bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of association between serum 25-hydroxyvitamin D levels and cervical human papillomavirus infection in systemic lupus erythematosus
Authors: García-Carrasco M , Mendoza-Pinto C , Munguía-Realpozo P , Rodríguez-Gallegos A , Vallejo-Ruiz V , Muñoz-Guarneros M , Méndez-Martínez S , Soto-Santillán P , Pezzat-Said E , Reyes-Leyva J , López-Colombo A , Ruiz-Argüelles A , Cervera R
Published: November 2014

Our objective was to evaluate whether vitamin D deficiency is associated with cervical human papilloma virus (HPV) infection in women with SLE. This is a cross-sectional study of 67 women with SLE. A structured questionnaire was administered to ascertain the possible risk factors associated with cervical HPV infection. A gynaecological evaluation and cervical cytology screening were made. HPV detection and genotyping was made by PCR and linear array assay. Serum 25 hydroxyvitamin D levels were quantified by chemiluminescence immunoassay. Mean age and disease duration were 44.8 ± 10.6 and 42.5 ± 11.8 years, respectively. Demographic characteristics were similar in patients with and without deficiency (<20 ng/ml and ≥20 ng/ml). There were 28.4% of women with cervical HPV infection and 68.4% had high-risk HPV infections. Patients with 25 hydroxyvitamin D levels <20 ng/ml had a higher prevalence of cervical HPV infection than those with levels ≥20 ng/ml (30.7% vs. 25.8%; p = 0.72). We found no significant difference when high-risk HPV infection was evaluated (36.8% vs. 31.5%; p = 0.73). In conclusion, women with SLE have a high prevalence of vitamin D deficiency and cervical HPV infection. However, we found no association between vitamin D deficiency and cervical HPV.
Smoking is highly associated with discoid lupus erythematosus and lupus erythematosus tumidus: analysis of 405 patients
Authors: Böckle B C , Sepp N T
Published: November 2014

Background

Environmental factors appear to play a role in the pathogenesis of lupus erythematosus (LE).

Objective

To determine the association between cigarette smoking and various types of cutaneous LE.

Design

Retrospective descriptive study at a dermatology clinic of a tertiary referral hospital.

Methods

All patients diagnosed with cutaneous and/or systemic LE from January 2000 to December 2012 at the outpatient clinic for dermatological autoimmune diseases were analyzed.

Results

405 patients were diagnosed with LE. Smokers were more common among patients with cutaneous LE, especially those with LE tumidus or discoid LE. The frequency of cigarette smokers was not significantly higher among patients with other LE-specific skin lesions and patients with systemic LE compared to the general population. Smoking at the onset of disease was associated with LE tumidus (odds ratio OR 4.5), discoid LE (OR 2.05), the male gender (OR 3.31), age < 50 years (OR 1.03), and photosensitivity (OR 2.07).

Limitations

A retrospective descriptive study at a tertiary referral hospital.

Conclusion

Smoking is highly associated with cutaneous LE, but not systemic LE. Various risk factors appear to be involved in the pathogenesis of cutaneous and systemic LE.
A stepped wedge design for testing an effect of intranasal insulin on cognitive development of children with Phelan-McDermid syndrome: A comparison of different designs
Authors: Van den Heuvel Edwin R , Zwanenburg Renée J , Van Ravenswaaij-Arts Conny MA
Published: November 2014

This paper compares the power of the parallel group design, the matched-pairs design, and several options for the stepped wedge and delayed start designs for testing a possible effect of intranasal insulin with respect to placebo on developmental growth of children with a rare disorder like Phelan-McDermid syndrome. A subject-specific linear mixed effects model for the primary outcome developmental age in a longitudinal setting with five time points was assumed. Monte Carlo simulation studies with small sample sizes were applied since the rare disorder prohibits large trials. The stepped wedge designs, which were initially preferred for ethical reasons, appear to be competitive in power to other designs and were in some settings even the best. The assumed statistical model also demonstrates that all of the designs can be viewed as a stepped wedge or delayed treatment design. Our results show that the stepped wedge design is an appropriate alternative for randomized controlled trials on developmental growth with small numbers of participants under the formulated statistical conditions.
Guiding the Process of Culturally Competent Care With Hispanic Patients
Authors: Sobel Linda L. , Metzler Sawin Erika
Published: November 2014

Purpose: To explore nursing care actions that lead to culturally competent care for Hispanic patients. Background: Nurses report apprehension when delivering nursing care because of language barriers and a lack of Hispanic cultural understanding. Research is needed to inform culturally aware nursing practice actions for Hispanic patients. Design: The study used a qualitative, grounded theory design to address the questions: (a) What cultural knowledge should nurses have when caring for Hispanic patients and families and (b) What nursing actions should nurses take to provide culturally competent care? Hispanic lay health promoters and Hispanic community members were interviewed to make recommendations for care. Results: A model was identified that informs culturally competent nursing care. “Connectedness,” the central phenomenon, describes nursing actions and contains subthemes explaining influences on nursing care. “Up to You” and “At the Mercy of the System” are descriptive themes influencing connectedness. Conclusion: Connectedness is central to culturally well-informed nurse–patient interactions.
Engagement in Simulation/Gaming
Authors: Moseley Alex , Whitton Nicola
Published: November 2014

This symposium considers the space where simulation/games and learning intersect, and explores the use, meaning, and relevance of the term engagement for that intersection. The 10 articles included in this collection explore engagement from a variety of different perspectives. Together, they define the field further, highlight the importance of engagement for game design (providing models and typologies to assist future design), explore options for measuring and diagnosing engagement (describing tools and methodologies through evidenced case studies), and tackle the all-important question of whether engagement has a connection to learning. As a whole, this symposium issue provides those designing, researching, or teaching with games a number of useful tools, perspectives, and methodologies for considering engagement as a core part of their work in the area.
An exposure assessment model of the prevalence of Salmonella spp. along the processing stages of Brazilian beef
Authors: Gonzales-Barrón Ursula , Piza Luciana , Xavier Cristina , Costa Ernane , Cadavez Vasco
Published: November 2014

Beef cattle carrying Salmonella spp. represents a risk for contamination of meat and meat products. This study aimed to build an exposure assessment model elucidating the changes in Salmonella prevalence in Brazilian beef along the processing stages. To this effect, the results of a number of published studies reporting Salmonella incidences were assembled in order to model conversion factors based on beta distributions representing the effect of every production stage on the Salmonella incidence on beef carcasses. A random-effects meta-analysis modelled the hide-to-carcass transfer of Salmonella contamination. The Monte Carlo simulation estimated the Salmonella prevalence in beef cuts from processing plants to be ∼6.1% (95% CI: 1.4–17.7%), which was in reasonable agreement with a pool ( n = 105) of surveys’ data of Salmonella in Brazilian beef cuts (mean 4.9%; 95% CI: 1.8–11.5%) carried out in commercial establishments. The results not only underscored the significant increase in Salmonella prevalence that can occur during evisceration/splitting and boning but also reinforced that, when hygienic slaughter procedures are properly implemented, the load of Salmonella can be reduced at dehiding, rinsing and chilling. As the model was based on a systematic review and meta-analysis, it synthesised all available knowledge on the incidence of Salmonella in Brazilian beef.
Constructing cultural Otherness within the Swedish welfare state: The cases of social workers in Sweden
Authors: Eliassi Barzoo
Published: November 2014

The aim of the article is to analyze how social workers frame the social problems of immigrant clients in Sweden. The study is based on in-depth interviews with 20 social workers in three different Swedish municipalities. While Swedish social work often assumes a discourse of color-blindness and universalism, this study indicates that Swedish social workers not only see cultural differences but also regard these differences as central when they frame, assess, and formulate their interventions. The discourse of culturalization not only produces and reinforces the ideas of cultural hierarchy and Swedish superiority, but it also tends to obstruct non-European immigrants from equal participation in the Swedish society since they are not allowed to enjoy their full citizenship. Consequently, there is a need for social work in Sweden to rethink its culturalist framework and go beyond cultural reductionism and take into consideration other issues such as unemployment, housing conditions, poverty, social isolation, marginalization, and ethnic discrimination.
Evaluation of the Effect of Changes in Dose Rate on Rat Lung Cells
Authors: Hurmuz Pervin , Kivanc Huseyin , Canbolat Abdulmecit , Yavas Guler , Yuce Deniz , Onder Sevgen Celik , Sargon Mustafa F. , Yildiz Ferah
Published: November 2014

The aim of this study is to evaluate the effect of dose rate (DR) on lung tissue. The rats included in the study were randomly grouped into 3 groups: Group (G) 1 was defined as control group, and in this group rats were sham irradiated. G2 was the group receiving a single dose of 12 Gy in DR of 300 monitor unit (MU)/min. G3 was the group receiving a single dose of 12 Gy in DR of 600 MU/min. Radiotherapy (RT) was applied under general anesthesia with 6-MV photon beams to both lungs. At the 6th and 16th week of the RT, animals from each group were killed for light and electron microscopy evaluation. We evaluated the scores of each group in the 6th and the 16th week and found that in G2, there were significant increases in the perivascular fibrosis ( P = .018), interstitial fibrosis ( P = .002), total inflammation ( P = .040), and total fibrosis ( P = .003) scores. In G3, we found statistically significant increases in perivascular fibrosis ( P = .001), interstitial fibrosis ( P = .002), and total fibrosis scores ( P = .029). There was no significant difference in the total inflammation score in G3 ( P = .225). When we compare G2 and G3 in the 6th week, we found significant increase in the interstitial thickening ( P = .039) and total inflammation ( P = .035) scores in G3. Dose rate per fraction may have an impact on normal tissue toxicity. The prominent effect of increased DR in lung tissue is fibrosis which should be kept in mind, especially in cases where higher doses per fraction are used.
Impact of Node Negative Target Volume Delineation on Contralateral Parotid Gland Dose Sparing Using IMRT in Head and Neck Cancer
Authors: Magnuson William J. , Urban Erich , Bayliss R. Adam , Harari Paul M.
Published: November 2014

There is considerable practice variation in treatment of the node negative (N0) contralateral neck in patients with head and neck cancer. In this study, we examined the impact of N0 neck target delineation volume on radiation dose to the contralateral parotid gland. Following institutional review board approval, 12 patients with head and neck cancer were studied. All had indications for treatment of the N0 neck, such as midline base of tongue or soft palate extension or advanced ipsilateral nodal disease. The N0 neck volumes were created using the Radiation Therapy Oncology Group head and neck contouring atlas. The physician-drawn N0 neck clinical target volume (CTV) was expanded by 25% to 200% to generate volume variation, followed by a 3-mm planning target volume (PTV) expansion. Surrounding organs at risk were contoured and complete intensity-modulated radiation therapy plans were generated for each N0 volume expansion. The median N0 target volume drawn by the radiation oncologist measured 93 cm3 (range 71-145). Volumetric expansion of the N0 CTV by 25% to 200% increased the resultant mean dose to the contralateral parotid gland by 1.4 to 8.5 Gray (Gy). For example, a 4.1-mm increase in the N0 neck CTV translated to a 2.0-Gy dose increase to the parotid, 7.4 mm to a 4.5 Gy dose increase, and 12.5 mm to an 8.5 Gy dose increase, respectively. The treatment volume designated for the N0 neck has profound impact on resultant dose to the contralateral parotid gland. Variations of up to 15 mm are routine across physicians in target contouring, reflecting individual preference and training expertise. Depending on the availability of immobilization and image guidance techniques, experts commonly recommend 3 to 10 mm margin expansions to generate the PTV. Careful attention to the original volume of the N0 neck CTV, as well as expansion margins, is important in achieving effective contralateral gland sparing to reduce the resultant xerostomia and dysguesia that may ensue after radiotherapy.
Investigation of Nonuniform Dose Voxel Geometry in Monte Carlo Calculations
Authors: Yuan Jiankui , Chen Quan , Brindle James , Zheng Yiran , Lo Simon , Sohn Jason , Wessels Barry
Published: November 2014

The purpose of this work is to investigate the efficacy of using multi-resolution nonuniform dose voxel geometry in Monte Carlo (MC) simulations. An in-house MC code based on the dose planning method MC code was developed in C++ to accommodate the nonuniform dose voxel geometry package since general purpose MC codes use their own coupled geometry packages. We devised the package in a manner that the entire calculation volume was first divided into a coarse mesh and then the coarse mesh was subdivided into nonuniform voxels with variable voxel sizes based on density difference. We name this approach as multi-resolution subdivision (MRS). It generates larger voxels in small density gradient regions and smaller voxels in large density gradient regions. To take into account the large dose gradients due to the beam penumbra, the nonuniform voxels can be further split using ray tracing starting from the beam edges. The accuracy of the implementation of the algorithm was verified by comparing with the data published by Rogers and Mohan. The discrepancy was found to be 1% to 2%, with a maximum of 3% at the interfaces. Two clinical cases were used to investigate the efficacy of nonuniform voxel geometry in the MC code. Applying our MRS approach, we started with the initial voxel size of 5 × 5 × 3 mm3, which was further divided into smaller voxels. The smallest voxel size was 1.25 × 1.25 × 3 mm3. We found that the simulation time per history for the nonuniform voxels is about 30% to 40% faster than the uniform fine voxels (1.25 × 1.25 × 3 mm3) while maintaining similar accuracy.
Cognitive-Behavioral Treatment of Social Anxiety Disorder and Comorbid Paranoid Schizophrenia
Authors: Williams Monnica T. , Capozzoli Michelle C. , Buckner Erica V. , Yusko David
Published: November 2014

We report on the cognitive-behavioral treatment (CBT) of a patient with comorbid social anxiety disorder (SAD), schizophrenia, and major depressive disorder, complicated by alcohol abuse. Symptoms included auditory hallucinations that commented on the patient’s behavior and paranoid thoughts. The paranoid symptoms affected his social interactions as this included the fear that his thoughts may be heard and judged by others. Therapeutic activities raised awareness as to how avoidance interferes with and perpetuates the cycle of depression and psychosis while maintaining symptoms of SAD. Psychoeducation was provided about factors that maintain social anxiety and increase social isolation. New skills were obtained by helping the patient discover alternative ways to view social situations, experimentation, and real-world application to disprove notions about others’ predicted behavior. Treatment led to a great reduction in social anxiety, depression, and suspicious thinking. This case study demonstrates that SAD symptoms in a patient experiencing psychosis can be effectively treated using CBT.
The Precariat
Authors: Standing Guy
Published: November 2014

Economist Guy Standing explains how millions of people are in the precariat, and in defining this emerging class, points to the dangerous political and social consequences as well as the exciting progressive revival that this class could produce.
Medicalizing Racism
Authors: Thomas James M.
Published: November 2014

Sociologist James M. Thomas (JT) examines how public and scientific accounts of racism draw upon medical and psychological models, and how this contributes to our understandings of racism as a medical, rather than social, problem.
Molly Deaths and The Failed War on Drugs
Authors: Anderson Tammy L.
Published: November 2014

Sociologist Tammy L. Anderson proposes that the 2003 RAVE Act may endanger ravers more than protect them. Today’s popularity of huge commercial raves—and the incidence of health complications at them—suggests this relic law of the twentieth century War on Drugs needs our attention.
Narrating the Transgressive Self
Authors: Goode Erich
Published: November 2014

Since Augustine penned his Confessions, authors of memoirs describing their transgressive behavior have teetered on a balance beam between telling an interesting, exciting, naughty story, and exculpating their character for their participation in it, through the use of deviance neutralizing devices; here sociologist Erich Goode explains how this balancing act is accomplished.
Hybrid endovascular and surgical approach for mycotic pseudoaneurysms of the extracranial internal carotid artery
Authors: Mazzaccaro Daniela , Stegher Silvia , Occhiuto Maria Teresa , Malacrida Giovanni , Righini Paolo , Tealdi Domenico G , Nano Giovanni
Published: November 2014

Objectives:

Mycotic pseudoaneurysms of the extracranial internal carotid artery are rare, and their management often represents a challenge, but treatment is necessary due to the high risk of rupture and distal brain embolization. Systemic antibiotics associated with open surgical excision of the infected tissues and carotid reconstruction using autologous grafts are the treatment of choice. The use of endovascular techniques still remains controversial in infective fields; however, it can be an attractive alternative in high-risk patients or more often as a “temporary” solution to achieve immediate bleeding control for a safe surgical reconstruction.

Methods:

We discuss the unusual case of an extracranial right internal carotid artery mycotic pseudoaneurysm following methicillin-resistant Staphylococcus aureus infection, in a patient with poor general conditions.

Results and Conclusion:

The lesion was successfully treated using a hybrid endovascular and surgical procedure.
A Plea for the Traditional Family: Situating Marriage within John Paul II's Realist, or Personalist, Perspective of Human Freedom
Authors: Schumacher Michele M.
Published: November 2014

This article is an attempt to defend the rights of the traditional family: not simply against the redefinition of marriage, but more fundamentally against a re-conceptualization of human freedom and human rights. To this end, it contrasts what Saint John Paul II calls an individualistic understanding of freedom and a personalistic notion of the same in order to argue that human freedom is called by the Creator to be in service of, and not in opposition to, the good of the human family. From this perspective—that of the social doctrine of the Catholic Church—it argues for the harmony between natural marriage and the respect of fundamental human rights, and it presents the social dimension of marriage as fundamental with respect to the legal and social protection of the family.
Platelet hyaluronidase-2: an enzyme that translocates to the surface upon activation to function in extracellular matrix degradation
Authors: Albeiroti Sami , Ayasoufi Katayoun , Hill David R. , Shen Bo , de la Motte Carol A.
Published: November 2014

Key Points

Platelet HYAL2 is stored in α-granules and upon activation it becomes surface expressed where it functions to degrade extracellular matrix. Platelets from IBD patients contain lower HYAL2 protein and activity than those from non-IBD controls.
Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate (BCLC B) hepatocellular carcinoma
Authors: Yin Xin , Zhang Lan , Wang Yan-Hong , Zhang Bo-Heng , Gan Yu-Hong , Ge Ning-Lin , Chen Yi , Li Li-Xin , Ren Zheng-Gang
Published: November 2014

Background

This study was designed to evaluate the effectiveness of radiofrequency ablation in patients with intermediate (BCLC B) stage hepatocellular carcinoma who underwent transcatheter arterial chemoembolization.

Methods

Included in this study were 211 patients with intermediate stage HCC who underwent initial transcatheter arterial chemoembolization and were potentially amendable for radiofrequency ablation (single tumor with diameter 5-8 cm, median 6.0 cm; 2–5 multiple nodules with diameter less than 5 cm) between January 2005 and December 2011. According to the inclusion and exclusion criteria, 55 patients were treated with following radiofrequency ablation, and the remaining 156 patients were treated with transcatheter arterial chemoembolization alone. The treatment effectiveness, local tumor control and survival outcome between the two groups were compared.

Results

The complete tumor necrosis rate after treatment was 76.9% in combination group vs. 46.5% in transcatheter arterial chemoembolization alone group (P = 0.02). The major complication rate was 1.8% in combination group vs. 2.6% in transcatheter arterial chemoembolization alone group. Follow-up observation showed that the total tumor control rate was 74.5% in combination group versus 54.5% in transcatheter arterial chemoembolization alone group (P < 0.001). The 1-, 3- and 5-year survival rates in combination group were significantly higher than those in TACE alone group (P = 0.01).

Conclusions

Radiofrequency ablation following initial transcatheter arterial chemoembolization delays tumor progression and prolongs overall survival of patients with intermediate stage HCC tumors.
Lysophosphatidic Acid and its Receptors LPA1 and LPA3 Mediate Paclitaxel-Induced Neuropathic Pain in Mice
Authors: Uchida Hitoshi , Nagai Jun , Ueda Hiroshi
Published: November 2014

Background:

Paclitaxel, which is widely used for the treatment of solid tumors, causes neuropathic pain via poorly understood mechanisms. Previously, we have demonstrated that lysophosphatidic acid (LPA) and its receptors (LPA1 and LPA3) are required for the initiation of peripheral nerve injury-induced neuropathic pain. The present study aimed to clarify whether LPA and its receptors could mediate paclitaxel-induced neuropathic pain.

Results:

Intraperitoneal administration of paclitaxel triggered a marked increase in production of LPA species (18:1-, 16:0-, and 18:0-LPA) in the spinal dorsal horn. Also, we found significant activations of spinal cytosolic phospholipase A2 and calcium-independent phospholipase A2 after the paclitaxel treatment. The paclitaxel-induced LPA production was completely abolished not only by intrathecal pretreatment with neurokinin 1 (NK1) or N-methyl-D-aspartate (NMDA) receptor antagonist, but also in LPA1 receptor-deficient ( Lpar1−/–) and LPA3 receptor-deficient ( Lpar3−/–) mice. In addition, the pharmacological blockade of NK1 or NMDA receptor prevented a reduction in the paw withdrawal threshold against mechanical stimulation after paclitaxel treatments. Importantly, the paclitaxel-induced mechanical allodynia was absent in Lpar1−/– and Lpar3−/– mice.

Conclusions:

These results suggest that LPA1 and LPA3 receptors-mediated amplification of spinal LPA production is required for the development of paclitaxel-induced neuropathic pain.
Aldosterone, Parathyroid Hormone, and the Use of Renin-Angiotensin-Aldosterone System Inhibitors: The Multi-Ethnic Study of Atherosclerosis
Authors: Brown Jenifer , de Boer Ian H. , Robinson-Cohen Cassianne , Siscovick David S. , Kestenbaum Bryan , Allison Matthew , Vaidya Anand
Published: November 2014

Context:

Aldosterone and PTH are implicated in the pathogenesis of cardiovascular and skeletal diseases. An expanding body of evidence supports a bidirectional and positive physiologic relationship between aldosterone and PTH. Large population-based studies confirming this relationship, and whether it may be targeted as a potential method to mitigate the clinical consequences associated with excess aldosterone and PTH, are needed.

Objective:

We hypothesized that higher aldosterone levels would associate with higher PTH, and that the use of renin-angiotensin-aldosterone system (RAAS) inhibitors would predict lower PTH in a large, multi-ethnic, community-based cohort.

Design, Setting, Participants:

We conducted cross-sectional analyses of participants in the Multi-Ethnic Study of Atherosclerosis without apparent primary hyperparathyroidism or chronic kidney disease (n = 5668). We evaluated associations of RAAS inhibitor use with PTH concentration among 1888 treated hypertensive participants. We also tested associations of serum aldosterone concentration with PTH concentration among 1547 participants with these measurements.

Outcome:

Serum PTH concentration.

Results:

Higher aldosterone associated with higher PTH (β = 0.19 pg/ml per 1 ng/dl of aldosterone, P < .0001), and this finding was most pronounced among those with a primary hyperaldosteronism-like phenotype. There was a stepwise increment in PTH when comparing untreated normotensives, hypertensives using RAAS inhibitors, untreated hypertensives, and treated hypertensives using non-RAAS inhibitors (40.8, 45.0, 46.2, 47.1 pg/ml, respectively). The use of any RAAS inhibitor independently associated with lower PTH (β = −2.327 pg/ml per use of RAAS inhibitor, P = .006), when compared with the use of any non-RAAS inhibitor medication.

Conclusions:

Higher serum aldosterone concentration is associated with higher serum PTH concentration, and the use of RAAS inhibitors is associated with lower PTH concentration. These results extend prior evidence from observational and intervention studies suggesting a potentially important and modifiable relationship between the RAAS and PTH in humans.
Precise and efficient genome editing in zebrafish using the CRISPR/Cas9 system
Authors: Irion Uwe , Krauss Jana , Nüsslein-Volhard Christiane
Published: November 2014

The introduction of engineered site-specific DNA endonucleases has brought precise genome editing in many model organisms and human cells into the realm of possibility. In zebrafish, loss-of-function alleles have been successfully produced; however, germ line transmission of functional targeted knock-ins of protein tags or of SNP exchanges have not been reported. Here we show by phenotypic rescue that the CRISPR/Cas system can be used to target and repair a premature stop codon at the albino (alb) locus in zebrafish with high efficiency and precision. Using circular donor DNA containing CRISPR target sites we obtain close to 50% of larvae with precise homology-directed repair of the albb4 mutation, a small fraction of which transmitted the repaired allele in the germ line to the next generation (3/28 adult fish). The in vivo demonstration of germ line transmission of a precise SNP exchange in zebrafish underscores its suitability as a model for genetic research.
Cell type-specific transcriptome analysis in the early Arabidopsis thaliana embryo
Authors: Slane Daniel , Kong Jixiang , Berendzen Kenneth W. , Kilian Joachim , Henschen Agnes , Kolb Martina , Schmid Markus , Harter Klaus , Mayer Ulrike , De Smet Ive , Bayer Martin , Jürgens Gerd
Published: November 2014

In multicellular organisms, cellular differences in gene activity are a prerequisite for differentiation and establishment of cell types. In order to study transcriptome profiles, specific cell types have to be isolated from a given tissue or even the whole organism. However, whole-transcriptome analysis of early embryos in flowering plants has been hampered by their size and inaccessibility. Here, we describe the purification of nuclear RNA from early stage Arabidopsis thaliana embryos using fluorescence-activated nuclear sorting (FANS) to generate expression profiles of early stages of the whole embryo, the proembryo and the suspensor. We validated our datasets of differentially expressed candidate genes by promoter-reporter gene fusions and in situ hybridization. Our study revealed that different classes of genes with respect to biological processes and molecular functions are preferentially expressed either in the proembryo or in the suspensor. This method can be used especially for tissues with a limited cell population and inaccessible tissue types. Furthermore, we provide a valuable resource for research on Arabidopsis early embryogenesis.
On the Origin and Structure of the Recently Observed Acetal in the Soai Reaction
Authors: Gridnev Ilya D , Vorobiev Andrey Kh
Published: November 2014

Recent observation of the acetal species in the course of autoamplifying Soai reaction was analysed by the formal kinetic analysis of the experimental data and DFT computations. Kinetic analysis demonstrated convincingly that the observed species cannot be a precursor of the reaction product. Hence, it is an off-loop species that is not important for the process of the chirality amplification. DFT search for a kinetically stable acetal species resulted in the location of a Zn3 cluster stabilized with three Zn–O–Zn bridges.
Nonconvex Equilibrium Prices in Prediction Markets
Authors: Seshadri Ashwin K.
Published: November 2014

Prediction markets are increasingly being used to estimate probabilities of future events, and market equilibrium prices depend on the distribution of subjective probabilities of underlying events. When each contract requires the payment of a dollar if the underlying event were to occur, equilibrium prices are usually used to estimate the mean probabilities of the corresponding events. This paper shows that under certain conditions, market equilibrium prices of such contracts can lie outside the convex hull of potential traders’ probability beliefs, and where this occurs, market forecasts can induce stochastically dominated group decisions. We describe examples of where this could occur and generalize these examples to characterize conditions for nonconvex prices. A necessary condition for nonconvex prices is that market risk premia for complementary contracts have opposite signs. Preference functions on the lines of prospect theory have this property.
ICU Admission Control: An Empirical Study of Capacity Allocation and Its Implication for Patient Outcomes
Authors: Kim Song-Hee , Chan Carri W. , Olivares Marcelo , Escobar Gabriel
Published: November 2014

This work examines the process of admission to a hospital’s intensive care unit (ICU). ICUs currently lack systematic admission criteria, largely because the impact of ICU admission on patient outcomes has not been well quantified. This makes evaluating the performance of candidate admission strategies difficult. Using a large patient-level data set of more than 190,000 hospitalizations across 15 hospitals, we first quantify the cost of denied ICU admission for a number of patient outcomes. We use hospital operational factors as instrumental variables to handle the endogeneity of the admission decisions and identify important specification issues that are required for this approach to be valid. Using the quantified cost estimates, we then provide a simulation framework for evaluating various admission strategies' performance. By simulating a hospital with 21 ICU beds, we find that we could save about $1.9 million per year by using an optimal policy based on observables designed to reduce readmissions and hospital length of stay. We also discuss the role of unobserved patient factors, which physicians may discretionarily account for when making admission decisions, and show that including these unobservables could result in a more than threefold increase in benefits compared to just optimizing the policy over the observable patient factors.

This paper was accepted by Serguei Netessine, operations management.
More Than Just a Mammogram: Breast Cancer Screening Perspectives of Relatives of Women With Intellectual Disability
Authors: Greenwood Nechama W. , Dreyfus Deborah , Wilkinson Joanne
Published: November 2014

Women with intellectual disability (ID) have similar rates of breast cancer as the general public, but higher breast cancer mortality and lower rates of regular screening mammography. Screening rates are lowest among women who live with their families. Though women with ID often make decisions in partnership with their relatives, we lack research related to family member perspectives on mammography. We conducted a qualitative study of family members of women with ID, with an interview guide focused on health care decision making and experiences, and breast cancer screening barriers, facilitators, and beliefs as related to their loved ones. Sixteen family members underwent semistructured interviews. Important themes included mammography as a reference point for other social and cultural concerns, such as their loved one's sexuality or what it means to be an adult woman; fear of having to make hard decisions were cancer to be diagnosed acting as a barrier to screening; a focus on quality of life; and desire for quality health care for their loved one, though quality care did not always equate to regular cancer screening. Adults with ID are valued members of their families, and their relatives are invested in their well-being. However, families fear the potentially complicated decisions associated with a cancer diagnosis and may choose to forgo screening due to misinformation and a focus on quality of life. Effective interventions to address disparities in mammography should focus on adults with ID and their families together, and incorporate the family context.
Quantitative Analysis of the Cellular Composition in Seminiferous Tubules in Normal and Genetically Modified Infertile Mice
Authors: Nakata Hiroki , Wakayama Tomohiko , Takai Yoshimi , Iseki Shoichi
Published: November 2014

The aim of this study was to establish a quantitative standard for the cellular composition in seminiferous tubules at each stage of spermatogenesis in the mouse testis, and thereby evaluate abnormalities in the infertile mouse testis. We applied a combination of lectin histochemistry for acrosomes and immunohistochemistry for various specific cell markers, both of which were visualized with fluorescence, on paraffin sections of the testis. We first examined seminiferous tubules from normal mice and counted the number of each cell type at each stage of spermatogenesis. We then examined seminiferous tubules from genetically modified mice deficient (-/-) for one of the cell adhesion molecules, nectin-2 or nectin-3, and compared the number of each cell type at each stage of spermatogenesis with the corresponding value in normal mice. In both nectin-2-/- and nectin-3-/- mice, which are infertile despite the apparently normal morphology of the seminiferous epithelia, we measured a progressive loss in the later-step spermatids, with significantly lower numbers of step 11–16 spermatids in nectin-3-/- mice and step 15–16 spermatids in nectin-2-/- mice as compared with that in normal control mice. The present study demonstrated that a quantitative analysis of cellular compositions at different stages in seminiferous tubules was useful for evaluating abnormalities in spermatogenesis.
Non-specific Immunostaining by a Rabbit Antibody against Gustducin α Subunit in Mouse Brain
Authors: Xiong Guoxiang , Redding Kevin , Chen Bei , Cohen Akiva S. , Cohen Noam A.
Published: November 2014

Gustducin is a guanosine nucleotide-binding protein functionally coupled with taste receptors and thus originally identified in taste cells of the tongue. Recently, bitter taste receptors and gustducin have been detected in the airways, digestive tracts and brain. The existing studies showing taste receptors and gustducin in the brain were carried out exclusively on frozen sections. In order to avoid the technical shortcomings associated with frozen sectioning, we performed immunofluorescence staining using vibratome-cut sections from mouse brains. Using a rabbit gustducin antibody, we could not detect neurons or astrocytes as reported previously. Rather, we found dense fibers in the nucleus accumbens and periventricular areas. We assumed these staining patterns to be specific after confirmation with conventional negative control staining. For the verification of this finding, we stained gustducin knockout mouse brain and tongue sections with the same rabbit gustducin antibody. Whereas negative staining was confirmed in the tongue, intensive fibers were constantly stained in the brain. Moreover, immunostaining with a goat gustducin antibody could not demonstrate the fibers in the brain tissue. The present study implies a cross immunoreaction that occurs with the rabbit gustducin antibody in mouse brain samples, suggesting that the conventional negative controls may not be sufficient when an immunostaining pattern is to be verified.
Gene Expression Profiling of Circulating Tumor Cells in Breast Cancer
Authors: Fina Emanuela , Callari Maurizio , Reduzzi Carolina , D'Aiuto Francesca , Mariani Gabriella , Generali Daniele , Pierotti Marco A , Daidone Maria G , Cappelletti Vera
Published: November 2014

BACKGROUND

Determining the transcriptional profile of circulating tumor cells (CTCs) may allow the acquisition of clinically relevant information while overcoming tumor heterogeneity-related biases associated with use of tissue samples for biomarker assessment. However, such molecular characterization is challenging because CTCs are rare and outnumbered by blood cells.

METHODS

Here, we describe a technical protocol to measure the expression of >29 000 genes in CTCs captured from whole blood with magnetic beads linked with antibodies against epithelial cell adhesion molecule (EpCAM) and the carcinoma-associated mucin, MUC1, designed to be used for CTC characterization in clinical samples. Low numbers of cells (5–200) from the MCF7 and MDA-MB-468 breast cancer cell lines were spiked in healthy donor blood samples and isolated with the AdnaTest EMT-1/Stem CellSelect kit. Gene expression profiles (GEPs) were obtained with the WG-DASL HT assay and compared with GEPs obtained from RNA isolated from cultured cell lines and unspiked samples.

RESULTS

GEPs from samples containing 25 or more spiked cells correlated (r = 0.95) with cognate 100-ng RNA input samples, clustered separately from blood control samples, and allowed MCF7 and MDA-MB-468 cells to be distinguished. GEPs with comparable technical quality were also obtained in a preliminary series of clinical samples.

CONCLUSIONS

Our approach allows technically reliable GEPs to be obtained from isolated CTCs for the acquisition of biologically useful information. It is reproducible and suitable for application in prospective studies to assess the clinical utility of CTC GEPs, provided that >25 CTCs can be isolated.
Quantitative Cell-Free Circulating BRAFV600E Mutation Analysis by Use of Droplet Digital PCR in the Follow-up of Patients with Melanoma Being Treated with BRAF Inhibitors
Authors: Sanmamed Miguel F , Fernández-Landázuri Sara , Rodríguez Carmen , Zárate Ruth , Lozano María D , Zubiri Leyre , Perez-Gracia José Luis , Martín-Algarra Salvador , González Alvaro
Published: November 2014

BACKGROUND

Around 50% of cutaneous melanomas harbor the BRAFV600E mutation and can be treated with BRAF inhibitors. DNA carrying this mutation can be released into circulation as cell-free BRAFV600E (cfBRAFV600E). Droplet digital PCR (ddPCR) is an analytically sensitive technique for quantifying small concentrations of DNA. We studied the plasma concentrations of cfBRAFV600E by ddPCR in patients with melanoma during therapy with BRAF inhibitors.

METHODS

Plasma concentrations of cfBRAFV600E were measured in 8 controls and 20 patients with advanced melanoma having the BRAFV600E mutation during treatment with BRAF inhibitors at baseline, first month, best response, and progression.

RESULTS

The BRAFV600E mutation was detected by ddPCR even at a fractional abundance of 0.005% in the wild-type gene. Agreement between tumor tissue BRAFV600E and plasma cfBRAFV600E was 84.3%. Baseline cfBRAFV600E correlated with tumor burden (r = 0.742, P < 0.001). cfBRAFV600E concentrations decreased significantly at the first month of therapy (basal median, 216 copies/mL; Q1–Q3, 27–647 copies/mL; first response median, 0 copies/mL; Q1–Q3, 0–49 copies/mL; P < 0.01) and at the moment of best response (median, 0 copies/mL; Q1–Q3, 0–33 copies/mL; P < 0.01). At progression, there was a significant increase in the concentration of cfBRAFV600E compared with best response (median, 115 copies/mL; Q1–Q3, 3–707 copies/mL; P = 0.013). Lower concentrations of basal cfBRAFV600E were significantly associated with longer overall survival and progression-free survival (27.7 months and 9 months, respectively) than higher basal concentrations (8.6 months and 3 months, P < 0.001 and P = 0.024, respectively).

CONCLUSIONS

cfBRAFV600E quantification in plasma by ddPCR is useful as a follow-up to treatment response in patients with advanced melanoma.
Refinement of Variant Selection for the LDL Cholesterol Genetic Risk Score in the Diagnosis of the Polygenic Form of Clinical Familial Hypercholesterolemia and Replication in Samples from 6 Countries
Authors: Futema Marta , Shah Sonia , Cooper Jackie A , Li KaWah , Whittall Ros A , Sharifi Mahtab , Goldberg Olivia , Drogari Euridiki , Mollaki Vasiliki , Wiegman Albert , Defesche Joep , D'Agostino Maria N , D'Angelo Antonietta , Rubba Paolo , Fortunato Giuliana , Waluś-Miarka Małgorzata , Hegele Robert A , Aderayo Bamimore Mary , Durst Ronen , Leitersdorf Eran , Mulder Monique T , Roeters van Lennep Jeanine E , Sijbrands Eric J G , Whittaker John C , Talmud Philippa J , Humphries Steve E
Published: November 2014

BACKGROUND

Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations in 1 of 3 genes. In the 60% of patients who are mutation negative, we have recently shown that the clinical phenotype can be associated with an accumulation of common small-effect LDL cholesterol (LDL-C)-raising alleles by use of a 12–single nucleotide polymorphism (12-SNP) score. The aims of the study were to improve the selection of SNPs and replicate the results in additional samples.

METHODS

We used ROC curves to determine the optimum number of LDL-C SNPs. For replication analysis, we genotyped patients with a clinical diagnosis of FH from 6 countries for 6 LDL-C-associated alleles. We compared the weighted SNP score among patients with no confirmed mutation (FH/M–), those with a mutation (FH/M+), and controls from a UK population sample (WHII).

RESULTS

Increasing the number of SNPs to 33 did not improve the ability of the score to discriminate between FH/M– and controls, whereas sequential removal of SNPs with smaller effects/lower frequency showed that a weighted score of 6 SNPs performed as well as the 12-SNP score. Metaanalysis of the weighted 6-SNP score, on the basis of polymorphisms in CELSR2 (cadherin, EGF LAG 7-pass G-type receptor 2), APOB (apolipoprotein B), ABCG5/8 [ATP-binding cassette, sub-family G (WHITE), member 5/8], LDLR (low density lipoprotein receptor), and APOE (apolipoprotein E) loci, in the independent FH/M– cohorts showed a consistently higher score in comparison to the WHII population (P < 2.2 × 10−16). Modeling in individuals with a 6-SNP score in the top three-fourths of the score distribution indicated a >95% likelihood of a polygenic explanation of their increased LDL-C.

CONCLUSIONS

A 6-SNP LDL-C score consistently distinguishes FH/M– patients from healthy individuals. The hypercholesterolemia in 88% of mutation-negative patients is likely to have a polygenic basis.
Fatty Acid Composition of Ostrich (Struthio Camelus) Abdominal Adipose Tissue
Authors: Belichovska Daniela , Hajrulai-Musliu Zehra , Uzunov Risto , Belichovska Katerina , Arapcheska Mila
Published: November 2014

Fatty acid composition of foods has a great impact on nutrition and health. Therefore, thе determination and knowledge of the fatty acid composition of food is very important for nutrition. Due to the high nutritional characteristics of ostrich meat and its products, the research determining their quality is of topical interest. The aim of the present investigation was the determination of fatty acid composition of ostrich adipose tissue. The content of fatty acids was determined according to AOAC Official Methods of Analysis and determination was performed using a gas chromatograph with a flame-ionization detector (GC-FID). The results are expressed as a percentage of the total content of fatty acids. The method was validated and whereupon the following parameters were determined: linearity, precision, recovery, limit of detection and limit of quantification. The repeatability was within of 0.99 to 2.15%, reproducibility from 2.01 to 4.57%, while recovery ranged from 94.89 to 101.03%. According to these results, this method is accurate and precise and can be used for analysis of fatty acids in foods. It was concluded that the content of saturated fatty acids (SFA) accounted 34.75%, of monounsaturated fatty acids (MUFA) 38.37%, of polyunsaturated fatty acids (PUFA) 26.88%, of total unsaturated fatty acids (UFA) 65.25% and of desirable fatty acids (DFA) (total unsaturated + stearic acid) 70.37% of the analysed samples. The ratio polyunsaturated/saturated fatty acids accounted 0.77. The most present fatty acid is the oleic (C18:1n9c) with 28.31%, followed by palmitic (C16:0) with 27.12% and linoleic (C18:2n6c) acid with 25.08%. Other fatty acids are contained in significantly lower quantities.
Advanced methods of microscope control using μManager software
Authors: D. Edelstein Arthur , A. Tsuchida Mark , Amodaj Nenad , Pinkard Henry , D. Vale Ronald , Stuurman Nico
Published: November 2014

µManager is an open-source, cross-platform desktop application, to control a wide variety of motorized microscopes, scientific cameras, stages, illuminators, and other microscope accessories. Since its inception in 2005, µManager has grown to support a wide range of microscopy hardware and is now used by thousands of researchers around the world. The application provides a mature graphical user interface and offers open programming interfaces to facilitate plugins and scripts. Here, we present a guide to using some of the recently added advanced µManager features, including hardware synchronization, simultaneous use of multiple cameras, projection of patterned light onto a specimen, live slide mapping, imaging with multi-well plates, particle localization and tracking, and high-speed imaging.