Relationship with Mom, Just like Mom, 'Kinda' like Mom, Different than Mom, and Mom's Influence on Children's Food Choices. Overall, participants used the photographs to illustrate how they were similar or different to their mothers, or other female family member, as well as how their mothers either supported or undermined control over their children's food choices. The "Mom effect" or matrilineal influence of mothers, aunts, and grandmothers on a mother's food choices was omnipresent, even though Mom was no longer living with the participants.

Conclusions

We found a matrilineal influence to have a residual and persistent influence on a family's food choices. This finding may be helpful for understanding the contextual elements of food choice and explaining why it is sometimes difficult to change mothers' food habits.
Increasing cell biomass in Saccharomyces cerevisiae increases recombinant protein yield: the use of a respiratory strain as a microbial cell factory
Authors: Ferndahl Cecilia , Bonander Nicklas , Logez Christel , Wagner Renaud , Gustafsson Lena , Larsson Christer , Hedfalk Kristina , Darby Richard AJ , Bill Roslyn M
Published: June 2010

Background

Recombinant protein production is universally employed as a solution to obtain the milligram to gram quantities of a given protein required for applications as diverse as structural genomics and biopharmaceutical manufacture. Yeast is a well-established recombinant host cell for these purposes. In this study we wanted to investigate whether our respiratorySaccharomyces cerevisiaestrain, TM6*, could be used to enhance the productivity of recombinant proteins over that obtained from corresponding wild type, respiro-fermentative strains when cultured under the same laboratory conditions.

Results

Here we demonstrate at least a doubling in productivity over wild-type strains for three recombinant membrane proteins and one recombinant soluble protein produced in TM6* cells. In all cases, this was attributed to the improved biomass properties of the strain. The yield profile across the growth curve was also more stable than in a wild-type strain, and was not further improved by lowering culture temperatures. This has the added benefit that improved yields can be attained rapidly at the yeast's optimal growth conditions. Importantly, improved productivity could not be reproduced in wild-type strains by culturing them under glucose fed-batch conditions: despite having achieved very similar biomass yields to those achieved by TM6* cultures, the total volumetric yields were not concomitantly increased. Furthermore, the productivity of TM6* was unaffected by growing cultures in the presence of ethanol. These findings support the unique properties of TM6* as a microbial cell factory.

Conclusions

The accumulation of biomass in yeast cell factories is not necessarily correlated with a proportional increase in the functional yield of the recombinant protein being produced. The respiratoryS. cerevisiaestrain reported here is therefore a useful addition to the matrix of production hosts currently available as its improved biomass properties do lead to increased volumetric yields without the need to resort to complex control or cultivation schemes. This is anticipated to be of particular value in the production of challenging targets such as membrane proteins.
Fas (CD95) induces rapid, TLR4/IRAK4-dependent release of pro-inflammatory HMGB1 from macrophages
Authors: Wang Feng , Lu Ziyue , Hawkes Michael , Yang Huan , Kain Kevin C , Liles W Conrad
Published: June 2010

Although Fas (CD95) is recognized as a death receptor that induces apoptosis, recent studies indicate that the Fas/FasL system can induce pro-inflammatory cytokine production by macrophages independent of conventional caspase-mediated apoptotic signaling. The precise mechanism(s) by which Fas activates macrophage inflammation is unknown. We hypothesized that Fas stimulates rapid release of high mobility group box 1 (HMGB1) that acts in an autocrine and/or paracrine manner to stimulate pro-inflammatory cytokine production via a Toll-like receptor-4 (TLR4)/Interleukin-1 receptor associated kinase-4 (IRAK4)-dependent mechanism. Following Fas activation, HMGB1 was released within 1 hr from viable RAW267.4 cells and primary murine peritoneal macrophages. HMGB1 release was more rapid following Fas activation compared to LPS stimulation. Neutralization of HMGB1 with an inhibitory anti-HMGB1 monoclonal antibody strongly inhibited Fas-induced production of tumor necrosis factor (TNF) and macrophage inflammatory protein-2 (MIP-2). Both Fas-induced HMGB1 release and associated pro-inflammatory cytokine production were significantly decreased fromTlr4-/-andIrak4-/-macrophages, but notTlr2-/-macrophages. These findings reveal a novel mechanism underlying Fas-mediated pro-inflammatory physiological responses in macrophages. We conclude that Fas activation induces rapid, TLR4/IRAK4-dependent release of HMGB1 that contributes to Fas-mediated pro-inflammatory cytokine production by viable macrophages.
Interleukin 11 is upregulated in uterine lavage and endometrial cancer cells in women with endometrial carcinoma
Authors: Yap Joanne , Salamonsen Lois A , Jobling Tom , Nicholls Peter K , Dimitriadis Evdokia
Published: June 2010

Background

Interleukin (IL) 11 is produced by human endometrium and endometrial cancer tissue. It has roles in endometrial epithelial cell adhesion and trophoblast cell invasion, two important processes in cancer progression. This study aimed to determine the levels of IL11 in uterine lavage fluid in women with endometrial cancer and postmenopausal women. It further aimed to determine the levels of IL11 protein and its signaling molecules in human endometrial cancer of varying grades, and endometrium from postmenopausal women and IL11 signalling mechanisms in endometrial cancer cell lines.

Methods

IL11 levels in uterine lavage were measured by ELISA. IL11, IL11 receptor(R) α, phosphorylated (p) STAT3 and SOCS3 were examined by immunohistochemistry in endometrial carcinomas and in control endometrium from postmenopausal women and normal cycling women. The effect of IL11 on pSTAT3/STAT3 and SOCS3 protein abundance in endometrial cancer cell lines and non-cancer endometrial epithelial cells was determined by Western blot.

Results

IL11 was present in uterine flushings and was significantly higher in women with Grade 1 carcinomas compared to postmenopausal women (p < 0.05). IL11 immunostaining was significantly elevated in the endometrial tumour epithelial cells from Grade 1 and 3 compared to endometrial epithelium from postmenopausal and cycling women. IL11Rα immunostaining intensity was increased in cancer epithelium in the Grades 1 and 2 tumours compared to epithelium from postmenopausal women. Both IL11 and IL11Rα localized to vascular endothelial and smooth muscle cells while IL11 also localized to subsets of leucocytes in the cancer tissues. pSTAT3 was found in both the tumour epithelial and stromal compartments but was maximal in the tumour epithelial cells, while SOCS3 was predominantly found in the tumour epithelial cells. pSTAT3 staining intensity was significantly higher in Grade 1 and 2 tumour epithelial cells compared to epithelial cells from cycling and postmenopausal women. SOCS3 staining intensity did not differ between between each tumour and postmenopausal endometrial epithelium but SOCS3 in cycling endometrium was significantly higher compared to postmonopausal and Tumour Grades 2 and 3. IL11 increased pSTAT3/STAT3 in all tumour cell lines, while SOCS3 abundance was increased only in one tumour cell line.

Conclusions

The present study suggests that IL11 in uterine washings may be useful as a diagnostic marker for early stage endometrial cancer. It indicates that IL11, along with its specific receptor, IL11Rα, and downstream signalling molecules, STAT3 and SOCS3, are likely to play a role in the progression of endometrial carcinoma. The precise role of IL11 in endometrial cancer remains to be elucidated.
Development and implementation of a lifestyle intervention to promote physical activity and healthy diet in the Dutch general practice setting: the BeweegKuur programme
Authors: Helmink Judith HM , Meis Jessie JM , de Weerdt Inge , Visser Femke N , de Vries Nanne K , Kremers Stef PJ
Published: June 2010

Background

The number of patients with diabetes is increasing. BeweegKuur (Dutch for 'Exercise Therapy') is a Dutch lifestyle intervention which aims to effectively and feasibly promote physical activity and better dietary behaviour in primary health care to prevent diabetes.

Methods

The goal of this paper is to present the development process and the contents of the intervention, using a model of systematic health promotion planning. The intervention consists of a 1-year programme for diabetic and prediabetic patients. Patients are referred by their general practitioner (GP) to a lifestyle advisor (LSA), usually the practice nurse or a physiotherapist. Based on specific inclusion criteria and in close collaboration with the patient, an individual exercise programme is designed and supervised by the LSA. This programme can be attended at existing local exercise facilities or (temporarily) under the supervision of a specialized exercise coach or physiotherapist. All participants are also referred to a dietician and receive diet-related group education. In the first pilot year (2008), the BeweegKuur programme was implemented in 7 regions in the Netherlands (19 GP practices and health centres), while 14 regions (41 GP practices and health centres) participated during the second year. The aim is to implement BeweegKuur in all regions of the Netherlands by 2012.

Discussion

The BeweegKuur programme was systematically developed in an evidence- and practice-based process. Formative monitoring studies and (controlled) effectiveness studies are needed to examine the diffusion process and the effectiveness and cost-effectiveness of the intervention.
Confocal analysis of nervous system architecture in direct-developing juveniles of Neanthes arenaceodentata (Annelida, Nereididae)
Authors: Winchell Christopher J , Valencia Jonathan E , Jacobs David K
Published: June 2010

Background

Members of Family Nereididae have complex neural morphology exemplary of errant polychaetes and are leading research models in the investigation of annelid nervous systems. However, few studies focus on the development of their nervous system morphology. Such data are particularly relevant today, as nereidids are the subjects of a growing body of "evo-devo" work concerning bilaterian nervous systems, and detailed knowledge of their developing neuroanatomy facilitates the interpretation of gene expression analyses. In addition, new data are needed to resolve discrepancies between classic studies of nereidid neuroanatomy. We present a neuroanatomical overview based on acetylated α-tubulin labeling and confocal microscopy for post-embryonic stages of Neanthes arenaceodentata, a direct-developing nereidid.

Results

At hatching (2-3 chaetigers), the nervous system has developed much of the complexity of the adult (large brain, circumesophageal connectives, nerve cords, segmental nerves), and the stomatogastric nervous system is partially formed. By the 5-chaetiger stage, the cephalic appendages and anal cirri are well innervated and have clear connections to the central nervous system. Within one week of hatching (9-chaetigers), cephalic sensory structures (e.g., nuchal organs, Langdon's organs) and brain substructures (e.g., corpora pedunculata, stomatogastric ganglia) are clearly differentiated. Additionally, the segmental-nerve architecture (including interconnections) matches descriptions of other, adult nereidids, and the pharynx has developed longitudinal nerves, nerve rings, and ganglia. All central roots of the stomatogastric nervous system are distinguishable in 12-chaetiger juveniles. Evidence was also found for two previously undescribed peripheral nerve interconnections and aspects of parapodial muscle innervation.

Conclusions

N. arenaceodentata has apparently lost all essential trochophore characteristics typical of nereidids. Relative to the polychaete Capitella, brain separation from a distinct epidermis occurs later in N. arenaceodentata, indicating different mechanisms of prostomial development. Our observations of parapodial innervation and the absence of lateral nerves in N. arenaceodentata are similar to a 19th century study of Alitta virens (formerly Nereis/Neanthes virens) but contrast with a more recent study that describes a single parapodial nerve pattern and lateral nerve presence in A. virens and two other genera. The latter study apparently does not account for among-nereidid variation in these major neural features.
Genetic characterization of wild-type measles viruses isolated in China, 2006-2007
Authors: Ji Yixin , Xu Songtao , Zhang Yan , Zhu Zhen , Mao Naiying , Jiang Xiaohong , Ma Chao , Lu Peishan , Wang Changyin , Liang Yong , Zheng Huanying , Liu Yang , Dai Defang , Zheng Lei , Zhou Jianhui , Wang Shuang , Zhang Zhenying , Wu Shengwei , Nan Lijuan , Li Li , Liang Xiaofeng , Featherstone David Alexander , Rota Paul A , Bellini William J , Xu Wenbo
Published: June 2010

Molecular characterization of wild-type measles viruses in China during 1995-2004 demonstrated that genotype H1 was endemic and widely distributed throughout the country. H1-associated cases and outbreaks caused a resurgence of measles beginning in 2005. A total of 210,094 measles cases and 101 deaths were reported by National Notifiable Diseases Reporting System (NNDRS) and Chinese Measles Laboratory Network (LabNet) from 2006 to 2007, and the incidences of measles were 6.8/100,000 population and 7.2/100,000 population in 2006 and 2007, respectively. Five hundred and sixty-five wild-type measles viruses were isolated from 24 of 31 provinces in mainland China during 2006 and 2007, and all of the wild type virus isolates belonged to cluster 1 of genotype H1. These results indicated that H1-cluster 1 viruses were the predominant viruses circulating in China from 2006 to 2007. This study contributes to previous efforts to generate critical baseline data about circulating wild-type measles viruses in China that will allow molecular epidemiologic studies to help measure the progress made toward China's goal of measles elimination by 2012.
Association of interleukin-10 gene polymorphisms with breast cancer in a Chinese population
Authors: Kong Fanjun , Liu Jie , Liu Yongheng , Song Bao , Wang Hualing , Liu Wenchao
Published: June 2010

Backgroud

Interleukin-10(IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population.

Methods

We genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP).

Results

There were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN) involvement (P= 0.041) and larger tumor size (P= 0.039) at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p= 0.022) and higher tumor stage(p= 0.028) of breast cancer at the time of diagnosis compared with others.

Conclusions

Our findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.
Improvement in symptoms and signs in the forefoot of patients with rheumatoid arthritis treated with anti‐TNF therapy
Authors: Bowen Catherine J , Edwards Christopher J , Hooper Lindsey , Dewbury Keith , Sampson Madeleine , Sawyer Sally , Burridge Jane , Arden Nigel K
Published: June 2010

Background

Inhibition of tumour necrosis factor (TNF) is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA), yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti‐TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability.

Methods

Consecutive RA patients starting anti‐TNF therapy (infliximab, etanercept, adalimumab) were assessed for presence of synovial hypertrophy and synovitis in the 2nd and 5th metatarso‐phalangeal (MTP) joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US) images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI).

Results

31 patients (24 female, 7 male) with RA (12 seronegative, 19 seropositive) completed the study: mean age 59.6 (SD 10.1) years, disease duration 11.1 (SD 10.5) years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6). Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t = 4.014, p < 0.001), C‐reactive protein (t = 3.889, p = 0.001), 28 joint Disease Activity Score (t = 3.712, p = 0.0001), Visual Analog Scale (t = 2.735, p = 0.011) and Manchester Foot Pain and Disability Index (t = 3.712, p = 0.001).

Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar) this was not significant.

Conclusions

Significant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.
Increased androgen receptor expression in serous carcinoma of the ovary is associated with an improved survival
Authors: Nodin Björn , Zendehrokh Nooreldin , Brändstedt Jenny , Nilsson Elise , Manjer Jonas , Brennan Donal J , Jirström Karin
Published: June 2010

Background

Altered androgen hormone homeostasis and androgen receptor (AR) activity have been implicated in ovarian carcinogenesis but the relationship between AR expression in ovarian cancer and clinical outcome remains unclear.

Methods

In this study, the prognostic impact of AR expression was investigated using immunohistochemistry in tissue microarrays from 154 incident cases of epithelial ovarian cancer (EOC) in the prospective, population-based cohorts Malmö Diet and Cancer Study and Malmö Preventive Project. A subset of corresponding fallopian tubes (n = 36) with no histopathological evidence of disease was also analysed.

Results

While abundantly expressed in the majority of fallopian tubes with more than 75% positive nuclei in 16/36 (44%) cases, AR was absent in 108/154 (70%) of EOC cases. AR expression was not related to prognosis in the entire cohort, but in the serous subtype (n = 90), AR positivity (> 10% positive nuclei) was associated with a prolonged disease specific survival in univariate (HR= 0.49; 95% CI 0.25-0.96; p= 0.038) and multivariate (HR= 0.46; 95% CI 0.22-0.97; p= 0.042) analysis, adjusted for age, grade and clinical stage.

Conclusions

AR expression is considerably reduced in EOC as compared to fallopian tubes, and in EOC of the serous subtype, high AR expression is a favourable prognostic factor. These results indicate that assessment of AR expression might be of value for treatment stratification of EOC patients with serous ovarian carcinoma.
Crosswell monitoring using virtual sources and horizontal wells
Authors: Byun Joongmoo , Yu Jeongmin , Seol Soon Jee
Published: June 2010

Time-lapse crosswell seismic provides an efficient way to monitor the migration of a [Formula: see text] plume or its leakage after [Formula: see text] injection into a geologic formation. Recently, crosswell seismic has become a powerful tool for monitoring underground variations, using the concept of a virtual source, with virtual sources positioned at the receivers installed in the well and thus the positions of sources and receivers can be invariant during monitoring. However, time-lapse crosswell seismic using vertical wells and virtual sources has difficulty in describing the front of a [Formula: see text] plume, which usually is parallel to the vertical wells, and in obtaining sufficient ray coverage for the first-arrival tomography. These problems arise because of the theoretical downward-illumination-directivity limitation of the virtual source. We have developed an effective monitoring method that uses virtual sources and two horizontal wells: one above and one below the [Formula: see text]sequestration reservoir. In our method, we redatum the traces that are recorded at geophones in horizontal wells from sources on the surface. The redatumed traces then become virtual traces recorded at geophones in the lower well and sent from virtual sources at the positions of the geophones in the upper well. The geometry of our method has advantages for locating the front of the [Formula: see text] plume, which is normal to the horizontal wells, compared with either real or virtual sources. The method also is advantageous in acquiring full ray coverage between the wells, and that coverage is superior to coverage acquired using vertical crosswell seismic with virtual sources. In addition, we can avoid problems related to any potential change in the medium above the reservoir and in the source and receiver positions. The results of applying our method to synthetic data that simulate [Formula: see text]-sequestration monitoring show that the front of a [Formula: see text] plume in the reservoir is depicted accurately in a velocity tomogram. The new method also can be used to monitor a reservoir during production of heavy oil.
Analysis of prior models for a blocky inversion of seismic AVA data
Authors: Theune Ulrich , Jensås Ingrid Østgård , Eidsvik Jo
Published: June 2010

Resolving thinner layers and focusing layer boundaries better in inverted seismic sections are important challenges in exploration and production seismology to better identify a potential drilling target. Many seismic inversion methods are based on a least-squares optimization approach that can intrinsically lead to unfocused transitions between adjacent layers. A Bayesian seismic amplitude variation with angle (AVA) inversion algorithm forms sharper boundaries between layers when enforcing sparseness in the vertical gradients of the inversion results. The underlying principle is similar to high-resolution processing algorithms and has been adapted from digital-image-sharpening algorithms. We have investigated the Cauchy and Laplace statistical distributions for their potential to improve contrasts betweenlayers. An inversion algorithm is derived statistically from Bayes’ theorem and results in a nonlinear problem that requires an iterative solution approach. Bayesian inversions require knowledge of certain statistical properties of the model we want to invert for. The blocky inversion method requires an additional parameter besides the usual properties for a multivariate covariance matrix, which we can estimate from borehole data. Tests on synthetic and field data show that the blocky inversion algorithm can detect and enhance layer boundaries in seismic inversions by effectively suppressing side lobes. The analysis of the synthetic data suggests that the Laplace constraint performs more reliably, whereas the Cauchy constraint may not find the optimum solution by converging to a local minimum of the cost function and thereby introducing some numerical artifacts.
2D and 3D elastic wavefield vector decomposition in the wavenumber domain for VTI media
Authors: Zhang Qunshan , McMechan George A.
Published: June 2010

A pragmatic decomposition of a vector wavefield into P- and S-waves is based on the Helmholtz theory and the Christoffel equation. It is applicable to VTI media when the plane-wave polarization is continuous in the vicinity of a given wavenumber and is uniquely defined by that wavenumber, except for the kiss singularities on the VTI symmetry axis. Unlike divergence and curl, which separate the wavefield into a scalar and a vector field, the decomposed P- and S-wavefields are both vector fields, with correct amplitude, phase, and physical units. If the vector components of decomposed wavefields are added, they reconstruct those of the original input wavefield. Wavefield propagation in any portions of a VTI medium that have the same polarization distribution (i.e., the same eigenvector) in the wavenumber domain have the same decomposition operators and can be recon-structed with a single 3D Fourier transform for each operator (e.g., one for P-waves and one for S-waves).This applies to isotropic wavefields and to VTI anisotropic wavefields, if the polarization distribution is constant, regardless of changes in the velocity. Because the anisotropic phase polarization is local, not global, the wavefield decomposition for inhomogeneous anisotropic media needs to be done separately for each region that has a different polarization distribution. The complete decomposed vector wavefield is constructed by combining the P-, SV-, and SH-wavefields in each region into the corresponding composite P-, SV-, and SH-wavefields that span the model. Potential practical applications include extraction of separate images for different wave types in prestack reverse time migration, inversion, or migration velocity analysis, and calculation of wave-propagation directions for common-angle gathers.
Multiple Endocrine Neoplasia Type 1 Deletion in Pancreatic α-Cells Leads to Development of Insulinomas in Mice
Authors: Shen H.-C. Jennifer , Ylaya Kris , Pechhold Klaus , Wilson Arianne , Adem Asha , Hewitt Stephen M. , Libutti Steven K.
Published: June 2010

The pancreatic α- and β-cells are critical components in regulating blood glucose homeostasis via secretion of glucagon and insulin, respectively. Both cell types are typically localized in the islets of Langerhans. However, little is known about the roles of paracrine interactions that contribute to their physiological functions. The lack of suitable cell lines to study α- and β-cells interactions have led us to develop an α-cell-specific Cre-expressing transgenic line utilizing a glucagon promoter sequence, the Glu-Cre transgenic mouse. Here, we demonstrate that the Glu-Cre could specifically and efficiently excise floxed target genes in adult islet α-cells. We further showed that deletion of the tumor suppressor gene, multiple endocrine neoplasia type 1 (Men1), in α-cells led to tumorigenesis. However, to our surprise, the lack of Men1 in α-cells did not result in glucagonomas but rather β-cell insulinomas. Because deletion of the Men1 alleles was only present in α-cells, our data suggested that cross communication between α- and β-cells contributes to tumorigenesis in the absence of Men1. Together, we believed that the new model systems described here will allow future studies to decipher cellular interactions between islet α- and β-cells in a physiological context.
Modulating Testicular Mass in Xenografting: A Model to Explore Testis Development and Endocrine Function
Authors: Schlatt Stefan , Gassei Kathrin , Westernströer Birgit , Ehmcke Jens
Published: June 2010

The hypothalamic-pituitary-gonadal (HPG) axis is involved in both the regulation of growth of the developing testis and in controlling spermatogenic and steroidogenic activity in the adult testis. Here, we develop a novel testicular xenografting model to examine to which degree testicular growth and function are controlled by intra- and extratesticular factors. Two or eight halves of neonatal Djungarian hamster testes were implanted into intact, hemicastrated, or castrated nude mouse recipients, and the development of the grafts under reduced or increased competition of testicular tissue was monitored and analyzed. We hypothesized that the outgrowth of the testicular grafts is influenced by the total amount of testicular tissue present in a host and that less testicular tissue in a host would result in more extended outgrowth of the grafts. Our results reveal that the hypothesis is wrong, because implanted hamster testis tissue irrespectively of the grafting condition grows to a similar size revealing an intrinsic mechanism for testicular growth. In contrast, similar size of seminal vesicle as bio-indicator of androgen levels in all hosts revealed that the steroidogenic activity is independent from the mass of testicular tissue and that steroid levels are extrinsically regulated by the recipient’s HPG axis. We propose that the model of testicular xenografting provides highly valuable options to explore testicular growth and endocrine regulation of the HPG axis.
Sex Steroid Hormones in Older Men: Longitudinal Associations with 4.5-Year Change in Hip Bone Mineral Density—The Osteoporotic Fractures in Men Study
Authors: Cauley Jane A. , Ewing Susan K. , Taylor Brent C. , Fink Howard A. , Ensrud Kristine E. , Bauer Douglas C. , Barrett-Connor Elizabeth , Marshall Lynn , Orwoll Eric S. ,   for the Osteoporotic Fractures in Men Study (MrOS) Research Group
Published: June 2010

Context: There is limited information on the association between sex hormones and bone loss in older men.

Objective: Our objective was to determine the longitudinal association between sex steroid hormones and bone mineral density (BMD).

Design and Setting: We conducted a prospective study of 5995 men aged at least 65 yr old at six U.S. clinical centers.

Participants: Sex steroid hormones were measured in a random sample of 1602 men. After exclusions, 1238 men were included in cross-sectional analyses and 969 in longitudinal analyses. Baseline sex hormones were measured using liquid chromatography-mass spectrometry. Bioavailable (Bio) estradiol (BioE2) and testosterone (BioT) were calculated from mass action equations. SHBG was measured using chemiluminescent substrate.

Main Outcome Measures: BMD of the total hip, measured at baseline and once or twice afterward over 4.6 yr of follow-up, was evaluated.

Results: The annualized percent change in hip BMD increased with decreasing BioE2 (P trend = 0.03). Men with the lowest BioE2 (<39.7 pmol/liter) compared with the highest BioE2 (≥66.0 pmol/liter) experienced 38% faster rate of BMD loss (P < 0.05). There was no association between BioT and hip BMD loss. Men with lowest BioE2, lowest BioT, and highest SHBG experienced a 3-fold faster rate of BMD loss compared with men with higher levels (P = 0.02). A threshold effect of SHBG was observed; the rate of hip BMD loss increased in men with SHBG of 49–60 nm.

Conclusions: Low BioE2 and high SHBG levels were associated with lower BMD and faster hip BMD loss. The combination of low BioE2, low BioT, and high SHBG was associated with significantly faster rates of BMD loss.
Characterization of and Risk Factors for the Acute-Phase Response after Zoledronic Acid
Authors: Reid I. R. , Gamble G. D. , Mesenbrink P. , Lakatos P. , Black D. M.
Published: June 2010

Context: Intravenous aminobisphosphonates often cause an acute-phase response (APR), but the precise components of this, its frequency, and the risk factors for its development have not been systematically studied.

Objective: The objective of the study was to characterize the APR and determine its frequency and the risk factors for its development.

Design: The study was an analysis of adverse events from a large randomized trial.

Setting: This was a multicenter international trial.

Patients: Patients included 7765 postmenopausal women with osteoporosis.

Intervention: Zoledronic acid 5 mg annually or placebo was the intervention.

Main Outcome Measure: Adverse events occurring within 3 d of zoledronic acid infusion were measured.

Results: More than 30 adverse events were significantly more common in the zoledronic acid group and were regarded collectively as constituting an APR. These were clustered into five groups: fever; musculoskeletal (pain and joint swelling); gastrointestinal (abdominal pain, vomiting, diarrhea); eye inflammation; and general (including fatigue, nasopharyngitis, edema). A total of 42.4% of the zoledronic acid group had an APR after the first infusion, compared with 11.7% of the placebo group. All APR components had their peak onset within 1 d, the median duration of the APR was 3 d, and severity was rated as mild or moderate in 90%. Stepwise regression showed that APR was more common in non-Japanese Asians, younger subjects, and nonsteroidal antiinflammatory drug users and was less common in smokers, patients with diabetes, previous users of oral bisphosphonates, and Latin Americans (P < 0.05 for all).

Conclusion: This analysis identifies new components of the APR and provides the first assessment of risk factors for it. Despite its frequency, APR rarely resulted in treatment discontinuation in this study.
The probabilities of absolute ruin in the renewal risk model with constant force of interest
Authors: Konstantinides Dimitrios G. , Ng Kai W. , Tang Qihe
Published: June 2010

In this paper we consider the probabilities of finite- and infinite-time absolute ruins in the renewal risk model with constant premium rate and constant force of interest. In the particular case of the compound Poisson model, explicit asymptotic expressions for the finite- and infinite-time absolute ruin probabilities are given. For the general renewal risk model, we present an asymptotic expression for the infinite-time absolute ruin probability. Conditional distributions of Poisson processes and probabilistic techniques regarding randomly weighted sums are employed in the course of this study.
A stochastic differential reinsurance game
Authors: Zeng Xudong
Published: June 2010

We study a stochastic differential game between two insurance companies who employ reinsurance to reduce the risk of exposure. Under the assumption that the companies have large insurance portfolios compared to any individual claim size, their surplus processes can be approximated by stochastic differential equations. We formulate competition between the two companies as a game with a single payoff function which depends on the surplus processes. One company chooses a dynamic reinsurance strategy in order to maximize this expected payoff, while the other company simultaneously chooses a dynamic reinsurance strategy so as to minimize the same quantity. We describe the Nash equilibrium of this stochastic differential game and solve it explicitly for the case of maximizing/minimizing the exit probability.