bluuebunny/crossref_metadata_2025 huggingface dataset:
Global simulations of Tayler instability in stellar interiors: the stabilizing effect of gravity
Authors: Guerrero G , Del Sordo F , Bonanno A , Smolarkiewicz P K
Published: October 2019

Unveiling the evolution of toroidal field instability, known as Tayler instability, is essential to understand the strength and topology of the magnetic fields observed in early-type stars, in the core of the red giants, or in any stellar radiative zone. We want to study the non-linear evolution of the instability of a toroidal field stored in a stably stratified layer, in spherical symmetry and in the absence of rotation. In particular, we intend to quantify the suppression of the instability as a function of the Brunt–Väisäla (ωBV) and the Alfvén (ωA) frequencies. We use the magnetohydrodynamic (MHD) equations as implemented in the anelastic approximation in the eulag–mhd code and perform a large series of numerical simulations of the instability exploring the parameter space for the ωBV and ωA. We show that beyond a critical value gravity strongly suppress the instability, in agreement with the linear analysis. The intensity of the initial field also plays an important role: weaker fields show much slower growth rates. Moreover, in the case of very low gravity, the fastest growing modes have a large characteristic radial scale, at variance with the case of strong gravity, where the instability is characterized by horizontal displacements. Our results illustrate that the anelastic approximation can efficiently describe the evolution of toroidal field instability in stellar interiors. The suppression of the instability as a consequence of increasing values of ωBV might play a role to explain the magnetic desert in Ap/Bp stars, since weak fields are only marginally unstable in the case of strong gravity.
On the beam properties of radio pulsars with interpulse emission
Authors: Johnston Simon , Kramer Michael
Published: October 2019

In the canonical picture of pulsars, radio emission arises from a narrow cone centred on the star’s magnetic axis but many basic details remain unclear. We use high-quality polarization data taken with the Parkes radio telescope to constrain the geometry and emission heights of pulsars showing interpulse emission, and include the possibility that emission heights in the main and interpulse may be different. We show that emission heights are low in the centre of the beam, typically less than 3 per cent of the light cylinder radius. The emission beams are underfilled in longitude, with an average profile width only 60 per cent of the maximal beamwidth and there is a strong preference for the visible emission to be located on the trailing part of the beam. We show substantial evidence that the emission heights are larger at the beam edges than in the beam centre. There is some indication that a fan-like emission beam explains the data better than conal structures. Finally, there is a strong correlation between handedness of circular polarization in the main and interpulse profiles, which implies that the hand of circular polarization is determined by the hemisphere of the visible emission.
RETRACTED: CGVD: a genomic variation database for Chinese populations
Authors: Zeng Jingyao , Yuan Na , Zhu Junwei , Pan Mengyu , Zhang Hao , Wang Qi , Shi Shuo , Du Zhenglin , Xiao Jingfa
Published: October 2019

Precision medicine calls upon deeper coverage of population-based sequencing and thorough gene-content and phenotype-based analysis, which lead to a population-associated genomic variation map or database. The Chinese Genomic Variation Database (CGVD; https://bigd.big.ac.cn/cgvd/) is such a database that has combined 48.30 million (M) SNVs and 5.77 M small indels, identified from 991 Chinese individuals of the Chinese Academy of Sciences Precision Medicine Initiative Project (CASPMI) and 301 Chinese individuals of the 1000 Genomes Project (1KGP). The CASPMI project includes whole-genome sequencing data (WGS, 25–30×) from ∼1000 healthy individuals of the CASPMI cohort. To facilitate the usage of such variations for pharmacogenomics studies, star-allele frequencies of the drug-related genes in the CASPMI and 1KGP populations are calculated and provided in CGVD. As one of the important database resources in BIG Data Center, CGVD will continue to collect more genomic variations and to curate structural and functional annotations to support population-based healthcare projects and studies in China and worldwide.
Progress in the brain–computer interface: an interview with Bin He
Authors: Li Chengyu , Zhao Weijie
Published: October 2019

What can the brain–computer interface (BCI) do? Wearing an electroencephalogram (EEG) headcap, you can control the flight of a drone in the laboratory by your thought; with electrodes inserted inside the brain, paralytic patients can drink by controlling a robotic arm with thinking. Both invasive and non-invasive BCI try to connect human brains to machines. In the past several decades, BCI technology has continued to develop, making science fiction into reality and laboratory inventions into indispensable gadgets. In July 2019, Neuralink, a company founded by Elon Musk, proposed a sewing machine-like device that can dig holes in the skull and implant 3072 electrodes onto the cortex, promising more accurate reading of what you are thinking, although many serious scientists consider the claim misleading to the public.

Recently, National Science Review (NSR) interviewed Professor Bin He, the department head of Biomedical Engineering at Carnegie Mellon University, and a leading scientist in the non-invasive-BCI field. His team developed new methods for non-invasive BCI to control drones by thoughts. In 2019, Bin’s team demonstrated the control of a robotic arm to follow a continuously randomly moving target on the screen. In this interview, Bin He recounted the history of BCI, as well as the opportunities and challenges of non-invasive BCI.
The Western diet: a blind spot of eating disorder research?—a narrative review and recommendations for treatment and research
Authors: Ayton Agnes , Ibrahim Ali
Published: October 2019

Over the last 50 years, in parallel with the obesity epidemic, the prevalence of eating disorders has increased and presentations have changed. In this narrative review, we consider recent research exploring the implications of changing patterns of food consumption on metabolic and neurobiological pathways, a hitherto neglected area in eating disorder research. One of the major changes over this time has been the introduction of ultra-processed (NOVA-4) foods, which are gradually replacing unprocessed and minimally processed foods. This has resulted in the increased intake of various sugars and food additives worldwide, which has important metabolic consequences: triggering insulin and glucose response, stimulating appetite, and affecting multiple endocrine and neurobiological pathways, as well as the microbiome. A paradigm shift is needed in the conceptual framework by which the vulnerability to, and maintenance of, different eating disorders may be understood, by integrating recent knowledge of the individual metabolic responses to modern highly processed foods into existing psychological models. This could stimulate research and improve treatment outcomes.
Insect Bite–Associated Invasive Fungal Infections
Authors: Kontoyiannis Panayiotis D , Koons Gerry L , Hicklen Rachel S , Mikos Antonios G , Kontoyiannis Dimitrios P
Published: October 2019

Insect bites are rarely reported to result in myocutaneous mycoses. We reviewed the literature and report 22 cases. Molds were the most common pathogens (15), especially Mucorales (9). Infections were typically misdiagnosed, and 68% had necrotizing features, often requiring amputation or extensive surgery. Both immunocompetent and immunosuppressed patients were affected.
Fall History and Associated Factors Among Adults Living With HIV-1 in the Cape Winelands, South Africa: An Exploratory Investigation
Authors: Berner Karina , Strijdom Hans , Essop M Faadiel , Webster Ingrid , Morris Linzette , Louw Quinette
Published: October 2019

Background

People with HIV-1 (PWH) exhibit a high fall incidence and increased fracture risk. As little is known about fall frequency and associated factors in PWH residing in lower-middle-income countries (LMIC), we investigated fall frequency, bone quality, and factors associated with fall history in a South African cohort.

Methods

Fifty PWH without obvious predisposing factors for mobility impairments attending 2 public primary care clinics in the Western Cape region participated. Demographic, clinical, and physical performance data were collected. Falls were assessed retrospectively over 12 months. Mobility and balance were evaluated using a physical performance battery. Bone mineral density was screened using quantitative ultrasound (QUS). Associations between variables and falls grouping were analyzed using chi-square tests, t tests, and Mann-Whitney U tests, and effect sizes (ES) were calculated.

Results

Thirty-four percent of PWH (median age, 36.6 years) reported falling during the past year, and 41.2% of fallers reported multiple falls. Fallers had more mobility problems (P = .013), higher fear of falling (P = .007), higher fracture history (P = .003), worse balance performance (P < .001), higher proportions of detectable viral loads (P = .021), and poorer bone quality (P = .040). Differences were of medium to large ES.

Conclusions

This exploratory study is the first to show that relatively young South African PWH without obvious predisposing factors for gait and balance impairments experience falls. The observed fall-associated factors warrant further research using larger samples and longitudinal designs to ascertain fall predictors within this population.
Is Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound a Repeatable Treatment Option? Case Report of a Retreated Patient With Tremor Combined With Parkinsonism
Authors: Valentino Francesca , Cosentino Giuseppe , Maugeri Rosario , Giammalva Roberto , Iacopino Gerardo Domenico , Marrale Maurizio , Bartolotta Tommaso Vincenzo , Gagliardo Cesare
Published: October 2019

INTRODUCTION

In recent years, transcranial Magnetic Resonance Imaging-guided Focused Ultrasound (tcMRgFUS) treatments for functional neurological disorders are giving a new thrust to the field of therapeutic brain lesioning.

OBJECTIVE

To present the case of a patient affected by tremor combined with Parkinsonism who underwent a second tcMRgFUS thalamotomy because of relapsing tremor after a few months from the first tcMRgFUS treatment.

METHODS

A 72-yr-old, right-handed man, came to our observation because of a disabling tremor affecting his upper limbs, refusing any invasive surgical procedure and already treated by tcMRgFUS left Vim thalamotomy. However, clinical benefit had brief duration, as a progressive recurrence of tremor on the right upper limb was observed after a few months from the first treatment. Thus, the patient underwent a new left-sided tcMRgFUS procedure 6 mo after the former treatment.

RESULTS

After the second procedure, an immediate and complete relief from tremor on the right upper limb was achieved with clinical benefit that persisted up to a 6-mo follow-up.

CONCLUSION

Since tcMRgFUS doesn’t use ionizing radiations and it is incision-less, repeated and staged treatment procedures have always been hypothesized. Our report suggests that tcMRgFUS retreatment might actually be a feasible, safe, and effective option in selected patients in whom an optimal clinical outcome is not achieved after the first treatment session. However, future well-designed studies in large samples are needed to assess the possible risks of retreatment and the optimal timing of reintervention as well as eligibility and exclusion criteria.
Synovial Cysts Confounding Access to the Dorsal S1 Neural Foramen in Transforaminal Epidural Steroid Injections
Authors: El-Yahchouchi Christine A , Willard Frank H , Kaufmann Timothy J , Wald John T , Diehn Felix E , Geske Jennifer R , Maus Timothy P
Published: October 2019

Objectives

The S1 dorsal foramen is the route for 30% of lumbar transforaminal epidural injections; it is therefore important to identify structures impeding S1 foraminal access. The study objective was to characterize the imaging findings, prevalence, and anatomic origin of synovial cysts presenting within the S1 neural foramen.

Methods

A case series (N = 14) established imaging characteristics of S1 synovial cysts. Imaging studies of 400 patients undergoing epidural injections were reviewed for lesions compromising S1 foraminal access. Cadaveric dissections defined the relationship of the inferior recess of the L5-S1 facet to the S1 dorsal foramen.

Results

Elderly patients (mean age = 76) exhibited S1 synovial cysts. Synovial cysts were typically 1–2 cm in diameter, hyperintense on sagittal T2 weighted magnetic resonance images (MRIs), fluid-density on computed tomography, and dorsal to the S1 spinal nerve. Sixty percent of cysts exhibited complex MRI signal characteristics (thick wall, internal structure). Tarlov cysts, in contrast, were larger, lobular, and exhibited pure fluid intensity. Lesions impeded access to the S1 dorsal foramina in 5% of reviewed imaging studies (16 Tarlov cysts, three synovial cysts, one conjoint S1-S2 nerve root). The multifidus muscle was interposed between the L5-S1 facet inferior recess and the S1 dorsal foramen on dissection specimens; severe atrophy of the ipsilateral multifidus was noted on imaging in 17/18 synovial cysts.

Conclusions

The S1 neural foramina should be inspected on sagittal MRI, when available, for confounding lesions before performing S1 epidural injections. Tarlov cysts are more common than synovial cysts; the latter are seen in elderly patients with severe multifidus atrophy.
Person-Centered Care and Physical Therapy: A “People-Like-Me” Approach
Authors: Kittelson Andrew J , Hoogeboom Thomas J , Schenkman Margaret , Stevens-Lapsley Jennifer E , van Meeteren Nico L U
Published: October 2019

In health care, “person centeredness” is a valued (though nebulous) concept. In physical therapy, clinical interactions often strive to be person-centered, for example, by focusing on participation and valuing patient empowerment. However, the available evidence has mostly been constructed around populations (or study samples) rather than individuals. In this perspective, an alternative evidence framework is described, constructed around measurements in routine practice. Specifically, the authors propose developing “people-like-me” reference charts, generated with historical outcomes data, to provide real-time information on an individual’s status relative to similar people. The authors present an example of how this could work using their experience with people rehabilitating after total knee arthroplasty. They also describe several challenges that must be addressed to bring this innovation into practice. First, the most important outcome measures for stakeholders (eg, patients, clinicians) need to be identified and monitored longitudinally to ensure that “people-like-me” estimates are useful and support the goals of person-centered care. Statistical methods for selecting “people-like-me” need to be examined and refined. Finally, the “people-like-me” information needs to be packaged in such a way that it is accessible, intuitive, and helpful at the point of care. Ideally, the entire process should recognize from the outset that practice patterns evolve, so databases, statistical models, and decision tools should be dynamic by design. Ultimately, the authors propose this framework as a practical mechanism to advance person-centered decisions in physical therapy according to the ideals of evidence-based practice.
Emergence of norovirus strains: A tale of two genes
Authors: Parra Gabriel I
Published: October 2019

Noroviruses are a very diverse group of viruses that infect different mammalian species. In humans, norovirus is a major cause of acute gastroenteritis. Multiple norovirus infections can occur in a lifetime as the result of limited duration of acquired immunity and cross-protection among different strains. A combination of advances in sequencing methods and improvements on surveillance has provided new insights into norovirus diversification and emergence. The generation of diverse norovirus strains has been associated with (1) point mutations on two different genes: ORF1, encoding the non-structural proteins, and ORF2, encoding the major capsid protein (VP1); and (2) recombination events that create chimeric viruses. While both mechanisms are exploited by all norovirus strains, individual genotypes utilize each mechanism differently to emerge and persist in the human population. GII.4 noroviruses (the most prevalent genotype in humans) present an accumulation of amino acid mutations on VP1 resulting in the chronological emergence of new variants. In contrast, non-GII.4 noroviruses present co-circulation of different variants over long periods with limited changes on their VP1. Notably, genetic diversity of non-GII.4 noroviruses is mostly related to the high number of recombinant strains detected in humans. While it is difficult to determine the precise mechanism of emergence of epidemic noroviruses, observations point to multiple factors that include host-virus interactions and changes on two regions of the genome (ORF1 and ORF2). Larger datasets of viral genomes are needed to facilitate comparison of epidemic strains and those circulating at low levels in the population. This will provide a better understanding of the mechanism of norovirus emergence and persistence.
Identification of a Recessive GenePmQConferring Resistance to Powdery Mildew in Wheat Landrace Qingxinmai Using BSR-Seq Analysis
Authors: Li Yahui , Shi Xiaohan , Hu Jinghuang , Wu Peipei , Qiu Dan , Qu Yunfeng , Xie Jingzhong , Wu Qiuhong , Zhang Hongjun , Yang Li , Liu Hongwei , Zhou Yang , Liu Zhiyong , Li Hongjie
Published: October 2019

Wheat powdery mildew is caused by Blumeria graminis f. sp. tritici (Bgt), a biotrophic fungal species. It is very important to mine new powdery mildew (Pm) resistance genes for developing resistant wheat cultivars to reduce the deleterious effects of the disease. This study was carried out to characterize the Pm gene in Qingxinmai, a winter wheat landrace from Xinjiang, China. Qingxinmai is resistant to many Bgt isolates collected from different wheat fields in China. F1, F2, and F2:3generations of the cross between Qingxinmai and powdery mildew susceptible line 041133 were developed. It was confirmed that a single recessive gene, PmQ, conferred the seedling resistance to a Bgt isolate in Qingxinmai. Bulked segregant analysis-RNA-Seq (BSR-Seq) was performed on the bulked homozygous resistant and susceptible F2:3families, which detected 57 single nucleotide polymorphism (SNP) variants that were enriched in a 40 Mb genomic interval on chromosome arm 2BL. Based on the flanking sequences of the candidate SNPs extracted from the Chinese Spring reference genome, 485 simple sequence repeat (SSR) markers were designed. Six polymorphic SSR markers, together with nine markers that were anchored on chromosome arm 2BL, were used to construct a genetic linkage map for PmQ. This gene was placed in a 1.4 cM genetic interval between markers Xicsq405 and WGGBH913 corresponding to 4.9 Mb physical region in the Chinese Spring reference genome. PmQ differed from most of the other Pm genes identified on chromosome arm 2BL based on its position and/or origin. However, this gene and Pm63 from an Iranian common wheat landrace were located in a similar genomic region, so they may be allelic.
Reassortment of Genome Segments Creates Stable Lineages Among Strains of Orchid Fleck Virus Infecting Citrus in Mexico
Authors: Roy Avijit , Stone Andrew L. , Otero-Colina Gabriel , Wei Gang , Brlansky Ronald H. , Ochoa Ronald , Bauchan Gary , Schneider William L. , Nakhla Mark K. , Hartung John S.
Published: October 2019

The genus Dichorhavirus contains viruses with bipartite, negative-sense, single-stranded RNA genomes that are transmitted by flat mites to hosts that include orchids, coffee, the genus Clerodendrum, and citrus. A dichorhavirus infecting citrus in Mexico is classified as a citrus strain of orchid fleck virus (OFV-Cit). We previously used RNA sequencing technologies on OFV-Cit samples from Mexico to develop an OFV-Cit–specific reverse transcription PCR (RT-PCR) assay. During assay validation, OFV-Cit–specific RT-PCR failed to produce an amplicon from some samples with clear symptoms of OFV-Cit. Characterization of this virus revealed that dichorhavirus-like particles were found in the nucleus. High-throughput sequencing of small RNAs from these citrus plants revealed a novel citrus strain of OFV, OFV-Cit2. Sequence comparisons with known orchid and citrus strains of OFV showed variation in the protein products encoded by genome segment 1 (RNA1). Strains of OFV clustered together based on host of origin, whether orchid or citrus, and were clearly separated from other dichorhaviruses described from infected citrus in Brazil. The variation in RNA1 between the original (now OFV-Cit1) and the new (OFV-Cit2) strain was not observed with genome segment 2 (RNA2), but instead, a common RNA2 molecule was shared among strains of OFV-Cit1 and -Cit2, a situation strikingly similar to OFV infecting orchids. We also collected mites at the affected groves, identified them as Brevipalpus californicus sensu stricto, and confirmed that they were infected by OFV-Cit1 or with both OFV-Cit1 and -Cit2. OFV-Cit1 and -Cit2 have coexisted at the same site in Toliman, Queretaro, Mexico since 2012. OFV strain-specific diagnostic tests were developed.
Risk Stratification of Fetal Cardiac Anomalies in an Underserved Population Using Telecardiology
Authors: Cuneo Bettina F. , Olson Christina A. , Haxel Caitlin , Howley Lisa , Gagnon Amy , Benson D. Woodrow , Kaizer Alexander M. , Thomas J. Fred
Published: October 2019

OBJECTIVE:

To evaluate a fetal telecardiology program in a medically underserved area.

METHODS:

We conducted a prospective case series of pregnant women at 18–38 weeks of gestation with risk factors for fetal congenital heart disease. Obstetric ultrasonographers performed fetal echocardiograms (local site) that were read in real time. The results were given to the mother by a fetal cardiologist at a children's hospital 243 miles and two mountain passes away (distant site). We evaluated the fetal telecardiology program in five domains: 1) education of obstetric ultrasonographers before initiation of telecardiology services, 2) process and efficiency, 3) patient satisfaction, 4) economic effects, and 5) accuracy of cardiac diagnosis and success of risk stratification.

RESULTS:

The program was initiated on November 12, 2015, and here we describe its first 37 months. Over the initial training period of 3 months and about 70 examinations, obstetric ultrasonographers improved their identification of fetal congenital heart disease. Telecardiology was performed once a week and also for suspected fetal congenital heart disease or arrhythmia outside clinic hours, for a total of 455 examinations. All mothers preferred having their fetal cardiac evaluations performed locally as opposed to traveling to the distant center. The estimated cost to parents for fetal cardiac evaluation at the distant center was nine times greater than that of telecardiology ($581 vs $61). Congenital heart disease or arrhythmia was diagnosed in 28 and 15 fetuses, respectively; there was one false-negative result. All fetuses were correctly risk-stratified with respect to delivery location.

CONCLUSIONS:

Neither diagnostic quality nor patient satisfaction were sacrificed with telecardiology. The program was feasible, empowered the local health care providers and ultrasonographers, offered strong economic advantages to families, and offered the benefit of timely standard-of-care, face-to-face consultation without travel. Based on the success of this program, further studies are warranted to assess its replicability.
Gestational Weight Gain and Adverse Birth Outcomes in Twin Pregnancies
Authors: Bodnar Lisa M. , Himes Katherine P. , Abrams Barbara , Lash Timothy L. , Parisi Sara M. , Eckhardt Cara L. , Braxter Betty J. , Minion Sarah , Hutcheon Jennifer A.
Published: October 2019

OBJECTIVE:

To evaluate the association between gestational weight gain in twin pregnancies and small-for-gestational-age (SGA) and large-for-gestational-age (LGA) birth, preterm birth before 32 weeks of gestation, cesarean delivery, and infant death within each prepregnancy body mass index (BMI) category.

METHODS:

Data in this population-based study came from Pennsylvania-linked infant birth and death records (2003–2013). We studied 54,836 twins born alive before 39 weeks of gestation. Total pregnancy weight gain (kg) was converted to gestational age-standardized z scores. Multivariable modified Poisson regression models stratified by prepregnancy BMI were used to estimate associations between z scores and outcomes. A probabilistic bias analysis, informed by an internal validation study, evaluated the effect of BMI and weight gain misclassification.

RESULTS:

Gestational weight gain z score was negatively associated with SGA and positively associated with LGA and cesarean delivery in all BMI groups. The relation between weight gain and preterm birth was U-shaped in nonobese women. An increased risk of infant death was observed for very low weight gain among normal-weight women and for high weight gain among women without obesity. Most excess risks of these outcomes were observed at weight gains at 37 weeks of gestation that are equivalent to less than 14 kg or more than 27 kg in underweight or normal-weight women, less than 11 kg or more than 28 kg in overweight women, and less than 6.4 kg or more than 26 kg in women with obesity. The bias analysis supported the validity of the conventional analysis.

CONCLUSION:

Very low or very high weight gains were associated with the adverse outcomes we studied. If the associations we observed are even partially reflective of causality, targeted modification of pregnancy weight gain in women carrying twins might improve pregnancy outcomes.
Long-Term Safety and Efficacy of Bremelanotide for Hypoactive Sexual Desire Disorder
Authors: Simon James A. , Kingsberg Sheryl A. , Portman David , Williams Laura A. , Krop Julie , Jordan Robert , Lucas Johna , Clayton Anita H.
Published: October 2019

OBJECTIVE:

To evaluate the long-term safety and efficacy of bremelanotide as treatment for hypoactive sexual desire disorder in premenopausal women.

METHODS:

Women who completed the 24-week double-blind core phase of RECONNECT, composed of two parallel phase 3 trials (301 and 302) examining the safety and efficacy of bremelanotide compared with placebo in premenopausal women with hypoactive sexual desire disorder, could enroll in the 52-week open-label extension, provided they had not experienced serious adverse events during the core phase. Efficacy was assessed using the coprimary endpoints from the core phase, and all adverse events were collected during the open-label extension. All statistical analyses were descriptive.

RESULTS:

The study 301 open-label extension began on July 17, 2015, and concluded on July 13, 2017; the study 302 open-label extension began on October 5, 2015, and concluded on June 29, 2017. Of the 856 eligible patients who completed the core phase, 684 elected to participate in the open-label extension, and 272 completed it. The most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%), and headache (12.0%), and the only severe treatment-emergent adverse event experienced by more than one participant in both studies was nausea during the open-label extension. The change in Female Sexual Function Index–desire domain score and Female Sexual Distress Scale–Desire/Arousal/Orgasm item 13 from baseline to end of the open-label extension ranged from 1.25 to 1.30 and −1.4 to −1.7, respectively, for patients who received bremelanotide during the core phase, and 0.70–0.77 and −0.9, respectively, for patients who received placebo during the core phase.

CONCLUSION:

During the 52-week open-label extension of RECONNECT, no new safety signals were observed, and premenopausal women treated with bremelanotide exhibited sustained improvements in hypoactive sexual desire disorder symptoms.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02333071 (study 301) and NCT02338960 (study 302).

FUNDING SOURCE:

Palatin Technologies, Inc., and AMAG Pharmaceuticals, Inc.
Comparison of Midwifery and Obstetric Care in Low-Risk Hospital Births
Authors: Souter Vivienne , Nethery Elizabeth , Kopas Mary Lou , Wurz Hannah , Sitcov Kristin , Caughey Aaron B.
Published: October 2019

OBJECTIVE:

To compare midwife and obstetrician labor practices and birth outcomes in women with low-risk pregnancies delivered in the hospital.

METHODS:

We conducted a retrospective cohort study of singleton births of 37 0/7–42 6/7 weeks of gestation at 11 hospitals between January 1, 2014, and December 31, 2018. Exclusions included intrapartum transfer from home-birth center, antepartum stillbirth, previous cesarean delivery, practitioner other than midwife or obstetrician, prelabor cesarean, prepregnancy maternal disease, and pregnancy complications or risk factors. Interventions (induction, artificial rupture of membranes, epidural, oxytocin, and episiotomy), mode of delivery, maternal outcomes (third- or fourth-degree laceration, postpartum hemorrhage, blood transfusion, and severe maternal morbidity), and newborn outcomes (shoulder dystocia, 5-minute Apgar score less than 7, resuscitation at delivery, birth trauma, and neonatal intensive care unit admission) were examined by practitioner type. We used modified Poisson regression models adjusted for individual confounders to assess risk ratios, stratified by parity, for health care provider type and perinatal outcomes.

RESULTS:

The study cohort comprised 23,100 births (3,816 midwife and 19,284 obstetrician). Compared with obstetricians, midwifery patients had significantly lower intervention rates, an approximately 30% lower risk of cesarean delivery in nulliparous patients (adjusted relative risk [aRR] 0.68; 95th% CI 0.57–0.82), and an approximately 40% lower risk of cesarean in multiparous patients (aRR 0.57; 95th% CI 0.36–0.89). Operative vaginal birth was also less common in nulliparous patients (aRR 0.73; 95th% CI 0.57–0.93) and multiparous patients (aRR 0.30; 95th% CI 0.14–0.63). Shoulder dystocia was more common in multiparous patients receiving midwifery care (aRR 1.42; 95th% CI 1.04–1.92).

CONCLUSIONS:

In low-risk pregnancies, midwifery care in labor was associated with decreased intervention, decreased cesarean and operative vaginal births, and, in multiparous women, an increased risk for shoulder dystocia. Greater integration of midwifery care into maternity services in the United States may reduce intervention in labor and potentially even cesarean delivery, in low-risk pregnancies. Larger research studies are needed to evaluate uncommon but important maternal and newborn outcomes.
Vasculitis and the ear: a literature review
Authors: Rahne Torsten , Plontke Stefan , Keyßer Gernot
Published: October 2019

Purpose of review

Systemic vasculitides as a group of inflammatory disorders of blood vessels may show clinical manifestations in the ear. This article reviews the recent literature about vasculitis of the ear or the cochleovestibular system, focusing on giant-cell arteritis, Takayasu's arteritis, polyarteritis nodosa, Kawasaki disease, microscopic polyangiitis, granulomatosis with polyangiitis (GPA), eosinophilic GPA, systemic lupus erythematosus, Cogan's syndrome and Behçet's disease.

Recent findings

In patients with vasculitis, hearing impairment is a frequent problem, followed by tinnitus and vertigo. The severity of sensorineural hearing loss can range from mild impairment to deafness. Autoimmune diseases can induce a conductive hearing loss as a result of effusions of the middle ear, the inflammation of the mucosa of the Eustachian tube, or the involvement of the ossicular chain. Vertigo may be caused by the temporary or permanent occlusion of the labyrinthine or the anterior vestibular artery. Middle ear inflammation is frequent in GPA and eosinophilic GPA.

The progressive sensorineural hearing loss in polyarteritis nodosa or Cogan's syndrome patients may be treated by cochlear implantation.
Immune checkpoint inhibitors and vasculitis
Authors: Boland Patrick , Heath Jacqueline , Sandigursky Sabina
Published: October 2019

Purpose of review

Clinical use of immune checkpoint inhibitor (ICI) therapy has revolutionized the therapeutic landscape of cancer. By activating the immune system using monoclonal anti-CTLA-4 and PD(L)-1 antibodies, remission can be induced in previously terminal cancers. However, these breakthroughs come at a price. Multiple de-novo autoimmune illnesses, termed immune-related adverse events (irAEs), have been reported with patients increasingly being referred to rheumatologists with varying diagnoses. Among these are vasculitic syndromes, which may be limited to an organ or systemic and potentially-life threatening. Relatively little is known about the prevalence, mechanisms, and phenotypes of vasculitis occurring in response to ICIs. Here, we review the literature and describe the frequency and patterns of presentation.

Recent findings

Vasculitis, while infrequent, has been described as an irAE in patients treated with ICI therapy with resultant morbidity and mortality.

Recognizing the risk and management of immune checkpoint inhibitor induced vasculitis in patients with cancer is important in the daily practice of rheumatology.
Allergic Immune Diseases and the Risk of Mortality Among Patients Hospitalized for Acute Infection*
Authors: Verhoef Philip A. , Bhavani Sivasubramanium V. , Carey Kyle A. , Churpek Matthew M.
Published: October 2019

Objectives:

The immune response during sepsis remains poorly understood and is likely influenced by the host’s preexisting immunologic comorbidities. Although more than 20% of the U.S. population has an allergic-atopic disease, the type 2 immune response that is overactive in these diseases can also mediate beneficial pro-resolving, tissue-repair functions. Thus, the presence of allergic immunologic comorbidities may be advantageous for patients suffering from sepsis. The objective of this study was to test the hypothesis that comorbid type 2 immune diseases confer protection against morbidity and mortality due to acute infection.

Design:

Retrospective cohort study of patients hospitalized with an acute infection between November 2008 and January 2016 using electronic health record data.

Setting:

Single tertiary-care academic medical center.

Patients:

Admissions to the hospital through the emergency department with likely infection at the time of admission who may or may not have had a type 2 immune-mediated disease, defined as asthma, allergic rhinitis, atopic dermatitis, or food allergy, as determined by International Classification of Diseases, 9th Revision, Clinical Modification codes.

Interventions:

None.

Measurements and Main Results:

Of 10,789 admissions for infection, 2,578 (24%) had a type 2 disease; these patients were more likely to be female, black, and younger than patients without type 2 diseases. In unadjusted analyses, type 2 patients had decreased odds of dying during the hospitalization (0.47; 95% CI, 0.38–0.59, p < 0.001), while having more than one type 2 disease conferred a dose-dependent reduction in the risk of mortality (p < 0.001). When adjusting for demographics, medications, types of infection, and illness severity, the presence of a type 2 disease remained protective (odds ratio, 0.55; 95% CI, 0.43–0.70; p < 0.001). Similar results were found using a propensity score analysis (odds ratio, 0.57; 95% CI, 0.45–0.71; p < 0.001).

Conclusions:

Patients with type 2 diseases admitted with acute infections have reduced mortality, implying that the type 2 immune response is protective in sepsis.
Circulating biomarkers for the detection of tumor recurrence in the postsurgical follow-up of differentiated thyroid carcinoma
Authors: Giovanella Luca
Published: October 2019

Purpose of review

To discuss advances and challenges in thyroglobulin and Tg-antibody (TgAb) measurement and their impact on clinical management of differentiated thyroid carcinoma (DTC).

Recent findings

Basal high-sensitive Tg (hsTg) measurement avoids the need for stimulation and greatly simplifies DTC patients’ management. In addition, patients with undetectable hsTg after thyroid ablation are at a very low risk of recurrence and can be safely managed by periodic hsTg measurement alone. When TgAb is present, its trend over time serves as primary (surrogate) tumor marker. However, an undetectable hsTg measurement appears to indicate a complete remission of DTC even in the presence of TgAb. Finally, reliable reference values are not yet available for low-risk DTC who are treated with less than total thyroid ablation, and caution is needed before well-designed studies addressing these issues have been published.

The use of hsTg assays has changed paradigms for DTC monitoring even in the presence of TgAb, and greatly reduced patients’ discomfort and overall case-management costs. Reliable Tg interpretation criteria are urgently needed for patients treated with less than total thyroid ablation.
Malignant pheochromocytoma and paraganglioma: management options
Authors: Corssmit Eleonora P.M. , Snel Marieke , Kapiteijn Ellen
Published: October 2019

Purpose of review

Although the majority of pheochromocytoma and paraganglioma are benign, 15–17% develop metastatic disease, being present at the initial diagnosis in about 11–31% of cases. The natural course of metastasized disease is highly heterogeneous, with an overall 5-year survival rate varying between 40% and 85%. For individual patients, overall survival, progression-free survival, and clinical outcome are difficult to predict. Management of metastasized pheochromocytoma and paraganglioma is challenging. Currently available therapeutic options are surgical debulking, treatment with radiopharmaceuticals (131I-MIBG, 90Y and 177Lu-DOTATATE), chemotherapy and targeted therapy.

Recent findings

The pathogenesis of pheochromocytoma and paraganglioma (PPGL) is largely driven by genomic alterations in PPGL susceptibility genes related to three different clusters: altered pseudo-hypoxic signaling (cluster-1), altered MAP-kinase signaling (cluster-2) and altered Wnt signaling (cluster-3). Novel targeted therapies (tyrosine kinase inhibitors) and potential future therapeutic options, guided by improved knowledge about the oncogenic cluster 1–3 signaling pathways, will be discussed.

Treatment of metastasized pheochromocytoma and paraganglioma remains challenging. Profiling of gene expression and methylation can serve as a powerful tool for characterizing disease clusters and for guiding targeted therapy to improve selectivity and efficacy. Current knowledge of signatures involved in molecular signaling, metabolism, and resistance mechanisms of PPGLs suggests that therapeutic regimens can be optimized to each molecular subtype.
Chemotherapy remains a cornerstone in the treatment of nonsmall cell lung cancer
Authors: Pirker Robert
Published: October 2019

Purpose of review

The purpose of the review is to summarize the current and future role of chemotherapy in the treatment of patients with nonsmall cell lung cancer (NSCLC).

Recent findings

Chemotherapy has been established in early-stage, locally advanced and metastatic NSCLC. Patients with driver mutation-positive NSCLC receive tyrosine kinase inhibitors as first-line therapy and chemotherapy later during the course of their disease. Immune checkpoint inhibitors have entered clinical practice as single agents or in combination with chemotherapy. These novel treatments will supplement chemotherapy in all tumor stages of NSCLC.

Targeted drugs and immune checkpoint inhibitors are gaining increasing importance in the treatment of NSCLC. They will supplement but not replace chemotherapy in the future.
Epstein–Barr Virus–Induced Cutaneous Diffuse Large B-Cell Lymphoma in a Patient With Angioimmunoblastic T-Cell Lymphoma
Authors: Poon Flora , Ieremia Eleni , Collins Graham , Matin Rubeta N.
Published: October 2019

Cutaneous manifestations of Epstein–Barr virus (EBV)-driven B-cell lymphoid proliferations occur rarely as a result of severe immunodeficiency. To date, only a few cases of extranodal EBV-associated B-cell lymphomas arising in patients with angioimmunoblastic T-cell lymphoma (AITL) have been reported, and less common is a cutaneous presentation. AITL is a rare aggressive tumor that carries a poor prognosis and prompt diagnosis, and recognition of EBV-associated diffuse B-cell lymphoma is essential in these patients to instigate the correct treatment.
Analysis of Neuroretinal Rim by Age, Race, and Sex Using High-Density 3-Dimensional Spectral-Domain Optical Coherence Tomography
Authors: Antar Hussein , Tsikata Edem , Ratanawongphaibul Kitiya , Zhang Jing , Shieh Eric , Lee Ramon , Freeman Madeline , Papadogeorgou Georgia , Simavli Huseyin , Que Christian , Verticchio Vercellin Alice C. , Khoueir Ziad , de Boer Johannes F. , Chen Teresa C.
Published: October 2019

Précis:

Neuroretinal rim minimum distance band (MDB) thickness is significantly lower in older subjects and African Americans compared with whites. It is similar in both sexes.

Purpose:

To evaluate the relationship between age, race, and sex with the neuroretinal rim using high-density spectral-domain optical coherence tomography optic nerve volume scans of normal eyes.

Methods:

A total of 256 normal subjects underwent Spectralis spectral-domain optical coherence tomography optic nerve head volume scans. One eye was randomly selected and analyzed for each subject. Using custom-designed software, the neuroretinal rim MDB thickness was calculated from volume scans, and global and quadrant neuroretinal rim thickness values were determined. The MDB is a 3-dimensional neuroretinal rim band comprised of the shortest distance between the internal limiting membrane and the termination of the retinal pigment epithelium/Bruch’s membrane complex. Multiple linear regression analysis was performed to determine the associations of age, race, and sex with neuroretinal rim MDB measurements.

Results:

The population was 57% female and 69% white with a mean age of 58.4±15.3 years. The mean MDB thickness in the normal population was 278.4±47.5 µm. For this normal population, MDB thickness decreased by 0.84 µm annually (P<0.001). African Americans had thinner MDBs compared with whites (P=0.003). Males and females had similar MDB thickness values (P=0.349).

Conclusion:

Neuroretinal rim MDB thickness measurements decreased significantly with age. African Americans had thinner MDB neuroretinal rims than whites.
The burden of corticosteroid overload in severe and difficult to treat asthma: how to reduce this?
Authors: Slisz Tomas , Vasakova Martina
Published: October 2019

Purpose of review

Severe asthma is a serious condition that requires an individualized approach combining several treatment agents administered simultaneously in order to reach adequate control. Glucocorticosteroid treatment, as the cornerstone of asthma pharmacotherapy, has great disease-controlling capability, although it may induce a vast amount of severe adverse effects. This review describes our current knowledge of the monitoring and managing options of these adverse effects and possibilities to prevent them, including new therapeutic options.

Recent findings

A large amount of new drugs is emerging, which may offer a better control of glucocorticosteroid-induced adverse effects. At the same time, major achievements in our understanding of the underlying mechanisms in severe asthma and in the field of biologic agents may help to substantially reduce the need of glucocorticosteroids in the first-line treatment.

We discuss new insights and approaches to treatment strategy of severe asthma allowing less oral glucocorticosteroid use and hence, substantial less severe adverse effects of the treatment.
Trend of Antitissue Transglutaminase Antibody Normalization in Children With Celiac Disease Started on Gluten‐free Diet
Authors: Sansotta Naire , Alessio Maria G. , Norsa Lorenzo , Previtali Giulia , Ferrari Alberto , Guerra Giovanni , D'Antiga Lorenzo
Published: October 2019

Background:

The aim of this study is to compare the performance of antitissue transglutaminase (atTG) chemiluminescence immunoassay (CLIA) with the standard enzyme‐linked immunosorbent assay (ELISA) methods in monitoring celiac children after the start of gluten‐free diet (GFD).

Methods:

Celiac children diagnosed between 2005 and 2016 at our centre were classified into 2 groups based on serum assay (ELISA vs CLIA) used for atTG monitoring, and were compared on percentage of decrease and time to normalization of atTG on GFD.

Results:

Among 260 included children, the rate of normalization of atTG levels at 30 months’ follow‐up was 86% and 70% in ELISA and CLIA group, respectively (P < 0.01). Median time to normalization was 11.7 and 14.7 months in ELISA and CLIA group respectively (P = 0.003). Marsh score at diagnosis was not associated with time to atTG normalization (P = 0.770), whereas older age at diagnosis and higher baseline atTG predicted longer time to atTG normalization (P = 0.01, P < 0.01).

Conclusions:

The percentage and the time of the atTG normalization in celiac children on GFD should be interpreted according to the utilized assay: at 30 months’ follow‐up children tested by CLIA are less likely to normalize atTG levels compared to those tested by ELISA. Younger age at diagnosis and lower baseline atTG are predictors of earlier atTG normalization, regardless of the adopted assay.
Improved Survival of Children, Adolescents, and Young Adults With Head and Neck Soft Tissue Sarcomas in Denmark
Authors: Mirian Christian , Grønhøj Christian , Rechnitzer Catherine , Charabi Birgitte , Hjalgrim Lisa L. , Krarup-Hansen Anders , von Buchwald Christian , Hjuler Thomas
Published: October 2019

Aim:

The aim of this study was to estimate nationally the survival of children, adolescents, and young adults with head and neck soft tissue sarcomas.

Materials and Methods:

The authors included patients 0 to 21 years of age and diagnosed with rhabdomyosarcoma (RMS) or nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) located in the head and neck between 1980 and 2014. Survival probabilities were estimated using the Kaplan-Meier method. The authors estimated the effect of covariates with univariate and multivariate Cox regression analyses. The cumulative recurrence in RMS was estimated when considering death as a competing risk.

Results:

We identified 72 patients (50% male individuals, whereas 72% had RMS). Elder patients (older than 15 y) did worse compared with younger patients (log-rank test P=0.001). Patients diagnosed from 1980 to 1999 did worse than patients diagnosed from 2000 to 2014 (log-rank test P=0.02). Similarly, younger (younger than 15 y) patients did significantly better when diagnosed from 2000 to 2014 with reference to those diagnosed from 1980 to 1999 (log-rank test P=0.026). The multivariate hazard ratio was 0.46 (95% confidence interval, 0.23-0.92) for patients diagnosed from 2000 to 2014 with reference to patients diagnosed from 1980 to 1999. The 1-year cumulative recurrence for RMS was 21.2% (95% confidence interval, 12.3%-35.0%).

Conclusion:

Overall survival has improved throughout the study period, which is attributable to advancement in diagnostics, treatment, and the application of standardized guidelines from international protocols.