bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Consequences of Decreasing Tumor Vasculature with Antiangiogenic Tyrosine Kinase Inhibitors in Combination with Therapeutic Vaccines
Authors: Farsaci Benedetto , Donahue Renee N. , Coplin Michael A. , Grenga Italia , Lepone Lauren M. , Molinolo Alfredo A. , Hodge James W.
Published: August 2014

This study investigated the effects on the tumor microenvironment (TME) of combining antiangiogenic tyrosine kinase inhibitors (TKI) with therapeutic vaccines, and in particular, how vascular changes affect tumor-infiltrating immune cells. We conducted studies using a TKI (sunitinib or sorafenib) in combination with recombinant vaccines in two murine tumor models: colon carcinoma (MC38-CEA) and breast cancer (4T1). Tumor vasculature was measured by immunohistochemistry using three endothelial cell markers: CD31 (mature), CD105 (immature/proliferating), and CD11b (monocytic). We assessed oxygenation, tight junctions, compactness, and pressure within tumors, along with the frequency and phenotype of tumor-infiltrating lymphocytes (TIL), myeloid-derived suppressor cells (MDSC), and tumor-associated macrophages (TAM) following treatment with antiangiogenic TKIs alone, vaccine alone, or the combination of a TKI with vaccine. The combined regimen decreased tumor vasculature, compactness, tight junctions, and pressure, leading to vascular normalization and increased tumor oxygenation. This combination therapy also increased TILs, including tumor antigen–specific CD8 T cells, and elevated the expression of activation markers FAS-L, CXCL-9, CD31, and CD105 in MDSCs and TAMs, leading to reduced tumor volumes and an increase in the number of tumor-free animals. The improved antitumor activity induced by combining antiangiogenic TKIs with vaccine may be the result of activated lymphoid and myeloid cells in the TME, resulting from vascular normalization, decreased tumor-cell density, and the consequent improvement in vascular perfusion and oxygenation. Therapies that alter tumor architecture can, thus, have a dramatic impact on the effectiveness of cancer immunotherapy. Cancer Immunol Res; 2(11); 1090–102. ©2014 AACR.
Oligoclonal CD8
+
T Cells Play a Critical Role in the Development of Hypertension
Authors: Trott Daniel W. , Thabet Salim R. , Kirabo Annet , Saleh Mohamed A. , Itani Hana , Norlander Allison E. , Wu Jing , Goldstein Anna , Arendshorst William J. , Madhur Meena S. , Chen Wei , Li Chung-I. , Shyr Yu , Harrison David G.
Published: August 2014

Recent studies have emphasized a role of adaptive immunity, and particularly T cells, in the genesis of hypertension. We sought to determine the T-cell subtypes that contribute to hypertension and renal inflammation in angiotensin II–induced hypertension. Using T-cell receptor spectratyping to examine T-cell receptor usage, we demonstrated that CD8
+
cells, but not CD4
+
cells, in the kidney exhibited altered T-cell receptor transcript lengths in Vβ3, 8.1, and 17 families in response to angiotensin II–induced hypertension. Clonality was not observed in other organs. The hypertension caused by angiotensin II in CD4
−/−
and MHCII
−/−
mice was similar to that observed in wild-type mice, whereas CD8
−/−
mice and OT1xRAG-1
−/−
mice, which have only 1 T-cell receptor, exhibited a blunted hypertensive response to angiotensin II. Adoptive transfer of pan T cells and CD8
+
T cells but not CD4
+
/CD25
−
cells conferred hypertension to RAG-1
−/−
mice. In contrast, transfer of CD4
+
/CD25
+
cells to wild-type mice receiving angiotensin II decreased blood pressure. Mice treated with angiotensin II exhibited increased numbers of kidney CD4
+
and CD8
+
T cells. In response to a sodium/volume challenge, wild-type and CD4
−/−
mice infused with angiotensin II retained water and sodium, whereas CD8
−/−
mice did not. CD8
−/−
mice were also protected against angiotensin-induced endothelial dysfunction and vascular remodeling in the kidney. These data suggest that in the development of hypertension, an oligoclonal population of CD8
+
cells accumulates in the kidney and likely contributes to hypertension by contributing to sodium and volume retention and vascular rarefaction.
Aither and the Four Roots in Empedocles
Authors: Shaw Michael M.
Published: August 2014

This paper surveys the meaning of aither (αἰθήρ) in Empedocles. Since Aristotle, Empedoclean aither has been generally considered synonymous with air (ἀήρ) and understood anachronistically in terms of its Aristotelian conception as hot and wet. In critiquing this interpretation, the paper first examines the meaning of “air” in Empedocles, revealing scant and insignificant use of the term. Next, the ancient controversy of Empedocles’ “four roots” is recast from the perspective that aither, rather than air, designates the fourth root. Finally, the nineteen instances of aither in Empedocles’ fragments are considered, revealing a bright and energetic root closely related to the force of life.
Ceriomicrodon petiolatus Hull, 1937 (Diptera, Syrphidae, Microdontinae): Redescription and new records
Authors: Miranda Gil Felipe Gonçalves
Published: August 2014

The monotypic genus Ceriomicrodon Hull, 1937 was known in the current literature by a few specimens, all from Brazil but with records only for Mato Grosso and Roraima states. The only species of the genus is here redescribed including the description of the female and its terminalia, in addition to a preliminary description of the egg. Images of male and female genitalia and egg are provided. New Brazilian records for Amazonas, Maranhão and Rondônia and a brief diagnosis to distinguish that genus from other similar Microdontinae genera are presented.
Attracting Skilled Immigrants: An Overview of Recent Policy Developments in Advanced Countries
Authors: Facchini Giovanni , Lodigiani Elisabetta
Published: August 2014

In this paper we review the policies put in place by the main Western destination countries to attract highly skilled migrants. Two main systems can be identified. On the one hand, employer-driven schemes typically call for the migrant to meet a set of minimum skill requirements and to have a job offer before a work visa can be issued. On the other, migrant-driven schemes typically do not require a job offer, and instead select the migrant based on a set of characteristics chosen by the policymaker. Employer-driven schemes are the dominant policy tool in the sample of countries we consider in the analysis, and only Australia, Canada and New Zealand have made migrant-driven schemes the mainstay of their skill selective immigration policy. The preliminary evidence we review suggests that the latter are more effective in increasing the skill level of the immigrant population, and casts doubts on the usefulness of new initiatives like the EU blue card that are still based on an employer-driven system.
The Long-Term Economic Impact of Reducing Migration in the UK
Authors: Lisenkova Katerina , Mérette Marcel , Sánchez-Martínez Miguel
Published: August 2014

This paper uses an OLG-CGE model for the UK to illustrate the long-term effect of migration on the economy. We use the current Conservative Party migration target to reduce net migration “from hundreds of thousands to tens of thousands” as an illustration. Achieving this target would require reducing recent net migration numbers by a factor of about 2. We undertake a simulation exercise to compare a baseline scenario, which incorporates the principal 2010-based ONS population projections, with a lower migration scenario, which assumes that net migration is reduced by around 50 per cent. The results show that such a significant reduction in net migration has strong negative effects on the economy. By 2060 the levels of both GDP and GDP per person fall by 11.0 per cent and 2.7 per cent respectively. Moreover, this policy has a significant impact on public finances. To keep the government budget balanced, the effective labour income tax rate has to be increased by 2.2 percentage points in the lower migration scenario.
Ranking Games
Authors: Osterloh Margit , Frey Bruno S.
Published: August 2014

Background:

Research rankings based on bibliometrics today dominate governance in academia and determine careers in universities.

Method:

Analytical approach to capture the incentives by users of rankings and by suppliers of rankings, both on an individual and an aggregate level.

Result:

Rankings may produce unintended negative side effects. In particular, rankings substitute the “taste for science” by a “taste for publication.” We show that the usefulness of rankings rests on several important assumptions challenged by recent research.

Conclusion:

We suggest as alternatives careful socialization and selection of scholars, supplemented by periodic self-evaluations and awards. The aim is to encourage controversial discourses in order to contribute meaningful to the advancement of science.
Matrix‐Metalloproteinases in Head and Neck Carcinoma–Cancer Genome Atlas Analysis and Fluorescence Imaging in Mice
Authors: Hauff Samantha J. , Raju Sharat C. , Orosco Ryan K. , Gross Andrew M. , Diaz‐Perez Julio A. , Savariar Elamprakash , Nashi Nadia , Hasselman Jonathan , Whitney Michael , Myers Jeffrey N. , Lippman Scott M. , Tsien Roger Y. , Ideker Trey , Nguyen Quyen T.
Published: August 2014

Objective

(1) Obtain matrix‐metalloproteinase (MMP) expression profiles for head and neck squamous cell carcinoma (HNSCC) specimens from the Cancer Genomic Atlas (TCGA). (2) Demonstrate HNSCC imaging using MMP‐cleavable, fluorescently labeled ratiometric activatable cell‐penetrating peptide (RACPP).

Study Design

Retrospective human cohort study; prospective animal study.

Setting

Translational research laboratory.

Subjects and Methods

Patient clinical data and mRNA expression levels of MMP genes were downloaded from TCGA data portal. RACPP provides complementary ratiometric fluorescent contrast (increased Cy5 and decreased Cy7 intensities) when cleaved by MMP2/9. HNSCC–tumor bearing mice were imaged in vivo after RACPP injection. Histology was evaluated by a pathologist blinded to experimental conditions. Zymography confirmed MMP‐2/9 activity in xenografts. RACPP was applied to homogenized human HNSCC specimens, and ratiometric fluorescent signal was measured on a microplate reader for ex vivo analysis.

Results

Expression of multiple MMPs including MMP2/9 is greater in patient HNSCC tumors than matched control tissue. In patients with human papilloma virus positive (HPV+) tumors, higher MMP2 and MMP14 expression correlates with worse 5‐year survival. Orthotopic tongue HNSCC xenografts showed excellent ratiometric fluorescent labeling with MMP2/9‐cleavable RACPP (sensitivity = 95.4%, specificity = 95.0%). Fluorescence ratios were greater in areas of higher tumor burden (P <. 03), which is useful for intraoperative margin assessment. Ex vivo, human HNSCC specimens showed greater cleavage of RACPP when compared to control tissue (P =. 009).

Conclusions

Human HNSCC tumors show increased mRNA expression of multiple MMPs including MMP2/9. We used RACPP, a ratiometric fluorescence assay of MMP2/9 activity, to show improved occult tumor identification and margin clearance. Ex vivo assays using RACPP in biopsy specimens may identify patients who will benefit from intraoperative RACPP use.
Exploring the Mechanisms of Self-Control Improvement
Authors: Inzlicht Michael , Legault Lisa , Teper Rimma
Published: August 2014

Good self-control is central to success across life domains, from school to work to relationships. In this article, we provide a framework to better understand how self-control can be improved. Using cybernetic principles, we identify and integrate important mechanisms for self-control improvement that have previously been overlooked. The cybernetic model suggests that control relies on three separate processes: setting goals, monitoring when behavior diverges from goals, and implementing behavior aligned with goals. Within each of these stages, we incorporate recent research identifying key features of good self-control, including setting the “right kind” of goals; the role of conflict detection, attention, and emotional acceptance in goal monitoring; and the effects of fatigue, shifting priorities, and intentions on implementing behavioral changes. Self-control is not easy, but by revealing it as reliant on these diverse processes, we offer a more comprehensive perspective on self-control, as well as routes through which it can be improved.
Examining the Interface of Children’s Sleep, Executive Functioning, and Caregiving Relationships
Authors: Bernier Annie , Matte-Gagné Célia , Bouvette-Turcot Andrée-Anne
Published: August 2014

Research in developmental psychology is increasingly showing that children’s biology, cognition, and social relationships, which have often been studied separately, are in fact closely tied and influence each other in complex ways. This article summarizes work by our team and others on the connections among young children’s sleep, their executive functioning, and the quality of their caregiving relationships. Overall, children exposed to higher-quality parenting perform better on executive tasks and get sleep of higher quality or duration. In turn, sleep relates to subsequent executive performance, while also modulating the links between parenting and child outcomes. We propose directions for future research to address causal relations and to better pinpoint the direction and magnitude of the associations between these areas of child development.
Austerity as a global prescription and lessons from the neoliberal Baltic experiment
Authors: Sommers Jeffrey , Woolfson Charles , Juska Arunas
Published: August 2014

This article analyses the 2008 economic crisis and its outcomes for the Baltic states. It then gives a genealogy of European economic policy responses to the crisis, tracing them from the emerging ‘freshwater’ school of economics (e.g. University of Chicago) that arose in opposition to Keynesian theory. The more immediate cause of the 2008 crisis, long in the making, was its reliance on private debt to sustain economic demand in light of profit-enhancing wage suppression. Following the 2008 financial shock, European Union policymakers crafted policy that placed the burden of adjustment on labour. A programme of austerity was chosen in much of the European Union, at odds with the post-war European ‘social model’. This represented a retreat from the notion of a European project that encouraged liberalisation of economic policy but at the same time could be harmonised with a social dimension to create a distinctive ‘Social Europe’. Nowhere was this austerity more vigorously applied than in the Baltic states. Its effects are examined here, along with lessons to be derived from that experience.
Reduction of nitric oxide level leads to spontaneous resumption of meiosis in diplotene-arrested rat oocytes culturedin vitro
Authors: Pandey Ashutosh N , Chaube Shail K
Published: August 2014

The present study was aimed to investigate whether a decrease of nitric oxide (NO) level is beneficial for sponateous resumptiom of meiosis in diplotene-arrested oocytes cultured in vitro. For this purpose, diplotene-arrested oocytes were collected from ovary of immature female rats after a single subcutaneous injection of 20 IU pregnant mare’s serum gonadotropins (PMSG) for 48 h. In vitro effects of S-nitroso-l-acetyl penicillamine (SNAP; an NO donor) and aminoguanidine (AG; an inducible NOS [iNOS] inhibitor), intracellular NO, cyclic guanosine monophosphate (cGMP), Cdc25B, Thr-14/Tyr-15 and Thr-161 phosphorylated cyclin-dependent kinase-1 (CDK1), and cyclin B1 levels were analyzed. The SNAP inhibited spontaneous meiotic resumption form diplotene arrest in a concentration-dependent manner, while AG-induced meiotic resumption form diplotene in 0.1 mmol/L 3-isobutyl-1-methylxanthine (IBMX)-treated oocytes in a concentration-dependent manner. The intracellular NO as well as cGMP levels were decreased significantly during spontaneous meiotic resumption from diplotene arrest. The reduction of Cdc25B expression level was associated with the accumulation of Thr-14/Tyr-15 phosphorylated CDK1 level. However, Thr-161 phosphorylated CDK1 as well as cyclin B1 levels were reduced significantly during meiotic resumption from diplotene arrest. Taken together, these data suggest that the inhibition of iNOS expression leads to a decrease of NO and cGMP levels thereby decreasing Cdc25B level. The reduced CDC25 B level leads to accumulation of Thr-14/Tyr-15 phosphorylated CDK1 level. As a result, Thr-161 phosphorylated CDK1 as well as cyclin B1 levels are decreased leading to maturation-promoting factor (MPF) inactivation. The inactive MPF finally induced meiotic resumption from diplotene stage in rat oocytes cultured in vitro.
Experimental investigations on energy absorption capacity of selected Al–Si–Mg casting alloys
Authors: Domitner J. , Bozorgi S. , Anders K. , Angermeier C. , Schumacher P.
Published: August 2014

Three hypoeutectic Fe containing Al–Si–Mg alloys for casting crash relevant automotive components are experimentally investigated. The comparatively short heat treatments include solutionising at 540°C for 5 min or at 465°C for 60 min respectively, compressed air quenching and artificial aging at 223°C for 120 min. Characteristic mechanical parameters are determined by tensile, plate bending and Charpy pendulum impact tests. Intermetallic phases are identified by scanning electron and by light microscopy. The results show that increasing the Mg content promotes the precipitation of Mg2Si particles, which enhance the strength. Increasing the Fe content promotes the formation of intermetallic Fe bearing particles which reduce the energy absorption capacity and the ductility. Increasing the Si content has the similar effect, since the volume fraction of the eutectic phase and the size of the intermetallic particles increase.
Comparative evaluation of molar distalization therapy with erupted second molar: Segmented versus Quad Pendulum appliance
Authors: Caprioglio Alberto , Cozzani Mauro , Fontana Mattia
Published: August 2014

Background

There are controversial opinions about the effect of erupted second molars on distalization of the first molars. Most of the distalizing devices are anchored on the first molars, without including second molars; so, differences between sequentially distalize maxillary molars (second molar followed by the first molar) or distalize second and first molars together are not clear. The aim of the study was to compare sequential versus simultaneous molar distalization therapy with erupted second molar using two different modified Pendulum appliances followed by fixed appliances.

Methods

The treatment sample consisted of 35 class II malocclusion subjects, divided in two groups: group 1 consisted of 24 patients (13 males and 11 females) with a mean pre-treatment age of 12.9 years, treated with the Segmented Pendulum (SP) and fixed appliances; group 2 consisted of 11 patients (6 males and 5 females) with a mean pre-treatment age of 13.2 years, treated with the Quad Pendulum (QP) and fixed appliances. Lateral cephalograms were obtained before treatment (T1), at the end of distalization (T2), and at the end of orthodontic fixed appliance therapy (T3). A Student t test was used to identify significant between-group differences between T1 to T2, T2 to T3, and T1 to T3.

Results

QP and SP were equally effective in distalizing maxillary molars (3.5 and 4 mm, respectively) between T1 and T2; however, the maxillary first molar showed less distal tipping (4.6° vs. 9.6°) and more extrusion (1.1 vs. 0.2 mm) in the QP group than in the SP group, as well as the vertical facial dimension, which increased more in the QP group (1.2°) than in the SP group (0.7°). At T3, the QP group maintained greater increase in lower anterior facial height and molar extrusion and decrease in overbite than the SP group.

Conclusion

Quad Pendulum seems to have greater increase in vertical dimension and molar extrusion than the Segmented Pendulum.
Modeling elastic anisotropy resulting from the application of triaxial stress
Authors: Collet Olivia , Gurevich Boris , Madadi Mahyar , Pervukhina Marina
Published: August 2014

Elastic wave velocities in rocks vary with stress due to the presence of discontinuities and microcracks within the rock. We analytically derived a model to account for stress dependency of seismic velocities when a rock is subjected to triaxial stresses. We first considered a linearly isotropic elastic medium permeated by a distribution of cracks with random orientations. The geometry of cracks is not specified; instead, their behavior is defined by a ratio [Formula: see text] of their normal to tangential excess compliances. When this isotropic rock is subjected to triaxial stresses, cracks tend to close depending on their orientation with respect to the applied stresses. For small stresses, the model predicts ellipsoidal anisotropy and expresses the ratios of Thomsen’s parameters [Formula: see text] in the three orthogonal planes of symmetry as a function of the compliance and Poisson’s ratios. It also establishes relationships between anisotropy parameters and stress ratios. Deriving the model for larger stresses shows that such results still hold for stresses as high as approximately 40 MPa. There is a reasonable agreement between the model predictions and laboratory measurements made on a sample of Penrith sandstone, although crack opening in the direction of maximum stress should be taken into account for larger stresses. The proposed model could be used to differentiate stress-induced anisotropy from fracture-induced anisotropy. Besides, if the cause of anisotropy is known, then this model could enable one to determine P-wave anisotropy from S-wave anisotropy.
Probabilistic lithofacies prediction from prestack seismic data in a heterogeneous carbonate reservoir
Authors: Zhao Luanxiao , Geng Jianhua , Cheng Jiubing , Han De-hua , Guo Tonglou
Published: August 2014

We mapped probabilities of lithology and fluid based on seismic and well observations in a heterogeneous carbonate reservoir of the Sichuan Basin, southwest China, thus characterizing the reservoir complexity and identifying the potential sweet spot. Rock physical analysis showed that the presence of a vuggy-fracture porosity system combined with the fluids’ effect complicate the elastic responses of heterogeneous carbonates. This also gives physical insight into how the elastic properties of different lithofluid classes can be distinguished. With the application of Bayesian linearized amplitude variation with offset inversion, we found that the posterior distribution of P- and S-wave velocities were reliably extracted, whereas the inverted density tended to show high uncertainty due to a lack of wide angle data in the migrated seismic gathers. Finally, a Bayesian approach was implemented to propagate uncertainty from prestack seismic data to lithofluid classes in an integrated framework. The gas-carbonate predictions with high posterior probabilities were consistent with well observations at the well location and the present geological continuity. The probability distributions for the anhydrite, limestone, and dolostone were essential to understand the reservoir architecture and delineate the reservoir heterogeneities. We also ascertained that the uncertainty of lithofacies prediction is determined by the uncertainty of seismic inversion as well as the uncertainty of the link between lithofacies to their corresponding elastic responses.
Introduction to this special section: China
Authors: Sun Sam Zandong
Published: August 2014

China is in an accelerating transition for exploring and developing diverse types of natural resources, including deep onshore and offshore hydrocarbons, shale gas, and coalbed methane. Complexities of these unconventional reservoirs and fluids give rise to tough problems or even unprecedented challenges for most routine practices. Nevertheless, remarkable achievements are accomplished, based on progress in theory and technology of multidisciplinary geosciences. Surely the role of geophysics is irreplaceable. Achievements have been made in almost every aspect of geophysics, including target-oriented seismic acquisition, processing, interpretation, passive seismic, OBC, VSP, EM methods, and so forth.
Technique evolvement and improvement for better fracture characterization using prestack P-wave seismic data
Authors: Sun Sam Zandong , Zhu Xinghui , Sun Xuekai
Published: August 2014

Anisotropic migration has become a routine practice for fracture prediction because of its remarkable capability of suppressing effects of geologic structures while preserving anisotropy induced by fractures. The quality of input seismic gathers is of the first priority among other factors for fracture prediction. Azimuth-sectored migration loses considerable accuracy and reliability because of its coarse and inappropriate manner in dealing with seismic data. A full-azimuth anisotropic migration in surface offset domain provides better efficiency in using data information. Furthermore, full-azimuth anisotropic migration in local angle domain (subsurface angle domain) allows for accurate and reliable exploitation of seismic wavefield information. Finally, influences of the above three anisotropic migration methods on fracture prediction are prescribed with a field example in which validations with formation micro-imager (FMI) information demonstrate that full-azimuth anisotropic migration in local angle domain is the state-of-the-art technique for recovering true properties of subsurface fractures.
3D VSP and surface full-azimuth seismic integrated study in northeastern China
Authors: Li Yanpeng , Ling Yun , Wang Ximing , Chen Yuanzhong , Wu Junjun
Published: August 2014

Great progress has been made on VSP techniques in recent years, especially the improvement of downhole geophone manufacture and VSP data-processing methods. In XJWZ area of Daqing oil field, the reservoir is formed mainly by volcanics, and its distribution is complex because of many periods of volcanic overlap in the area. Early seismic surveys in the area had been mainly 2D and narrow-azimuth 3D, which are not suitable for anisotropy analysis and fracture identification. Therefore, a joint survey of 3D VSP and full-azimuth surface seismic was implemented. The project was an attempt to combine the advantages of VSP and surface seismic by 3D VSP and full-azimuth surface-seismic simultaneous survey. Q factor and anisotropy parameters estimated from VSP are applied to 3D seismic processing. Reservoir characterization and gas-saturation prediction with final images showed encouraging results. Suggested wells have been drilled and wet gas has been found, so the validity of this method has been proved.
Risk-Adjusted Pathologic Margin Positivity Rate As a Quality Indicator in Rectal Cancer Surgery
Authors: Massarweh Nader N. , Hu Chung-Yuan , You Y. Nancy , Bednarski Brian K. , Rodriguez-Bigas Miguel A. , Skibber John M. , Cantor Scott B. , Cormier Janice N. , Feig Barry W. , Chang George J.
Published: August 2014

Purpose

Margin positivity after rectal cancer resection is associated with poorer outcomes. We previously developed an instrument for calculating hospital risk-adjusted margin positivity rate (RAMP) that allows identification of performance-based outliers and may represent a rectal cancer surgery quality metric.

Methods

This was an observational cohort study of patients with rectal cancer within the National Cancer Data Base (2003 to 2005). Hospital performance was categorized as low outlier (better than expected), high outlier (worse than expected), or non-RAMP outlier using standard observed-to-expected methodology. The association between outlier status and overall risk of death at 5 years was evaluated using Cox shared frailty modeling.

Results

Among 32,354 patients with cancer (mean age, 63.8 ± 13.2 years; 56.7% male; 87.3% white) treated at 1,349 hospitals (4.9% high outlier, 0.7% low outlier), 5.6% of patients were treated at high outliers and 3.0% were treated at low outliers. Various structural (academic status and volume), process (pathologic nodal evaluation and neoadjuvant radiation therapy use), and outcome (sphincter preservation, readmission, and 30-day postoperative mortality) measures were significantly associated with outlier status. Five-year overall survival was better at low outliers (79.9%) compared with high outliers (64.9%) and nonoutliers (68.9%; log-rank test, P < .001). Risk of death was lower at low outliers compared with high outliers (hazard ratio [HR], 0.61; 95% CI, 0.50 to 0.75) and nonoutliers (HR, 0.69; 95% CI, 0.57 to 0.83). Risk of death was higher at high outliers compared with nonoutliers (HR, 1.12; 95% CI, 1.03 to 1.23).

Conclusion

Hospital RAMP outlier status is a rectal cancer surgery composite metric that reliably captures hospital quality across all levels of care and could be integrated into existing quality improvement initiatives for hospital performance.
Learning While Caring: Medicine's Epistemology
Authors: Hellman Samuel
Published: August 2014

An essential epistemic consideration is the conditional nature of medical knowledge. This uncertainty must be understood when acquiring new knowledge or designing treatments. We must value all sources of information, neither discarding those deemed lower on the current value scale, nor slavishly accepting randomized clinical trials or their meta-analyses as the fount of all knowledge. Generally, the tension between clinical investigation and individual care can be framed in a utilitarian versus deontologic or rights-based philosophy. The utilitarian is clearly appropriate to public health considerations, but what is learned for public health may not necessarily be in the best interest of an individual patient. In utilitarianism, the distribution of goods—in this case, health—is not important; rather, it is the amount of total good gained that is to be maximized. Too often we assume that survival or cure is a sufficient metric, with no similar quantitative measure of other factors. This often leads to the so-called best treatment being not what the patient wants. All personal care requires consideration of both the helpful and harmful consequences of treatment in the context of individual patient comorbidity, preferences, and fears. Knowledge of patients in general is not what is required; rather, it is how to apply the information to the particular patient that is the heart of medical practice. Each patient's episode of illness is the consequence of a unique interaction of that individual with the disease. Good patient care considers the disease and its management in the context of each patient's values.
Important considerations for microRNA extraction methods from whole blood and peripheral blood mononuclear cells
Authors: Atarod Sadaf , Smith Hannah , Dickinson Anne , Wang Xiao-Nong
Published: August 2014

MicroRNAs are non-coding RNAs that negatively regulate mRNA expression and play significant roles in both health and disease. Differential microRNA expression has been used to aid diagnosis and discriminate disease stages. The accuracy and reliability of microRNA expression measurement is of utmost importance. For diagnostic investigations, microRNA expression in human peripheral blood is commonly detected using total RNA extracted using different methods. To date, no convincing data have been available showing whether microRNA expression levels are comparable when total RNA has been extracted from whole blood or peripheral blood mononuclear cells (PBMCs). The present study examined miR-146a-5p and miR-155-5p expression using total RNA extracted in parallel from whole blood and PBMCs of 14 healthy volunteers. MicroRNA expression levels were significantly different between whole blood and PBMCs. No significant difference was observed in microRNA expression between fresh and cryopreserved PBMCs (p=0.125 for both). Further observations revealed that gender differences did not influence miR-146a-5p or miR-155-5p expression regardless of using whole blood

(p = 0.797 and 1.00 respectively) or PBMC (p = 0.190 and 0.898 respectively). Our results demonstrate that microRNA expression could be subjective to the methods used for total RNA extraction which highlights the importance of using uniform extraction methods.
A Two-Phase Iterative Heuristic Approach for the Production Routing Problem
Authors: Absi N. , Archetti C. , Dauzère-Pérès S. , Feillet D.
Published: August 2014

This paper investigates the integrated optimization of production, distribution, and inventory decisions related to supplying multiple retailers from a central production facility. A single-item capacitated lot-sizing problem is defined for optimizing production decisions and inventory management. The optimization of daily distribution is modeled as a traveling salesman problem or a vehicle routing problem depending on the number of vehicles. A two-phase iterative method, from which several heuristics are derived, is proposed that iteratively focuses on lot-sizing and distribution decisions. Computational results show that our best heuristic outperforms existing methods.
Making practice education visible: Challenging assumptions about the patient's place in placement environments
Authors: Kell Clare
Published: August 2014

Background/aims

Reviews of high-profile scandals in healthcare challenge health professionals to put the patient first in everything they do, including in the education of students. This paper focusses on learning in placement settings and, adopting a social perspective of learning, questions whether the rhetoric of patient-centred professional education is visible in the learning activities that students enact.

Methods

Informed by interaction and workplace studies, this study comprised an ethnomethodologically-informed ethnographic observation of physiotherapy student placement education in two hospital-based settings. The study followed six final-year students for two full days each as they undertook their everyday placement activities with their 28 educators and their patient workload. Using a novel notation system combining field notes and proxemics sketches, this study makes the minutiae of naturally-occurring, student-present interactions visible.

Findings

The results suggest that physiotherapy placement education interactions, which the educator, the student and the patient coproduce unquestioningly, frame patients as person-absent audiovisual aids to learning.

Conclusions

This paper illustrates the use of a new method to develop evidence-informed discussions about the rhetoric vs. the reality of patient-centred care in health-care education interactions. Studying interaction practices throws light onto previously unnoticed and unquestioned habits and norms in professional practice.
Developing the Bridges self-management programme for New Zealand stroke survivors: A case study
Authors: Hale Leigh , Jones Fiona , Mulligan Hilda , Levack William , Smith Cath , Claydon Leica , Milosavljevic Stephan , Taylor Denise , Allan Joanna , MacKenzie Nina , Flannery James , Edwards Sara , Rabone Trudy , Alcock Mark
Published: August 2014

Background/aim

This case study describes the adaptation of the UK-developed Bridges stroke self-management programme (Bridges SMP) into a version relevant and acceptable to the New Zealand (NZ) context.

Methods

Stakeholder consultation and qualitative methodology explored the acceptability and relevance of the Bridges SMP in NZ. Focus group discussions were held with stroke survivors (n=60) and neurorehabilitation therapists (n= 17). Semi-structured interviews were conducted with 22 stroke survivors. Based on data gathered the authors culturally and contextually adapted the accompanying Bridges SMP workbook. This study piloted the adapted programme with six stroke survivors and used semi-structured interviews to explore their perceptions of it.

Findings

The Bridges SMP was considered acceptable and beneficial for developing skills to self-manage recovery following stroke. The main recommended adaptation was the inclusion of NZ stories into the accompanying workbook. Four themes reflected the six pilot study participants' perceptions of the programme: you are not alone, reflection and taking action, life continues after stroke, and taking responsibility.

Conclusions

The Bridges SMP was considered relevant and only required moderate adaptation for use in NZ. The process the authors undertook to contextualise Bridges SMP for NZ will provide guidance to the programme's introduction into other international regions.
Biomechanical investigations of the secondary stability of commercial short dental implants in porcine ribs
Authors: Wilhelm Rebecca , Hasan Istabrak , Keilig Ludger , Heinemann Friedhelm , Stark Helmut , Bourauel Christoph
Published: August 2014

The use of short implants has increased widely within the last years. However, the stability of these implants has not yet been comprehensively investigated, in particular the difference in geometry and dimension of short implants. The aim of the present study was to investigate experimentally the difference of the secondary stability of different commercial short implants by measuring their displacements. Eleven implant geometries were investigated in this study. A total of 22 implants were inserted in porcine rib segments, two implants for each system. Implant displacements were measured using a self-developed biomechanical hexapod measurement system (HexMeS). The highest displacement was observed with Straumann BL NC 3.3×8.0 mm (266 μm), followed by Straumann Standard 4.1×6.0 mm (156 μm), while the lowest displacement of 61 μm was shown by Dentaurum type 1 implant (4.2×5.0 mm). No obvious difference of displacements was observed between hammered and screw-shaped implants with relevant dimensions. The experimental results were in good agreement with the numerical ones (19–42%) for Dentaurum implants. However, a difference of 70–80% was obtained for the Astra implant (4.0×6.0 mm) and Bicon implant (6.0×5.7 mm). The geometry of short implants directly affects their stability within the bone.
In vitro inhibitory effects of herbal supplements on tamoxifen and irinotecan metabolism
Authors: Grappe Fran , Nance Gwen , Coward Lori , Gorman Greg
Published: August 2014

Background: As the use of herbal supplements continues to rise throughout the world, the potential for drug-herbal interactions also increases. For chemotherapeutic prodrugs, this interaction could prevent the metabolic conversion of the prodrug to its active metabolite(s), thereby potentially resulting in subtherapeutic systemic exposure of the drug and reduced efficacy of the therapy.

Methods: In this study, in vitro metabolism with human liver microsomes is used to measure the impact of ten commonly used herbal supplements on the biotransformation of the chemotherapeutic prodrugs tamoxifen (TAM) and irinotecan (IR).

Results: Four of the herbals tested, echinacea, ginseng, lemon balm, and skullcap, were found to be strong inhibitors of the CYP450 enzymatic bioactivation pathways of TAM with IC50 values as percent of a single dose ranging from 0.019% to 0.34%. Two of the herbals, skullcap and lemon balm, were found to inhibit the carboxyesterase pathway of IR with values of 0.21 and 0.25, respectively.

Conclusions: Our data suggests that based on the measured IC50 values that skullcap and lemon balm could have potential negative clinical impact on the bioactivation of TAM but not likely with IR.
Synthesis and antimicrobial evaluation of purine substituted N-acyl-α-carboxamides via the Ugi four-component reaction
Authors: Kaur Gurpreet , Gupta Parul , Harjai Kusum , Singh Vasundhara
Published: August 2014

A series of novel purine based N-acyl-α-carboxamides were prepared via the Ugi four-component reaction approach using the pharmacophoric 2-amino-6-chloropurine moiety as the amine component coupled with various aldehydes, carboxylic acids and isocyanides affording a library of multisubstituted compounds 2a–x. These compounds were screened for their antimicrobial activity against Gram negative strains Escherichia coli, Pseudomonas aeruginosa and Gram positive strains Staphylococcus aureus, Staphylococcus epidermidis demonstrating significant biological potency. The best potency for all the strains was found for compound 2x, which is comparable with ampicillin trihydrate as the standard drug.
Optimal Design Strategies for Sibling Studies with Binary Exposures
Authors: Li Zhigang , McKeague Ian W. , Lumey Lambert H.
Published: August 2014

Sibling studies have become increasingly popular because they provide better control over confounding by unmeasured family-level risk factors than can be obtained in standard cohort studies. However, little attention has been devoted to the development of efficient design strategies for sibling studies in terms of optimizing power. We here address this issue in commonly encountered types of sibling studies, allowing for continuous and binary outcomes and varying numbers of exposed and unexposed siblings. For continuous outcomes, we show that in families with sibling pairs, optimal study power is obtained by recruiting discordant (exposed–control) pairs of siblings. More generally, balancing the exposure status within each family as evenly as possible is shown to be optimal. For binary outcomes, we elucidate how the optimal strategy depends on the variation of the binary response; as the within-family correlation increases, the optimal strategy tends toward only recruiting discordant sibling pairs (as in the case of continuous outcomes). R code for obtaining the optimal strategies is included.
Influence of extracellular media’s ionic strength on the osmotic stability of Sahel goat erythrocytes
Authors: Igbokwe Nanacha Afifi , Igbokwe Ikechukwu Onyebuchi
Published: August 2014

Background: Heparinised blood was exposed to osmotic lysis in hypotonic buffered saline to evaluate erythrocyte membrane stability. When K3 EDTA blood was used, it added more to the ionic content of blood than heparin. The influence of suspending media’s ionic strength on the osmotic stability of Sahel goat erythrocytes was investigated by replacing the ionic saline with non-ionic saccharide (sucrose or glucose) and assessing the effect of using EDTA blood instead of heparinised blood.

Results: The erythrocyte osmotic fragility curve in saline was hyperbolic even when the ionic concentration was reduced by 50% with saccharides. Haemolysis was higher with EDTA than heparinised blood at saline concentrations of 90 and 150–180 mosmol/L. The fragility curve was sigmoidal and shifted to the left when saline was completely substituted with a saccharide. The non-ionic saccharides increased erythrocyte osmotic resistance linearly (r=0.88; p<0.02) from median to minimal hyposmolarities (150–300 mosmol/L) and reduced the osmolyte concentration at median fragility by 36%. No effect occurred at <30–120 mosmol/L and >90% fragility; and saccharide concentrations were almost non-lytic at comparable saline concentrations evoking <10% haemolysis. Fragilities were neither affected by period (30–60 min) of incubation nor the type of saccharide used.

Conclusions: In this study, the variation in osmotic stability of caprine erythrocytes was linked to ionic strength of the suspending extracellular media which seemed to exert an influence through transmembrane ion fluxes and regulatory volume changes in erythrocytes.
Inadvertent use of bevacizumab in pregnant women with diabetes mellitus type 1
Authors: Polizzi Silvio , Ferrara Giovanna , Restaino Stefano , Rinaldi Silvia , Tognetto Daniele
Published: August 2014

Background: The use of vascular endothelial growth factor (VEGF) inhibitors may cause fetal harm and systemic side effects in the mother, so these drugs are contraindicated in pregnancy. We report a case of inadvertent administration of two intravitreal bevacizumab injections in a woman with diabetes mellitus type 1, 5 days before ovulation (±3 days) and during the 5th gestational week, respectively. The patient had a past history of both miscarriage and requirement for cesarean section for preeclampsia.

Methods: Observational case report.

Results: The patient did not have any drug-related adverse event and delivered a healthy full-term infant, reaching all developmental milestones appropriately during infancy.

Conclusions: Intravitreal drug injections did not result in any detectable adverse event in the mother and infant although she had a significant past obstetric history. However, there have been no studies evaluating the effects of bevacizumab in pregnant women and suggesting that intravitreal drug injection in this patient is safe. Until more is known about this, it seems reasonable to avoid treatment with this drug a few weeks before and during pregnancy.
The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance
Authors: Gutiérrez Medina Sonsoles , Gavela-Pérez Teresa , Domínguez-Garrido María Nieves , Gutiérrez-Moreno Elisa , Rovira Adela , Garcés Carmen , Soriano-Guillén Leandro
Published: August 2014

: Puberty can affect vitamin D levels.

The goal of this study was to analyze the relation between vitamin D deficiency and puberty in obese Spanish children, along with the possible interrelation between vitamin D status and degree of insulin resistance.

A cross-sectional study was carried out, in which clinical and biochemical data were gathered from 120 obese and 50 normal weight children between January 2011 and January 2013.

: Mean vitamin D levels were 19.5 and 31.6 ng/mL in obese pubertal and obese prepubertal children, respectively. About 75% of the obese pubertal subjects and 46% of the obese prepubertal subjects had vitamin D deficiency. Vitamin D levels were significantly lower in pubescent subjects compared with pre-pubescent subjects in summer, fall, and winter. There was no apparent relation between vitamin D levels and homeostasis model assessment index for insulin resistence (expressed in standard deviation score for sex and Tanner stage) in either puberty or pre-puberty.

: Puberty may be a risk factor for the vitamin D deficiency commonly found in the obese child population. This deficiency is not associated with higher insulin resistance in obese pubertal children compared with obese prepubertal children.
Pure gonadal dysgenesis (Swyer syndrome) due to microdeletion in the SRY gene: a case report
Authors: Mutlu Gül Yesiltepe , Kırmızıbekmez Heves , Aydın Hatip , Çetiner Handan , Moralıoğlu Serdar , Celayir Ayşenur Cerrah
Published: August 2014

46,XY complete gonadal dysgenesis (Swyer syndrome) is a rare cause of disorder of sexual development. This syndrome is caused by a defect in the determination of sex during embryogenesis and is characterised with female external genitalia, normal or rudimentary uterus, and streak gonads, despite the presence of the 46,XY karyotype. Most of the studied cases presented with leak of secondary sex characteristics and primary amenorrhea during adolescence. Laboratory findings reveal hypergonadotropic hypogonadism. Herein we present the case of a female with a 46,XY karyotype who was admitted with delayed puberty and detected to have a microdeletion in the
Hyperostosis-hyperphosphatemia syndrome (HHS): report of two cases with a recurrent mutation and review of the literature
Authors: Ghafouri-Fard Soudeh , Abbasi Farzaneh , Azizi Faezeh , Javaheri Mona , Mehdizadeh Mehrzad , Setoodeh Arya
Published: August 2014

Hyperostosis-hyperphosphatemia syndrome (HHS) is a rare autosomal recessive metabolic disorder caused by mutations in the
Fossorial morphotype does not make a species in water voles
Authors: Kryštufek Boris , Koren Toni , Engelberger Simon , Horváth Győző F. , Purger Jenő J. , Arslan Atilla , Chişamera Gabriel , Murariu Dumitru
Published: August 2014

Phenetic and ecological plasticity in