bluuebunny/crossref_metadata_2025 huggingface dataset:
How many people need expert symptom assessment but are not in the last year of life?
Authors: Maher J. , McConnel H.
Published: November 2015

Introduction

Earlier palliative assessment and support for symptom self management may reduce distress and health resource use in incurable illness. The end of life tariff includes assessment of unstable symptoms, even if not in the last year of life. Current hospital recording systems do not allow timely identification of these individuals. Understanding how many people have palliative needs but are not in the last year of life will be increasingly important.

Aims and Methods

To identify people living with cancer at different phases across the care pathway including those at risk of developing complex symptoms, with progressive illness or at end of life. Using available data and clinically led assumptions we make indicative estimates of the number of people in different health states – particularly those with palliative care needs and not in the last year of life.

Results

We estimate pathway phases for breast, prostate, colorectal and lung cancers. For example, we estimate that in one year 48,000 women develop breast cancer in the UK and 12,000 are in the last year of life 24,000 have progressive illness and are not in the last year of life.

Conclusion

We provide ‘good enough’ estimates of the number of patients with different health needs and transition points in the cancer care pathway to stimulate debate and inform commissioners about areas of need. While cancer is seen to have the most predictable pattern of deterioration, as more incurable cancers become treatable, illness trajectories will become more comparable to other chronic illness. A similar approach might be taken with other illnesses.
Lymphocyte subsets contribute to the degree of lobulitis and ductitis in sclerosing lymphocytic lobulitis of the breast
Authors: Chen Lin-Ying , Tsang Julia Y S , Ni Yun-Bi , Chan Siu-Ki , Chan Kui-Fat , Zhang Sheng , Tse Gary M
Published: November 2015

Aims

Sclerosing lymphocytic lobulitis (SLL) of the breast is characterised by lymphocytic lobulitis, ductitis, vasculitis and dense keloidal fibrosis with epithelioid fibroblasts. However, the subsets of the infiltrating lymphocytes and their contribution to disease progression have not been fully explored.

Methods

CD20, CD3, CD4, CD8 and regulatory T (Treg) lymphocytes were evaluated in the epithelial and vascular areas in SLL. The relationship between the lymphocyte subset in different regions and the degree of inflammation was analysed.

Results

Lymphocytic infiltration was mainly located in peri-lobular, peri-ductal and peri-vascular areas. No significant differences between CD20 and CD3 lymphocytes were found in peri-epithelial areas. However, there were more intra-ductal/lobular epithelial CD3 than CD20 lymphocytes (p<0.001). For T lymphocyte subsets, more CD4 than CD8 lymphocytes were found in the peri-lobular/vascular regions (p≤0.026); but an opposite trend was seen in the intra-ductal/lobular regions (p<0.001). In the peri-lobular/vascular regions, generally, different lymphocyte subsets correlated with each other. Interestingly, in the peri-ductal region, only CD4 lymphocytes showed significant correlations with all other subsets (p≤0.020). Regarding their relationship with the degree of inflammation, significant positive correlations were observed for all subsets in peri-vascular/lobular regions (p≤0.045). Only regulatory T cells, but not the others, at the peri-ductal region showed significant correlation with the degree of inflammation at all three regions (p≤0.014).

Conclusions

In addition to B lymphocyte subsets, T lymphocyte subsets could be involved differently in SLL. CD4 lymphocytes may have a pivotal role in recruiting other subsets to the inflamed site, and triggered the cascade of inflammatory changes resulting in fibrosis.
One-step tumor detection from dynamic morphology tracking on aptamer-grafted surfaces
Authors: Mahmood Mohammed Arif I. , Hasan Mohammad Raziul , Khan Umair J. M. , Allen Peter B. , Kim Young-tae , Ellington Andrew D. , Iqbal Samir M.
Published: November 2015

In this paper, we report a one-step tumor cell detection approach based on the dynamic morphological behavior tracking of cancer cells on a ligand modified surface. Every cell on the surface was tracked in real time for several minutes immediately after seeding until these were finally attached. Cancer cells were found to be very active in the aptamer microenvironment, changing their shapes rapidly from spherical to semi-elliptical, with much flatter spread and extending pseudopods at regular intervals. When incubated on a functionalized surface, the balancing forces between cell surface molecules and the surface-bound aptamers, together with the flexibility of the membranes, caused cells to show these distinct dynamic activities and variations in their morphologies. On the other hand, healthy cells remained distinguishingly inactive on the surface over the same period. The quantitative image analysis of cell morphologies provided feature vectors that were statistically distinct between normal and cancer cells.
Research on the Functional Dispersal and Population Governance for China’s Megacities
Authors: LI Hongyu , LI Jie
Published: November 2015

This paper analyzes the functional features of Chinese megacities and the problems faced by functional dispersal, as well as China’s current population governance mode and future trends. The paper summarizes the mode and experience of functional dispersal and population governance of megacities in some developed countries, such as US and Japan. And on this basis, it is pointed out that the functional dispersal of China’s megacities includes dis-functionalization, spatial structure optimization and reasonable population diffusion. Also, the paper proposes the basic principles and methods of functional dispersal and population governance of megacities that are suitable to China’s status quo, thus providing a research orientation for the functional dispersal and population governance for megacities.
Evolution of small-scale flow barriers in German Rotliegend siliciclastics
Authors: Busch Benjamin , Winkler Rebecca , Osivandi Keyvan , Nover Georg , Amann-Hildenbrand Alexandra , Hilgers Christoph
Published: November 2015

Many siliciclastic reservoirs contain millimetre-scale diagenetic and structural phenomena affecting fluid flow. We identified three major types of small-scale flow barriers in a clastic Rotliegend hydrocarbon reservoir: cataclastic deformation bands; dissolution seams; and bedding-parallel cementation. Deformation bands of various orientations were analysed on resistivity image logs and in core material. They are mainly conjugates, and can be used to validate seismically observable faults and infer subseismic faults. Bedding-parallel dissolution seams are related to compaction and post-date at least one set of deformation bands. Bedding-parallel cementation is accumulated in coarser-grained layers and depends on the amount of clay coatings.

Apparent permeability data related to petrographical image interpretation visualizes the impact of flow barriers on reservoir heterogeneity. Transmissibility multiplier calculations indicate the small efficiency of the studied deformation bands on flow properties in the reservoir. Deformation bands reduce the host-rock permeability by a maximum of two orders of magnitude. However, host-rock anisotropies are inferred to reduce the permeability by a maximum of four orders of magnitude. The relative timing of these flow barriers, as well as the assessment of reservoir heterogeneities, are the basis for state-of-the-art reservoir prediction modelling.
Burial estimates constrained by clumped isotope thermometry: example of the Lower Cretaceous Qishn Formation (Haushi-Huqf High, Oman)
Authors: John Cédric M.
Published: November 2015

Accurate determination of the thermal history of sedimentary basins is critical to constrain the timing of diagenetic processes. Here, clumped isotope palaeothermometry is used to estimate minimum burial depth of the Lower Cretaceous Qishn Formation in east central Oman. Fossil oysters were collected in a soft argillaceous unit, thin-sectioned, and studied under petrographical and cathodoluminescence microscopy, revealing a variable state of shell preservations with early silica replacement of carbonate and late-stage calcite cementation. Clumped isotopes values varied from 0.602 to 0.666‰, with the best-preserved oyster shell yielding a temperature of 37 ± 4°C and a calculated oxygen isotope ratio in seawater (δ
18
O
seawater
) compatible with Cretaceous seawater having experienced moderate evaporation (1.0–1.5‰ VSMOW). The new minimum estimates for the burial depth of the Qishn Formation is 1.0–1.2 km, based on the temperature difference between the well-preserved oyster and the partially neomorphosed oyster recording the highest burial temperature (63 ± 4°C). This is in excess of what was predicted by previous studies (<400 m), but compatible with conodonts alteration index temperatures (<80°C). This study highlights the potential of clumped isotopes as a quantitative tool to estimate temperature and burial depth in fine-grained carbonate succession where fluid inclusions are absent, and offers a new tool to constrain the thermal histories of sedimentary basins.
Hemodynamic and neural responses to renal denervation of the nerve to the clipped kidney by cryoablation in two-kidney, one-clip hypertensive rats
Authors: Rossi Noreen F. , Pajewski Russell , Chen Haiping , Littrup Peter J. , Maliszewska-Scislo Maria
Published: November 2015

Renal artery stenosis is increasing in prevalence. Angioplasty plus stenting has not proven to be better than medical management. There has been a reluctance to use available denervation methodologies in this condition. We studied conscious, chronically instrumented, two-kidney, one-clip (2K-1C) Goldblatt rats, a model of renovascular hypertension, to test the hypothesis that renal denervation by cryoablation (cryo-DNX) of the renal nerve to the clipped kidney decreases mean arterial pressure (MAP), plasma and tissue ANG II, and contralateral renal sympathetic nerve activity (RSNA). Five-week-old male Sprague-Dawley rats underwent sham (ShC) or right renal artery clipping (2K-1C), placement of telemetry transmitters, and pair-feeding with a 0.4% NaCl diet. After 6 wk, rats were randomly assigned to cryo-DNX or sham cryotreatment (sham DNX) of the renal nerve to the clipped kidney. MAP was elevated in 2K-1C and decreased significantly in both ShC cryo-DNX and 2K-1C cryo-DNX. Tissue norepinephrine was ∼85% lower in cryo-DNX kidneys. Plasma ANG II was higher in 2K-1C sham DNX but not in 2K-1C cryo-DNX vs ShC. Renal tissue ANG II in the clipped kidney decreased after cryo-DNX. Baseline integrated RSNA of the unclipped kidney was threefold higher in 2K-1C versus ShC and decreased in 2K-1C cryo-DNX to values similar to ShC. Maximum reflex response of RSNA to baroreceptor unloading in 2K-1C was lower after cryo-DNX. Thus, denervation by cryoablation of the renal nerve to the clipped kidney decreases not only MAP but also plasma and renal tissue ANG II levels and RSNA to the contralateral kidney in conscious, freely moving 2K-1C rats.
Innate Immune Signaling Activated by MDR Bacteria in the Airway
Authors: Parker Dane , Ahn Danielle , Cohen Taylor , Prince Alice
Published: November 2015

Health care-associated bacterial pneumonias due to multiple-drug resistant (MDR) pathogens are an important public health problem and are major causes of morbidity and mortality worldwide. In addition to antimicrobial resistance, these organisms have adapted to the milieu of the human airway and have acquired resistance to the innate immune clearance mechanisms that normally prevent pneumonia. Given the limited efficacy of antibiotics, bacterial clearance from the airway requires an effective immune response. Understanding how specific airway pathogens initiate and regulate innate immune signaling, and whether this response is excessive, leading to host-induced pathology may guide future immunomodulatory therapy. We will focus on three of the most important causes of health care-associated pneumonia, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, and review the mechanisms through which an inappropriate or damaging innate immune response is stimulated, as well as describe how airway pathogens cause persistent infection by evading immune activation.
Robust NonlinearH∞Control Design via Stable Manifold Method
Authors: Abe Yoshiki , Nishida Gou , Sakamoto Noboru , Yamamoto Yutaka
Published: November 2015

This paper proposes a systematic numerical method for designing robust nonlinearH∞controllers without a priori lower-dimensional approximation with respect to solutions of the Hamilton-Jacobi equations. The method ensures the solutions are globally calculated with arbitrary accuracy in terms of the stable manifold method that is a solver of Hamilton-Jacobi equations in nonlinear optimal control problems. In this realization, the existence of stabilizing solutions of the Hamilton-Jacobi equations can be derived from some properties of the linearized system and the equivalent Hamiltonian system that is obtained from a transformation of the Hamilton-Jacobi equation. A numerical example is shown to validate the design method.
LMI-Based Stability Criterion for Impulsive CGNNs via Fixed Point Theory
Authors: Wang Xiongrui , Rao Ruofeng , Zhong Shouming
Published: November 2015

Linear matrices inequalities (LMIs) method and the contraction mapping theorem were employed to prove the existence of globally exponentially stable trivial solution for impulsive Cohen-Grossberg neural networks (CGNNs). It is worth mentioning that it is the first time to use the contraction mapping theorem to prove the stability for CGNNs while only the Leray-Schauder fixed point theorem was applied in previous related literature. An example is given to illustrate the effectiveness of the proposed methods due to the large allowable variation range of impulse.
Research on Construction Method of Operational Reliability Control Model for Space Manipulator Based on Particle Filter
Authors: Gao Xin , Wang Yifan , Sun Hanxu , Jia Qingxuan , Yang Xiaojian , Du Mingtao , Huang Jingyu
Published: November 2015

The operational reliability of the space manipulator is closely related to the control method. However the existing control methods seldom consider the operational reliability from the system level. A method to construct the operational reliability system control model based on particle filter for the space manipulator is presented in this paper. Firstly, the definition of operational reliability and the degree of operational reliability are given and the state space equations of the control system are established as well. Secondly, based on the particle filter algorithm, a method to estimate the distribution of the end position error and calculate the degree of operational reliability with any form of noise distribution in real time is established. Furthermore, a performance model based on quality loss theory is built and a performance function is obtained to evaluate the quality of the control process. The adjustment value of the end position of the space manipulator can be calculated by using the performance function. Finally, a large number of simulation results show that the control method proposed in this paper can improve the task success rate effectively compared to the simulation results using traditional control methods and control methods based on Bayesian estimation.
An Image Denoising Method with Enhancement of the Directional Features Based on Wavelet and SVD Transforms
Authors: Wang Min , Li Zhen , Duan Xiangjun , Li Wei
Published: November 2015

This paper proposes an image denoising method, using the wavelet transform and the singular value decomposition (SVD), with the enhancement of the directional features. First, use the single-level discrete 2D wavelet transform to decompose the noised image into the low-frequency image part and the high-frequency parts (the horizontal, vertical, and diagonal parts), with the edge extracted and retained to avoid edge loss. Then, use the SVD to filter the noise of the high-frequency parts with image rotations and the enhancement of the directional features: to filter the diagonal part, one needs first to rotate it 45 degrees and rotate it back after filtering. Finally, reconstruct the image from the low-frequency part and the filtered high-frequency parts by the inverse wavelet transform to get the final denoising image. Experiments show the effectiveness of this method, compared with relevant methods.
“HealthOmeter”: An Aid in Advancing Preventive Medicine Media Revolution
Authors: Trell Erik
Published: November 2015

Subjective wellbeing is an important issue on the preventive medicine and political agenda and for mutual communication, information, and interaction in society and its individuals “requires new tools for measuring phenomena previously believed unmeasurable, as well as conceptual frameworks for interpreting such measurements…considering both happiness and misery.” The task is difficult, however, due to the great span of parameters and variables of age and gender, settings, socioeconomic conditions, wellness and illness, activities and functions, roles and habits, thoughts and feelings, and experiences and expectations involved over the panorama. HealthOmeter is a clinically tested and validated instrument with design and capacity in distinct coherent chapters to meet the new measurement and interpretation demands both contentwise and operationwise. Over the range of subjective and objective health it enables, in a uniform normalized layout in quintile balance between positive and negative, an all-round self-assessment and counsel in multimedia, preferably computer/mobile app distribution including storage, collation, and follow-up in full integrity and secrecy on the individual and aggregated level.
Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells
Authors: Casimiro Mathew C. , Di Sante Gabriele , Ju Xiaoming , Li Zhiping , Chen Ke , Crosariol Marco , Yaman Ismail , Gormley Michael , Meng Hui , Lisanti Michael P. , Pestell Richard G.
Published: November 2015

Therapy resistance and poor outcome in prostate cancer is associated with increased expression of cyclin D1. Androgens promote DNA double-strand break repair to reduce DNA damage, and cyclin D1 was also shown to enhance DNA damage repair (DDR). In this study, we investigated the significance of cyclin D1 in androgen-induced DDR using established prostate cancer cells and prostate tissues from cyclin D1 knockout mice. We demonstrate that endogenous cyclin D1 further diminished the dihydrotestosterone (DHT)-dependent reduction of γH2AX foci in vitro. We also show that cyclin D1 was required for the androgen-dependent DNA damage response both in vitro and in vivo. Furthermore, cyclin D1 was required for androgen-enhanced DDR and radioresistance of prostate cancer cells. Moreover, microarray analysis of primary prostate epithelial cells from cyclin D1-deficient and wild-type mice demonstrated that most of the DHT-dependent gene expression changes are also cyclin D1 dependent. Collectively, our findings suggest that the hormone-mediated recruitment of cyclin D1 to sites of DDR may facilitate the resistance of prostate cancer cells to DNA damage therapies and highlight the need to explore other therapeutic approaches in prostate cancer to prevent or overcome drug resistance. Cancer Res; 76(2); 329–38. ©2015 AACR.
An Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy
Authors: Noguchi Masanori , Matsumoto Kazumasa , Uemura Hirotsugu , Arai Gaku , Eto Masatoshi , Naito Seiji , Ohyama Chikara , Nasu Yasutomo , Tanaka Masatoshi , Moriya Fukuko , Suekane Shigetaka , Matsueda Satoko , Komatsu Nobukazu , Sasada Tetsuro , Yamada Akira , Kakuma Tatsuyuki , Itoh Kyogo
Published: November 2015

Purpose: The prognosis of platinum-based chemotherapy–resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity.

Experimental Design: In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity.

Results: Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4–1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34–0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5–12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8–6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions.

Conclusions: PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results. Clin Cancer Res; 22(1); 54–60. ©2015 AACR.
A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients with Advanced Cancer
Authors: Patnaik Amita , Haluska Paul , Tolcher Anthony W. , Erlichman Charles , Papadopoulos Kyriakos P. , Lensing Janet L. , Beeram Muralidhar , Molina Julian R. , Rasco Drew W. , Arcos Rebecca R. , Kelly Claudia S. , Wijayawardana Sameera R. , Zhang Xuekui , Stancato Louis F. , Bell Robert , Shi Peipei , Kulanthaivel Palaniappan , Pitou Celine , Mulle Lynette B. , Farrington Daphne L. , Chan Edward M. , Goetz Matthew P.
Published: November 2015

Purpose: p38 MAPK regulates the production of cytokines in the tumor microenvironment and enables cancer cells to survive despite oncogenic stress, radiotherapy, chemotherapy, and targeted therapies. Ralimetinib (LY2228820 dimesylate) is a selective small-molecule inhibitor of p38 MAPK. This phase I study aimed to evaluate the safety and tolerability of ralimetinib, as a single agent and in combination with tamoxifen, when administered orally to patients with advanced cancer.

Experimental Design: The study design consisted of a dose-escalation phase performed in a 3+3 design (Part A; n = 54), two dose-confirmation phases [Part B at 420 mg (n = 18) and Part C at 300 mg (n = 8)], and a tumor-specific expansion phase in combination with tamoxifen for women with hormone receptor–positive metastatic breast cancer refractory to aromatase inhibitors (Part D; n = 9). Ralimetinib was administered orally every 12 hours on days 1 to 14 of a 28-day cycle.

Results: Eighty-nine patients received ralimetinib at 11 dose levels (10, 20, 40, 65, 90, 120, 160, 200, 300, 420, and 560 mg). Plasma exposure of ralimetinib (Cmax and AUC) increased in a dose-dependent manner. After a single dose, ralimetinib inhibited p38 MAPK–induced phosphorylation of MAPKAP-K2 in peripheral blood mononuclear cells. The most common adverse events, possibly drug-related, included rash, fatigue, nausea, constipation, pruritus, and vomiting. The recommended phase II dose was 300 mg every 12 hours as monotherapy or in combination with tamoxifen. Although no patients achieved a complete response or partial response,19 patients (21.3%) achieved stable disease with a median duration of 3.7 months, with 9 of these patients on study for ≥6 cycles.

Conclusions: Ralimetinib demonstrated acceptable safety, tolerability, and pharmacokinetics for patients with advanced cancer. Clin Cancer Res; 22(5); 1095–102. ©2015 AACR.
Identification of an “Exceptional Responder” Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted Therapy
Authors: Gannon Hugh S. , Kaplan Nathan , Tsherniak Aviad , Vazquez Francisca , Weir Barbara A. , Hahn William C. , Meyerson Matthew
Published: November 2015

The identification of somatic genetic alterations that confer sensitivity to pharmacologic inhibitors has led to new cancer therapies. To identify mutations that confer an exceptional dependency, shRNA-based loss-of-function data were analyzed from a dataset of numerous cell lines to reveal genes that are essential in a small subset of cancer cell lines. Once these cell lines were determined, detailed genomic characterization from these cell lines was utilized to ascertain the genomic aberrations that led to this extreme dependency. This method, in a large subset of lung cancer cell lines, yielded a single lung adenocarcinoma cell line, NCI-H1437, which is sensitive to RNA interference of MAP2K1 expression. Notably, NCI-H1437 is the only lung cancer cell line included in the dataset with a known activating mutation in MAP2K1 (Q56P). Subsequent validation using shRNA and CRISPR-Cas9 confirmed MAP2K1 dependency. In vitro and in vivo inhibitor studies established that NCI-H1437 cells are sensitive to MEK1 inhibitors, including the FDA-approved drug trametinib. Like NCI-H1437 cells, the MAP2K1-mutant cell lines SNU-C1 (colon) and OCUM-1 (gastric) showed decreased viability after MAP2K1 depletion via Cas9-mediated gene editing. Similarly, these cell lines were particularly sensitive to trametinib treatment compared with control cell lines. On the basis of these data, cancers that harbor driver mutations in MAP2K1 could benefit from treatment with MEK1 inhibitors. Furthermore, this functional data mining approach provides a general method to experimentally test genomic features that confer dependence in tumors.

Implications: Cancers with an activated RAS/MAPK pathway driven by oncogenic MAP2K1 mutations may be particularly sensitive to MEK1 inhibitor treatments. Mol Cancer Res; 14(2); 207–15. ©2015 AACR.
Role of Toll-Like Receptor 3 Gene Polymorphisms in Preeclampsia
Authors: Chen Aiping , Li Congying , Wang Jingli , Sha Han , Piao Shunfu , Liu Shiguo
Published: November 2015

Background/Aims: Accumulating evidence suggests that an excessive maternal systemic inflammatory response to pregnancy with exaggerated activation of the innate immune system plays a critical role in the development of preeclampsia (PE). In this study, we investigated whether polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with susceptibility to PE in the Chinese Han population. Methods: We recruited 987 PE patients and 1227 healthy pregnant women. Two polymorphisms (rs3775291 and rs3775296) located in TLR3 were genotyped by TaqMan allelic discrimination real-time PCR. The association between the genotype or allele frequencies and PE was examined using chi-square tests. Clinical data were compared between cases and controls using Student's t test. Results: No significant difference was determined in the genetic distribution of rs3775291 and rs3775296 between cases and controls. There were also no significant differences in the genotype and allele frequencies of either SNP between healthy pregnant women and patients with late or early onset PE, or with mild or severe PE. Conclusion: Although this is the first study of the association between TLR3 polymorphisms and preeclampsia, we found that TLR3 polymorphisms are unlikely to play a significant role in the development of preeclampsia in the Chinese Han population.
Expression of Nodal on Bronchial Epithelial Cells Influenced by Lung Microbes Through DNA Methylation Modulates the Differentiation of T-Helper Cells
Authors: Wang Lili , Wu Guojun , Qin Xiaoqun , Ma Qiongshan , Zhou Yigang , Liu Shuiping , Tan Yurong
Published: November 2015

Background/Aims: The previous study in our lab showed that Nodal molecule on bronchial epithelial cells (BECs) was modulated by all kinds of lung microbes. The present study was designed to determine the effects of Nodal on proliferation of BECs and BECs-induced differentiation of T-helper (Th) cells. The epigenetic mechanisms of Nodal expression following treatments of different lung microbes were also identified. Methods: Real-time polymerization chain reaction (PCR) and western blot were used to determine the expression of Nodal. Flow cytometry was used to observe the effects of proliferation of BECs and subsequent BECs-induced differentiation of Th cells. Methylation levels of CpG islands in Nodal promoters were also analyzed by time of flight mass spectrometry. Results: The results showed that Nodal promoted proliferation of BECs and BECs-induced differentiation of Th cell from Th1 to Th2 and Th17. Nodal promoter showed a hyper-methylation in normal BECs. Through methylation modification in the promoter, P. aeruginosa or A.baumanni inhibited the expression of Nodal while RSV promoted the expression of Nodal. Conclusions: Our data showed that Nodal promoted Th2 and Th17 differentiation and inhibited Th1 differentiation which may cause imbalance of airway microenvironment. P. aeruginosa or A.baumanni may be hopeful for the treatment of airway hyperresponsveness by inhibition Nodal expression through DNA methylation modification in the promoter.
Nefiracetam Attenuates Pro-Inflammatory Cytokines and GABA Transporter in Specific Brain Regions of Rats with Post-Ischemic Seizures
Authors: Fu Chuan-Yi , He Xu-Ying , Li Xi-Feng , Zhang Xin , Huang Zhi-Wei , Li Jun , Chen Min , Duan Chuan-Zhi
Published: November 2015

Background/Aims: Prior studies demonstrated that pro-inflammatory cytokines (PICs) including IL-1β, IL-6 and TNF-α contribute to regulation of epilepsy-associated pathophysiological processes in the specific brain regions, namely the parietal cortex, hippocampus and amygdala. Moreover, GABA transporter type 1 and 3 (GAT-1 and GAT-3) modulating extracellular GABA levels are engaged in the role played by PICs in epileptogenesis. Note that brain ischemic injury also elevates cerebral PICs. Thus, in this report we examined the effects of nefiracetam (NEF), a pyrrolidone derivative, on the levels of IL-1β, IL-6 and TNF-α, and expression of GAT-1 and GAT-3 in the parietal cortex, hippocampus and amygdala using a rat model of post-ischemic nonconvulsive seizure (NCS). Methods: NCS was evoked by the middle cerebral artery occlusion (MCAO). ELISA and Western Blot analysis were employed to determine the levels of PICs and GAT-1/GAT-3, respectively. Results: MCAO significantly increased IL-1β, IL-6 and TNF-α in the parietal cortex, hippocampus and amygdala as compared with sham control animals (P<0.05 vs. control rats). Also, in these specific brain regions expression of GAT-1 and GAT-3 was amplified; and the levels of GABA were decreased in rats following MCAO (P<0.05 vs. control rats). Systemic administration of NEF significantly attenuated the elevated PICs, amplified GAT-1 and GAT-3 as well as impaired GABA. NEF also attenuated the number of NCS events following MCAO. Conclusion: our data demonstrate that NEF improves post-ischemia evoked-NCS by altering PICs, GABA transporters thereby alleviating GABA in the parietal cortex, hippocampus and amygdala. This support a role for PICs and GABA in engagement of the adaptive responses associated with epileptic activity, but also suggests that NEF has anti-epileptic effects via PICs-GABA mechanisms, having pharmacological implications to target the specific PICs for neuronal dysfunction and vulnerability related to post-ischemic seizures and cognitive impairment.
Patterns of Emphysema Heterogeneity
Authors: Valipour Arschang , Shah Pallav L. , Gesierich Wolfgang , Eberhardt Ralf , Snell Greg , Strange Charlie , Barry Robert , Gupta Avina , Henne Erik , Bandyopadhyay Sourish , Raffy Philippe , Yin Youbing , Tschirren Juerg , Herth Felix J.F.
Published: November 2015

Background: Although lobar patterns of emphysema heterogeneity are indicative of optimal target sites for lung volume reduction (LVR) strategies, the presence of segmental, or sublobar, heterogeneity is often underappreciated. Objective: The aim of this study was to understand lobar and segmental patterns of emphysema heterogeneity, which may more precisely indicate optimal target sites for LVR procedures. Methods: Patterns of emphysema heterogeneity were evaluated in a representative cohort of 150 severe (GOLD stage III/IV) chronic obstructive pulmonary disease (COPD) patients from the COPDGene study. High-resolution computerized tomography analysis software was used to measure tissue destruction throughout the lungs to compute heterogeneity (≥15% difference in tissue destruction) between (inter-) and within (intra-) lobes for each patient. Emphysema tissue destruction was characterized segmentally to define patterns of heterogeneity. Results: Segmental tissue destruction revealed interlobar heterogeneity in the left lung (57%) and right lung (52%). Intralobar heterogeneity was observed in at least one lobe of all patients. No patient presented true homogeneity at a segmental level. There was true homogeneity across both lungs in 3% of the cohort when defining heterogeneity as ≥30% difference in tissue destruction. Conclusion: Many LVR technologies for treatment of emphysema have focused on interlobar heterogeneity and target an entire lobe per procedure. Our observations suggest that a high proportion of patients with emphysema are affected by interlobar as well as intralobar heterogeneity. These findings prompt the need for a segmental approach to LVR in the majority of patients to treat only the most diseased segments and preserve healthier ones.
From Sin to Crime: Laws on Infanticide in the Middle Ages
Authors: Obladen Michael
Published: November 2015

This is the second of three papers investigating the legislative history concerning infanticide. It compares the efforts of various states to protect the newborn infant between 534 and 1532 CE. When the Roman Empire collapsed in the 5th century, the jurisdiction of infanticide was relegated to the church, which regarded carnal delicts a sin rather than a crime. The punishment - public penance of the mother for 7-15 years - was milder than that which the murder of an adult would incur. The Council of Florence decreed in 1439 that the souls of children who died without having been baptized descend to hell. This turned infanticide from a penitential sin to the most heinous of all crimes. The states passed laws that abominated infanticide even more than the murder of older humans and punished women with ever more cruel forms of execution. Towards the men, however, who usually abandoned the women they had impregnated, the laws were lenient. Churches and society continued to vilify illegitimate birth, thus enhancing rather than preventing infanticide. The Habsburg-German legislation of 1532 ordained to torture any woman who had concealed pregnancy and birth and claimed the infant was stillborn. Legislation developed similarly in other countries, albeit at a different speed. French (1556) and British (1623) legislation reversed the burden of proof and demanded the death penalty for concealing pregnancy and birth when a dead infant was found.
The Development of a New Medical Device for Standardized Episiotomy: A Pre-Clinical Validation Study
Authors: Mulder Femke , Piersma Dorine , Veersema Sebastiaan , van der Post Joris , Roovers Jan-Paul
Published: November 2015

Background: The aim of this study was to present the validation and optimization process for a new innovative medical device to create a standardized episiotomy. Design: We performed a preclinical validation study. Setting: This study was performed at the University hospital. Sample: Animal, cadaver. Methods: Together with technical engineers, we designed a new medical device that involves a knife and cuts back from buttock toward introitus, in contrast to the conventional episiotomy. We optimized the design and its performance in consecutive animal and cadaver studies. Main Outcome Measures: Ability to perform a standardized incision, ease of use. Results: After multiple adjustments, based on the results of multiple animal and cadaver studies, a medical device was developed to perform a standardized clean-cut episiotomy of 4-6 cm length. Conclusion: We have shown that optimizing the technical performance and safety of an innovative device in animals, prior to opposing patients to its potential hazards, is feasible. Our design optimizing study can be used as a model for the pre-clinical validation of future innovative medical devices.
Outborns or Inborns: Where Are the Differences? A Comparison Study of Very Preterm Neonatal Intensive Care Unit Infants Cared for in Australia and New Zealand and in Canada
Authors: Hossain Sadia , Shah Prakesh S. , Ye Xiang Y. , Darlow Brian A. , Lee Shoo K. , Lui Kei ,   on behalf of the Canadian Neonatal Network and Australian and New Zealand Neonatal Network
Published: November 2015

Background: Very preterm infants born outside tertiary centers are at higher risks of adverse outcomes than inborn infants. Regionalization of perinatal care has been introduced worldwide to improve outcomes. Objective: To compare the risk-adjusted outcomes of both inborn and outborn infants cared for in tertiary neonatal intensive care units in Australia and New Zealand and in Canada. Methods: Deidentified data of infants <32 weeks' gestational age from the 29 Australian and New Zealand Neonatal Network units (ANZNN; n = 9,893) and 26 Canadian Neonatal Network units (CNN; n = 7,133) between 2005 and 2007 were analyzed for predischarge adverse outcomes. Results: ANZNN had lower rates of outborns compared to CNN (13 vs. 19%), particularly of late admissions (>2 days of age; 5.8 vs. 22.2% of outborns) who had high morbidity rates. After adjusting for confounding variables including gestation, ANZNN inborn infants had lower odds of chronic lung disease [CLD; 17.0 vs. 23.3%; adjusted odds ratio (AOR) = 0.70, 95% CI: 0.64-0.77], severe neurological injuries on ultrasound (SNI; 4.1 vs. 6.7%; AOR = 0.62, 95% CI: 0.53-0.73), severe retinopathy (5.6 vs. 7%; AOR = 0.71, 95% CI: 0.59-0.84) and necrotizing enterocolitis (3.5 vs. 5.4%; AOR = 0.67, 95% CI: 0.56-0.79), but no difference in mortality odds. After excluding the late outborn admissions, ANZNN outborns had lower odds of SNI (AOR = 0.43, 95% CI: 0.32-0.58) and CLD (AOR = 0.63, 95% CI: 0.49-0.81) than CNN. Conclusions: ANZNN inborn and early admitted outborn infants had lower odds of neonatal morbidities than their CNN counterparts. However, compared to ANZNN, the higher CNN rates of outborns and their late admissions are likely related to the differences in regionalization and referral practices, and may explain differences in outcomes.
Reference Ranges for Neonatal Basal Ganglia Perfusion as Measured by Fractional Moving Blood Volume
Authors: Schindler Timothy , Stevenson Gordon , Jayatilake Sonali , Gilbert Yasmin , Oei Ju Lee , Welsh Alec
Published: November 2015

Background: Regional changes in cerebral blood flow and perfusion are implicated in the pathogenesis of adverse neurological events that lead to death and severe disability in the newborn infant. The basal ganglia, in particular, are extremely sensitive to acute hypoxia in the perinatal period, but normal perfusion to this area is unknown. Objectives: To establish a reference range for regional basal ganglia perfusion using fractional moving blood volume (FMBV) as an index. Methods: Head ultrasounds were performed on neonates from 25 to 41 weeks' gestation. Power Doppler images were obtained from a pre-specified coronal plane. FMBV was calculated offline after selecting the basal ganglia as a region of interest. The average of five calculations was considered to be representative of the regional perfusion for each neonate. The data were analysed, and a neonatal reference range was defined. Results: 124 neonates were included in the study, and all had analysable data. The mean FMBV was 28.8% (±9.6) with a reference range defined as 10-48%. The mean FMBV for neonates <32 weeks', 32-35 weeks' and >35 weeks' gestation were 29.4% (±7.8), 29.2% (±11.0) and 27.4% (±9.7), respectively. Analysis of variance showed no significant difference between neonates based on gestation. Conclusions: We have successfully used the index FMBV to define a reference range for perfusion in the basal ganglia. These data can be used as a reference for subsequent studies that evaluate basal ganglia perfusion in pathological conditions.
Progressive Scleral Necrosis following I-125 Plaque Radiotherapy for Ciliochoroidal Melanoma with Protruding Extraocular Mass
Authors: Hill Jordan R. , Corrêa Zélia M.
Published: November 2015

Purpose: The aim of this study was to describe the side effects of I-125 brachytherapy in the treatment of uveal melanoma. Methods: This study was conducted as a case report. Results: We report a case of scleral necrosis and protruding episcleral mass following the treatment of uveal melanoma with I-125 brachytherapy. Conclusions: Scleral necrosis after plaque radiotherapy can clinically simulate tumor recurrence with extraocular extension. The management of uveal melanoma requires a careful clinical follow-up, weighing the implications of treatment morbidity and mortality.
Pediatric Hereditary Angioedema
Authors: Christiansen Sandra C. , Davis Donna K. , Castaldo Anthony J. , Zuraw Bruce L.
Published: November 2015

Hereditary angioedema (HAE) typically presents in childhood. Large gaps remain in our understanding of the natural history of HAE during childhood. We examined age of onset, delay in diagnosis, androgen exposure, and their influence on ultimate disease severity in a large cohort of patients with HAE. Median age of first swelling was 11 years with a median age at diagnosis of 19 years. Earlier onset of symptoms correlated with longer delays in diagnosis ( P < .001) and predicted a more severe disease course, including increased number of attacks per year ( P = .0009) and hospital admissions ( P = .009). Earlier age of onset also significantly correlated with increased perceived HAE severity ( P = .0002), negative overall life impact ( P < .0001), and use of anabolic androgen. Our observations highlight the importance of early HAE diagnosis and suggest the necessity of a disease management plan once the diagnosis has been made.
The prevalence and predictors of self-stigma of individuals with mental health illness in two Chinese cities
Authors: Young Daniel Kim-Wan , Ng Petrus Yat-Nam
Published: November 2015

Background:

Although self-stigma is found to have adverse effects on the lives of persons with mental illness, little is known on the self-stigma of these individuals in Chinese societies.

Objective:

This research study explores the prevalence rate and predicting factors of self-stigma of consumers in two Chinese cities, Hong Kong and Guangzhou.

Methods:

A cross-sectional research design is adopted which involves a random sample of 266 consumers from Hong Kong and a convenient sample of 208 consumers from Guangzhou. These individuals have been assessed in terms of their self-stigma, recovery, self-esteem and quality of life by using standardized assessment scales.

Results:

In all, 38.3% of the Hong Kong participants and 49.5% of the Guangzhou participants report to have self-stigma. Also, self-stigma is found to be negatively related to self-esteem and quality of life. A logistic regression analysis shows that hope and well-being are predicting factors of self-stigma.

Conclusion:

Self-stigma is found to be higher in Guangzhou, probably due to the influence of traditional cultural values. Also, as hope and well-being are found to be predicting factors of self-stigma, suitable recovery-orientated interventions that facilitate hope and well-being should be developed so as to reduce self-stigma of consumers in Chinese societies.
Postirradiation Leiomyosarcoma of Rectum Presenting as a Polyp
Authors: Jayakumar Rajeswari , Basu Prithwijit Patrick , Huang Tao , Axiotis Constantine A.
Published: November 2015

Radiation-induced leiomyosarcomas of the gastrointestinal tract are rare. Very few cases have been documented to date. The histological similarity to gastrointestinal stromal tumor has raised doubts if many of the cases originally reported to be leiomyosarcoma before the widespread use of CD117 were indeed gastrointestinal stromal tumors. We present a case of post-irradiation leiomyosarcoma presenting as a rectal polyp and review the literature.
Accidental exposure to politics on social media as online participation equalizer in Germany, Italy, and the United Kingdom
Authors: Valeriani Augusto , Vaccari Cristian
Published: November 2015

We assess whether and how accidental exposure to political information on social media contributes to citizens’ online political participation in comparative perspective. Based on three online surveys of samples representative of German, Italian, and British Internet users in the aftermath of the 2014 European Parliament elections, we find that accidental exposure to political information on social media is positively and significantly correlated with online participation in all three countries, particularly so in Germany where overall levels of participation were lower. We also find that interest in politics moderates this relationship so that the correlation is stronger among the less interested than among the highly interested. These findings suggest that inadvertent encounters with political content on social media are likely to reduce the gap in online engagement between citizens with high and low interest in politics, potentially broadening the range of voices that make themselves heard.
Impact of Fenestrated Endovascular Abdominal Aortic Aneurysm Repair on Renal Function
Authors: Saratzis Athanasios N. , Bath Michael F. , Harrison Seamus C. , Sayers Robert D. , Bown Matthew J.
Published: November 2015

Purpose: To investigate the impact of fenestrated endovascular aneurysm repair (fEVAR) on renal function perioperatively and at midterm. Methods: A case-controlled study was performed involving 58 patients (mean age 75±7 years; 51 men) who underwent elective fEVAR for a juxtarenal or short-necked abdominal aortic aneurysm (AAA) matched on age, sex, smoking, diabetes, and baseline estimated glomerular filtration rate (eGFR) with a contemporaneous group undergoing open aneurysm repair (OAR) for the same indications. Perioperative incidence of acute kidney injury (AKI) and levels of eGFR at 30 days and 1 year were compared. A systematic literature review was performed to identify studies that had used eGFR as renal outcome after fEVAR; the pooled data were meta-analyzed using an eGFR drop >30% at 1 month and the latest follow-up as endpoints. Results are reported as the pooled proportion and 95% confidence interval (CI). Results: The incidence of AKI after fEVAR was 28% compared to 10% after OAR (p=0.03). Following fEVAR, the mean eGFR dropped from 78±8 to 74±9 mL/min/1.73 m2 at 30 days compared to a change from 79±8 to 80±16 mL/min/1.73 m2 after OAR (p<0.01). However, the absolute drop in eGFR between fEVAR and OAR at 1 year was similar (7 mL/min/1.73 m2; p=0.53); 7% of the fEVAR patients had an eGFR drop >30% at that point compared with none for OAR (p=0.12). The systematic literature review identified eGFR outcomes for 193 fEVAR patients. Combining these patients with the 58 from our cohort study, the pooled proportions of eGFR drop >30% were 20% (95% CI 9% to 39%) at 30 days and 8% (95% CI 0.5% to 13%) at the end of follow-up. Conclusion: fEVAR has a significant perioperative impact on renal function, but 1-year results are similar to OAR. fEVAR patients may benefit from targeted AKI prevention strategies that need to be assessed in relevant studies.