bluuebunny/crossref_metadata_2025 huggingface dataset:
(r)Alpha Lipoic Acid Is a Safe, Effective Pharmacologic Therapy of Chronic Orthostatic Hypotension Associated with Low Sympathetic Tone
Authors: Murray Gary L. , Colombo Joseph
Published: February 2019

Chronic orthostatic hypotension (OH), affecting 10 to 30% of the elderly, is associated with falls, and increased morbidity and mortality. Current pharmacologic therapy can cause or worsen hypertension and fluid retention. (r)α lipoic acid (ALA), a powerful natural antioxidant, avoids those complications and may assist management of chronic neurogenic orthostatic hypotension (NOH). The purpose of this study is to demonstrate improvement in the symptoms of orthostatic dysfunction with r-ALA, including improved sympathetic (S) and blood pressure (BP) responses to head-up postural change (standing).

A cohort of 109 patients with low S tone upon standing was detected using the ANX −3.0, Autonomic Monitor, ANSAR Medical Technologies, Inc., Philadelphia, PA. From the cohort, 29 patients demonstrated NOH (change in (∆) standing BP ≥ −20/–10 mm Hg); 60 patients demonstrated orthostatic intolerance (OI, ∆ standing systolic BP between –6 and –19 mm Hg). These 89 were given ALA orally: either 590 to 788 mg (r)ALA or 867 to 1,500 mg of the less expensive 50 to 50% mixture (r)ALA and inactive (s)ALA. Changes in their S and parasympathetic (P) tone, and BPs, were compared with 20 control patients during mean follow-up of 2.28 years.

Nineteen of 29 (66%) NOH patients responded with a ∆ standing BP from –28/–6 mm Hg to 0/+2 mm Hg. Forty of 60 (67%) of patients with OI responded with a ∆ standing BP of –9/+1 mm Hg to +6/+2 mm Hg. Although all patients treated with ALA increased S tone, the ∆ BP depended upon the pretreatment of S tone. Those with the lowest S tone responded the least well. The only treatment side effects were nausea, intolerable in only 5%. Nausea improved with routine gastrointestinal medications. Glucose levels improved in the 28% of patients who were diabetic. Also, resting hypertension improved. Control patients had no ∆ BP and no increase in S tone.

(r)ALA improves S-, and BP, responses to head-up postural change, and thereby NOH/OI, in a majority of patients without causing harmful side effects.
Importance of Flaxseed and its Components in the Management of Hypertension
Authors: Prasad Kailash
Published: February 2019

This review paper describes the effects of flaxseed and its components (flax oil, secoisolariciresinol diglucoside [SDG], flax lignan complex [FLC], and flaxseed protein hydrolysate [FPH]) on blood pressure (BP) in Sprague Dawley rats (SDR), spontaneously hypertensive rats (SHR), and humans. Flaxseed, flax oil, and FLC had variable effects on BP in humans, while SDG and FPH significantly reduced the BP in SDR and SHR. The effect of SDG was dose-dependent and long lasting. The lowering of BP is mediated through inhibition of soluble epoxide by α-linolenic acid in flax oil, stimulation of guanylate cyclase and inhibition of angiotensin converting enzyme (ACE) by SDG, and inhibition of renin and ACE activity by FPH. Flaxseed, flax oil, and FLC have variable effects on BP (none, slight, and significant). They are effective in lowering BP in individuals with hypertension and metabolic syndrome but ineffective in healthy individuals' ineffectiveness of flaxseed and its compounds in lowering BP may be due to their low doses, long interval of dosing, short duration of consumption, and patient status. In conclusion, the data at present suggest that flaxseed, flax oil, and FLC cannot serve as therapeutic agents for the treatment of hypertension. However, they can be used as an adjunct in the treatment of hypertension. A clinical trial should be conducted of these agents with higher doses which would be given twice daily for long duration. Pure SDG and FPS may serve as therapeutic agents for the treatment of hypertension but they have not been tried in humans.
Phosphate graphene as an intrinsically osteoinductive scaffold for stem cell-driven bone regeneration
Authors: Arnold Anne M. , Holt Brian D. , Daneshmandi Leila , Laurencin Cato T. , Sydlik Stefanie A.
Published: February 2019

Significance

Traumatic bone injuries or deformities are among the most common conditions that require surgical intervention affecting patients in the United States today. Current treatment options suffer shortcomings, clearly demonstrating a clinical need for tissue replacement techniques. An ideal treatment consists of a scaffold that promotes regeneration, matches the chemical and mechanical properties of bone, and degrades with a timeline matching the healing process. However, this ideal scaffold has not been realized. Here, we present a degradable, graphene-based material that mimics the chemical and mechanical composition of bone, promotes differentiation of stem cells, and leads to the formation of new bone in an animal model.
Antidepressants are modifiers of lipid bilayer properties
Authors: Kapoor Ruchi , Peyear Thasin A. , Koeppe Roger E. , Andersen Olaf S.
Published: February 2019

The two major classes of antidepressants, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), inhibit neurotransmitter reuptake at synapses. They also have off-target effects on proteins other than neurotransmitter transporters, which may contribute to both desired changes in brain function and the development of side effects. Many proteins modulated by antidepressants are bilayer spanning and coupled to the bilayer through hydrophobic interactions such that the conformational changes underlying their function will perturb the surrounding lipid bilayer, with an energetic cost (ΔGdef) that varies with changes in bilayer properties. Here, we test whether changes in ΔGdef caused by amphiphilic antidepressants partitioning into the bilayer are sufficient to alter membrane protein function. Using gramicidin A (gA) channels to probe whether TCAs and SSRIs alter the bilayer contribution to the free energy difference for the gramicidin monomer⇔dimer equilibrium (representing a well-defined conformational transition), we find that antidepressants alter gA channel activity with varying potency and no stereospecificity but with different effects on bilayer elasticity and intrinsic curvature. Measuring the antidepressant partition coefficients using isothermal titration calorimetry (ITC) or cLogP shows that the bilayer-modifying potency is predicted quite well by the ITC-determined partition coefficients, and channel activity is doubled at an antidepressant/lipid mole ratio of 0.02–0.07. These results suggest a mechanism by which antidepressants could alter the function of diverse membrane proteins by partitioning into cell membranes and thereby altering the bilayer contribution to the energetics of membrane protein conformational changes.
Membrane physiologists of all kinds meet at Woods Hole
Authors: Robertson Janice L. , Faraldo-Gómez José D.
Published: February 2019

A special issue of JGP celebrates the 2018 Symposium of the Society of General Physiologists, where diversity and world-class science went hand in hand.
Invited Commentary: Examining Sex/Gender Differences in Risk of Alzheimer Disease and Related Dementias—Challenges and Future Directions
Authors: Mayeda Elizabeth Rose
Published: February 2019

The majority of people living with Alzheimer disease (AD) and related dementias are women. Longer life expectancy is one factor thought to contribute to this observation, but possible sex-specific biological mechanisms have received considerable attention from the research community. In the current issue of the Journal, Buckley et al. (Am J Epidemiol. 2019;188(7):1213–1223) use death certificate information on all deaths occurring among adults aged ≥60 years in Australia between 2006 and 2014 to evaluate sex/gender differences in rates of death with dementia (all types), AD dementia, and vascular dementia listed on the death certificate. The paper by Buckley et al. highlights several important methodological challenges for research examining sex/gender differences in risk of AD and related dementias, including challenges in measurement, survival bias and competing risks, and selection bias arising from sample selection. The current evidence on possible sex-specific biological risk factors for AD is intriguing, but there are numerous alternative explanations for differences in AD dementia and AD biomarkers between women and men. Triangulation of evidence from study designs with different strengths and weaknesses and transdisciplinary collaboration will be vital to generating conclusive evidence about sex/gender differences in risk of AD and related dementias.
Monitoring temperature-sensitive vaccines and immunologic drugs, including anthrax vaccine
Authors: Frank Kirk J.
Published: February 2019

The experience of the U.S. Army Medical Materiel Center, Europe (USAMMCE), in monitoring temperature-sensitive vaccines and immunologic drugs, including anthrax vaccine, during storage and shipment is discussed.

USAMMCE uses an electronic monitoring device to monitor and archive the time-temperature history of shipments of various vaccines, immunoglobulins, and other drugs requiring refrigeration. Using these monitors, USAMMCE can track its carriers’ performance, reduce product loss, and validate quality. USAMMCE trains people to pack refrigerated items and to activate and place the monitoring device inside the packing container. Over 1200 temperature-monitor readings from 44 U.S. military logistical depots, hospitals, and clinics located outside the United States are evaluated annually by the USAMMCE pharmacist; each reading represents one shipment or packed box. When deactivated during unpacking, the device flashes green for a successful shipment (all temperature readings within the ideal range) or red for a potentially problematic shipment. From January through October 1998, the device was used in 750 temperature-sensitive shipments; 72% of the devices were returned to USAMMCE in green condition and the remainder in red. Of the red-flashing monitors, 15% were determined to signal that the drugs were received in unacceptable condition. USAMMCE successfully shipped more than 26,000 vials of anthrax vaccine from February through October 1998 within the manufacturer’s guidelines for storage temperature.

Temperature monitoring is essential for proper storage and transport of vaccines and immunologic drugs.
Cooperative effects of sequential PGF2α and IL-1β on IL-6 and COX-2 expression in human myometrial cells
Authors: Leimert Kelycia B , Verstraeten Barbara S E , Messer Angela , Nemati Rojin , Blackadar Kayla , Fang Xin , Robertson Sarah A , Chemtob Sylvain , Olson David M
Published: February 2019

The change from the state of pregnancy to the state of parturition, which we call uterine transitioning, requires the actions of inflammatory mediators and results in an activated uterus capable of performing the physiology of labor. Interleukin (IL)-1β and prostaglandin (PG)F2α are two key mediators implicated in preparing the uterus for labor by regulating the expression of uterine activation proteins (UAPs) and proinflammatory cytokines and chemokines. To investigate this process, primary human myometrial smooth muscle cells (HMSMC) isolated from the lower segment of women undergoing elective cesarean sections at term (not in labor) were used to test the inflammatory cytokine and UAP outputs induced by PGF2α and IL-1β alone or in sequential combinations. PGF2α and IL-1β regulate mRNA abundance of the PGF2α receptor FP, the IL-1 receptor system, interleukin 6, and other UAPs (OXTR, COX2), driving positive feedback interactions to further amplify their own proinflammatory effects. Sequential stimulation of HMSMC by PGF2α and IL-1β in either order results in amplified upregulation of IL-6 and COX-2 mRNA and protein, compared to their effects individually. These profound increases were unique to myometrium and not observed with stimulation of human fetal membrane explants. These results suggest that PGF2α and IL-1β act cooperatively upstream in the birth cascade to maximize amplification of IL-6 and COX-2, to build inflammatory load and thereby promote uterine transition. Targeting PGF2α or IL-1β, their actions, or intermediates (e.g. IL-6) would be an effective therapeutic intervention for preterm birth prevention or delay.
The Role of Humour in the Social Care Professions: An Exploratory Study
Authors: Fogarty Molly , Elliot Dely Lazarte
Published: February 2019

Six social care professionals were recruited to take part in in-depth interviews that sought to explore their phenomenological experiences of humour within their place of work. Using an Interpretative Phenomenological Analysis (IPA) approach, the results suggest that humour serves various important functions within social care. Humour can allow social care professionals to relieve themselves of negative emotions, to avoid stress and cynicism, to achieve a sense of normality and perspective and to engage with service users. The positive impact humour appears to have upon these professionals is in keeping with the humour–health hypothesis, which posits that humour enhances well-being. However, results from this study also suggest that humour may be capable of negatively impacting well-being. Arguably, these findings highlight the need to extend the humour–health hypothesis and incorporate the negative effects humour can have upon well-being. Results also indicate that, if used appropriately, humour can be utilised to benefit work performance and service user outcomes. The findings of this research hold important implications for how humour may be understood and fostered in social care training, practice and policy.
Identification of long non-coding RNA HERC2P2 as a tumor suppressor in glioma
Authors: Yang Chao , Wang Lin , Sun Jia , Zhou Jun-hu , Tan Yan-li , Wang Yun-fei , You Hua , Wang Qi-xue , Kang Chun-sheng
Published: February 2019

Long non-coding RNAs (lncRNAs) have been reported to play important roles in glioma; however, most of them promote glioma progression. We constructed a competing endogenous (ceRNA) network based on the Chinese Glioma Genome Atlas dataset, and lncRNA hect domain and RLD 2 pseudogene 2 (HERC2P2) is the core of this network. Highly connected genes in the ceRNA network classified the glioma patients into three clusters with significantly different survival rates. The expression of HERC2P2 is positively correlated with survival and negatively correlated with clinical grade. Cell colony formation, Transwell and cell scratch tests were performed to evaluate the role of HERC2P2 in glioblastoma growth. Furthermore, we overexpressed HERC2P2 in U87 cells and established a mouse intracranial glioma model to examine the function of HERC2P2 in vivo. In conclusion, we identified a lncRNA with tumor suppressor functions in glioma that could be a potential biomarker for glioma patients.
Effect of antipsychotics on community structure in functional brain networks
Authors: Flanagan Ryan , Lacasa Lucas , Towlson Emma K , Lee Sang Hoon , Porter Mason A
Published: February 2019

Schizophrenia, a mental disorder that is characterized by abnormal social behaviour and failure to distinguish one’s own thoughts and ideas from reality, has been associated with structural abnormalities in the architecture of functional brain networks. In this article, we (1) investigate whether mesoscale network properties give relevant information to distinguish groups of patients from controls in different scenarios and (2) use this lens to examine network effects of different antipsychotic treatments. Using various methods of network analysis, we examine the effect of two classical therapeutic antipsychotics—Aripiprazole and Sulpiride—on the architecture of functional brain networks of both controls (i.e., a set of people who were deemed to be healthy) and patients (who were diagnosed with schizophrenia). We compare community structures of functional brain networks of different individuals using mesoscopic response functions, which measure how community structure changes across different scales of a network. Our approach does a reasonably good job of distinguishing patients from controls, and the distinction is sharper for patients and controls who have been treated with Aripiprazole. Unexpectedly, we find that this increased separation between patients and controls is associated with a change in the control group, as the functional brain networks of the patient group appear to be predominantly unaffected by this drug. This suggests that Aripiprazole has a significant and measurable effect on community structure in healthy individuals but not in individuals who are diagnosed with schizophrenia, something that conflicts with the naive assumption that the drug alters the mesoscale network properties of the patients (rather than the controls). By contrast, we are less successful at separating the networks of patients from those of controls when the subjects have been given the drug Sulpiride. Taken together, in our results, we observe differences in the effects of the drugs (and a placebo) on community structure in patients and controls and also that this effect differs across groups. From a network-science perspective, we thereby demonstrate that different types of antipsychotic drugs selectively affect mesoscale properties of brain networks, providing support that structures such as communities are meaningful functional units in the brain.
Flight initiation distance, color and camouflage
Authors: Møller Anders Pape , Liang Wei , Samia Diogo S M
Published: February 2019

Camouflage is widespread throughout the animal kingdom allowing individuals to avoid detection and hence save time and energy rather than escape from an approaching predator. Thus, camouflage is likely to have co-evolved with antipredator behavior. Here, we propose that camouflage results in dichotomous escape behavior within and among species with classes of individuals and species with cryptic coloration having shorter flight initiation distances (FIDs; the distance at which an individual takes flight when approached by a human). We report the results of 2 tests of this hypothesis. First, bird species with cryptically colored plumage have consistently shorter FID than closely related species without such color. Within species with sexually dimorphic plumage, brightly colored adult male common pheasants Phasianus colchicus and golden pheasants Chrysolophus pictus have long and variable FID, whereas cryptically colored juveniles and adult females have short and invariable FID. Second, FID in females was predicted by presence or absence of cryptic color, FID in males and their interaction. These findings are consistent with the hypothesis that risk-taking behavior has been attuned to camouflage, and that species with different levels of camouflage differ consistently in their FID.
Surgery for anomalous aortic origin of coronary arteries: a multicentre study from the European Congenital Heart Surgeons Association†
Authors: Padalino Massimo A , Franchetti Nicola , Hazekamp Mark , Sojak Vladimir , Carrel Thierry , Frigiola Alessandro , Lo Rito Mauro , Horer Jurgen , Roussin Regine , Cleuziou Julie , Meyns Bart , Fragata Jose , Telles Helena , Polimenakos Anastasios C , Francois Katrien , Veshti Altin , Salminen Jukka , Rocafort Alvaro Gonzalez , Nosal Matej , Vedovelli Luca , Guariento Alvise , Vida Vladimiro L , Sarris George E , Boccuzzo Giovanna , Stellin Giovanni
Published: February 2019

OBJECTIVES:

We sought to describe early and late outcomes in a large surgical series of patients with anomalous aortic origin of coronary arteries.

METHODS:

We performed a retrospective multicentre study including surgical patients with anomalous aortic origin of coronary arteries since 1991. Patients with isolated high coronary takeoff and associated major congenital heart disease were excluded.

RESULTS:

We collected 156 surgical patients (median age 39.5 years, interquartile range 15–53) affected by anomalous right (67.9%), anomalous left (22.4%) and other anatomical abnormalities (9.6%). An interarterial course occurred in 86.5%, an intramural course in 62.8% and symptoms in 85.9%. The operations included coronary unroofing (56.4%), reimplantation (19.2%), coronary bypass graft (15.4%) and other (9.0%). Two patients with preoperative cardiac failure died postoperatively (1.3%). All survivors were discharged home in good clinical condition. At a median follow-up of 2 years (interquartile range 1–5, 88.5% complete), there were 3 deaths (2.2%), 9 reinterventions in 8 patients (5 interventional, 3 surgical); 91.2% are in New York Heart Association functional class ≤ II, but symptoms persisted in 14.2%; 48.1% of them returned to sport activity. On Kaplan–Meier analysis, event-free survival at follow-up was 74.6%. Morbidity was not significantly different among age classes, anatomical variants and types of surgical procedures. Furthermore, return to sport activity was significantly higher in younger patients who participated in sports preoperatively.

CONCLUSIONS:

Surgical repair of anomalous aortic origin of coronary arteries is effective and has few complications. Unroofing and coronary reimplantation are safe and are the most common procedures. The occurrence of late adverse events is not negligible, and long-term surveillance is mandatory. Most young athletes can return to an unrestrained lifestyle.
Double orifice and atrioventricular septal defect: dealing with the zone of apposition†
Authors: Pontailler Margaux , Haidar Moussa , Méot Mathilde , Moreau de Bellaing Anne , Gaudin Régis , Houyel Lucile , Metton Olivier , Moceri Pamela , Bonnet Damien , Vouhé Pascal , Raisky Olivier
Published: February 2019

OBJECTIVES

A double orifice of the left atrioventricular valve (LAVV) associated with atrioventricular septal defects (AVSD) can significantly complicate surgical repair. This study reports our experience of AVSD repair over 3 decades, with special attention to the zone of apposition (ZoA) of the main orifice, and presents a technique of hemivalve pericardial extension in specific situations.

METHODS

We performed a retrospective study from 1987 to 2016 on 1067 patients with AVSD of whom 43 (4%) had a double orifice, plus 2 additional patients who required LAVV pericardial enlargement. Median age at repair was 1.3 years. Mean follow-up was 8.2 years (1 month–32 years).

RESULTS

Associated abnormalities of the LAVV subvalvular apparatus were found in 7 patients (5 parachute LAVV and 2 absence of LAVV subvalvular apparatus). ZoA was noted in 4 patients (9%): partially closed in 15 (35%) and completely closed in 24 (56%). Four patients required, either at first repair or secondarily, a hemivalve enlargement using a pericardial patch without closure of the ZoA. The early mortality rate was 7% (n = 3), all before 2000. Two patients had unbalanced ventricles and the third had a single papillary muscle. There were no late deaths. Six patients (14%) required 7 reoperations (3 early and 4 late reoperations) for LAVV regurgitation and/or dysfunction, of whom 4 (9%) required mechanical LAVV replacement (all before 2000). Freedom from late LAVV reoperation was 97% at 1 year, 94% at 5 years and 87% at 10, 20 and 30 years. Unbalanced ventricles (P = 0.045), subvalvular abnormalities (P = 0.0037) and grade >2 LAVV postoperative regurgitation (P = 0.017) were identified as risk factors for LAVV reoperations. Freedom from LAVV mechanical valve replacement was 95% at 1 year, 90% at 5 years and 85% at 10, 20 and 30 years. An anomalous LAVV subvalvular apparatus was identified as a risk factor for mechanical valve replacement (P = 0.010). None of the patients who underwent LAVV pericardial extension had significant LAVV regurgitation at the last follow-up examination.

CONCLUSIONS

Repair of AVSD and double orifice can be tricky. Preoperative LAVV regurgitation was not identified as an independent predictor of surgical outcome. LAVV hemivalve extension appears to be a useful and effective alternate surgical strategy when the ZoA cannot be closed.
Next Generation Strategies for Geroprotection via mTORC1 Inhibition
Authors: Dumas Sabrina N , Lamming Dudley W
Published: February 2019

Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of model organisms including rodents, with evidence now emerging that rapamycin and its analogs may also have rejuvenative effects in dogs and humans. However, the side effects associated with long-term rapamycin treatment, many of which are due to inhibition of a second mTOR complex, mTORC2, have seemed to preclude the routine use of rapamycin as a therapy for age-related diseases. Here, we discuss recent findings suggesting that strong, chronic inhibition of both mTOR complexes may not be necessary to realize the geroprotective effects of rapamycin. Instead, modestly but specifically inhibiting mTORC1 via a variety of emerging techniques, including intermittent or transient treatment with rapamycin derivatives, or specific dietary regimens, may be sufficient to promote health and longevity with reduced side effects. We will also discuss prospects for the development of new molecules that, by harnessing the detailed molecular understanding of mTORC1 signaling developed over the last decade, will provide new routes to the selective inhibition of mTORC1. We conclude that therapies based on the selective inhibition of mTORC1 may soon permit the safer treatment of diseases of aging.
Streptococcus Salivarius: A Potential Salivary Biomarker for Orofacial Granulomatosis and Crohn’s Disease?
Authors: Goel Rishi M , Prosdocimi Erica M , Amar Ariella , Omar Yasmin , Escudier Michael P , Sanderson Jeremy D , Wade William G , Prescott Natalie J
Published: February 2019

Background

Orofacial granulomatosis (OFG) is a rare disease characterised by chronic, noncaseating, granulomatous inflammation primarily affecting the oral cavity. Histologically, it is similar to Crohn’s disease (CD), and a proportion of patients have both OFG and CD. The cause of OFG remains elusive, but it has been suggested that microbial interactions may be involved. The aim of this study was to compare the salivary microbial composition of subjects with OFG and/or CD and healthy controls.

Methods

Two hundred sixty-one subjects were recruited, of whom 78 had OFG only, 40 had both OFG and CD, 97 had CD only with no oral symptoms, and 46 were healthy controls. Bacterial community profiles were obtained by sequencing the V1-V3 region of the 16S rRNA gene.

Results

There were no differences in richness or diversity of the salivary bacterial communities between patient groups and controls. The relative abundance of the Streptococcus salivarius group was raised in patients with OFG or CD only compared with controls, whereas that of the Streptococcus mitis group was lower in CD compared with both OFG and controls. One S. salivarius oligotype made the major contribution to the increased proportions seen in patients with OFG and CD.

Conclusions

The salivary microbiome of individuals with OFG and CD was similar to that found in health, although the proportions of S. salivarius, a common oral Streptococcus, were raised. One specific strain-level oligotype was found to be primarily responsible for the increased levels seen.
Is microwave ablation more effective than radiofrequency ablation in achieving local control for primary pulmonary malignancy?
Authors: Tsakok Maria Theresa , Jones Daniel , MacNeill Alice , Gleeson Fergus Vincent
Published: February 2019

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was ‘Is microwave ablation (MWA) more effective than radiofrequency ablation (RFA) in achieving local control for primary lung cancer?’. Altogether, 439 papers were found, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Both are thermal ablative techniques, with microwave ablation (MWA) the newer technique and radiofrequency ablation (RFA) with a longer track record. Lack of consensus with regard to definitions of technical success and efficacy and heterogeneity of study inclusions limits studies for both. The only direct comparison study does not demonstrate a difference with either technique in achieving local control. The quality of evidence for MWA is very limited by retrospective nature and heterogeneity in technique, power settings and tumour type. Tumour size and late-stage cancer were shown to be associated with higher rates of local recurrence in 1 MWA study. RFA studies were generally of a higher level of evidence comprising prospective trials, systematic review and meta-analysis. The recurrence rates for MWA and RFA overlapped, and for the included studies ranged between 16% and 44% for MWA and 9% and 58% for RFA. The current evidence, therefore, does not clearly demonstrate a benefit of MWA over RFA in achieving local control in primary lung cancer.
Expanding Cone and Applications to Homogeneous Dynamics
Authors: Shi Ronggang
Published: February 2019

Let $U$ be a horospherical subgroup of a noncompact simple Lie group $H$ and let $A$ be a maximal split torus in the normalizer of $U$. We define the expanding cone $A_U^+$ in $A$ with respect to $U$ and show that it can be explicitly calculated. We prove several dynamical results for translations of $U$-slices by elements of $A_U^+$ on a finite volume homogeneous space $G/\Gamma $ where $G$ is a Lie group containing $H$. More precisely, we prove quantitative nonescape of mass and equidistribution of a $U$-slice. If $H$ is a normal subgroup of $G$ and the $H$ action on $G/\Gamma $ has a spectral gap, we prove effective multiple equidistribution and pointwise equidistribution with an error rate. In this paper, we formulate the notion of the expanding cone and prove the dynamical results above in the more general setting where $H$ is a semisimple Lie group without compact factors. In the appendix, joint with Rene Rühr, we prove a multiple ergodic theorem with an error rate.
Status, Stratified Rights, and Accommodation in International Relations
Authors: Ward Steven
Published: February 2019

Denied status claims can produce serious interstate conflict and accommodation may thus be an important means of avoiding conflict with rising and reemerging status seekers such as China and Russia. But accommodation is an underdeveloped concept. This article draws on scholarship about recognition and hierarchy to propose a novel means of understanding status accommodation: as behavior that sends signals to status seekers about the validity of claims to stratified rights. This framework implies that acts that signal status denial (and thus cause conflict over status) may be driven by three broad kinds of processes: anxiety about a state's position in the world; incompatibility between nonstatus interests and claims to status-implicated rights; and fears about the implications of status accommodation for the validity of discourses and ideas that produce both international and domestic order. These dynamics—especially the latter two—may be linked to domestic political mechanisms and concerns in ways that analysts do not fully appreciate. I illustrate the framework by examining the forces that drove the United States to deny Japanese claims to equal status during the decades before World War II.
Optimizing Postoperative Surveillance of Pediatric Low-Grade Glioma Using Tumor Behavior Patterns
Authors: Zaazoue Mohamed A , Manley Peter E , Mehdar Mohammed Al , Ullrich Nicole J , Dasenbrock Hormuzdiyar H , Chordas Christine A , Goumnerova Liliana C
Published: February 2019

BACKGROUND

Pediatric low-grade gliomas are among the most common childhood neoplasms, yet their post-treatment surveillance remains nonstandardized, relying on arbitrarily chosen imaging intervals.

OBJECTIVE

To optimize postoperative magnetic resonance imaging (MRI) surveillance protocols for pediatric low-grade gliomas.

METHODS

Patients aged 0 to 21 yr with pediatric low-grade gliomas, treated between 1990 and 2016 were retrospectively analyzed. The timing of surveillance imaging and radiologic tumor outcomes were extracted, and the effect of patient age, tumor location, histology, and extent of resection as prognostic factors was studied. An algorithm was developed to analyze the detection efficacy and cost of all possible surveillance protocols.

RESULTS

A total of 517 patients were included with a median follow-up of 7.7 yr (range: 2-25.1 yr) who underwent 8061 MRI scans (mean 15.6 scans per patient). Tumor recurrence was detected radiologically in 292 patients (56.5%), of whom, 143 underwent reoperation. The hazards ratio (HR) of recurrence was higher in patients who underwent biopsy (HR = 3.60; 95% confidence interval (CI): 2.45-5.30; P < .001), subtotal resection (HR = 2.97; 95% CI: 2.18-4.03; P < .001), and near-total resection (HR = 2.03; 95% CI: 1.16-3.54; P = .01), compared to patients with gross total resection (GTR). For all patients, an 8-image surveillance protocol at 0, 3, 6, 12, 24, 36, 60, and 72 mo (total cost: $13 672 per patient) yielded comparative detection rates to the current 15-image protocol ($25 635). For patients who underwent GTR, a 6-image protocol at 0, 3, 9, 24, 36, and 60 mo ($10 254) is sufficient.

CONCLUSION

Our data suggest that postoperative surveillance of pediatric low-grade gliomas can be effectively performed using less frequent imaging compared to current practice, thereby improving adherence to follow-up, and quality-of-life, while reducing costs.
Reduced risk of new onset stroke after kidney transplantation in Asian dialysis patients: a propensity score-matched, competing risk study in Taiwan
Authors: Weng S -F , Shen Y -C , Wang J -J , Tien K -J
Published: February 2019

Background

Kidney transplantation (KT) has been found to reduce cardiovascular events and mortality in chronic dialysis patients. There is little data, however, regarding the risk reduction of cerebrovascular events after KT in Asian populations. This study evaluates the risk of cerebrovascular events after KT in Taiwan.

Methods

Tapping Taiwan’s National Health Insurance claims data of patients with a diagnosis of end-stage renal disease (ESRD), we enrolled all KT recipients from 1999 to 2011 (n = 2908). For each KT patient, four controls (patients also diagnosed with ESRD) without KT were propensity matched by birth date, sex, selected comorbidities and duration of dialysis. All subjects were followed to the end of 2011.

Results

The incidence rate for stroke in the KT recipients and comparison group were 52.63 and 137.26 per 10 000 person-years, respectively. After adjustment for age, gender and comorbidities with competing mortality, KT recipients had 60% reduction in all kinds of stroke, compared to those who did not receive procedure. They were found to have a 48 and 74% reduction in ischemic and hemorrhagic stroke risk, respectively. Subgroup analyses also showed similar trends in the improvement of stroke after KT. While elderly patients, men, and those with diabetes, hypertension and coronary artery disease are at increased risk for stroke, our log-rank test revealed those that received KT had significantly lower cumulative incidence rates of stroke than those that did not (P < 0.001).

Conclusions

KT was associated with reduced risk of new onset stroke in chronic dialysis patients in Taiwan.
New approaches to political economy
Authors: Amable Bruno , Regan Aidan , Avdagic Sabina , Baccaro Lucio , Pontusson Jonas , Van der Zwan Natascha
Published: February 2019

The discussion on ‘New Approaches to Political Economy (PE)’ gives us a state-of-the-art overview of the main theoretical and conceptual developments within the concept of political economy. Thereby, it invites us to broaden our knowledge regarding manifold novel approaches, which make use of more complex methods to study the less stable, less predictable, but faster changing realities of smaller or bigger geographical regions. In this discussion forum, Amable takes a closer look on the nature of ‘conflict’ as well as the relationship between conflict and institutional change or stability. After stressing the relevance of comparative capitalism in general, Regan also zooms in on the political conflicts in comparative political economy from three different perspectives (electoral politics, organized interest groups and business-state elites), where he finds new avenues, tensions and research agendas are opening up. From a different perspective, Avdagic reviews the broad developments in the field of political economy with respect to the supply and demand side of redistributive policy. Thereafter, Baccaro and Pontusson sketch an alternative ‘growth model perspective’, which puts demand and distribution at the center of the analysis. Finally, Van der Zwan analyses the usefulness of financialization studies for the study of (comparative) political economy.
How does water flow from vessel to vessel? Further investigation of the tracheid bridge concept
Authors: Pan Ruihua , Tyree Melvin T
Published: February 2019

Hydraulic safety and efficiency have become the central concept of the interpretation of the structure and function of vessels and their interconnections. Plants form an appropriate xylem network structure to maintain a balance of hydraulic safety vs efficiency. The term ‘tracheid bridge’ is used to describe a possible pathway of water transport between neighboring vessels via tracheids, and this pathway could also provide increased safety against embolisms. However, the only physiological study of such a structure thus far has been in Hippophae rhamnoides Linn. To test the function of tracheid bridges, this research examined four species that have relatively long and solitary vessels, which are two of the criteria for efficient tracheid bridges. Tracheids contributed less than 2.2% of the total conductance of the vessels in these species, but in theory, tracheids could serve as very efficient transport connector pathways that may or may not make direct vessel-to-vessel contact via pit fields between adjacent vessels. In some species, tracheid bridges may represent the dominant pathway for water flow between vessels, whereas in other species, tracheid bridges may be sub-dominant or virtually nil. Broader searches of woody taxa are needed to reveal the functional importance of tracheid bridges in vascular plants.
From prevalence to incidence - a new approach in the hospital setting
Authors: Willrich Niklas , Haller Sebastian , Eckmanns Tim , Zacher Benedikt , Kärki Tommi , Plachouras Diamantis , Cassini Alessandro , Suetens Carl , Behnke Michael , Gastmeier Petra , Walter Jan
Published: February 2019

Point-prevalence surveys (PPSs) are often used to estimate the prevalence of healthcare-associated infections (HAIs). Methods for estimating incidence of HAIs from prevalence have been developed, but application of these methods is often difficult because key quantities, like the average length of infection, cannot be derived directly from the data available in a PPS. We propose a new theory-based method to estimate incidence from prevalence data dealing with these limitations and compare it to other estimation methods in a simulation study. In contrast to previous methods, our method does not depend on any assumptions on the underlying distributions of length of infection and length of stay. As a basis for the simulation study we use data from the second study of nosocomial infections in Germany (Nosokomiale Infektionen in Deutschland, Erfassung und Prävention - NIDEP2) and the European surveillance of HAIs in intensive care units (HAI-Net ICU). The new method compares favourably with the other estimation methods and has the advantage of being consistent in its behaviour across the different setups. It is implemented in an R-package prevtoinc which will be freely available on CRAN (http://cran.r-project.org/).
Highly sensitive and multiplexed in situ protein profiling with cleavable fluorescent streptavidin
Authors: Liao Renjie , Mastroeni Diego , Coleman Paul D. , Guo Jia
Published: February 2019

The ability to perform highly sensitive and multiplexed in situ protein analysis is crucial to advance our understanding of normal physiology and disease pathogenesis. To achieve this goal, here we develop an approach using cleavable biotin conjugated antibodies and cleavable fluorescent streptavidin (CFS). In this approach, protein targets are first recognized by the cleavable biotin labeled antibodies. Subsequently, CFS is applied to stain the protein targets. Though layer-by-layer signal amplification using cleavable biotin conjugated orthogonal antibodies and CSF, the protein detection sensitivity can be enhanced by at least 10 fold, compared with the existing methods. After imaging, the fluorophores and the biotins unbound to streptavidin are removed by chemical cleavage. The leftover streptavidin is blocked by biotin. Upon reiterative analysis cycles, a large number of different proteins with a wide range of expression levels can be unambiguously detected in individual cell in situ.
Optical flow analysis reveals that Kinesin-mediated advection impacts on the orientation of microtubules in theDrosophilaoocyte
Authors: Drechsler Maik , Lang Lukas F. , Al-Khatib Layla , Dirks Hendrik , Burger Martin , Schönlieb Carola-Bibiane , Palacios Isabel M.
Published: February 2019

The orientation of microtubule networks is exploited by motors to deliver cargoes to specific intracellular destinations, and is thus essential for cell polarity and function. Reconstitutedin vitrosystems have largely contributed to understanding the molecular framework regulating the behavior of microtubule filaments. In cells however, microtubules are exposed to various biomechanical forces that might impact on their orientation, but little is known about it. Oocytes, which display forceful cytoplasmic streaming, are excellent model systems to study the impact of motion forces on cytoskeletonsin vivo. Here we implement variational optical flow analysis as a new approach to analyze the polarity of microtubules in theDrosophilaoocyte, a cell that displays distinct Kinesin-dependent streaming. After validating the method as robust for describing microtubule orientation from confocal movies, we find that increasing the speed of flows results in aberrant plus end growth direction. Furthermore, we find that in oocytes where Kinesin is unable to induce cytoplasmic streaming, the growth direction of microtubule plus ends is also altered. These findings lead us to propose that cytoplasmic streaming - and thus motion by advection – contributes to the correct orientation of MTsin vivo. Finally, we propose a possible mechanism for a specialised cytoplasmic actin network (the actin mesh) to act as a regulator of flow speeds; to counteract the recruitment of Kinesin to microtubules.

HIGHLIGHT SUMMARY

Cytoskeletal networks do not exist in isolation, but experience crowded and dynamic intracellular environments. However, microtubule-environment interactions are not well understood, and such system-environment interactions are an unresolved question in biology that demands bridging across disciplines. Here we introduce an optical flow motion estimation approach to study microtubule orientation in theDrosophilaoocyte, a cell displaying substantial cytoplasmic streaming. We show that microtubule polarity is affected by the regime of these flows, and furthermore, that the presence of flows is necessary for MTs to adopt their proper polarity. With these findings we are contributing to further understanding how microtubules organize in their impacting natural environment.
Unbiased estimation of linkage disequilibrium from unphased data
Authors: Ragsdale Aaron P. , Gravel Simon
Published: February 2019

Linkage disequilibrium is used to infer evolutionary history and to identify regions under selection or associated with a given trait. In each case, we require accurate estimates of linkage disequilibrium from sequencing data. Unphased data presents a challenge because the co-occurrence of alleles at different loci is ambiguous. Commonly used estimators for the common statisticsr2andD2exhibit large and variable upward biases that complicate interpretation and comparison across cohorts. Here, we show how to find unbiased estimators for a wide range of two-locus statistics, includingD2, for both single and multiple randomly mating populations. These provide accurate estimates over three orders of magnitude in LD. We also use these estimators to construct an estimator forr2that is less biased than commonly used estimators, but nevertheless argue for usingrather thanr2for population size estimates.
Gut Microbiome Analysis In Adult Tropical Gars (Atractosteus tropicus)
Authors: Méndez-Pérez Roberto , García-López Rodrigo , Bautista-López J. Santiago , Vázquez-Castellanos Jorge F. , Peña-Marín Emyr S. , Martínez-García Rafael , Domínguez-Rodríguez Verónica I. , Adams-Schroeder Randy H. , Baltierra-Trejo Eduardo , Valdés Carolina Melgar , Moya Andrés , Alvarez-González Carlos A. , Gómez-Cruz Rodolfo
Published: February 2019

Tropical gar (Atractosteus tropicus), is freshwater and estuarine fish that has inhabited the Earth since the Mesozoic era, undergoing limited physiological variation ever since. This omnivorous fish is endemic to southern Mexico and part of Central America. Besides its recognized cultural and scientific relevance, the species has seen remarkable growth in its economic impact due to pisciculture. Previous studies have highlighted the role of microbial communities in fish, particularly those in the gut microbiome, in maintaining their host homeostasis or disease. In this study, we present the first report of the whole taxonomic composition of microbial communities in gut contents of adults’A. tropicus, by sex (female/male) and origin (wild/cultivated). Using culture-independent techniques, we extracted metagenomic DNA that was used for high throughput 16S rDNA profiling by amplifying the V4 – V5 hypervariable regions of the bacterial gene. A total of 364,735 total paired-end reads were obtained on an Illumina MiSeq sequencing platform, belonging to 508 identified genera, with the most and least abundant areCetobacterium, Edwardsiella, Serratia, Clostridium sensu stricto, PaludibacterandCampylobacter, Snodgrassella, Albirhodobacter, Lentilitoribacter, respectively. We detected that, by sex and origin, Proteobacteria, Fusobacteria, Firmicutes and Bacteroidetes phyla are the core gut microbiome of the adults’A. tropicus. We discover the Deinococcus-Thermus phylum sequence, wildtype males only, with extremophile capacity in another freshwater fish. We also identified the speciesLactococcus lactisstrains CAU929 and CAU6600, Cp6 and CAU9951,Cetobacteriumstrain H69,Aeromonas hydrophilastrains P5 and WR-5-3-2,Aeromonas sobriastrain CP DC28 andAeromonas hydrophilawith probiotic potential in aquaculture within the three dominant phyla, especially in wild-type organisms.