bluuebunny/crossref_metadata_2025 huggingface dataset:
Indications and outcomes of vitrectomy surgery in a series of 1000 black African eyes
Authors: Okonkwo Ogugua Ndubuisi , Lewis Karinya , Hassan Adekunle Olubola , Gyasi Micheal Ekuoba , Oluyadi Banji , Ogunro Adunola , Oderinlo Olufemi , Ulaikere Mildred
Published: May 2019

Objective

To determine the common indications for, and outcomes of pars plana vitrectomy surgery among black Africans in a low-resource setting.

Methods and Analysis

A retrospective, non-comparative case review was undertaken. Data from 1000 consecutive eyes of 1000 patients in a single centre who underwent pars plana vitrectomy surgery between May 2005 and July 2013 were used for the study. Demographic data, primary indication for surgery, ocular status and outcomes were assessed.

Results

Rhegmatogenous retinal detachment was the most common primary indication occurring in 61.8% of eyes. Diabetic vitrectomy, trauma and proliferative sickle cell retinopathy were also common indications occurring in 10.1%, 6.1% and 4.5% of eyes, respectively. At presentation, 33% of patients with retinal detachment had some form of proliferative vitreoretinopathy, and half of those had the more advanced grades C and D. Patients presented on an average of 13.5 months after onset of symptoms. As a result, visual outcomes were less than other reported studies.

Conclusion

Retinal detachment was the most common indication for vitrectomy, but even these cases presented late with an advanced presentation. This study highlights the need for affordable and accessible vitreoretinal services in Sub-Saharan Africa and increased awareness of general eye health, along with strategies to reduce trauma and identify early those at risk of chronic eye diseases, such as diabetic retinopathy and sickle cell retinopathy.
Impact of armed conflict on cardiovascular disease risk: a systematic review
Authors: Jawad Mohammed , Vamos Eszter P , Najim Muhammad , Roberts Bayard , Millett Christopher
Published: May 2019

Objectives

Prolonged armed conflict may constrain efforts to address non-communicable disease in some settings. We assessed the impact of armed conflict on cardiovascular disease (CVD) risk among civilians in low/middle-income countries (LMICs).

Methods

In February 2019, we performed a systematic review searching Medline, Embase, PsychINFO, Global Health and Web of Science without language or date restrictions. We included adult, civilian populations in LMICs. Outcomes included CVDs and diabetes, and eight clinical and behavioural factors (blood pressure, blood glucose, lipids, tobacco, alcohol, body mass index, nutrition, physical activity). We systematically reanalysed data from original papers and presented them descriptively.

Results

Sixty-five studies analysed 23 conflicts, and 66% were of low quality. We found some evidence that armed conflict is associated with an increased coronary heart disease, cerebrovascular and endocrine diseases, in addition to increased blood pressure, lipids, alcohol and tobacco use. These associations were more consistent for mortality from chronic ischaemic heart disease or unspecified heart disease, systolic blood pressure and tobacco use. Associations between armed conflict and other outcomes showed no change, or had mixed or uncertain evidence. We found no clear patterning by conflict type, length of follow-up and study quality, nor strong evidence for publication bias.

Conclusions

Armed conflict may exacerbate CVDs and their risk factors, but the current literature is somewhat inconsistent. Postconflict reconstruction efforts should deliver low-resource preventative interventions through primary care to prevent excess CVD-related morbidity and mortality.

PROSPERO registration number

CRD42017065722
Diagnosis of acute myocardial infarction in the presence of left bundle branch block
Authors: Nestelberger Thomas , Cullen Louise , Lindahl Bertil , Reichlin Tobias , Greenslade Jaimi H , Giannitsis Evangelos , Christ Michael , Morawiec Beata , Miro Oscar , Martín-Sánchez Francisco Javier , Wussler Desiree Nadine , Koechlin Luca , Twerenbold Raphael , Parsonage William , Boeddinghaus Jasper , Rubini Gimenez Maria , Puelacher Christian , Wildi Karin , Buerge Tobias , Badertscher Patrick , DuFaydeLavallaz Jeanne , Strebel Ivo , Croton Lukas , Bendig Garnet , Osswald Stefan , Pickering John William , Than Martin , Mueller Christian
Published: May 2019

Objective

Patients with suspected acute myocardial infarction (AMI) in the setting of left bundle branch block (LBBB) present an important diagnostic and therapeutic challenge to the clinician.

Methods

We prospectively evaluated the incidence of AMI and diagnostic performance of specific ECG and high-sensitivity cardiac troponin (hs-cTn) criteria in patients presenting with chest discomfort to 26 emergency departments in three international, prospective, diagnostic studies. The final diagnosis of AMI was centrally adjudicated by two independent cardiologists according to the universal definition of myocardial infarction.

Results

Among 8830 patients, LBBB was present in 247 (2.8%). AMI was the final diagnosis in 30% of patients with LBBB, with similar incidence in those with known LBBB versus those with presumably new LBBB (29% vs 35%, p=0.42). ECG criteria had low sensitivity (1%–12%) but high specificity (95%–100%) for AMI. The diagnostic accuracy as quantified by the receiver operating characteristics (ROC) curve of hs-cTnT and hs-cTnI concentrations at presentation (area under the ROC curve (AUC) 0.91, 95% CI 0.85 to 0.96 and AUC 0.89, 95% CI 0.83 to 0.95), as well as that of their 0/1-hour and 0/2-hour changes, was very high. A diagnostic algorithm combining ECG criteria with hs-cTnT/I concentrations and their absolute changes at 1 hour or 2 hours derived in cohort 1 (45 of 45(100%) patients with AMI correctly identified) showed high efficacy and accuracy when externally validated in cohorts 2 and 3 (28 of 29 patients, 97%).

Conclusion

Most patients presenting with suspected AMI and LBBB will be found to have diagnoses other than AMI. Combining ECG criteria with hs-cTnT/I testing at 0/1 hour or 0/2 hours allows early and accurate diagnosis of AMI in LBBB.

Trial registration number

APACE:NCT00470587; ADAPT: ACTRN12611001069943; TRAPID-AMI: RD001107;Results.
From randomised controlled trial to real world implementation of a novel home-based heart failure tool: pooled and comparative analyses of two clinical controlled trials
Authors: Hovland-Tånneryd Ann , Melin Michael , Hägglund Ewa , Hagerman Inger , Persson Hans E
Published: May 2019

Objectives

A home-based tool for heart failure (HF) patients, was evaluated in a specialist setting as a randomised controlled trial (RCT) and also in a validation cohort in a primary care setting in a clinical controlled trial (CCT). The tool provides education, symptom monitoring and titration of diuretics. The aim of this study was thus to extend validity of the previous RCT findings in order to describe applicability of the tool in clinical practice.

Methods

Data from both trials were analysed separately, as well as a pooled data set (n=172). Data were analysed with respect to HF related in-hospital days, self-care behaviour and system adherence, during a 6-month intervention. The analysis of in-hospital days for the pooled data was adjusted for baseline differences between the two study cohorts, relating to disease state.

Results

In the RCT (n=72) the intervention group (IG) consisted of 32 patients and the control group (CG) of 40 patients. The risk ratio (RR) for in-hospital days was RR: 0.72, 95% CI 0.61 to 0.84, p<0.05 in favour of the IG. In the CCT (n=100) both the IG and the CG consisted of 50 patients and the IG had fewer in-hospitals days, comparable to the RCT findings with RR: 0.67; 95% CI 0.45 to 0.99; p<0.05. For the pooled data set made up of 172 patients, the groups were well balanced but with a higher prevalence of hypertension in the CG. The RR relating to in-hospital days for the pooled data set was 0.71; 95% CI 0.61 to 0.82; p<0.05 in favour of the IG. There was a statistically significant improvement in self-care by 27% and the median system adherence was 94%.

Conclusions

These analyses suggest that the evaluated tool might reduce HF related in-hospital days in the general HF population, which adds to the external validity of previous findings.

Clinical Trial Registration

NCT03655496.
Evaluation of the performances of ‘typical’ imaging abnormalities of axial spondyloarthritis: results of the cross-sectional ILOS-DESIR study
Authors: Molto Anna , Gossec Laure , Lefèvre-Colau Marie-Martine , Foltz Violaine , Beaufort Romain , Laredo Jean-Denis , Richette Pascal , Dieude Philippe , Goupille Philippe , Feydy Antoine , Dougados Maxime
Published: May 2019

Objective

To evaluate the prevalence and performance as axial Spondyloarthritis (axSpA) diagnostic feature of radiographic and MRI lesions ‘typical’ of axSpA of the sacroiliac joint (SIJ) and spine in a mechanical chronic back pain (CBP) population and in an axSpA cohort.

Methods

Cross-sectional multicentre study. Patients: (1) recent onset axSpA (DESIR cohort) and (2) mechanical non-axSpA CBP matched for age and gender (ILOS study). Imaging: radiographs and MR scans were performed identically in both groups. All images were centrally read, blinded for diagnosis and for other imaging findings in the same patient. Statistical analysis: prevalence of lesions ‘typical of axSpA’ were compared in both groups. Sensitivity, specificity and positive likelihood ratios (LR+) of each lesion (and combination of lesions) were calculated.

Results

A total of 98 patients with CBP were included, and compared with 100 patients with recent onset axSpA. SIJ lesions were consistently more frequent in the axSpA group (35.0% vs 11.8% p<0.001, 35.0% vs 8.4% p<0.001% and 32.0% vs 10.0%. p<0.001 for modified New York criteria, MRI sacroiliitis and ≥3 erosions of the SIJ on MRI, respectively), and performed well (LR+ for ≥3 erosions 3.0 (95% CI 1.6 to 5.8)). Spine lesions were comparable across groups: radiographic lesions were rare, while all MRI lesions were frequent.

Conclusion

Our study confirms that ‘typical’ lesions can also be observed in patients with non-axSpA CBP but that SIJ lesions by all modalities remain the most valuable for diagnosis, including structural lesions of the SIJ. This suggests the potential interest of adding MRI SIJ structural lesions in the definition of MRI abnormalities for axSpA classification.
Distribution and morphology of inner-shelf sand bodies off southwest Newfoundland based on merged multibeam sonar and LiDAR data
Authors: Shaw John , Wu Yongsheng , Potter D. Patrick
Published: May 2019

The inner shelf off southwest Newfoundland, bordering the Laurentian Channel, was mapped with multi-beam sonar between depths of 200 and ∼20 m, overlapping with coverage by marine/terrestrial LiDAR from maximum depths of 30 m to above sea level. The new data provide the first clear view of linkages between terrestrial and nearshore coastal systems and the inner shelf. Offshore sand reservoirs associated with adjacent sandy coastal barriers and spits are thin (∼2 m), and isolated from one another, so that bedrock is the dominant seafloor terrain on the inner most shelf. The offshore sand reservoirs link with complex nearshore bar systems, from which it is inferred that sediment exchange with terrestrial systems can occur. Several isolated sand bodies are interpreted as residuals from former coastal systems destroyed during the Holocene transgression. The new data reveal the unexpected existence of a submarine canyon that facilitates transport of sediment from the inner shelf into the deep glacial trough of the Laurentian Channel.
Disordered interfaces in soft fluids with suspended colloids
Authors: Tiribocchi A. , Lauricella M. , Montessori A. , Melchionna S. , Succi S.
Published: May 2019

Computer simulations of bi-continuous two-phase fluids with interspersed dumbbells show that, unlike rigid colloids, soft dumbbells do not lead to arrested coarsening. However, they significantly alter the curvature dynamics of the fluid–fluid interface, whose probability density distributions are shown to exhibit (i) a universal spontaneous transition (observed even in the absence of colloids) from an initial broad-shape distribution towards a highly localized one and (ii) super-diffusive dynamics with long-range effects. Both features may prove useful for the design of novel families of soft porous materials.
Immediate effects of a novel walking assist device with auxiliary illuminator on patients after acute strokes
Authors: Huang Wan-Yun , Tuan Sheng-Hui , Li Min-Hui , Liu Xin-Yu , Hsu Pei-Te
Published: May 2019

Background: Many patients after acute stage of stroke are present with abnormal gait pattern due to weakness or hypertonicity of the affected limbs. Facilitation of normal gait is a primary goal of rehabilitation on these patients.

Objective: We aimed to investigate whether walking assist device with auxiliary illuminator (quad-cane with laser) providing visual feedback during ambulation could improve parameters of gait cycle immediately among patients with subacute and chronic stroke.

Methods: This was a cross-sectional study and 30 participants (male 23, female 7, group 1) with mean age [Formula: see text] years were recruited. Among them, 22 used ankle-foot orthosis [(AFO), group 2] and 8 did not use AFO (group 3) at usual walking. All the participants walked along a strait corridor with even surface for 20[Formula: see text]m without and with using a quad-cane with laser, respectively. A gait analyzer (Reha-Watch1 system) was used to measure the changes of the parameters of gait cycle, including stride length, cadence, gait speed, stance phase, swing phase, duration of single support and double support, the angle between toes and the ground at the time of toe-off (the toe-off angle) and the angle between calcaneus and the ground at the time of heel-strike (the heel-strike angle), before and with the use of a quad-cane with laser.

Results: The increase in the heel-strike angle reached a significant difference in groups 1 2, and 3 ([Formula: see text], and [Formula: see text], respectively). However, the stride length, the gait speed, the cadence, percentage of the stance phase, swing phase, single-support phase, and double-support phase in a gait cycle, and the toe-off angle showed no significant change with the use of quad-cane with laser.

Conclusion: Patients after acute stroke had an immediate and significant increase in the heel-stroke angle by using a quad-cane with laser during ambulation, which might help the patients to reduce knee hyperextension moment and lessen the pressure of heel at loading phase.
Tc Toxin Complexes: Assembly, Membrane Permeation, and Protein Translocation
Authors: Roderer Daniel , Raunser Stefan
Published: May 2019

Tc toxin complexes are virulence factors of many bacteria, including insect and human pathogens. Tc toxins are composed of three subunits that act together to perforate the host membrane, similar to a syringe, and translocate toxic enzymes into the host cell. The reactions of the toxic enzymes lead to deterioration and ultimately death of the cell. We review recent high-resolution structural and functional data that explain the mechanism of action of this type of bacterial toxin at an unprecedented level of molecular detail. We focus on the steps that are necessary for toxin activation and membrane permeation. This is where the largest conformational transitions appear. Furthermore, we compare the architecture and function of Tc toxins with those of anthrax toxin and vertebrate teneurin.
Acetaldehyde suppresses the display of HBV-MHC class I complexes on HBV-expressing hepatocytes
Authors: Ganesan Murali , Krutik Vjaceslav M. , Makarov Edward , Mathews Saumi , Kharbanda Kusum K. , Poluektova Larisa Y. , Casey Carol A , Osna Natalia A.
Published: May 2019

Hepatitis B virus (HBV) infection and alcoholism are major public health problems worldwide, contributing to the development of end-stage liver disease. Alcohol intake affects HBV infection pathogenesis and treatment outcomes. HBV-specific cytotoxic T lymphocytes (CTLs) play an important role in HBV clearance. Many previous studies have focused on alcohol-induced impairments of the immune response. However, it is not clear whether alcohol alters the presentation of HBV peptide-major histocompatibility complex (MHC) class I complexes on infected hepatocytes resulting in escape of its recognition by CTLs. Hence, the focus of this study was to investigate the mechanisms by which ethanol metabolism affects the presentation of CTL epitope on HBV-infected hepatocytes. As demonstrated here, although continuous cell exposure to acetaldehyde-generating system (AGS) increased HBV load in HepG2.2.15 cells, it decreased the expression of HBV core peptide 18–27-human leukocyte antigen-A2complex (CTL epitope) on the cell surface. Moreover, we observed AGS-induced suppression of chymotrypsin- and trypsin-like proteasome activities necessary for peptide processing by proteasome as well as a decline in IFNγ-stimulated immunoproteasome (IPR) function and expression of PA28 activator and immunoproteasome subunits LMP7 and LMP2. Furthermore, IFNγ-induced activation of peptide-loading complex (PLC) components, such as transporter associated with antigen processing (TAP1) and tapasin, were suppressed by AGS. The attenuation of IPR and PLC activation was attributed to AGS-triggered impairment of IFNγ signaling in HepG2.2.15 cells. Collectively, all these downstream events reduced the display of HBV peptide-MHC class I complexes on the hepatocyte surface, which may suppress CTL activation and the recognition of CTL epitopes on HBV-expressing hepatocytes by immune cells, thereby leading to persistence of liver inflammation.

NEW & NOTEWORTHY Our study shows that in HBV-expressing HepG2.2.15 cells, acetaldehyde alters HBV peptide processing by suppressing chymotrypsin- and trypsin-like proteasome activities and decreases IFNγ-stimulated immunoproteasome function and expression of PA28 activator and immunoproteasome subunits. It also suppresses IFNγ-induced activation of peptide-loading complex (PLC) components due to impairment of IFNγ signaling via the JAK-STAT1 pathway. These acetaldehyde-induced dysfunctions reduced the display of HBV peptide-MHC class I complexes on the hepatocyte surface, thereby leading to persistence of HBV infection.
Contralateral fatigue during severe-intensity single-leg exercise: influence of acute acetaminophen ingestion
Authors: Morgan Paul T. , Bailey Stephen J. , Banks Rhys A. , Fulford Jonathan , Vanhatalo Anni , Jones Andrew M.
Published: May 2019

Exhaustive single-leg exercise has been suggested to reduce time to task failure (Tlim) during subsequent exercise in the contralateral leg by exacerbating central fatigue development. We investigated the influence of acetaminophen (ACT), an analgesic that may blunt central fatigue development, on Tlim during single-leg exercise completed with and without prior fatiguing exercise of the contralateral leg. Fourteen recreationally active men performed single-leg severe-intensity knee-extensor exercise to Tlim on the left (Leg1) and right (Leg2) legs without prior contralateral fatigue and on Leg2 immediately following Leg1 (Leg2-CONTRA). The tests were completed following ingestion of 1-g ACT or maltodextrin [placebo (PL)] capsules. Intramuscular phosphorus-containing metabolites and substrates and muscle activation were assessed using 31P-MRS and electromyography, respectively. Tlim was not different between Leg1ACT and Leg1PL conditions (402 ± 101 vs. 390 ± 106 s, P = 0.11). There was also no difference in Tlim between Leg2ACT-CONTRA and Leg2PL-CONTRA (324 ± 85 vs. 311 ± 92 s, P = 0.10), but Tlim was shorter in Leg2ACT-CONTRA and Leg2PL-CONTRA than in Leg2CON (385 ± 104 s, both P < 0.05). There were no differences in intramuscular phosphorus-containing metabolites and substrates or muscle activation between Leg1ACT and Leg1PL and between Leg2ACT-CONTRA and Leg2PL-CONTRA (all P > 0.05). These findings suggest that levels of metabolic perturbation and muscle activation at Tlim are not different during single-leg severe-intensity knee-extensor exercise completed with or without prior fatiguing exercise of the contralateral leg. Despite contralateral fatigue, ACT ingestion did not alter neuromuscular responses, muscle metabolites, or exercise performance.
A critical time window for recovery extends beyond one-year post-stroke
Authors: Ballester Belén Rubio , Maier Martina , Duff Armin , Cameirão Mónica , Bermúdez Sergi , Duarte Esther , Cuxart Ampar , Rodríguez Susana , San Segundo Mozo Rosa María , Verschure Paul F. M. J.
Published: May 2019

The impact of rehabilitation on post-stroke motor recovery and its dependency on the patient’s chronicity remain unclear. The field has widely accepted the notion of a proportional recovery rule with a “critical window for recovery” within the first 3–6 mo poststroke. This hypothesis justifies the general cessation of physical therapy at chronic stages. However, the limits of this critical window have, so far, been poorly defined. In this analysis, we address this question, and we further explore the temporal structure of motor recovery using individual patient data from a homogeneous sample of 219 individuals with mild to moderate upper-limb hemiparesis. We observed that improvement in body function and structure was possible even at late chronic stages. A bootstrapping analysis revealed a gradient of enhanced sensitivity to treatment that extended beyond 12 mo poststroke. Clinical guidelines for rehabilitation should be revised in the context of this temporal structure.

NEW & NOTEWORTHY Previous studies in humans suggest that there is a 3- to 6-mo “critical window” of heightened neuroplasticity poststroke. We analyze the temporal structure of recovery in patients with hemiparesis and uncover a precise gradient of enhanced sensitivity to treatment that expands far beyond the limits of the so-called critical window. These findings highlight the need for providing therapy to patients at the chronic and late chronic stages.
Diverse Cell Types, Circuits, and Mechanisms for Color Vision in the Vertebrate Retina
Authors: Thoreson Wallace B. , Dacey Dennis M.
Published: May 2019

Synaptic interactions to extract information about wavelength, and thus color, begin in the vertebrate retina with three classes of light-sensitive cells: rod photoreceptors at low light levels, multiple types of cone photoreceptors that vary in spectral sensitivity, and intrinsically photosensitive ganglion cells that contain the photopigment melanopsin. When isolated from its neighbors, a photoreceptor confounds photon flux with wavelength and so by itself provides no information about color. The retina has evolved elaborate color opponent circuitry for extracting wavelength information by comparing the activities of different photoreceptor types broadly tuned to different parts of the visible spectrum. We review studies concerning the circuit mechanisms mediating opponent interactions in a range of species, from tetrachromatic fish with diverse color opponent cell types to common dichromatic mammals where cone opponency is restricted to a subset of specialized circuits. Distinct among mammals, primates have reinvented trichromatic color vision using novel strategies to incorporate evolution of an additional photopigment gene into the foveal structure and circuitry that supports high-resolution vision. Color vision is absent at scotopic light levels when only rods are active, but rods interact with cone signals to influence color perception at mesopic light levels. Recent evidence suggests melanopsin-mediated signals, which have been identified as a substrate for setting circadian rhythms, may also influence color perception. We consider circuits that may mediate these interactions. While cone opponency is a relatively simple neural computation, it has been implemented in vertebrates by diverse neural mechanisms that are not yet fully understood.
Reflection Characteristics of a Near‐Interface Cavity in Ice at Supercritical Incidence
Authors: Wang Wen-Kai , Zhu Guang-Ping , Yin Jing-Wei , Sun Hui
Published: May 2019

The long‐range propagation modes in an acoustic channel under ice are basically caused by supercritical incidence. The energy distribution and transmission loss in the acoustic channel under ice are changed by a scatter in ice. The influence of a slender cylindrical cavity near and parallel to the ice‐water interface on the sound propagation is analyzed using Fourier‐Bessel series and Sommerfeld‐Watson transformation. The research found that the acoustic field presents a beam in the mirror reflection direction at supercritical incidence, and the beam‐width is proportional to secant of incident angle; meanwhile, the reflected coefficient is proportional to cosine of incident angle. The reflection coefficient increases with relative depth and Helmholtz number if the incident angle is a constant.
MR Angiography of the Head/Neck Vascular System in Mice on a Clinical MRI System
Authors: Reimann Carolin , Brangsch Julia , Adams Lisa Christine , Thöne-Reineke Christa , Hamm Bernd , Makowski Marcus Richard
Published: May 2019

Background. Magnetic resonance angiography (MRA) represents a clinical reference standard for the in vivo assessment of the vasculature. In this study, the potential of non-contrast-enhanced and contrast-enhanced angiography of the head/neck vasculature in mice on a clinical MR imaging system was tested. Methods. All in vivo magnetic resonance imaging was performed with a 3T clinical system (Siemens). Non-contrast-enhanced (time-of-flight, TOF) and contrast-enhanced angiography (gadofosveset-trisodium, GdT) were performed in C57BL/6J mouse strain. Lumen-to-muscle ratios (LMRs) and area measurements were assessed. Histology was performed as reference standard of all relevant vascular structures. Results. A close correlation between TOF (R2 = 0.79; p<0.05) and contrast-enhanced (GdT) angiography (R2 = 0.92; p<0.05) with histological area measurements was found. LMRs were comparable between both sequences. Regarding interobserver reproducibility, contrast-enhanced (GdT) angiography yielded a smaller 95% confidence interval and a closer interreader correlation compared to non-contrast-enhanced (TOF) measurements (−0.73–0.89; R2 = 0.81 vs. −0.55–0.56; R2 = 0.94). Conclusion. This study demonstrates that non-contrast-enhanced and contrast-enhanced angiographies of the head/neck vasculature of small animals can reliably performed on a clinical 3T MR scanner. Contrast-enhanced angiography enables the visualization of vascular structures with higher intravascular contrast and higher reproducibility.
An Analytical Survey of Trace Heavy Elements in Insecticides
Authors: Abdallah Alnuwaiser Maha
Published: May 2019

There are many types of insecticides traded in the local and international markets, which vary depending on the type of target insect (e.g., whether crawling or flying). This paper aimed to assess the concentration of trace elements present in the various pesticide formulations (solid, liquid, and gaseous). This study was conducted in two groups: the first group was comprised of zinc, copper, iron, chromium, phosphorus, selenium, and cobalt; the second group included four heavy toxic elements (arsenic, thallium, lead, and mercury). These elements were analyzed by inductively coupled plasma/optical emission spectrometry (ICP-OES).
Age at Menopause and Risk of Developing Endometrial Cancer: A Meta-Analysis
Authors: Wu Yanjun , Sun Wenjun , Liu Hui , Zhang Dongfeng
Published: May 2019

Object. The association of age at menopause with endometrial cancer remains controversial. Therefore, we quantitatively summarized the evidence from observational studies with a meta-analysis.Methods. We searched PubMed, Web of Science, Embase, Medline, Chinese National Knowledge Infrastructure (CNKI), and Wan Fang Med online up to March 2019, and all eligible case-control and cohort studies were included in the study. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using the random-effects model. The dose-response relationship was assessed by restricted cubic spline model. The heterogeneity among studies was evaluated by I2. Metaregression was used to explore the potential sources of between-study heterogeneity. Egger’s test was used to estimate publication bias.Results. Eighteen articles including 957242 subjects with 4781 cases were included in the meta-analysis. The pooled RR (95%CI) of endometrial cancer for the highest versus the lowest age at menopause was 1.89 (95%CI: 1.58-2.26). For dose-response analysis, a nonlinear relationship was found between age at menopause and endometrial cancer, and the positive association became statistically significant when age at menopause was greater than 46.5 years old.Conclusions. This meta-analysis suggested that age at menopause was positively associated with endometrial cancer. For women whose menopausal age over 46.5 years old, the risk of endometrial cancer increased with the age at menopause.
IL15 by Continuous Intravenous Infusion to Adult Patients with Solid Tumors in a Phase I Trial Induced Dramatic NK-Cell Subset Expansion
Authors: Conlon Kevin C. , Potter E. Lake , Pittaluga Stefania , Lee Chyi-Chia Richard , Miljkovic Milos D. , Fleisher Thomas A. , Dubois Sigrid , Bryant Bonita R. , Petrus Michael , Perera Liyanage P. , Hsu Jennifer , Figg William D. , Peer Cody J. , Shih Joanna H. , Yovandich Jason L. , Creekmore Stephen P. , Roederer Mario , Waldmann Thomas A.
Published: May 2019

Purpose:

The first-in-human clinical trial with human bolus intravenous infusion IL15 (rhIL15) was limited by treatment-associated toxicity. Here, we report toxicity, immunomodulation, and clinical activity of rhIL15 administered as a 10-day continuous intravenous infusion (CIV) to patients with cancers in a phase I trial.

Patients and Methods:

Patients received treatment for 10 days with CIV rhIL15 in doses of 0.125, 0.25, 0.5, 1, 2, or 4 μg/kg/day. Correlative laboratory tests included IL15 pharmacokinetic (PK) analyses, and assessment of changes in lymphocyte subset numbers.

Results:

Twenty-seven patients were treated with rhIL15; 2 μg/kg/day was identified as the MTD. There were eight serious adverse events including two bleeding events, papilledema, uveitis, pneumonitis, duodenal erosions, and two deaths (one due to likely drug-related gastrointestinal ischemia). Evidence of antitumor effects was observed in several patients, but stable disease was the best response noted. Patients in the 2 μg/kg/day group had a 5.8-fold increase in number of circulating CD8+ T cells, 38-fold increase in total NK cells, and 358-fold increase in CD56bright NK cells. Serum IL15 concentrations were markedly lower during the last 3 days of infusion.

Conclusions:

This phase I trial identified the MTD for CIV rhIL15 and defined a treatment regimen that produced significant expansions of CD8+ T and NK effector cells in circulation and tumor deposits. This regimen has identified several biological features, including dramatic increases in numbers of NK cells, supporting trials of IL15 with anticancer mAbs to increase antibody-dependent cell-mediated cytotoxicity and anticancer efficacy.
Synchronous Detection of Circulating Tumor Cells in Blood and Disseminated Tumor Cells in Bone Marrow Predicts Adverse Outcome in Early Breast Cancer
Authors: Magbanua Mark Jesus M. , Yau Christina , Wolf Denise M. , Lee Jin Sun , Chattopadhyay Aheli , Scott Janet H. , Bowlby-Yoder Erin , Hwang E. Shelley , Alvarado Michael , Ewing Cheryl A. , Delson Amy L. , van't Veer Laura J. , Esserman Laura , Park John W.
Published: May 2019

Purpose:

We examined the prognostic impact of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) detected at the time of surgery in 742 untreated patients with early breast cancer.

Experimental Design:

DTCs in bone marrow were enumerated using the EPCAM-based immunomagnetic enrichment and flow cytometry (IE/FC) assay. CTCs in blood were enumerated either by IE/FC or CellSearch. Median follow-up was 7.1 years for distant recurrence-free survival (DRFS) and 9.1 years for breast cancer–specific survival (BCSS) and overall survival (OS). Cox regressions were used to estimate hazard ratios for DRFS, BCSS, and OS in all patients, as well as in hormone receptor–positive (HR-positive, 87%) and HR-negative (13%) subsets.

Results:

In multivariate models, CTC positivity by IE/FC was significantly associated with reduced BCSS in both all (n = 288; P = 0.0138) and HR-positive patients (n = 249; P = 0.0454). CTC positivity by CellSearch was significantly associated with reduced DRFS in both all (n = 380; P = 0.0067) and HR-positive patients (n = 328; P = 0.0002). DTC status, by itself, was not prognostic; however, when combined with CTC status by IE/FC (n = 273), double positivity (CTC+/DTC+, 8%) was significantly associated with reduced DRFS (P = 0.0270), BCSS (P = 0.0205), and OS (P = 0.0168). In HR-positive patients, double positivity (9% of 235) was significantly associated with reduced DRFS (P = 0.0285), BCSS (P = 0.0357), and OS (P = 0.0092).

Conclusions:

Detection of CTCs in patients with HR-positive early breast cancer was an independent prognostic factor for DRFS (using CellSearch) and BCSS (using IE/FC). Simultaneous detection of DTCs provided additional prognostic power for outcome, including OS.
EC359: A First-in-Class Small-Molecule Inhibitor for Targeting Oncogenic LIFR Signaling in Triple-Negative Breast Cancer
Authors: Viswanadhapalli Suryavathi , Luo Yiliao , Sareddy Gangadhara R. , Santhamma Bindu , Zhou Mei , Li Mengxing , Ma Shihong , Sonavane Rajni , Pratap Uday P. , Altwegg Kristin A. , Li Xiaonan , Chang Annabel , Chávez-Riveros Alejandra , Dileep Kalarickal V. , Zhang Kam Y.J. , Pan Xinlei , Murali Ramachandran , Bajda Marek , Raj Ganesh V. , Brenner Andrew J. , Manthati Vijaya , Rao Manjeet K. , Tekmal Rajeshwar R. , Nair Hareesh B. , Nickisch Klaus J. , Vadlamudi Ratna K.
Published: May 2019

Leukemia inhibitory factor receptor (LIFR) and its ligand LIF play a critical role in cancer progression, metastasis, stem cell maintenance, and therapy resistance. Here, we describe a rationally designed first-in-class inhibitor of LIFR, EC359, which directly interacts with LIFR to effectively block LIF/LIFR interactions. EC359 treatment exhibits antiproliferative effects, reduces invasiveness and stemness, and promotes apoptosis in triple-negative breast cancer (TNBC) cell lines. The activity of EC359 is dependent on LIF and LIFR expression, and treatment with EC359 attenuated the activation of LIF/LIFR-driven pathways, including STAT3, mTOR, and AKT. Concomitantly, EC359 was also effective in blocking signaling by other LIFR ligands (CTF1, CNTF, and OSM) that interact at LIF/LIFR interface. EC359 significantly reduced tumor progression in TNBC xenografts and patient-derived xenografts (PDX), and reduced proliferation in patient-derived primary TNBC explants. EC359 exhibits distinct pharmacologic advantages, including oral bioavailability, and in vivo stability. Collectively, these data support EC359 as a novel targeted therapeutic that inhibits LIFR oncogenic signaling.

See related commentary by Shi et al., p. 1337
G-CSF for Extensive STEMI
Authors: Achilli Felice , Pontone Gianluca , Bassetti Beatrice , Squadroni Lidia , Campodonico Jeness , Corrada Elena , Facchini Camilla , Mircoli Luca , Esposito Giovanni , Scarpa Daniele , Pidello Stefano , Righetti Stefano , Di Gennaro Filiberto , Guglielmo Marco , Muscogiuri Giuseppe , Baggiano Andrea , Limido Alberto , Lenatti Laura , Di Tano Giuseppe , Malafronte Cristina , Soffici Federica , Ceseri Martina , Maggiolini Stefano , Colombo Gualtiero I. , Pompilio Giulio ,   On behalf of the STEM-AMI OUTCOME CMR Sub-Study Investigators
Published: May 2019

Rationale:

In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment–elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term.

Objective:

The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment–elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain.

Methods and Results:

Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment–elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (
P
=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m
2
in the change of indexed LV end-systolic volume in favor of G-CSF group (
P
=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (
P
=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (
P
=0.04). Global circumferential strain significantly improved in G-CSF group only (
P
=0.006).

Conclusions:

Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment–elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01969890.
Roman Religion in the Time of Augustus
Authors: Bondioli Nelson de Paiva
Published: May 2019

This article first discusses the term “Roman religion” and the different views and meanings that it possesses, favoring an analysis of the sacra publica. It then considers the model of the polis-religion, both its common usage and its relevance or adequacy in the study of Roman religion. These discussions are followed by an analysis of the articulation of the idea of the mos maiorum within Augustan religious reforms.
a. d. viiii Kalendas Octobres, dies natalis Augusti. Some Considerations on the Astronomical Orientation of Roman Cologne and the Imperial Cult
Authors: Espinosa-Espinosa David , González-García A. César
Published: May 2019

A key factor in planning and orienting towns in the Roman world, and in particular in Augustan towns, was cosmology. The application of cosmological criteria in these towns, associated with specific political and religious principles of the principate of Augustus, has been already identified in Italia, Gallia, and Hispania. In this article we examine the orientation of the Roman town of Ara Ubiorum (present day Cologne) that could be related with the dies natalis Augusti. Based on these results, such a relation could have been deliberately sought by Roman and Ubian authorities to connect the newly founded town, where there was an ara of the Imperial cult probably consecrated to Rome and Augustus, with Augustus, who was identified with Apollo-Sol.
Occultist Identity Formations Between Theosophy and Socialism in fin-de-siècle France
Authors: Strube Julian
Published: May 2019

Fin-de-siècle occultism is usually regarded within the context of an “occult revival” that implies the modernization of an older esoteric tradition. However, this notion is rooted in esoteric identificatory discourses at the end of the nineteenth century. This article will discuss two major aspects of these discourses. First, French esotericists polemically distanced themselves from the “Eastern” esotericism of the Theosophical Society by constructing an ésotérisme occidental. It will be shown that this separation of “East” and “West” occurred as a reaction to the T.S., and should thus be seen as a “nationalist” response to a global phenomenon. Second, another major aspect of occultist identity formations will be highlighted: socialism. It will be shown that fin-de-siècle occultists were deeply involved with socialist theories in the July Monarchy vein but ambiguously distanced themselves from contemporary “materialist” socialisms. An analysis of this context will further help to understand the construction of an esoteric tradition.
How Cosmic War Ends
Authors: Juergensmeyer Mark
Published: May 2019

Like many other extremist movements, the Islamic State (isis) is propelled by an image of engagement in a grand cosmic war. Under what conditions does cosmic war end? The case of isis gives several possible answers, though we have to take both internal and external perspectives into account. The internal conditions include a loss of divine sanctions, in-fighting, a sense of rising doubt about the mission of the movement, discredited leadership when the leader is seen as less than legitimate, and the availability of alternative opportunities when combatants see opportunities for their roles in a non-war state. External conditions for ending cosmic war are equally important. Responses by government authorities include the maintenance of strong limitations on the ability of a movement to become violent, providing ways for the accommodation and rehabilitation of troops and leaders involved in the defeated movement, and an attitude of respect and cultural acceptance for communities that may have supported the extremist movements. In Iraq and Syria, it remains to be seen how Sunni Arab culture and leadership will be treated in a post-isis society. Military liberation is only part of the process of reintegration of the Arab Sunni population into the political life of those countries. A full acceptance into the political process will also be required. Failing that, the spirit of cosmic war will in all probability continue, and the conditions will be ripe for a renewal of militant encounter in the future.
Challenging the Curious Erasure of Religion from the Study of Religious Terrorism
Authors: Dawson Lorne L.
Published: May 2019

The role that religion plays in the motivation of “religious terrorism” is the subject of much ongoing dispute, even in the case of jihadist groups. Some scholars, for differing reasons, deny that it has any role; others acknowledge the religious character of jihadism in particular, but subtly discount the role of religion, while favoring other explanations for this form of terrorism. Extending an argument begun elsewhere (Dawson 2014, 2017), this article delineates and criticizes the influence of a normative religious bias, on the one hand, and a normative secular bias, on the other hand, on scholarship addressing the relationship between religiosity and terrorism. I examine two illustrative studies to demonstrate the complexity of the conceptual issues at stake: Karen Armstrong’s best-selling book Fields of Blood: Religion and the History of Violence (2014) and a recent article by Bart Schuurman and John G. Horgan on the rationales for terrorist violence in homegrown jihadist groups (2016).
“Among the Believers Are Men”
Authors: Nanninga Pieter
Published: May 2019

This article examines how the Islamic State has framed its extraordinary losses of manpower by analyzing the role of early-Islamic traditions in the martyr biographies included in its magazines Dabiq and Rumiyah. After exploring how is has composed these biographies, by focusing on their narrative structure and central themes, the article demonstrates that early-Islamic traditions about jihad and martyrdom form an important subtext of these articles. They contain many implicit references to stories about Muḥammad and his companions, by means of which is attempts to define and authorize the status of its killed operatives as martyrs and therefore as potentially powerful witnesses of its cause. Yet, the article subsequently argues, the martyrs as portrayed in the magazines are also thoroughly modern characters reflecting contemporary processes such as globalization, individualization, and deculturation. is thus invests classical Islamic traditions with new meanings by employing them in new contexts. Hence, the article concludes that understanding the dynamic role of Islamic scriptures in is’s discourse is crucial if we are to grasp the composition and appeal of is’s biographies and therefore also how is frames its losses and motivates actions of self-sacrifice among its operatives and supporters.
Repackaging India’s Sacred Geography: Travel Agencies and Pilgrimage-Related Travel
Authors: Aukland Knut
Published: May 2019

This article is an attempt to open up the study of pilgrimage and tourism by concentrating on the role of travel agencies in developing Hindu pilgrimage in India. Identifying two limitations in the ongoing debate, it makes use of less-explored themes and concepts including travel menus, package tours, itineraries, day tours, circuits, and scheduling. Surveying 46 travel brochures and popular tours promoted by travel agencies in Delhi, Haridwar, and Vrindavan, it investigates how travel agencies repackage the sacred geography of Hinduism, tying it up with the broader tourist geography of India. Turning to the varied motivations of participants in day tours to pilgrimage sites, I present my analysis of the overarching developments in what I call pilgrimage-related travel. Crucially, visits to pilgrimage sites are increasingly framed as darshan tours reflecting how increased scheduling privileges darshan and donation as the principal religious act.
Aristotle, Metaphysics Θ.8, 1050b6-28
Authors: Judson Lindsay
Published: May 2019

The standard interpretation of this passage sees Aristotle as claiming that if a thing is F eternally, its being F is not the exercise of any potentiality to be F, and as explicitly applying this claim to the heavenly bodies. This interpretation faces a number of difficulties: I shall offer a different reading which avoids these, and which brings out interesting connections between this passage and some arguments in Λ.6-7.
Hierocles and the Stoic Theory of Blending
Authors: Helle Reier
Published: May 2019

In Stoic physics, blending (κρᾶσις) is the relation between active pneuma and passive matter; natural bodies from rocks and logs to plants, animals and the cosmos itself are blends of pneuma and matter. Blending structures the Stoic cosmos. I develop a new interpretation of the Stoic theory of blending, based on passages from Hierocles. The theory of blending, I argue, has been misunderstood. Hierocles allows us to see in detail how the theory is supposed to work and how it fits into Stoic physics.