bluuebunny/crossref_metadata_2025 huggingface dataset:
Aristolochic Acid‐Induced Autophagy Promotes Epithelial‐to‐Myofibroblast Transition in Human Renal Proximal Tubule Epithelial Cells
Authors: Man Yu-Lin , Rui Hong-Liang , Chen Yi-Pu , Wang Guo-qin , Sun Li-Jun , Cheng Hong
Published: October 2017

Autophagy plays an essential role in cellular homeostasis in kidney. Previous studies have found that aristolochic acid (AA) can induce autophagy of renal tubular epithelial cells and epithelial‐to‐myofibroblast transition (EMT). However, the relationship between AA‐induced autophagy and EMT is unclear. Our results showed that, after AA stimulation, the appearance of autophagy preceded EMT. Autophagy of HKC cells began to increase gradually from the 3rd hour, reached the peak at 12th hour, and then weakened gradually until 36th hour; the EMT process of HKC continued to increase from 6th hour to 36th hour after AA stimulation. The enhancement of autophagy using autophagy inducers, rapamycin or serum‐free medium, led to an aggravation of EMT and upregulated expression of fibronectin, a component of extracellular matrix, in AA‐treated HKC cells. In contrast, the inhibition of autophagy by autophagy inhibitor, 3‐methyladenine, or by knockdown of Beclin 1 led to an attenuation of EMT and downregulated expression of fibronectin in AA‐treated HKC cells. Taken together, our study suggests that, after AA stimulation, two types of cell responses of HKC cells, autophagy and EMT, will successively appear, and autophagy can promote EMT of HKC.
The Modulatory Effect of Acupuncture on the Activity of Locus Coeruleus Neuronal Cells: A Review
Authors: Lee Gihyun , Kim Woojin
Published: October 2017

The Locus Coeruleus (LC) is a small collection of noradrenergic neurons located in the pons. In the brain, noradrenaline (NE) is primarily produced by noradrenergic cell groups in the LC, which is the largest group of noradrenergic neurons in the central nervous system. Acupuncture, including the electroacupuncture which is a modified acupuncture method, is known to be effective in various kinds of diseases, and the involvement of noradrenergic system in the central nervous system has been reported by previous studies. However, on whether acupuncture can modulate the LC neuronal cells activities, results vary from studies to studies. In this paper, we included twelve articles, which observed the effect of acupuncture on the activities of LC in humans and animals. Our study shows that, among twelve included studies, six reported decrease of LC activities, whereas six showed increase of LC activities after acupuncture treatment. Although it is difficult to draw a firm conclusion, the authors suggest that the difference of frequencies may play an important role in the modulatory effect of acupuncture on LC. Further studies are needed to clarify the precise mechanism of acupuncture on LC, as it can lead to a new therapeutic method for various LC‐NE related diseases.
Restoration of Natural Killer Cell Antimetastatic Activity by IL12 and Checkpoint Blockade
Authors: Ohs Isabel , Ducimetière Laura , Marinho Joana , Kulig Paulina , Becher Burkhard , Tugues Sonia
Published: October 2017

Immune checkpoint therapies target tumor antigen-specific T cells, but less is known about their effects on natural killer (NK) cells, which help control metastasis. In studying the development of lung metastases, we found that NK cells lose their cytotoxic capacity and acquire a molecular signature defined by the expression of coinhibitory receptors. In an effort to overcome this suppressive mechanism, we evaluated NK cell responses to the immunostimulatory cytokine IL12. Exposure to IL12 rescued the cytotoxicity of NK cells but also led to the emergence of an immature NK cell population that expressed high levels of the coinhibitory molecules PD-1, Lag-3, and TIGIT, thereby limiting NK cell–mediated control of pulmonary metastases. Notably, checkpoint blockade therapy synergized with IL12 to fully enable tumor control by NK cells, demonstrating that checkpoint blockers are not only applicable to enhance T cell–mediated immunotherapy, but also to restore the tumor-suppressive capacity of NK cells. Cancer Res; 77(24); 7059–71. ©2017 AACR.
SOCS1 Gene Therapy Improves Radiosensitivity and Enhances Irradiation-Induced DNA Damage in Esophageal Squamous Cell Carcinoma
Authors: Sugase Takahito , Takahashi Tsuyoshi , Serada Satoshi , Fujimoto Minoru , Hiramatsu Kosuke , Ohkawara Tomoharu , Tanaka Koji , Miyazaki Yasuhiro , Makino Tomoki , Kurokawa Yukinori , Yamasaki Makoto , Nakajima Kiyokazu , Kishimoto Tadamitsu , Mori Masaki , Doki Yuichiro , Naka Tetsuji
Published: October 2017

STAT3 has been implicated recently in radioresistance in cancer. In this study, we investigated the association between STAT3 and radioresistance in esophageal squamous cell carcinoma (ESCC). Strong expression of activated phospho-STAT3 (p-STAT3) was observed in 16/22 ESCC patients with preoperative chemoradiotherapy (CRT), compared with 9 of 24 patients with surgery alone, where the prognosis of those with CRT was poor. Expression of p-STAT3 and the antiapoptotic proteins Mcl-1 and survivin was strongly induced in ESCC cells by irradiation. Ectopic STAT3 expression increased radioresistance, whereas expression of the STAT3 negative regulator SOCS1 via an adenoviral vector improved radioresponse. Inhibiting the STAT3–Mcl-1 axis by SOCS1 enhanced DNA damage after irradition and induced apoptosis. Combining SOCS1 with radiotherapy enhanced antitumor responses in a murine xenograft model compared with the individual therapies. Tumor repopulation occurred transiently after treatment by irradiation but not the combination SOCS1/radiotherapy. Tumors subjected to this combination expressed high levels of γH2AX and low levels of Ki-67, which was maintained after cessation of treatment. Overall, we demonstrated that inhibiting the STAT3–Mcl-1 signaling axis by ectopic SOCS1 improved radiosensitivity by inducing apoptosis and enhancing DNA damage after radiotherapy, offering a mechanistic rationale for a new ESCC treatment. Cancer Res; 77(24); 6975–86. ©2017 AACR.
Aortic-Brachial Pulse Wave Velocity Ratio: A Measure of Arterial Stiffness Gradient Not Affected by Mean Arterial Pressure
Authors: Fortier Catherine , Desjardins Marie-Pier , Agharazii Mohsen
Published: October 2017

Background: Aortic stiffness, measured by carotid-femoral pulse wave velocity (cf-PWV), is used for the prediction of cardiovascular risk. This mini-review describes the nonlinear relationship between cf-PWV and operational blood pressure, presents the proposed methods to adjust for this relationship, and discusses a potential place for aortic-brachial PWV ratio (a measure of arterial stiffness gradient) as a blood pressure-independent measure of vascular aging. Summary: PWV is inherently dependent on the operational blood pressure. In cross-sectional studies, PWV adjustment for mean arterial pressure (MAP) is preferred, but still remains a nonoptimal approach, as the relationship between PWV and blood pressure is nonlinear and varies considerably among individuals due to heterogeneity in genetic background, vascular tone, and vascular remodeling. Extrapolations from the blood pressure-independent stiffness parameter β (β0) have led to the creation of stiffness index β, which can be used for local stiffness. A similar approach has been used for cardio-ankle PWV to generate a blood pressure-independent cardio-ankle vascular index (CAVI). It was recently demonstrated that stiffness index β and CAVI remain slightly blood pressure-dependent, and a more appropriate formula has been proposed to make the proper adjustments. On the other hand, the negative impact of aortic stiffness on clinical outcomes is thought to be mediated through attenuation or reversal of the arterial stiffness gradient, which can also be influenced by a reduction in peripheral medium-sized muscular arteries in conditions that predispose to accelerate vascular aging. Arterial stiffness gradient, assessed by aortic-brachial PWV ratio, is emerging to be at least as good as cf-PWV for risk prediction, but has the advantage of not being affected by operating MAP. Key Messages: The negative impacts of aortic stiffness on clinical outcomes are proposed to be mediated through attenuation or reversal of arterial stiffness gradient. Aortic-brachial PWV ratio, a measure of arterial stiffness gradient, is independent of MAP.
Prediction of the Future Need for Institutional Care in Finnish Older People: A Comparison of Two Birth Cohorts
Authors: Salminen Marika , Eloranta Sini , Vire Jenni , Viikari Paula , Viikari Laura , Vahlberg Tero , Lehtonen Aapo , Arve Seija , Wuorela Maarit , Viitanen Matti
Published: October 2017

Background: More recent birth cohorts of older people have better physical and cognitive status than earlier cohorts. As such, this could be expected to diminish the need for institutional care. The prediction of the future need for institutional care provides essential information for the planning and delivery of future care and social services as well as the resources needed. Objective: To predict the future need for institutional care among older Finnish people born in 1940. Methods: Representative samples of home-dwelling 70-year-olds from Turku, Finland were examined with similar methods in 1991 (those born in 1920) (n = 1,032) and in 2011 (those born in 1940) (n = 956). Predictors of institutionalization rates from the earlier 1920 cohort, together with data of sociodemographic factors, health, psychosocial and physical status, the need for help, and health behavior, were used to predict the future institutionalization rate among the 1940 cohort in this study using Cox regression models. Results: Health as well as psychosocial and physical status were significantly better in the 1940 cohort compared to the earlier cohort. In the 1940 cohort, the predicted rates of institutionalization were 1.8, 10.4, and 26.0% at the ages of 80 (year 2020), 85 (year 2025), and 90 years (year 2030), respectively. At every age (80, 85, and 90 years), the predicted rates of institutionalization by Mini-Mental State Examination (MMSE) were about two-fold among those with MMSE scores 18-26 (3.0-38.8%) compared to those with scores 27-30 (1.6-23.7%) and those with a body mass index (BMI) <25 (2.5-34.3%) compared to those with a BMI of 25-29.9 (1.4-20.9%), and about three-fold among participants with several falls (5.3-57.0%) compared to participants with no falls (1.5-23.1%). Conclusions: The 1940 cohort performed better in health as well as psychosocial and physical status than the 1920 cohort. Nevertheless, the predicted rates of future need for institutional care were high, especially at the ages of 85 and 90 years, among those with a lowered cognitive or physical status.
Retreatment of Exudative Age-Related Macular Degeneration after Loading 3-Monthly Intravitreal Ranibizumab
Authors: Sugiyama Atsushi , Sakurada Yoichi , Honda Shigeru , Miki Akiko , Matsumiya Wataru , Yoneyama Seigo , Kikushima Wataru , Iijima Hiroyuki
Published: October 2017

Purpose: The aim of this study was to investigate the clinical implications of required retreatment after 3-monthly intravitreal ranibizumab (IVR) injections followed by as-needed reinjections up to 5 years in eyes with exudative age-related macular degeneration (AMD). Methods: A retrospective cohort study was conducted for 165 treatment-naïve eyes from 165 patients with exudative AMD. Visual changes were investigated in terms of the required retreatments. Results: Retreatment-free proportions were 37.0, 23.7, 16.6, 12.1, and 10.5% at 12, 24, 36, 48, and 60 months, respectively. Visual changes were significantly better in eyes which did not require retreatment at every yearly checkpoint within the 5 years. A multivariate logistic regression analysis revealed that requirement of additional IVR treatments in the first 12-24 months was associated with the T allele (risk allele) of ARMS2 A69S (p = 0.010 and 0.015, respectively). Cox regression analysis revealed that older age (p = 0.046) and the T allele of ARMS2 A69S (p = 0.036) were associated with required retreatment within the 5-year follow-up period. Conclusions: Age and the T allele of ARMS2 A69S are the risk factors requiring retreatments, leading to poor visual change in eyes with exudative AMD following the initial 3-monthly IVR.
Effectiveness of a Home-Based Active Video Game Programme in Young Cystic Fibrosis Patients
Authors: del Corral Tamara , Cebrià i Iranzo Maria Àngels , López-de-Uralde-Villanueva Ibai , Martínez-Alejos Roberto , Blanco Isabel , Vilaró Jordi
Published: October 2017

Background: Exercise-based rehabilitation is already a part of cystic fibrosis (CF) treatment; however, patient adherence is low. Objectives: To assess the effectiveness of a home exercise programme using active video games (AVGs) as a training modality for children and adolescents with CF. Methods: Thirty-nine children with CF were randomised to a control group (CG, n = 20, age 11 ± 6 years; FEV1 86.2 ± 20.5% of predicted) or a training group (AVGG, n = 19, age 13 ± 3 years; FEV1 82.7 ± 21.7% of predicted). The home training protocol consisted of 30- to 60-min sessions, 5 days/week, for 6 weeks using a Nintendo Wii™ platform. Exercise capacity was measured by the 6-min walk test (6MWT) and modified shuttle walk test (MSWT); muscular strength was estimated using the horizontal jump test (HJT), medicine ball throw (MBT), and hand grip strength (right [RHG]; left [LHG]); and quality of life was rated using the Cystic Fibrosis Questionnaire-Revised (CFQ-R). All the children were measured at baseline, after rehabilitation, and at 12 months. Results: For the group × time interaction ANOVAs, the AVGG showed significant between-group differences in exercise capacity: 6MWT farthest walking distance, 38.4 m (p < 0.01); MSWT farthest walking distance, 78.4 m (p < 0.05); and muscular strength: HJT 9.8 cm, MBT 30.8 cm, RHG 7 kg, and LHG 6.5 kg (p < 0.01), before versus after intervention. The CFQ-R reported significantly higher scores on respiratory symptoms after the intervention and favoured the AVGG, and there was an improvement in other domains after 12 months. Adherence to the home exercise programme was 95% during the 6- week intervention period. Conclusion: A home-based programme using AVGs can effectively improve exercise capacity, muscular strength and quality of life in the short-term in children and adolescents with CF. The effects of training on muscle performance and quality of life were sustained over 12 months.
Hepatocellular Carcinoma with Macrovascular Invasion: Defining the Optimal Treatment Strategy
Authors: Costentin Charlotte E. , Ferrone Cristina R. , Arellano Ronald S. , Ganguli Suvranu , Hong Theodore S. , Zhu Andrew X.
Published: October 2017

Background: Tumoral macrovascular invasion (MVI) of hepatic and/or portal vein branches is a common phenomenon in hepatocellular carcinoma (HCC) and is associated with poorer prognosis when compared to HCC without MVI. Summary: Current international guidelines for the management of HCC recommend sorafenib as the only treatment option in case of MVI. Despite guideline recommendations, several alternative options have been tested to manage HCC with MVI: surgery, transarterial chemoembolization, external or internal radiation, hepatic arterial infusion chemotherapy, percutaneous treatment, cryotherapy, or the combination of two or more of these strategies, with or without sorafenib. Here we will provide a comprehensive state-of-the-art review for the management of this challenging clinical entity based on the most recent available data. Key Messages: There is a growing body of evidence suggesting that alternative strategies to standard-of-care sorafenib might improve survival in patients with advanced HCC with MVI but the level of evidence remains weak. Randomized phase III trials are ongoing and will hopefully provide information leading towards a more personalized treatment algorithm.
Reference Ranges for Fetal Atrioventricular and Ventriculoatrial Time Intervals and Their Ratios during Normal Pregnancy
Authors: Mosimann Beatrice , Arampatzis Georgios , Amylidi-Mohr Sofia , Bessire Anice , Spinelli Marialuigia , Koumoutsakos Petros , Surbek Daniel , Raio Luigi
Published: October 2017

Background: The diagnostic assessment of fetal arrhythmias relies on the measurements of atrioventricular (AV) and ventriculoatrial (VA) time intervals. Pulsed Doppler over in- and outflow of the left ventricle and tissue Doppler imaging are well-described methods, while Doppler measurements between the left brachiocephalic vein and the aortic arch are less investigated. The aim of this study was to compare these methods of measurement, to find influencing factors on AV and VA times and their ratio, and to create reference ranges. Methods: Echocardiography was performed between 16 and 40 weeks of gestation in normal singleton pregnancies. Nomograms for the individual measurements were created using quantile regression with Matlab Data Analytics. Statistical analyses were performed with GraphPad version 5.0 for Windows. Results: A total of 329 pregnant women were enrolled. A significant correlation exists between AV and VA times and gestational age (GA) (p = 0.0104 to <0.0001, σ = 0.1412 to 0.3632). No correlation was found between the AV:VA ratio and GA (p = 0.08 to 0.60). All measurements differed significantly amongst the studied methods (p < 0.0001). Conclusions: AV and VA intervals increase proportionally with GA; no other independent influencing factors could be identified. As significant differences exist between the three methods of assessment, it is crucial to use appropriate reference ranges to diagnose pathologies.
Impact of Gastric Cancer Surgery in Elderly Patients
Authors: Wakahara Tomoyuki , Ueno Nozomi , Maeda Tetsuo , Kanemitsu Kiyonori , Yoshikawa Takuro , Tsuchida Shinobu , Toyokawa Akihiro
Published: October 2017

Objectives: This study aimed to investigate the validity of gastric cancer surgery in elderly patients. Methods: A total of 544 patients who underwent elective gastrectomy for gastric cancer were divided into an elderly group (age ≥75 years, n = 171) and a control group (age <75 years, n = 373). The clinicopathological data of the patients were reviewed. Results: The overall morbidity rate (26.3 vs. 16.1%, p = 0.005) and the incidence rate of anastomotic leakage (6.4 vs. 1.6%, p = 0.003) were significantly higher in the elderly group. The proportion of patients who had severe complications (≥grade IIIa) was relatively higher in the elderly group (10.5 vs. 5.7%); however, the difference was not significant (p = 0.074). A stage-matched survival analysis revealed no significant differences between the groups (stage I: p = 0.978; stage II: p = 0.964; stage III: p = 0.199). For the pathological stages II and III, the overall survival of the patients in the elderly group who received adjuvant chemotherapy for >3 months was significantly better than that of the patients who received it for ≤3 months or did not receive it (p = 0.023). Conclusions: An aggressive treatment strategy should be adopted in selected elderly patients with gastric cancer.
Genetic Depletion or Hyperresponsiveness of Natural Killer Cells Do Not Affect Atherosclerosis Development
Authors: Nour-Eldine Wared , Joffre Jérémie , Zibara Kazem , Esposito Bruno , Giraud Andréas , Zeboudj Lynda , Vilar José , Terada Megumi , Bruneval Patrick , Vivier Eric , Ait-Oufella Hafid , Mallat Ziad , Ugolini Sophie , Tedgui Alain
Published: October 2017

Rationale:

Chronic inflammation is central in the development of atherosclerosis. Both innate and adaptive immunities are involved. Although several studies have evaluated the functions of natural killer (NK) cells in experimental animal models of atherosclerosis, it is not yet clear whether NK cells behave as protective or proatherogenic effectors. One of the main caveats of previous studies was the lack of specificity in targeting loss or gain of function of NK cells.

Objectives:

We used 2 selective genetic approaches to investigate the role of NK cells in atherosclerosis: (1)
Ncr1

iCre/+

R26

lsl−

DTA/+

mice in which NK cells were depleted and (2)
Noé
mice in which NK cells are hyperresponsive.

Methods and Results:

No difference in atherosclerotic lesion size was found in
Ldlr
−/−
(low-density lipoprotein receptor null) mice transplanted with bone marrow (BM) cells from
Ncr1

iCre

R26R

lsl−

DTA

,
Noé
, or wild-type mice. Also, no difference was observed in plaque composition in terms of collagen content, macrophage infiltration, or the immune profile, although
Noé
chimera had more IFN (interferon)-γ–producing NK cells, compared with wild-type mice. Then, we investigated the NK-cell selectivity of anti–asialoganglioside M1 antiserum, which was previously used to conclude the proatherogenicity of NK cells. Anti–asialoganglioside M1 treatment decreased atherosclerosis in both
Ldlr
−/−
mice transplanted with
Ncr1

iCre

R26R

lsl−

DTA

or wild-type bone marrow, indicating that its antiatherogenic effects are unrelated to NK-cell depletion, but to CD8
+
T and NKT cells. Finally, to determine whether NK cells could contribute to the disease in conditions of pathological NK-cell overactivation, we treated irradiated
Ldlr
−/−
mice reconstituted with either wild-type or
Ncr1

iCre

R26R

lsl−

DTA

bone marrow with the viral mimic polyinosinic:polycytidylic acid and found a significant reduction of plaque size in NK-cell–deficient chimeric mice.

Conclusions:

Our findings, using state-of-the-art mouse models, demonstrate that NK cells have no direct effect on the natural development of hypercholesterolemia-induced atherosclerosis, but may play a role when an additional systemic NK-cell overactivation occurs.
Predictors of Death in Adults With Duchenne Muscular Dystrophy–Associated Cardiomyopathy
Authors: Cheeran Daniel , Khan Shaida , Khera Rohan , Bhatt Anish , Garg Sonia , Grodin Justin L. , Morlend Robert , Araj Faris G. , Amin Alpesh A. , Thibodeau Jennifer T. , Das Sandeep , Drazner Mark H. , Mammen Pradeep P. A.
Published: October 2017

Background

Duchenne muscular dystrophy (
DMD
) is frequently complicated by development of a cardiomyopathy. Despite significant medical advances provided to
DMD
patients over the past 2 decades, there remains a group of
DMD
patients who die prematurely. The current study sought to identify a set of prognostic factors that portend a worse outcome among adult
DMD
patients.

Methods and Results

A retrospective cohort of 43 consecutive patients was followed in the adult
UT
Southwestern Neuromuscular Cardiomyopathy Clinic. Clinical data were abstracted from the electronic medical record to generate baseline characteristics. The population was stratified by survival to time of analysis and compared with characteristics associated with death. The
DMD
population was in the early 20s, with median follow‐up times over 2 years. All the patients had developed a cardiomyopathy, with the majority of the patients on angiotensin‐converting enzyme inhibitors (86%) and steroids (56%), but few other guideline‐directed heart failure medications. Comparison between the nonsurviving and surviving cohorts found several poor prognostic factors, including lower body mass index (17.3 [14.8–19.3] versus 25.8 [20.8–29.1] kg/m
2
,
P
<0.01), alanine aminotransferase levels (26 [18–42] versus 53 [37–81] units/L,
P
=0.001), maximum inspiratory pressures (13 [0–30] versus 33 [25–40] cmH
2
O,
P
=0.03), and elevated cardiac biomarkers (N‐terminal pro‐brain natriuretic peptide: 288 [72–1632] versus 35 [21–135] pg/mL,
P
=0.03].

Conclusions

The findings demonstrate a
DMD
population with a high burden of cardiomyopathy. The nonsurviving cohort was comparatively underweight, and had worse respiratory profiles and elevated cardiac biomarkers. Collectively, these factors highlight a high‐risk cardiovascular population with a worse prognosis.
Cardiovascular and Metabolic Consequences of Testosterone Supplements in Young and Old Male Spontaneously Hypertensive Rats: Implications for Testosterone Supplements in Men
Authors: Dalmasso Carolina , Patil Chetan N. , Yanes Cardozo Licy L. , Romero Damian G. , Maranon Rodrigo O.
Published: October 2017

Background

The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (
SHR)
, long‐term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin‐angiotensin system.

Methods and Results

In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks‐
YMSHR
) and old (21–22 months‐
OMSHR
) male
SHR
that increased serum testosterone by 2‐fold in young males and by 4‐fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in
YMSHR
but had no effect in
OMSHR
. Mean arterial pressure (
MAP
) was significantly higher in
OMSHR
than in
YMSHR
and testosterone supplements decreased
MAP
in
OMSHR
, but significantly increased
MAP
in
YMSHR
. Enalapril, the angiotensin‐converting enzyme inhibitor, reduced
MAP
in both control and testosterone‐supplemented
YMSHR
, but had a greater effect on
MAP
in testosterone‐treated rats, suggesting the mechanism responsible for the increase in
MAP
in
YMSHR
is mediated at least in part by activation of the renin‐angiotensin system.

Conclusions

Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long‐term or short‐term.
Relative Survival After Transcatheter Aortic Valve Implantation: How Do Patients Undergoing Transcatheter Aortic Valve Implantation Fare Relative to the General Population?
Authors: Martin Glen P. , Sperrin Matthew , Hulme William , Ludman Peter F. , de Belder Mark A. , Toff William D. , Alabas Oras , Moat Neil E. , Doshi Sagar N. , Buchan Iain , Deanfield John E. , Gale Chris P. , Mamas Mamas A. ,   the National Institute of Cardiovascular Outcomes Research (NICOR)
Published: October 2017

Background

Transcatheter aortic valve implantation (
TAVI
) is indicated for patients with aortic stenosis who are intermediate‐high surgical risk. Although all‐cause mortality rates after
TAVI
are established, survival attributable to the procedure is unclear because of competing causes of mortality. The aim was to report relative survival (
RS
) after
TAVI
, which accounts for background mortality risks in a matched general population.

Methods and Results

National cohort data (n=6420) from the 2007 to 2014
UK TAVI
registry were matched by age, sex, and year to mortality rates for England and Wales (population, 57.9 million). The Ederer
II
method related observed patient survival to that expected from the matched general population. We modelled
RS
using a flexible parametric approach that modelled the log cumulative hazard using restricted cubic splines. RS of the
TAVI
cohort was 95.4%, 90.2%, and 83.8% at 30 days, 1 year, and 3 years, respectively. By 1‐year follow‐up, mortality hazards in the >85 years age group were not significantly different from those of the matched general population; by 3 years, survival rates were comparable. The flexible parametric
RS
model indicated that increasing age was associated with significantly lower excess hazards after the procedure; for example, by 2 years, a 5‐year increase in age was associated with 20% lower excess mortality over the general population.

Conclusions

RS
after
TAVI
was high, and survival rates in those aged >85 years approximated those of a matched general population within 3 years. High rates of
RS
indicate that patients selected for
TAVI
tolerate the risks of the procedure well.
Intersectionality, Gender Liminality and Ben Sira’s Attitude to the Eunuch
Authors: Bolle Helena M. , Llewelyn Stephen R.
Published: October 2017

Ben Sira twice cites the eunuch in sayings that play on his sexual impotence. In so doing he diverges from what we know of the Hebraic tradition before him. Blending theory is used to interpret the sayings and their apparently malicious intent. After appraising the ambiguous status/identity of the eunuch in terms of ‘intersectionality’, Ben Sira’s attitude is contextualised using the concepts of ‘gender liminality’ and ‘hybridity’ and set against the strict binary system that underlies his understanding of gender more generally. It is suggested that Ben Sira’s theology of creation, like that of the Wisdom tradition more generally, forms the principal basis for this binary system. At the same time, the more accepting attitude to the eunuch in Isaiah 56 is considered and its notion of the ‘new creation’.
Ezra in Egypt? The Significance of Hananyah’s Mission
Authors: van der Toorn Karel
Published: October 2017

The history of the Jewish community at Elephantine plays a crucial role in the reconstruction of the early history of Judaism. One document in particular sheds a light on the emerging Jewish identity in the diaspora. It is Hananyah’s so-called Passover Letter. This contribution investigates the significance of Hananyah’s mission in Egypt, and more particularly its relationship with the missions of Ezra and Nehemiah. The investigation permits three conclusions. One, the Persians did not distinguish between ethnicity and religion; two, the codification of Jewish ritual preceded the codification of the Torah; and three, Jewish identity in the late 5th century allowed significant latitude in matters of doctrine and lifestyle.
La fin du récit sacerdotal de la création : Gn 2,4a ou Gn 2,3 ?
Authors: Marx Alfred
Published: October 2017

The present note argues that, as formerly mostly accepted, the P account of the creation ends in Gn 2,4a.
On the Compositional Models for Ezekiel 38-39: A Response to William Tooman’s Gog of Magog
Authors: Strine C. A.
Published: October 2017

William Tooman’s monograph Gog of Magog: Reuse of Scripture and Compositional Technique in Ezekiel 38-39 has quickly become a seminal study of Ezek 38-39. This article examines and critiques Tooman’s influential position that Ezek 38-39 were composed by a method called thematic pastiche, which only emerged in second temple Jewish texts. By showing inconsistencies in the limits of what constitutes thematic pastiche and by re-examining the evidence that Ezek 38-39 depends upon Joel 1:6; 2:27; 3:1-2; Isa 62:2; 66:18-19, this article demonstrates that Joel 3:1-2 and Isa 66:18-19 may even reuse Ezek 39:21, 29 as source texts, thus re-opening the search for which texts provide the compositional model for the Gog oracles. As a logical consequence of that finding, this article highlights problems with Tooman’s widely adopted proposal, albeit provisional, that Ezek 38-39 dates from the 4th to 2nd century bce.
Contempt for Court in Russia: The Impact of Litigation Experience
Authors: Hendley Kathryn
Published: October 2017

This article explores how Russians think about their courts and whether court veterans are distinguishable from those who have never used the courts. The analysis is based on data generated by a nationally representative survey fielded in 2010. The analysis clearly shows that users and nonusers think differently about courts and law. Users are both more positive and more negative about the courts, depending on the context. Although they praise the work of judges and other courthouse personnel in their own cases, they seem to emerge with lingering negative views of the courts that come into focus when asked more general questions. Nonusers tend to be more optimistic about the potential of courts to achieve justice.
Ritual Consecration in the Context of Writing the Holy Scrolls: Jews in Medieval Europe between Demarcation and Acculturation
Authors: Martini Annett
Published: October 2017

The objective of this article is to outline a hitherto neglected aspect of writing holy scrolls for ritual use, which in medieval Europe became a crucial subject of discussion: the ritual consecration of certain processes during the manufacturing of STaM with a special emphasis on writable skins. Taking into account Jewish and Christian sources, many of which have not been scrutinized to date, a paradox that perfectly reflects the ambivalent relationship of Jews and Christians in the Middle Ages will be revealed. On the one hand, the ritual sanctification can be read as an act of demarcation by which Jews drew a clear line between holy and profane—and Jews and non-Jews. On the other hand, it becomes evident that there was not only an artisanal exchange but a mutual interaction in terms of ritual and performance as well.
Abuse of Diplomatic Privileges and the Balance between Immunities and the Duty to Respect the Local Laws and Regulations under the Vienna Conventions: The Recent Indian Experience
Authors: Subramanian S. R.
Published: October 2017

The successful adoption of the Vienna Convention on Diplomatic Relations is hailed as the ‘landmark of the highest significance in the codification of international law’. It represented the first significant codification of any international instrument since the United Nations was established. However, despite the codification of the above rules, which is largely based on the pre-existing customary international law, the scope of diplomatic protection was not free from issues and controversies. In recent times, unfortunately, there is a growing tendency amongst the diplomats to abuse their diplomatic status to commit acts prohibited by law and still claim immunity from legal process. The States-parties also aggravate this situation by selectively interpreting the rules in their favor, ignoring the fact that reciprocity is the basis for the successful functioning of the diplomatic protection. In this connection, this paper addresses the problem of abuse of immunities and privileges and its adverse implications on the balance between immunities and the duty to respect the local laws and regulations, especially with special reference to the recent Indian experience. It explores the two recent Indian diplomatic confrontations, namely, the arrest of Devyani Khobragade and the travel ban on Daniele Mancini. Based on the study, it highlights the need for a well-balanced and equitable enforcement of the Vienna Conventions in the interest of maintenance of cordial diplomatic relations in the international community.
The Juridification of Religion?
Authors: Årsheim Helge , Slotte Pamela
Published: October 2017

This article sets out to explore the extent to which developments currently taking place at the interface between law and religion in domestic, regional and international law can be conceptualized as instances of larger, multidimensional processes of juridification. We rely on an expansive notion of juridification, departing from the more narrow sense of juridificiation as the gradually increasing “colonization of the lifeworld” proposed by Jürgen Habermas in his Theory of Communicative Action (1987; Vol. 2, Beacon Press). More specifically, the article adapts the multidimensional notion of juridification outlined by Anders Molander and Lars Christian Blichner in their article ‘Mapping Juridification’ (2008; 14 European Law Journal 36), and develops it into a more context-specific notion of juridification that is attendant to the specific nature of religion as a subject matter for law.
Tegoribatidae of North America, with proposal of Protectoribates gen. nov., and new species (Acari, Oribatida, Tegoribatidae)
Authors: BEHAN-PELLETIER VALERIE M.
Published: October 2017

The oribatid mite family Tegoribatidae has been represented in continental North America by the genera Tegoribates and Tectoribates. Herein, I describe a new genus of Tegoribatidae from North America, Protectoribates, and two new species: Protectoribates occidentalis sp. nov., from forest habitats in western North American, and Tegoribates walteri sp. nov., from forest habitats in California, based on adults and immatures. The descriptions of adults of the type species of Tegoribates, T. subniger Ewing, and other North American species, T. americanus Hammer and T. bryophilus Woolley, are expanded and immatures of T. americanus are described for the first time. Immatures of Protectoribates are apheredermous whereas those of Tegoribates are eupheredermous, though retaining centrodorsal setae. Scutozetes Hammer 1952 is transferred from Tegoribatidae to Ceratozetidae after re-examination of type material. I provide a revised diagnosis for Tegoribates and a key to tegoribatid genera and species for North America. Finally, I provide a revised diagnosis for Tegoribatidae based on world genera.
A new species of Marmara (Lepidoptera: Gracillariidae: Marmarinae), with an Annotated List of Known Hostplants for the Genus
Authors: EISEMAN CHARLES S. , DAVIS DONALD R. , BLYTH JULIA A. , WAGNER DAVID L. , PALMER MICHAEL W. , FELDMAN TRACY S.
Published: October 2017

Larvae of the New World gracillariid moth genus Marmara are primarily stem/bark miners, with some species mining in leaves or fruits. We describe a new species, M. viburnella Eiseman & Davis, which feeds on Viburnum, initially mining the leaves but completing development as a stem miner. The type series is from Nantucket Island, Massachusetts, with observations of leaf mines indicating the species is widespread in the eastern USA. Combining previously published data, our own observations, and other sources, we present a list of known Marmara hostplants, many of which represent undescribed species.
Can We Optimize the Assimilation Order in the Serial Ensemble Kalman Filter? A Study with the Lorenz-96 Model
Authors: Kotsuki Shunji , Greybush Steven J. , Miyoshi Takemasa
Published: October 2017

With the serial treatment of observations in the ensemble Kalman filter (EnKF), the assimilation order of observations is usually assumed to have no significant impact on analysis accuracy. However, Nerger derived that analyses with different assimilation orders are different if covariance localization is applied in the observation space. This study explores whether the assimilation order can be optimized to systematically improve the filter estimates. A mathematical demonstration of a simple two-dimensional case indicates that different assimilation orders can cause different analyses, although the differences are two orders of magnitude smaller than the analysis increments if two identical observation error variances are the same size as the two identical state error variances. Numerical experiments using the Lorenz-96 40-variable model show that the small difference due to different assimilation orders could eventually result in a significant difference in analysis accuracy. Several ordering rules are tested, and the results show that an ordering rule that gives a better forecast relative to future observations improves the analysis accuracy. In addition, the analysis is improved significantly by ordering observations from worse to better impacts using the ensemble forecast sensitivity to observations (EFSO), which estimates how much each observation reduces or increases the forecast error. With the EFSO ordering rule, the change in error during the serial assimilation process is similar to that obtained by the experimentally found best sampled assimilation order. The ordering has more impact when the ensemble size is smaller relative to the degrees of freedom of the dynamical system.
Survival and Complications of Single Dental Implants in the Edentulous Mandible Following Immediate or Delayed Loading: A Randomized Controlled Clinical Trial
Authors: Kern M. , Att W. , Fritzer E. , Kappel S. , Luthardt R.G. , Mundt T. , Reissmann D.R. , Rädel M. , Stiesch M. , Wolfart S. , Passia N.
Published: October 2017

It was the aim of this 24-mo randomized controlled clinical trial to investigate whether the survival of a single median implant placed in the edentulous mandible to retain a complete denture is not compromised by immediate loading. Secondary outcomes were differences in prosthetic complications between the loading principles. Each of the 158 patients who received an implant was randomly assigned to the immediate loading group ( n = 81) or the delayed loading group ( n = 77). Recall visits were performed 1 mo after implant placement (for only the delayed loading group) and 1, 4, 12, and 24 mo after implant loading. Nine implants failed in the immediate loading group, all within the first 3 mo of implant loading, and 1 implant failed in the delayed loading group prior to loading. Noninferiority of implant survival of the immediate loading group, as compared with the delayed loading group, could not be shown ( P = 0.81). Consistent with this result, a secondary analysis with Fisher exact test revealed that the observed difference in implant survival between the treatment groups was indeed statistically significant ( P = 0.019). The most frequent prosthetic complications and maintenance interventions in the mandible were retention adjustments, denture fractures, pressure sores, and matrix exchanges. There was only 1 statistically significant difference between the groups regarding the parameter “fracture of the denture base in the ball attachment area” ( P = 0.007). The results indicate that immediate loading of a single implant in the edentulous mandible reveals inferior survival than that of delayed loading and therefore should be considered only in exceptional cases (German Clinical Trials Register: DRKS00003730).
Neuroscience and the Social Unconscious
Authors: Bacha Claire
Published: October 2017

The social unconscious is an abstract concept which describes a real force, like the concept of gravity. The social unconscious can only be seen by its effects. However, it is also the force that holds everything together from individual internal coherence to the largest social phenomena. It is proposed here that the new knowledge from neuroscience helps us understand the implications of having an unconscious that is also social, although its appearance is individual. Furthermore, although the brain’s appearance is structural and balanced, it has been found that brain processes actually operate in dynamic equilibrium, where tiny adjustments provide precarious balance and change is constant.
‘You End Up with Nothing’: The Experience of Being a Statistic of ‘In-Work Poverty’ in the UK
Authors: McBride Jo , Smith Andrew , Mbala Marcell
Published: October 2017

Set in the context of the recent unprecedented upsurge of in-work poverty (IWP) in the UK – which currently exceeds out of work poverty – this article presents an account of the realities of experiencing poverty and being employed. Central issues of low-pay, limited working hours, underemployment and constrained employment opportunities combine to generate severe financial complexities and challenges. This testimony, taken comparatively over a year, reveals the experiences of, not only IWP, but of deep poverty, and of having insufficient wages to fulfil the basic essentials of nourishing food and adequate clothing. This article contributes to current academic and social policy debates around low-paid work, IWP, the use of foodbanks and underemployment. New dimensions are offered regarding worker vulnerabilities, given the recent growth of the IWP phenomenon.
International Perceptions of Cyberbullying Within Higher Education
Authors: Luker Julie Marie , Curchack Barbara C.
Published: October 2017

In this study, we investigated perceptions of cyberbullying within higher education among 1,587 professionals from Australia, Canada, the United Kingdom, and the United States. Regardless of country or professional role, participants presented essentially the same bleak picture. Almost half of all participants observed cyberbullying between students within the last year, about one in every five intervened in an incident, and only 10% felt completely prepared to do so. Likewise, 85% of participants perceived their institution to be less than completely prepared to handle cyberbullying, with fewer than 50% even aware whether their school had a cyberbullying policy and fewer than 25% having a policy that specifically addresses cyberbullying. The majority of participants perceived cyberbullying as negative; however, approximately 10% dissented from this view. Finally, a group-serving bias was replicated; cyberbullying was perceived as more problematic at other institutions than their own. This research calls for evidence-based, systematic policy development and implementation, including how to train those who see cyberbullying as a positive phenomenon.
Drawing the Line at Age 14: Why Adolescents Should Be Able to Consent to Participation in Research
Authors: Schwartz Robert
Published: October 2017

This article argues that teenagers become fully capable of consenting to participation in most IRB-approved research involving human subjects at age 14, four years earlier than they are allowed to consent under virtually all states' laws, and, consequently, four years younger than they are able to consent under currently applicable federal regulations. In determining the age at which person is old enough to have decision-making authority, legal institutions look at the intellectual and emotional maturity of someone of the age of the decision-maker, the risks and benefits of allowing the decision to be made by someone of that age, and the risks and benefits of denying a person of that age the authority to make the decision. Given the high level of safety of participating in IRB approved research, the value of doing so for both the society and the teenage subject, and the psychological and neuropsychological research on the specific nature of emotional and intellectual development during the teen years, the balance comes out in favor of allowing younger teens, by the age of 14, authority to consent to participate as subjects in IRB approved research. The current process requiring both teen assent and parental permission should give way to a process that requires only a teen's consent.
Central IRB Review Is an Essential Requirement for Cancer Clinical Trials
Authors: Schnipper Lowell E.
Published: October 2017

There are compelling medical, ethical, and legal arguments that support mandating use of a central institutional review board (CIRB) for the review of clinical trials performed at multiple institutional sites. Progress against serious diseases depends on this.
Can Central IRBs Replace Local Review?
Authors: Moon Margaret R.
Published: October 2017

The NIH has initiated a plan to mandate use of central IRBs for all multi-site research. This manuscript argues against the mandate, proposing that there is inadequate evidence to support the purported gains in efficiency and that the ethical integrity of research may suffer with any exclusion of the local review voice.
Informed Consent for Comparative Effectiveness Research Should Include Risks of Standard Care
Authors: Shepherd Lois
Published: October 2017

This paper explains why informed consent for randomized comparative effectiveness research (CER) must include risks of standard care. Disclosures of such risks are both legally and ethically required and, for reasons discussed in the paper, should remain so.