bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapy Effects of Wogonin on Ovarian Cancer Cells
Authors: Ruibin Jiang , Bo Jin , Danying Wan , Chihong Zhu , Jianguo Feng , Linhui Gu
Published: October 2017

Background. Wogonin is a plant monoflavonoid and has been reported to induce apoptosis of cancer cells and show inhibitory effect on cancer cell growth. However, the detailed and underlying molecular mechanisms are not elucidated. In this study, we investigated the molecular and biological effects of wogonin in human ovarian A2780 cancer cells. Materials and Methods. We determined the effects of wogonin on the changes of cell cycling and apoptotic responses of cells. Western blot analysis was used to measure the effects of wogonin on protein expressions. Results. Our results showed that treatment with wogonin inhibited the cancer cell proliferation, decreased the percentage of G0/G1 subpopulation, and reduced invasiveness of A2780 cells. Exposure to wogonin also resulted in downregulated protein levels of estrogen receptor alpha (ER-α), VEGF, Bcl-2, and Akt and increased expressions of Bax and p53. In addition, exposure to wogonin increased caspase-3 cleavage and induced apoptosis in A2780 cells. Our study further showed that MPP, a specific ER-α inhibitor, significantly enhanced antitumor effects of wogonin in A2780 cells. Conclusion. Our results suggest a potential clinical impact of wogonin on management of ovarian cancer.
Differential Response of Glioma Stem Cells to Arsenic Trioxide Therapy Is Regulated by MNK1 and mRNA Translation
Authors: Bell Jonathan B. , Eckerdt Frank , Dhruv Harshil D. , Finlay Darren , Peng Sen , Kim Seungchan , Kroczynska Barbara , Beauchamp Elspeth M. , Alley Kristen , Clymer Jessica , Goldman Stewart , Cheng Shi-Yuan , James C. David , Nakano Ichiro , Horbinski Craig , Mazar Andrew P. , Vuori Kristiina , Kumthekar Priya , Raizer Jeffrey , Berens Michael E. , Platanias Leonidas C.
Published: October 2017

Mesenchymal (MES) and proneural (PN) are two distinct glioma stem cell (GSC) populations that drive therapeutic resistance in glioblastoma (GBM). We screened a panel of 650 small molecules against patient-derived GBM cells to discover compounds targeting specific GBM subtypes. Arsenic trioxide (ATO), an FDA-approved drug that crosses the blood–brain barrier, was identified as a potent PN-specific compound in the initial screen and follow-up validation studies. Furthermore, MES and PN GSCs exhibited differential sensitivity to ATO. As ATO has been shown to activate the MAPK-interacting kinase 1 (MNK1)-eukaryotic translation initiation factor 4E (eIF4E) pathway and subsequent mRNA translation in a negative regulatory feedback manner, the mechanistic role of ATO resistance in MES GBM was explored. In GBM cells, ATO-activated translation initiation cellular events via the MNK1–eIF4E signaling axis. Furthermore, resistance to ATO in intracranial PDX tumors correlated with high eIF4E phosphorylation. Polysomal fractionation and microarray analysis of GBM cells were performed to identify ATO's effect on mRNA translation and enrichment of anti-apoptotic mRNAs in the ATO-induced translatome was found. Additionally, it was determined that MNK inhibition sensitized MES GSCs to ATO in neurosphere and apoptosis assays. Finally, examination of the effect of ATO on patients from a phase I/II clinical trial of ATO revealed that PN GBM patients responded better to ATO than other subtypes as demonstrated by longer overall and progression-free survival.

Implications: These findings raise the possibility of a unique therapeutic approach for GBM, involving MNK1 targeting to sensitize MES GSCs to drugs like arsenic trioxide. Mol Cancer Res; 16(1); 32–46. ©2017 AACR.
Very-Low-Dose Decitabine Is Effective in Treating Intermediate- or High-Risk Myelodysplastic Syndrome
Authors: Li Hongmin , Wang Liru , Wu Yue , Su Li , Zhao Hong , Zhang Yongqing , Wang Zhao , Huang Dayong , Huang Zhongxia , Wu Xiaoxiong , Li Xiaohong , Ye Fang , Yu Fan , Liu Hui , Wang Jing-Wen , Cong Jia , Sun Wanjun , Chen Hui-Ren , Wang Jingbo , Han Bing
Published: October 2017

Nowadays, the regular recommended dose of decitabine for the treatment of myelodysplastic syndrome (MDS) is 20 mg/m2/day for 5 consecutive days with a relatively high incidence of treatment-related morbidities and costs. In this study, a retrospective and multicenter analysis was performed to explore the very-low-dose decitabine schedule for the treatment of patients with IPSS intermediate- or high-risk MDS. A total of 31 newly diagnosed MDS cases from 14 hospitals in Beijing received decitabine monotherapy (decitabine 6 mg/m2/day intravenously for 7 consecutive days, repeated every 4 weeks). With a medium follow-up of 4 months, 10 patients achieved complete remission (32.3%), 8 (25.8%) partial remission, and 3 (9.7%) hematological improvement. The overall response rate (ORR) was 67.7%. Rates of 21.7% for severe infections and 11.6% for severe bleedings were observed among all courses. The median cost of each course was USD 5,300, 3,000, 2,900, and 2,000, respectively. Multivariate analysis identified bone marrow blast cells ≥10% and a Charlson comorbidity index ≥1 as 2 independent factors for efficacy. In conclusion, very-low-dose decitabine showed relatively good efficacy, good tolerance, and low medical cost in the treatment of intermediate- or high-risk MDS. Elderly patients with more than 1 complication or patients with a higher proportion of blast cells may be the most suitable candidates for this regimen.
MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a
Authors: Tang Lian , Yin Yiran , Liu Juncai , Li Zhong , Lu Xiaobo
Published: October 2017

Background/Aims: With the aging population increases, senile osteoporosis has become a global public health problem. Previous evidence has shown that miR-124 has important effects on the occurrence and development of osteoporosis. However, the role of miR-124 in the process of osteoclastogenesis is still obscure. Methods: First of all, we measured the expression level of miR-124 in bone marrow monocytes (BMMs) of osteoporotic mice (ovariectomized mice: OVX). Next, we evaluated the alteration of miR-124 during osteoclast differentiation of BMMs. Then, BMMs were transfected with miR-124 mimics or inhibitors to explore the influences of miR-124 on osteoclast differentiation of BMMs in vitro. Furthermore, bioinformatics analysis and luciferase reporter assay were performed for prediction and identification of the target of miR-124. Results: BMMs from OVX mice exhibited lower expression of miR-124 compared with Sham mice. Additionally, miR-124 was down-regulated when BMMs differentiated into osteoclasts. In addition, inhibition of miR-124 promoted BMMs differentiated into osteoclasts in vitro, whereas overexpression of miR-124 attenuated this procedure, demonstrated by increased expression of osteoclast specific genes and TRAP staining. Furthermore, Rab27a was confirmed to be the direct target of miR-124 by bioinformatics, Western blot and luciferase reporter assay analysis. Conclusion: Our findings revealed that miR-124 has an important role in osteoclastogenesis via targeting Rab27a. Thus, targeting miR-124 promises a therapeutic potential in the treatment of osteoporosis.
Quantitative Renal Echogenicity as a Tool for Diagnosis of Advanced Chronic Kidney Disease in Patients with Glomerulopathies and no Liver Disease
Authors: Libório Alexandre B. , de Oliveira Neves Fernanda Macedo , Torres de Melo Candice Bezerra , Leite Tacyano Tavares , de Almeida Leitão Renata
Published: October 2017

Background/Aims: Glomerulopathy patients are prone to developing transitory reduced glomerular filtration rate (GFR), which can be difficult to differentiate from irreversible chronic kidney disease (CKD). Renal ultrasound can be useful, but differently from renal length, quantitative renal echogenicity has not been formerly evaluated regarding its capacity to identify irreversible advanced CKD. Methods: A prospective study was performed, where quantitative renal echogenicity was performed during renal biopsy in patients with suspected glomerular disease (n=197). Quantitative echogenicity was measured as the inverse of the ratio between the mean pixel densities of the renal cortex and adjacent liver using ScionImage software. Patients were followed during a six-months period to ascertain irreversible advanced CKD. Quantitative renal echogenicity and histopathology parameters discriminatory capacity were compared regarding their capacity to detect advanced and irreversible CKD - estimated GFR less than 30mL/min/1.73m2 confirmed after a six-month follow-up. Results: At renal biopsy, the mean eGFR was 53.9±33.6 mL/min/1.73m2 and 63 (32.0%) patients had an eGFR less than 30 mL/min/1.73m2. Mean kidney/liver echogenicity ratio was 1.06±0.19 and it was inversely correlated with eGFR at follow-up (r=-0.684, p<0.001). Multivariate analysis was performed to create a histopathology index that correctly identifies irreversible advanced CKD. Renal echogenicity discriminatory capacity to identify irreversible advanced CKD was 0.793 (0.719 -0.867), similar to the histopathology index. Elevated renal echogenicity with best discriminatory capacity was a kidney/liver ratio greater than 1.15. This cutoff had a predictive positive value of 92% in patients with eGFR less than 30mL/min/1.73m2. Conclusion: Quantitative renal echogenicity can be a useful tool in patients with glomerular disease and normal kidney size (>8cm) to identify those patients with irreversible advanced CKD.
Influence of Contrast Media Dose and Osmolality on the Diagnostic Performance of Contrast Fractional Flow Reserve
Authors: Nishi Takeshi , Johnson Nils P. , De Bruyne Bernard , Berry Colin , Gould K. Lance , Jeremias Allen , Oldroyd Keith G. , Kobayashi Yuhei , Choi Dong-Hyun , Pijls Nico H.J. , Fearon William F.
Published: October 2017

Background—

Contrast fractional flow reserve (cFFR) is a method for assessing functional significance of coronary stenoses, which is more accurate than resting indices and does not require adenosine. However, contrast media volume and osmolality may affect the degree of hyperemia and therefore diagnostic performance.

Methods and Results—

cFFR, instantaneous wave–free ratio, distal pressure/aortic pressure at rest, and FFR were measured in 763 patients from 12 centers. We compared the diagnostic performance of cFFR between patients receiving low or iso-osmolality contrast (n=574 versus 189) and low or high contrast volume (n=341 versus 422) using FFR≤0.80 as a reference standard. The sensitivity, specificity, and overall accuracy of cFFR for the low versus iso-osmolality groups were 73%, 93%, and 85% versus 87%, 90%, and 89%, and for the low versus high contrast volume groups were 69%, 99%, and 83% versus 82%, 93%, and 88%. By receiver operating characteristics (ROC) analysis, cFFR provided better diagnostic performance than resting indices regardless of contrast osmolality and volume (
P
<0.001 for all groups). There was no significant difference between the area under the curve of cFFR in the low- and iso-osmolality groups (0.938 versus 0.957;
P
=0.40) and in the low- and high-volume groups (0.939 versus 0.949;
P
=0.61). Multivariable logistic regression analysis showed that neither contrast osmolality nor volume affected the overall accuracy of cFFR; however, both affected the sensitivity and specificity.

Conclusions—

The overall accuracy of cFFR is greater than instantaneous wave–free ratio and distal pressure/aortic pressure and not significantly affected by contrast volume and osmolality. However, contrast volume and osmolality do affect the sensitivity and specificity of cFFR.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02184117.
Thrombus Aspiration for ST-Segment–Elevation Myocardial Infarction in Modern Era
Authors: Ge Junhua , Schäfer Andreas , Ertl Georg , Nordbeck Peter
Published: October 2017

The role of manual thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) for acute ST-segment–elevation myocardial infarction has been a matter of intense research and debate now. Although recent randomized controlled clinical trials (notably TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia] and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) do not supply evidence supporting the routine use of TA in patients with ST-segment–elevation myocardial infarction, manual TA remains a therapeutic option for interventional cardiologists when treating patients with substantial thrombus burden during PPCI. It remains unknown whether patients might actually benefit from TA applied in a more selective manner depending on the thrombus burden during PPCI, instead of routine application. In this review, we summarize current knowledge on the instruments used in the TA procedure, positive as well as negative clinical effects of TA during PPCI, and analyze the potential reasons for observed effects, in an effort to help the clinical decision making by physicians for the use of TA in individual ST-segment–elevation myocardial infarction patients during PPCI.
Angiotensin II Receptor–Neprilysin Inhibitor Sacubitril/Valsartan Improves Endothelial Dysfunction in Spontaneously Hypertensive Rats
Authors: Seki Takunori , Goto Kenichi , Kansui Yasuo , Ohtsubo Toshio , Matsumura Kiyoshi , Kitazono Takanari
Published: October 2017

Background

We have previously demonstrated that antihypertensive treatment with renin‐angiotensin system inhibitors restores the impaired endothelium‐dependent hyperpolarization (
EDH
)–mediated responses in spontaneously hypertensive rats (
SHR
s). Herein, we investigated whether the angiotensin
II
receptor–neprilysin inhibitor sacubitril/valsartan (
LCZ
696) would improve reduced
EDH
‐mediated responses and whether
LCZ
696 would exert additional effects on endothelium‐dependent and endothelium‐independent vasorelaxation compared with an angiotensin
II
type 1 receptor blocker alone during hypertension.

Methods and Results

SHR
s were treated for 3 months with either
LCZ
696 or valsartan, from the age of 8 to 11 months. Age‐matched, untreated
SHR
s and Wistar‐Kyoto rats served as controls. Membrane potentials and contractile responses were recorded from the isolated superior mesenteric arteries. Acetylcholine‐induced,
EDH
‐mediated responses were impaired in untreated
SHR
s compared with Wistar‐Kyoto rats.
EDH
‐mediated responses were similarly improved in the
LCZ
696‐ and valsartan‐treated
SHR
s. No difference was observed in acetylcholine‐induced, nitric oxide‐mediated relaxations among the 4 groups. Endothelium‐independent relaxations in response to a nitric oxide donor, sodium nitroprusside, and those to levcromakalim, an
ATP
‐sensitive K
+
‐channel opener, were similar among the 4 groups; however, the sensitivities to levcromakalim were significantly higher in both
LCZ
696‐ and valsartan‐treated
SHR
s.

Conclusions

LCZ
696 appears to be as effective as valsartan in improving the impaired
EDH
‐mediated responses during hypertension.
LCZ
696 and valsartan exert similar beneficial effects on endothelium‐independent relaxation via enhanced sensitivity of the
ATP
‐sensitive K
+
channel. However, the dual blockade of renin‐angiotensin system and neutral endopeptidase with
LCZ
696 does not appear to provide additional benefit over valsartan alone on vasomotor function in mesenteric arteries of
SHR
s.
Validation of the Telephone Interview of Cognitive Status and Telephone Montreal Cognitive Assessment Against Detailed Cognitive Testing and Clinical Diagnosis of Mild Cognitive Impairment After Stroke
Authors: Zietemann Vera , Kopczak Anna , Müller Claudia , Wollenweber Frank Arne , Dichgans Martin
Published: October 2017

Background and Purpose—

Assessment of cognitive status poststroke is recommended by guidelines but follow-up can often not be done in person. The Telephone Interview of Cognitive Status (TICS) and the Telephone Montreal Cognitive Assessment (T-MoCA) are considered useful screening instruments. Yet, evidence to define optimal cut-offs for mild cognitive impairment (MCI) after stroke is limited.

Methods—

We studied 105 patients enrolled in the prospective DEDEMAS study (Determinants of Dementia After Stroke; NCT01334749). Follow-up visits at 6, 12, 36, and 60 months included comprehensive neuropsychological testing and the Clinical Dementia Rating scale, both of which served as reference standards. The original TICS and T-MoCA were obtained in 2 separate telephone interviews each separated from the personal visits by 1 week (1 before and 1 after the visit) with the order of interviews (TICS versus T-MoCA) alternating between subjects. Area under the receiver-operating characteristic curves was determined.

Results—

Ninety-six patients completed both the face-to-face visits and the 2 interviews. Area under the receiver-operating characteristic curves ranged between 0.76 and 0.83 for TICS and between 0.73 and 0.94 for T-MoCA depending on MCI definition. For multidomain MCI defined by multiple-tests definition derived from comprehensive neuropsychological testing optimal sensitivities and specificities were achieved at cut-offs <36 (TICS) and <18 (T-MoCA). Validity was lower using single-test definition, and cut-offs were higher compared with multiple-test definitions. Using Clinical Dementia Rating as the reference, optimal cut-offs for MCI were <36 (TICS) and approximately 19 (T-MoCA).

Conclusions—

Both the TICS and T-MoCA are valid screening tools poststroke, particularly for multidomain MCI using multiple-test definition.
Remote Ischemic Conditioning May Improve Outcomes of Patients With Cerebral Small-Vessel Disease
Authors: Wang Yuan , Meng Ran , Song Haiqing , Liu Gang , Hua Yang , Cui Dehua , Zheng Lemin , Feng Wuwei , Liebeskind David S. , Fisher Marc , Ji Xunming
Published: October 2017

Background and Purpose—

We aimed to evaluate the efficacy of remote ischemic conditioning (RIC) in patients with cerebral small-vessel disease.

Methods—

Thirty patients with cerebral small-vessel disease–related mild cognitive impairment were enrolled in this prospective, randomized controlled study for 1 year. Besides routine medical treatment, participants were randomized into the experimental group (n=14) undergoing 5 cycles consisting of ischemia followed by reperfusion for 5 minutes on both upper limbs twice daily for 1 year or the control group (n=16) who were treated with sham ischemia–reperfusion cycles. The primary outcome was the change of brain lesions, and secondary outcomes were changes of cognitive function, plasma biomarkers, and cerebral hemodynamic parameters both at baseline and at the end of 1-year follow-up.

Results—

Compared with pretreatment, the post-treatment white matter hyperintensities volume in the RIC group was significantly reduced (9.10±7.42 versus 6.46±6.05 cm
3
;
P
=0.020), whereas no significant difference was observed in the sham-RIC group (8.99±6.81 versus 8.07±6.56 cm
3
;
P
=0.085). The reduction of white matter hyperintensities volume in the RIC group was more substantial than that in sham group (−2.632 versus −0.935 cm
3
;
P
=0.049). No significant difference was found in the change of the number of lacunes between 2 groups (0 versus 0;
P
=0.694). A significant treatment difference at 1 year on visuospatial and executive ability was found between the 2 groups (0.639 versus 0.191;
P
=0.048). RIC showed greater effects compared with sham-RIC on plasma triglyceride (−0.433 versus 0.236 mmol/L;
P
=0.005), total cholesterol (−0.975 versus 0.134 mmol/L;
P
<0.001), low-density lipoprotein (−0.645 versus −0.029 mmol/L;
P
=0.034), and homocysteine (−4.737 versus −1.679 µmol/L;
P
=0.044). Changes of the pulsation indices of middle cerebral arteries from the baseline to 1 year were different between the 2 groups (right: −0.075 versus 0.043;
P
=0.030; left: −0.085 versus 0.043;
P
=0.010).

Conclusions—

RIC seems to be potentially effective in patients with cerebral small-vessel disease in slowing cognition decline and reducing white matter hyperintensities.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01658306.
Justice and the City: A Reading of Amos 3:9-15
Authors: Ben-Dov Jonathan
Published: October 2017

The article strives to understand the urban prophecies in the Book of Amos with a view to spatial and literary concepts. Amos 3:9-15 is a collection of short prophecies, with v. 12 serving as its linchpin. The imagery of vv. 9-11 is part of an urban tradition in biblical literature, which underscores the importance of justice and peace for the maintenance of the city. Verses 12 and 15 constitute one prophecy about Samaria, which intensifies the tension between the city and its surroundings by contrasting items from the urban scenery with a gruesome picture of the lion in prey. Vv. 13-14 constitute a Bethel prophecy, introduced in between the Samaria prophecies. The city is poetically defined by the unification of its surroundings (the wall) with the edifices at its heart. Several cruxes in the interpretation of Amos 3:9-15 are elucidated throughout the discussion.
A Mother’s Refrain: Judges 5:28-30 in Cultural Context
Authors: Baker Robin
Published: October 2017

The Song of Deborah’s unusual language and style, and the potency of its imagery combine to make it one of the most analysed and debated texts in the Hebrew Bible. Although many aspects of the Song have remained opaque, there is scholarly consensus that it was composed in approximately the form we have it in the period of the Judges. This consensus is largely founded on linguistic analysis of the text. This article approaches the Song from a different direction. It considers the cultural markers found in Judges 5:28-30 and analyses what they reveal about the Sitz im Leben of these verses.
The Constitutional Right to Self-determination as a Response to the ‘Question of Nationalities’ in Ethiopia
Authors: Assefa Getachew
Published: October 2017

Characterising the crises of Ethiopian state-society relations in the 20th century as resulting from ethnic/national oppression, proponents of the ‘question of nationalities’ who have been in control of state power since 1991, have devised an ethnic-based federal system that bestows the right to secession on every ethno-national group in the country. This article argues that the diagnosis of the problems of 20th century Ethiopia as only resulting from national oppression is counterfactual. The problems that drove the Ethiopian state close to the brink of collapse during the final decade of the last century resulted from a host of factors, to which the controversial fact of ‘ethnic oppression’ contributed only a small and instrumental part. The article seeks to show that bad governance and the unbearable economic and social misery of the Ethiopian people as a whole were the most important reasons for the state crises that were experienced.
Punishment and Sovereignty in De Indis and De iure belli ac pacis
Authors: Hinshelwood Brad
Published: October 2017

Grotius’s theory of punishment provides a unique lens through which to view his evolving thought on sovereignty between De Indis and De iure belli ac pacis and the implications of that evolution for Grotius’s theory of the ius in bello. Throughout both works, Grotius attempted to leave open the possibility of private punishment and private warfare, a position not easily squared with prevailing views of sovereign authority. Initially, Grotius was content with a theory marrying the private right of punishment with more traditional Scholastic views of sovereignty through a transfer of the private right from individuals into the hands of the sovereign. This theory also adopted traditional views of subject responsibility for sovereign acts—and, by extension, the exposure of subjects to punishment for the acts of their sovereign. By the time of his mature work, however, Grotius turned away from natural law justifications for collective responsibility and collective punishment, denying that subjects had to answer for the acts of their sovereign as a necessary incident of the compact creating civil society. This led Grotius to refer virtually all forms of collective responsibility, such as reprisal or punishment exacted through war, to the law of nations. This sharp reduction of the natural consequences of the creation of sovereign power also enabled Grotius’s argument that the private right of war, and in particular the private right of punishment, remained available after the creation of civil society.
A new species of Eurypeza Lacroix, 2006 (Coleoptera: Scarabaeidae: Melolonthinae: Tanyproctini) from Kenya
Authors: SEHNAL RICHARD
Published: October 2017

The Afrotropical genus Eurypeza Lacroix, 2006 (Coleoptera: Scarabaeidae: Melolonthinae: Tanyproctini) was established for one species, Eurypeza evansi Lacroix, 2006, from Somalia. The genus belongs to the first group of Afrotropical Tanyproctini sensu Lacroix (2007), and is characterized by protarsomeres 1–4 and mesotarsomeres 1–4 broadened and ventrally macrosetaceous, protarsomere 5 and mesotarsomere 5 simple, and labrum transverse and shallowly bilobed. The genus Eurypeza differs from other genera of Lacroix’s (2007) first group by club with five antennomeres, antennomere 3 and 4 of equal length, labial palpi with three palpomeres, clypeus broadly rounded, protibia bidentate with proximal tooth well developed, and metatibial carina incomplete (for details, see also Lacroix 2006, 2007).
Variability of the Antarctic Slope Current System in the Northwestern Weddell Sea
Authors: Azaneu Marina , Heywood Karen J. , Queste Bastien Y. , Thompson Andrew F.
Published: October 2017

The dense water outflow from the Antarctic continental shelf is closely associated with the strength and position of the Antarctic Slope Front. This study explores the short-term and spatial variability of the Antarctic Slope Front system and the mechanisms that regulate cross-slope exchange using highly temporally and spatially resolved measurements from three ocean gliders deployed in 2012. The 22 sections along the eastern Antarctic Peninsula and west of the South Orkney Islands are grouped regionally and composited by isobaths. There is consistency in the front position around the Powell Basin, varying mostly between the 500- and 800-m isobaths. In most of the study area the flow is bottom intensified. The along-slope transport of the Antarctic Slope Current (upper 1000 m) varies between 0.2 and 5.9 Sv (1 Sv ≡ 106 m3 s−1) and does not exhibit a regional pattern. The magnitude of the velocity field shows substantial variability, up to twice its mean value. Higher eddy kinetic energy (0.003 m2 s−2) is observed in sections with dense water, possibly because of baroclinic instabilities in the bottom layer. Distributions of potential vorticity show an increase toward the shelf along isopycnals and also in the dense water layer. Glider sections located west of the South Orkney Islands indicate a northward direction of the flow associated with the Weddell Front, which differs from previous estimates of the mean circulation. This study provides some of the first observational confirmation of the high-frequency variability associated with an active eddy field that has been suggested by recent numerical simulations in this region.
Tropical Cyclone Genesis Guidance Using the Early Stage Dvorak Analysis and Global Ensembles
Authors: Yamaguchi Munehiko , Koide Naohisa
Published: October 2017

TC genesis guidance using the early stage Dvorak analysis technique (EDA) and global ensembles is investigated as one of the statistical–dynamical TC genesis guidance schemes. The EDA is a scheme that enables the analysis of tropical disturbances at earlier stages by adding T numbers of 0.0 and 0.5 to the conventional Dvorak technique. This unique analysis method has been in operation at JMA since 2001. The global ensembles used in this study are the ECMWF, JMA, NCEP, and UKMO ensembles covering from 2010 to 2013. First, probabilities that tropical disturbances analyzed with the EDA reach tropical storm intensity within a certain lead time up to 5 days are statistically investigated. For example, the probabilities that a tropical disturbance analyzed with T numbers of 0.0, 0.5, and 1.0 reaches tropical storm intensity within 2 days are 15%, 23%, and 57%, respectively. While the false alarm ratio (FAR) is found to decrease if the global ensembles simulate the tropical disturbance analyzed with the EDA in the models, it tends to decrease with the increasing number of such ensemble members. Also, it should be noted that the probability of detection (POD) decreases with the increasing number of such ensemble members. One of the potential uses of these verification results is that forecasters could issue TC genesis forecasts by counting ensemble members that successfully simulate a targeted tropical disturbance and then refer to the FAR and POD corresponding to the number of the ensemble members. These would provide some confidence information of the forecasts.
Public Health Detailing to Increase Routine HIV Screening in Baltimore, Maryland: Satisfaction, Feasibility, and Effectiveness
Authors: Safi Amelia Greiner , Perin Jamie , Mantsios Andrea , Schumacher Christina , Chaulk C. Patrick , Jennings Jacky M.
Published: October 2017

The objective of this study was to evaluate the satisfaction with, and the feasibility and effectiveness of, a public health detailing project focused on increasing routine human immunodeficiency virus (HIV) screening of people aged 13-64 by primary care providers working in areas of Baltimore City, Maryland, with high rates of HIV transmission (defined as a mean geometric viral load of ≥1500 copies/mL per census tract). In public health detailing, trained public health professionals (ie, detailers) visit medical practice sites to meet with providers and site staff members, with the intention of influencing changes in clinical practice policy and/or behavior. During 2014, detailers made personal visits and gave HIV Testing Action Kits containing maps, educational and guideline documents, and resource lists to 166 providers and office managers at 85 primary care sites. At follow-up, 88 of 91 (96.7%) providers and 37 of 38 (97.4%) clinic managers were very satisfied or satisfied with the project. Of the 79 sites eligible at follow-up (ie, those that had not closed or merged with another practice), 76 (96.2%) had accepted at least 1 HIV Testing Action Kit, and 67 of 90 (74.4%) providers had increased their HIV screening. Public health detailing projects can be used to educate and support providers, establish relationships between providers and local health departments, and disseminate public health messages.
Supratentorial lesions contribute to trigeminal neuralgia in multiple sclerosis
Authors: Fröhlich Kilian , Winder Klemens , Linker Ralf A , Engelhorn Tobias , Dörfler Arnd , Lee De-Hyung , Hilz Max J , Schwab Stefan , Seifert Frank
Published: October 2017

Background

It has been proposed that multiple sclerosis lesions afflicting the pontine trigeminal afferents contribute to trigeminal neuralgia in multiple sclerosis. So far, there are no imaging studies that have evaluated interactions between supratentorial lesions and trigeminal neuralgia in multiple sclerosis patients.

Methods

We conducted a retrospective study and sought multiple sclerosis patients with trigeminal neuralgia and controls in a local database. Multiple sclerosis lesions were manually outlined and transformed into stereotaxic space. We determined the lesion overlap and performed a voxel-wise subtraction analysis. Secondly, we conducted a voxel-wise non-parametric analysis using the Liebermeister test.

Results

From 12,210 multiple sclerosis patient records screened, we identified 41 patients with trigeminal neuralgia. The voxel-wise subtraction analysis yielded associations between trigeminal neuralgia and multiple sclerosis lesions in the pontine trigeminal afferents, as well as larger supratentorial lesion clusters in the contralateral insula and hippocampus. The non-parametric statistical analysis using the Liebermeister test yielded similar areas to be associated with multiple sclerosis-related trigeminal neuralgia.

Conclusions

Our study confirms previous data on associations between multiple sclerosis-related trigeminal neuralgia and pontine lesions, and showed for the first time an association with lesions in the insular region, a region involved in pain processing and endogenous pain modulation.
Experimental and numerical investigations on rotor–stator rub
Authors: Praveen Krishna I R , Padmanabhan C
Published: October 2017

The focus of the current study is on the dynamics of rubbing between the rotor and stator parts in a rotating machine. Rub is a malfunction associated with the physical contact of rotating and stationary parts, which are otherwise not in contact. Because of the nonlinear nature of the problem the simulation time is significant even for small size systems. The rubbing is localized in space, either at the seal locations or at the interface between the rotor blade and stator. Since the nonlinearity is localized, reduced models can be developed for efficient computation. The objective of the present study is to develop a computationally efficient methodology for analyzing the rotor stator rub, by applying model reduction techniques using component mode synthesis, solving the reduced problem using harmonic balance method and time variational method. A hypersphere-based continuation algorithm is used for tracing the unstable branches and a backward differentiation formula based predictor is used for the Newton–Raphson update. The numerical results are validated by performing experiments.
Synergistic real-time compensation of tracking and contouring errors for precise parametric curved contour following systems
Authors: Song De-Ning , Ma Jian-Wei , Jia Zhen-Yuan , Qin Feng-Ze , Zhao Xiao-Xuan
Published: October 2017

The tracking and contouring errors are inevitable in real computer numerical control contour following because of the reasons such as servo delay and dynamics mismatch. In order to improve the motion accuracy, this paper proposes a synergistic real-time compensation method of tracking and contouring errors for precise parametric curve following of the computer numerical control systems. The tracking error for each individual axis is first compensated, by using the feed-drive models with the consideration of model uncertainties, to enhance the tracking performances of all axes. Further, the contouring error is estimated and compensated to improve the contour accuracy directly, where a high-precision contouring-error estimation algorithm, based on spatial circular approximation of the desired contour neighboring the actual motion position, is presented. Considering that the system structure is coupled after compensation, the stability of the coupled system is analyzed for design of the synergistic compensator. Innovative contributions of this study are that not only the contouring-error can be estimated with a high precision in real time, but also the tracking and contouring performances can be simultaneously improved although there exist modeling errors and disturbances. Simulation and experimental tests demonstrate the effectiveness and advantages of the proposed method.
Iron-based reversible adhesives: Effect of particles size on mechanical properties
Authors: Ciardiello R , Martorana B , Lambertini VG , Brunella V
Published: October 2017

A hot melt adhesive – mainly used for bonding plastic component in automotive field – was modified with different iron-based particles to give it a reversible behaviour. Mechanical and physical properties of these reversible adhesives were experimentally assessed in the work. The modified adhesives, coupled with electromagnetic induction, are able to guarantee separation of the joints without any damage to the substrates for recycling, reuse or repairing of components. Single lap joint specimens were prepared using epoxy/glass fibres substrates and tests were carried out on neat and modified adhesive with 5% weight of iron and iron oxide. Three different Fe particles size were tested: 450 µm, 60 µm and 1–6 µm. The particles size of iron oxide was 50 nm. Separation was studied using single lap joint specimens under electro-magnetic induction. Experimental results showed that the maximum peak load decreases when the average particles sizes increase. The peak loads of the smallest particles were equal to the ones of the pristine adhesive. The elongation of the adhesives increases when the adhesive is modified with both iron and iron oxide particles. Finally, experimental tests on single lap joints coupled with electro-magnetic induction showed that separation of the substrates is possible using iron oxide particles. Electro-magnetic tests conducted on particles alone, helped to understand that bigger particles are able to overcome the melting temperature of the adhesive but hot-melt adhesives modified with these particles are not able to reach the melting. These tests showed that the number of particles into the adhesive matrix is very important for this kind of tests.
When Is Participation in Research a Moral Duty?
Authors: Rhodes Rosamond
Published: October 2017

In this paper I argue for recognizing the moral duty to participate in research. I base my argument on the need for biomedical research and the fact that at some point studies require human participants, what I call collaborative necessity. In presenting my position, I argue against the widely accepted views of Han Jonas and all of those who have accepted his declarations without challenge. I go on to show why it is both just and fair to invite and encourage people to participate in studies. It is just because research participation is the necessary means to achieve the broadly shared goals of preventing and curing disease and alleviating disease symptoms. Mutual love requires us to be willing to do for others what we would want them to do for us. It is fair because the approach treats similarly situated people in the same way. Research participation is morally required because failing to do one's part in the collaborative project of advancing biomedical science would be free-riding. People who exempt themselves from participation while eagerly accepting benefits from others doing their part are taking advantage of their compatriots and treating themselves as more deserving than others when they are not.
The Moral Case for Granting Catastrophically Ill Patients the Right to Access Unregistered Medical Interventions
Authors: Schuklenk Udo , Smalling Ricardo
Published: October 2017

Using the case of Ebola Virus Disease as an example, this paper shows why patients at high risk for death have a defensible moral claim to access unregistered medical interventions (UMI), without having to enrol in randomized placebo controlled trials.

A number of jurisdictions permit and facilitate such access under emergency circumstances. One controversial question is whether patients should only be permitted access to UMI after trials investigating the interventions are fully recruited. It is argued that regulatory regimes should not prioritise trial recruitment over patient access, even if this results in drug research and development delays.

We describe how the moral duty to rescue impacts on others' duties to oblige patients seeking emergency access to unregistered medical interventions. The view that eligible patients are owed the provision of access to UMI regardless of their willingness to enrol in a randomised controlled trial (RCT) is defended.
The Medical Surrogate as Fiduciary Agent
Authors: Howard Dana
Published: October 2017

Within bioethics, two prevailing approaches structure how we think about the role of medical surrogates and the decisions that they must make on behalf of incompetent patients. One approach views the surrogate primarily as the patient's agent, obediently enacting the patient's predetermined will. The second approach views the surrogate as the patient's custodian, judging for herself how to best safeguard the patient's interests. This paper argues that both of these approaches idealize away some of the ethically relevant features of advance care planning that make patient preferences so inscrutable and surrogate decision-making so burdensome. It proposes a new approach to surrogate decision-making, the Fiduciary Agency Approach. On this novel approach, the surrogate has authority to not only act on the patient's behalf as the patient's agent but also to decide on the patient's behalf as the patient's fiduciary. One upshot of this new approach is that surrogates must sometimes go against the expressed dictates of the patients' advance directives not necessarily because doing so would be in the patient's best interest but rather because doing so would best represent the patients' will.
The Flapwise Bending Free Vibration Analysis of Micro-rotating Timoshenko Beams Using the Differential Transform Method
Authors: Arvin Hadi
Published: October 2017

The flapwise bending free vibration analysis of isotropic rotating Timoshenko microbeams, including the size effects, is presented in this paper. A nonclassical theory, i.e. the Modified Couple Stress theory, has been employed to include the size effect in the presented formulation. By consideration of the Timoshenko beam assumptions the shear deformation and the rotary inertia effects are taken into account. The Hamilton’s principle is applied to the obtained strain and kinetic energy relations to derive the nonlinear equations of motion and the associated boundary conditions. After nondimensionalization of the equations of motion and the corresponding boundary conditions, the linearized form of the equations of motion and the accompanied boundary conditions are developed. A semi-analytical approach, i.e. the differential transform method, is implemented to achieve the flapping and axial frequencies. The achieved results are validated via comparison with the available results in the literature. The material length scale, shear deformation consideration, rotating speed and the slenderness ratio influences on the natural frequencies are examined. The results demonstrate that the slenderness ratio and the thickness to the material length scale parameter quotient are the dominant indicators in determining the usage of the nonclassical theories against classical theories. On the other hand, the precision in determination of the higher modes frequencies motivates us to implement the Timoshenko beam model instead of the Euler–Bernoulli beam model.
Effect of home telehealth care on blood pressure control: A public healthcare centre model
Authors: Lu Ju-Fen , Chen Ching-Min , Hsu Chien-Yeh
Published: October 2017

Objective

This study aimed to evaluate the effectiveness of home telehealth care combined with case management by public health nurses, in improving blood pressure control in patients with hypertension.

Methods

This cohort study examined the data of patients with hypertension obtained from a telehealth service centre database, between July 2011– June 2012. Eligible patients were adults (≥40 years old) with both prehypertension and hypertension, living alone or in the remote suburbs of metropolitan areas. Demographic data were collected from 12 district public health centre in Taipei, Taiwan. Following enrolment, patients received an appropriate and validated home telehealth device kit for automatic blood pressure monitoring and automated modem via a telephone line or a desktop computer with Internet connection to enable data transmission between the patient’s home and telehealth service centre. Patients were instructed to upload the measured data immediately every day. The study outcomes included blood pressure and home telehealth service utilisation.

Results

Of the 432 patients recruited, 408 (94%) completed data collection. Linear regression analysis found an average 22.1 mm Hg reduction in systolic blood pressure after one year. The mean slope of systolic blood pressure was classified as decreased or non-decreased. An systolic blood pressure decreasing trend was observed in 52.2% patients, while 47.8% patients showed an increasing systolic blood pressure trend. Patients in the decreased systolic blood pressure group tended to be older ( p = 0. 0001), with a greater proportion of hypertension alarms ( p = 0. 001), improved self-blood pressure monitoring behaviour ( p = 0.009) and higher self-measured blood pressure monitoring frequency ( p = 0. 010). Patients in the decreased systolic blood pressure group had a higher self-measured blood pressure monitoring frequency (odds ratio = 0.95, 95% confidence interval, 0.91–0.99, p = 0. 013) than their counterparts.

Conclusions

Home telehealth care combined with care management by public health nurses based in public health care centre was feasible and effective for improving blood pressure control among patients with hypertension. Further studies should conduct a thorough analysis of the cost-effectiveness of this intervention. A randomised controlled trial with a longer follow-up period is required to examine the effects of the improved home telehealth device kit on the care of patients with hypertension.
Caught between ideal and reality: A study on occupational burnout among inside-system legal professionals under the rule-of-law reform in contemporary China
Authors: Bi Xiangyang
Published: October 2017

This paper analyzes job burnout of inside-system legal professionals under the rule-of-law reform in China and its possible causes. Social cognitive theory, including cognitive dissonance, expectancy theory, and social comparison theory, provides the analytic framework for this study. The conclusion reveals a relatively high level of job burnout among inside-system legal professionals in China. Further analysis indicates that the individual’s commitment to the rule of law, confidence in the legal reform, and practice of non-rule-of-law in daily work are influential factors affecting his/her job burnout levels. Importantly, the interaction coefficients between these variables are statistically significant, clearly demonstrating that the discrepancy between expectation and reality is one of the root causes of job burnout in the legal profession. The discrepancy causes cognitive dissonance and psychological imbalance. At a theoretical level, this finding opens a new way of examining a particular type of occupational burnout. It shows that under the rule-of-law reform, Chinese inside-system legal professionals exhibit cognitive dissonance between ideals and reality, which constitutes a micro-political psychological basis for organizational change as speculated by neo-institutionalists and, in turn, reveals insights that may help us to understand the legal reform process within the bureaucratic system.
Taking Assent to New Heights: A Case Report on Do-Not-Resuscitate Status in Pediatric Palliative Care Procedures
Authors: Ballard Heather A. , Suresh Santhanam
Published: October 2017

Dying adolescents presenting for palliative procedures have complicated developmental and ethical issues, especially when reconsidering do-not-resuscitate orders. Though the American Academy of Pediatrics has guidelines, there is limited information in the literature on how to take care of these patients. We describe the case of a 14-year-old patient presenting to the interventional radiology suite for management of superior vena cava syndrome. The patient’s goals of treatment were elucidated through a comprehensive care team consisting of the procedural and oncology teams. Effective communication with the patient and family was paramount for success.