bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Biochemical Screening and a Woman’s Long-Term Risk of Cancer: A Population-Based Cohort Study
Authors: Park Alison L , Huang Tianhua , Meschino Wendy S , Iqbal Javaid , Ray Joel G
Published: September 2019

Background

Some hormones measured in pregnancy are linked to certain hormone-sensitive cancers. We investigated whether routine serum screening in pregnancy is associated with a woman’s subsequent risk of hormone-sensitive cancer.

Methods

This population-based cohort study included women aged 12–55 years who underwent prenatal screening between 11 weeks + 0 days of gestation to 20 weeks + 6 days of gestation in Ontario, Canada, 1993–2011, where universal health care is available. The hazard ratio of newly diagnosed breast, ovarian, endometrial, and thyroid cancer—arising at 21 weeks + 0 days of gestation or thereafter—was estimated in association with an abnormally low (≤5th) or high (>95th) percentile multiple of the median (MoM) for alpha-fetoprotein (AFP), total human chorionic gonadotropin (hCG), unconjugated estriol, pregnancy-associated plasma protein A, and dimeric inhibin A.

Results

Among 677 247 pregnant women followed for a median of 11.0 years (interquartile range = 7.5–16.1), 7231 (1.07%) developed breast cancer, 515 (0.08%) ovarian cancer, 508 (0.08%) endometrial cancer, and 4105 (0.61%) thyroid cancer. In multivariable adjusted models, abnormally high hCG greater than the 95th percentile MoM was associated with a doubling in the risk of endometrial cancer (adjusted hazard ratio [aHR] = 1.98, 95% confidence interval [CI] = 1.33 to 2.95), and abnormally low AFP at the fifth percentile or less MoM conferred a moderately greater risk of thyroid cancer (aHR = 1.21, 95% CI = 1.07 to 1.38). Abnormally low pregnancy-associated plasma protein A at the fifth percentile or less MoM was not statistically significantly associated with breast cancer after multivariable adjustment (aHR = 1.19, 95% CI = 0.98 to 1.36).

Conclusions

Women with abnormally high levels of serum hCG or low AFP in early pregnancy may be at a greater future risk of certain types of hormone-sensitive cancers.
Desmoplastic Infantile Ganglioglioma: A MAPK Pathway-Driven and Microglia/Macrophage-Rich Neuroepithelial Tumor
Authors: Blessing Melissa M , Blackburn Patrick R , Krishnan Chandra , Harrod Virginia L , Barr Fritcher Emily G , Zysk Christopher D , Jackson Rory A , Milosevic Dragana , Nair Asha A , Davila Jaime I , Balcom Jessica R , Jenkins Robert B , Halling Kevin C , Kipp Benjamin R , Nageswara Rao Amulya A , Laack Nadia N , Daniels David J , Macon William R , Ida Cristiane M
Published: September 2019

MAPK pathway activation has been recurrently observed in desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA) with reported disproportionally low mutation allele frequencies relative to the apparent high tumor content, suggesting that MAPK pathway alterations may be subclonal. We sought to expand the number of molecularly profiled cases and investigate if tumor cell composition could account for the observed low mutation allele frequencies. Molecular (targeted neuro-oncology next-generation sequencing/RNA sequencing and OncoScan microarray) and immunohistochemical (CD68-PGM1/CD163/CD14/CD11c/lysozyme/CD3/CD20/CD34/PD-L1) studies were performed in 7 DIG. Activating MAPK pathway alterations were identified in 4 (57%) cases: 3 had a BRAF mutation (V600E/V600D/V600_W604delinsDQTDG, at 8%–27% variant allele frequency) and 1 showed a TPM3-NTRK1 fusion. Copy number changes were infrequent and nonrecurrent. All tumors had at least 30% of cells morphologically and immunophenotypically consistent with microglial/macrophage lineage. Two subtotally resected tumors regrew; 1 was re-excised and received adjuvant treatment (chemotherapy/targeted therapy), with clinical response to targeted therapy only. Even with residual tumor, all patients are alive (median follow-up, 83 months; 19–139). This study further supports DIG as another MAPK pathway-driven neuroepithelial tumor, thus expanding potential treatment options for tumors not amenable to surgical cure, and suggests that DIG is a microglia/macrophage-rich neuroepithelial tumor with frequent low driver mutation allele frequencies.
Meningococcal Serogroup B Disease in Vaccinated Children
Authors: Soler-Garcia Aleix , Fernández de Sevilla Mariona , Abad Raquel , Esteva Cristina , Alsina Laia , Vázquez Julio , Muñoz-Almagro Carmen , Noguera-Julian Antoni
Published: September 2019

Background

Neisseria meningitidis serogroup B (MenB) is the most frequent cause of invasive meningococcal disease (IMD) in Spain. The multicomponent vaccine against MenB (4CMenB) was approved in Spain in January 2014.

Methods

We present 4 cases of children who developed MenB-associated IMD despite previous vaccination with 4CMenB. Extensive immunologic diagnostic work-up was performed in order to rule out any immunodeficiency. Also, molecular characterization of the MenB strain was conducted to determine whether bacterial antigens matched vaccine antigens.

Results

Among the 4 patients (2 girls), 2 had previous risk factors for IMD (recurrent bacterial meningitis of unknown origin and treatment with eculizumab). All patients developed meningitis, but only 2 developed septic shock; they were all cured without sequelae. No other primary or secondary immunodeficiencies were detected. MenB sequence type 213 was identified in 3 cases. With the exception of neisserial heparin-binding antigen peptide 465 present in 1 isolate, the rest of the isolated strains harbored vaccine antigen variants that did not match antigen variants included in the vaccine.

Conclusions

We present 4 children who developed MenB-associated IMD despite previous vaccination with 4CMenB. In 2 cases, the antibodies induced by 4CMenB likely were not effective against the isolated strains. A high level of suspicion for IMD seems advisable regardless of the patient’s vaccination history.
Prepositions and the Grammaticalization of Ancient Hebrew Bipartite Reciprocal Markers
Authors: Staps Camil
Published: October 2019

Besides using the verbal niphal and hitpael stems, ancient Hebrew can indicate semantic reciprocity with bipartite reciprocal markers such as , literally ‘someone with his brother’. In contrast to the Western European counter-parts of these constructions (e.g. English each other), the ancient Hebrew variants are not fully grammaticalized into a single morphological unit like . This article considers one type of bipartite reciprocal marker (the one using ‘someone’ and a term denoting kinship or fellowship) in detail, to see whether the preposition in the construction (e.g., ‘with’) may have prevented further grammaticalization. Since no bleaching of the preposition can be observed in the corpus of Biblical and Qumran Hebrew, we conclude that prepositions continued to have a significant semantic value, which indeed suggests that their near-obligatory presence has prevented further grammaticalization.
An improved test of the binary black hole hypothesis for quasars with double-peaked broad Balmer lines
Authors: Doan Anh , Eracleous Michael , Runnoe Jessie C , Liu Jia , Mathes Gavin , Flohic Helene M L G
Published: September 2019

Velocity offsets in the broad Balmer lines of quasars and their temporal variations serve as indirect evidence for bound supermassive black hole binaries (SBHBs) at sub-parsec separations. In this work, we test the SBHB hypothesis for 14 quasars with double-peaked broad emission lines using their long-term (14–41 yr) radial velocity curves. We improve on the previous work by (i) using elliptical instead of circular orbits for the SBHBs, (ii) adopting a statistical model for radial velocity jitter, (iii) employing a Markov chain Monte Carlo method to explore the orbital parameter space efficiently and build posterior distributions of physical parameters, and (iv) incorporating new observations. We determine empirically that jitter comprises approximately Gaussian distributed fluctuations about the smooth radial velocity curves that are larger than the measurement errors by factors of a few. We initially treat jitter by enlarging the effective error bars and then verify this approach via a variety of Gaussian process models for it. We find lower mass limits for the hypothesized SBHBs in the range 108–1011 M⊙. For seven objects, the SBHB scenario appears unlikely based on goodness-of-fit tests. For two additional objects, the minimum SBHB masses are unreasonably large (>1010 M⊙), strongly disfavouring the SBHB scenario. Using constraints on the orbital inclination angle (which requires some assumptions) makes the minimum masses of four more objects unreasonably large. We also cite physical and observational arguments against the SBHB hypothesis for nine objects. We conclude that the SBHB explanation is not the favoured explanation of double-peaked broad emission lines.
Synthetic 26Al emission from galactic-scale superbubble simulations
Authors: Rodgers-Lee D , Krause M G H , Dale J , Diehl R
Published: October 2019

Emission from the radioactive trace element 26Al has been observed throughout the Milky Way with the COMPTEL and INTEGRAL satellites. In particular, the Doppler shifts measured with INTEGRAL connect 26Al with superbubbles, which may guide 26Al flows off spiral arms in the direction of Galactic rotation. In order to test this paradigm, we have performed galaxy-scale simulations of superbubbles with 26Al injection in a Milky Way-type galaxy. We produce all-sky synthetic γ-ray emission maps of the simulated galaxies. We find that the 1809 keV emission from the radioactive decay of 26Al is highly variable with time and the observer’s position. This allows us to estimate an additional systematic variability of 0.2 dex for a star formation rate derived from 26Al for different times and measurement locations in Milky Way-type galaxies. High-latitude morphological features indicate nearby emission with correspondingly high-integrated γ-ray intensities. We demonstrate that the 26Al scale height from our simulated galaxies depends on the assumed halo gas density. We present the first synthetic 1809 keV longitude-velocity diagrams from 3D hydrodynamic simulations. The line-of-sight velocities for 26Al can be significantly different from the line-of-sight velocities associated with the cold gas. Over time, 26Al velocities consistent with the INTEGRAL observations, within uncertainties, appear at any given longitude, broadly supporting previous suggestions that 26Al injected into expanding superbubbles by massive stars may be responsible for the high velocities found in the INTEGRAL observations. We discuss the effect of systematically varying the location of the superbubbles relative to the spiral arms.
The ASAS-SN catalogue of variable stars – V. Variables in the Southern hemisphere
Authors: Jayasinghe T , Stanek K Z , Kochanek C S , Shappee B J , Holoien T W-S , Thompson T A , Prieto J L , Dong S , Pawlak M , Pejcha O , Shields J V , Pojmanski G , Otero S , Hurst N , Britt C A , Will D
Published: September 2019

The All-Sky Automated Survey for Supernovae (ASAS-SN) provides long baseline (∼4 yr) light curves for sources brighter than V ≲ 17 mag across the whole sky. As part of our effort to characterize the variability of all the stellar sources visible in ASAS-SN, we have produced ∼30.1 million V-band light curves for sources in the Southern hemisphere using the APASS DR9 (AAVSO Photometric All-Sky Survey Data Release) catalogue as our input source list. We have systematically searched these sources for variability using a pipeline based on random forest classifiers. We have identified ${\sim } 220\, 000$ variables, including ${\sim } 88\, 300$ new discoveries. In particular, we have discovered ${\sim }48\, 000$ red pulsating variables, ${\sim }23\, 000$ eclipsing binaries, ∼2200 δ-Scuti variables, and ${\sim }10\, 200$ rotational variables. The light curves and characteristics of the variables are all available through the ASAS-SN variable stars data base (https://asas-sn.osu.edu/variables). The pre-computed ASAS-SN V-band light curves for all the ∼30.1 million sources are available through the ASAS-SN photometry data base (https://asas-sn.osu.edu/photometry). This effort will be extended to provide ASAS-SN light curves for sources in the Northern hemisphere and for V ≲ 17 mag sources across the whole sky that are not included in APASS DR9.
WASP-South hot Jupiters: WASP-178b, WASP-184b, WASP-185b, and WASP-192b
Authors: Hellier Coel , Anderson D R , Barkaoui K , Benkhaldoun Z , Bouchy F , Burdanov A , Cameron A Collier , Delrez L , Gillon M , Jehin E , Nielsen L D , Maxted P F L , Pepe F , Pollacco D , Pozuelos F J , Queloz D , Ségransan D , Smalley B , Triaud A H M J , Turner O D , Udry S , West R G
Published: September 2019

We report on four new transiting hot Jupiters discovered by the WASP-South survey. WASP-178b transits a V = 9.9, A1V star with Teff = 9350 ± 150 K, the second-hottest transit host known. It has a highly bloated radius of 1.81 ± 0.09 RJup, in line with the known correlation between high irradiation and large size. With an estimated temperature of 2470 ± 60 K, the planet is one of the best targets for studying ultrahot Jupiters that is visible from the Southern hemisphere. The three host stars WASP-184, WASP-185, and WASP-192 are all post-main-sequence G0 stars of ages 4–8 Gyr. The larger stellar radii (1.3–1.7 M⊙) mean that the transits are relatively shallow (0.7–0.9 per cent) even though the planets have moderately inflated radii of 1.2–1.3 RJup. WASP-185b has an eccentric orbit (e = 0.24) and a relatively long orbital period of 9.4 d. A star that is 4.6 arcsec from WASP-185 and 4.4 mag fainter might be physically associated.
Continuous gravitational wave from magnetized white dwarfs and neutron stars: possible missions for LISA, DECIGO, BBO, ET detectors
Authors: Kalita Surajit , Mukhopadhyay Banibrata
Published: October 2019

Recent detection of gravitational wave from nine black hole merger events and one neutron star merger event by LIGO and VIRGO shed a new light in the field of astrophysics. On the other hand, in the past decade, a few super-Chandrasekhar white dwarf candidates have been inferred through the peak luminosity of the light curves of a few peculiar Type Ia supernovae, though there is no direct detection of these objects so far. Similarly, a number of neutron stars with mass $>\! 2\, \mathrm{M}_\odot$ have also been observed. Continuous gravitational wave can be one of the alternate ways to detect these compact objects directly. It was already argued that magnetic field is one of the prominent physics to form super-Chandrasekhar white dwarfs and massive neutron stars. If such compact objects are rotating with certain angular frequency, then they can efficiently emit gravitational radiation, provided their magnetic field and rotation axes are not aligned, and these gravitational waves can be detected by some of the upcoming detectors, e.g. LISA, BBO, DECIGO, Einstein Telescope, etc. This will certainly be a direct detection of rotating magnetized white dwarfs as well as massive neutron stars.
Prevalent externally driven protoplanetary disc dispersal as a function of the galactic environment
Authors: Winter Andrew J , Kruijssen J M Diederik , Chevance Mélanie , Keller Benjamin W , Longmore Steven N
Published: October 2019

The stellar birth environment can significantly shorten protoplanetary disc (PPD) lifetimes due to the influence of stellar feedback mechanisms. The degree to which these mechanisms suppress the time and mass available for planet formation is dependent on the local far-ultraviolet (FUV) field strength, stellar density, and ISM properties. In this work, we present the first theoretical framework quantifying the distribution of PPD dispersal time-scales as a function of parameters that describe the galactic environment. We calculate the probability density function for FUV flux and stellar density in the solar neighbourhood. In agreement with previous studies, we find that external photoevaporation is the dominant environment-related factor influencing local stellar populations after the embedded phase. Applying our general prescription to the Central Molecular Zone of the Milky Way (i.e. the central $\sim 250~\mbox{${\rm pc}$}$), we predict that $90{{\ \rm per\ cent}}$ of PPDs in the region are destroyed within 1 Myr of the dispersal of the parent molecular cloud. Even in such dense environments, we find that external photoevaporation is the dominant disc depletion mechanism over dynamical encounters between stars. PPDs around low-mass stars are particularly sensitive to FUV-induced mass-loss, due to a shallower gravitational potential. For stars of mass ∼1 M⊙, the solar neighbourhood lies at approximately the highest gas surface density for which PPD dispersal is still relatively unaffected by external FUV photons, with a median PPD dispersal time-scale of ∼4 Myr. We highlight the key questions to be addressed to further contextualize the significance of the local galactic environment for planet formation.
DNA damage and repair in neuropsychiatric disorders. What do we know and what are the future perspectives?
Authors: Czarny Piotr , Bialek Katarzyna , Ziolkowska Sylwia , Strycharz Justyna , Sliwinski Tomasz
Published: September 2019

Over the past two decades, extensive research has been done to elucidate the molecular etiology and pathophysiology of neuropsychiatric disorders. In majority of them, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), bipolar disorder (BD), schizophrenia and major depressive disorder, increased oxidative and nitrosative stress was found. This stress is known to induce oxidative damage to biomolecules, including DNA. Accordingly, increased mitochondrial and nuclear DNA, as well as RNA damage, were observed in patients suffering from these diseases. However, recent findings indicate that the patients are characterised by impaired DNA repair pathways, which may suggest that these DNA lesions could be also a result of their insufficient repair. In the current systematic, critical review, we aim to sum up, using available literature, the knowledge about the involvement of nuclear and mitochondrial DNA damage and repair, as well as about damage to RNA in pathoetiology of neuropsychiatric disorders, i.e., AD, PD, ALS, BD, schizophrenia and major depressive disorder, as well as the usefulness of the discussed factors as being diagnostic markers and targets for new therapies. Moreover, we also underline the new directions to which future studies should head to elucidate these phenomena.
SINEUP non-coding RNAs rescue defective frataxin expression and activity in a cellular model of Friedreich's Ataxia
Authors: Bon Carlotta , Luffarelli Riccardo , Russo Roberta , Fortuni Silvia , Pierattini Bianca , Santulli Chiara , Fimiani Cristina , Persichetti Francesca , Cotella Diego , Mallamaci Antonello , Santoro Claudio , Carninci Piero , Espinoza Stefano , Testi Roberto , Zucchelli Silvia , Condò Ivano , Gustincich Stefano
Published: September 2019

Friedreich's ataxia (FRDA) is an untreatable disorder with neuro- and cardio-degenerative progression. This monogenic disease is caused by the hyper-expansion of naturally occurring GAA repeats in the first intron of the FXN gene, encoding for frataxin, a protein implicated in the biogenesis of iron-sulfur clusters. As the genetic defect interferes with FXN transcription, FRDA patients express a normal frataxin protein but at insufficient levels. Thus, current therapeutic strategies are mostly aimed to restore physiological FXN expression. We have previously described SINEUPs, natural and synthetic antisense long non-coding RNAs, which promote translation of partially overlapping mRNAs through the activity of an embedded SINEB2 domain. Here, by in vitro screening, we have identified a number of SINEUPs targeting human FXN mRNA and capable to up-regulate frataxin protein to physiological amounts acting at the post-transcriptional level. Furthermore, FXN-specific SINEUPs promote the recovery of disease-associated mitochondrial aconitase defects in FRDA-derived cells. In summary, we provide evidence that SINEUPs may be the first gene-specific therapeutic approach to activate FXN translation in FRDA and, more broadly, a novel scalable platform to develop new RNA-based therapies for haploinsufficient diseases.
A pilot randomized controlled trial of exercise to improve cognitive performance in patients with stable glioma: a proof of concept
Authors: Gehring Karin , Stuiver Martijn M , Visser Eva , Kloek Corelien , van den Bent Martin , Hanse Monique , Tijssen Cees , Rutten Geert-Jan , Taphoorn Martin J B , Aaronson Neil K , Sitskoorn Margriet M
Published: September 2019

Background

Patients with glioma often suffer from cognitive deficits. Physical exercise has been effective in ameliorating cognitive deficits in older adults and neurological patients. This pilot randomized controlled trial (RCT) explored the possible impact of an exercise intervention, designed to improve cognitive functioning in glioma patients, regarding cognitive test performance and patient-reported outcomes (PROs).

Methods

Thirty-four clinically stable patients with World Health Organization grades II/III glioma were randomized to a home-based remotely coached exercise group or an active control group. Patients exercised 3 times per week for 20–45 minutes, with moderate to vigorous intensity, during 6 months. At baseline and immediate follow-up, cognitive performance and PROs were assessed with neuropsychological tests and questionnaires, respectively. Linear regression analyses were used to estimate effect sizes of potential between-group differences in cognitive performance and PROs at 6 months.

Results

The exercise group (n = 21) had small- to medium-sized better follow-up scores than the control group (n = 11) on several measures of attention and information processing speed, verbal memory, and executive function, whereas the control group showed a slightly better score on a measure of sustained selective attention. The exercise group also demonstrated small- to medium-sized better outcomes on measures of self-reported cognitive symptoms, fatigue, sleep, mood, and mental health–related quality of life.

Conclusions

This small exploratory RCT in glioma patients provides a proof of concept with respect to improvement of cognitive functioning and PROs after aerobic exercise, and warrants larger exercise trials in brain tumor patients.
Identification of shared genomic aberrations between angiomatous and microcystic meningiomas
Authors: Kuroi Yasuhiro , Akagawa Hiroyuki , Shibuya Makoto , Onda Hideaki , Maegawa Tatsuya , Kasuya Hidetoshi
Published: September 2019

Background

Angiomatous and microcytic meningiomas are classified as rare subtypes of grade I meningiomas by World Health Organization (WHO). They typically exhibit distinct histopathological features as indicated by their WHO titles; however, these angiomatous and microcystic features are often intermixed. Recently, angiomatous meningiomas were reported to show characteristic chromosomal polysomies unlike the other WHO grade I meningiomas. In the present study, we hypothesize that microcystic meningiomas share similar cytogenetic abnormalities with angiomatous meningioma.

Methods

We performed copy number analysis using single nucleotide polymorphism (SNP) arrays for three angiomatous and eight microcystic meningiomas. Of these, three angiomatous and three microcystic meningiomas were also analyzed by whole exome sequencing and RNA sequencing.

Results

We first analyzed three angiomatous and three microcystic meningiomas for which both frozen tissues and peripheral blood were accessible. Copy number analysis confirmed previously reported multiple polysomies in angiomatous meningiomas, which were entirely replicated in microcystic meningiomas when analyzed on different analytical platforms with five additional samples prepared from formalin-fixed paraffin-embedded tumors. Polysomy of chromosome 5 was found in all cases, along with chromosome 6, 12, 17, 18, and 20 in more than half of the cases including both angiomatous and microcystic meningiomas. Furthermore, next generation sequencing did not reveal any distinctive somatic point mutations or differences in gene expression characterizing either angiomatous or microcystic meningiomas, indicating a common genetic mechanism underlying tumorigenesis.

Conclusions

Angiomatous and microcystic meningiomas have substantially similar genetic profiles represented by the characteristic patterns of multiple polysomies originating from chromosome 5 amplification.
Management of cutaneous neurofibroma: current therapy and future directions
Authors: Chamseddin Bahir H , Le Lu Q
Published: October 2019

Neurofibromatosis type 1 (NF1) is a life-long neurocutaneous disorder characterized by a predisposition to tumor development, including cutaneous neurofibroma (cNF), the hallmark of the disease. cNF is a histologically benign, multicellular tumor formed in virtually most individuals with NF1. It is considered the most burdensome feature of the disorder due to their physical discomfort, cosmetically disfiguring appearance, and psychosocial burden. Management of cNF remains a challenge in the medical field. Effective medicinal treatment for cNF does not exist at this time. Trials aimed at targeting individual components of the neoplasm such as mast cells with Ketotifen have not shown much success. Physical removal or destruction has been the mainstay of therapy. Surgical removal gives excellent cosmetic results, but risk in general anesthesia may require trained specialists. Destructive laser such as CO2 laser is effective in treating hundreds of tumors at one time but has high risk of scarring hypopigmentation or hyperpigmentation that alter cosmetic outcomes. A robust, low-risk surgical technique has been developed, which may be performed in clinic using traditional biopsy tools that may be more accessible to NF1 patients worldwide than contemporary techniques including Er:YAG or Nd:YAG laser. In this review, specific recommendations for management of cNFs are made based on symptoms, clinical expertise, and available resources. Additionally, antiproliferative agents aimed at stimulating cellular quiescence are explored.
Health complaints and work experiences among adults with neurofibromatosis 1
Authors: Fjermestad Krister W
Published: September 2019

Background

Neurofibromatosis type 1 (NF1) is a rare genetic disorder with usually benign nerve tumours, skin problems, pain and cardiovascular problems among common complications.

Aims

To examine work participation and experiences in relation to health complaints among adults with NF1.

Methods

We conducted a cross-sectional self-reported survey among 142 persons with NF1 (mean age = 50.3 years, SD = 12.0; 62% females). We measured physical and social dimensions of work experiences with eight items from the third wave of the epidemiological survey ‘Nord-Trøndelag Health Study’ (HUNT3). We compared NF1 data to 27 036 HUNT3 controls. We measured health complaints with the 29-item Subjective Health Complaints Inventory (SHC; subscales musculoskeletal pain, pseudoneurology and gastrointestinal problems) and compared NF1 data to norms.

Results

Compared to controls, significantly more persons with NF1 reported workplace bullying (13% versus 5%) and work as physically exhausting (74% versus 44%), whereas fewer reported work autonomy (64% versus 80%). Women with NF1 reported significantly more SHC than female norms (99% versus 86%). Men with NF1 reported significantly more pseudoneurology and gastrointestinal problems compared to male norms (76% versus 58%). SHC explained 9% of the variance in physical work experiences (β = −0.47; 95% CI −0.76 to −0.19) and 8% of the variance in social work experiences (β = 0.48; 95% CI 0.18–0.78).

Conclusion

Persons with NF1 experience more physical and social work problems, and both work domains were related to health complaints. Individualized assessment and information to co-workers and managers may represent ways to increase work participation among persons with NF1.
Higher MICs (>2 mg/L) Predict 30-Day Mortality in Patients With Lower Respiratory Tract Infections Caused by Multidrug- and Extensively Drug-Resistant Pseudomonas aeruginosa Treated With Ceftolozane/Tazobactam
Authors: Rodríguez-Núñez Olga , Periañez-Parraga Leonor , Oliver Antonio , Munita Jose M , Boté Anna , Gasch Oriol , Nuvials Xavier , Dinh Aurélien , Shaw Robert , Lomas Jose M , Torres Vicente , Castón Juanjo , Araos Rafael , Abbo Lilian M , Rakita Robert , Pérez Federico , Aitken Samuel L , Arias Cesar A , Martín-Pena M Luisa , Colomar Asun , Núñez M Belén , Mensa Josep , Martínez José Antonio , Soriano Alex
Published: September 2019

Background

Ceftolozane/tazobactam (C/T) efficacy and safety in ventilator-associated pneumonia (VAP) is being evaluated at a double dose by several trials. This dosing is based on a pharmacokinetic (PK) model that demonstrated that 3 g q8h achieved ≥90% probability of target attainment (50% ƒT > minimal inhibitory concentration [MIC]) in plasma and epithelial lining fluid against C/T-susceptible P. aeruginosa. The aim of this study was to evaluate the efficacy of different C/T doses in patients with lower respiratory infection (LRI) due to MDR- or XDR-P. aeruginosa considering the C/T MIC.

Methods

This was a multicenter retrospective study of 90 patients with LRI caused by resistant P. aeruginosa who received a standard or high dose (HDo) of C/T. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality.

Results

The median age (interquartile range) was 65 (51–74) years. Sixty-three (70%) patients had pneumonia, and 27 (30%) had tracheobronchitis. Thirty-three (36.7%) were ventilator-associated respiratory infections. The median C/T MIC (range) was 2 (0.5–4) mg/L. Fifty-four (60%) patients received HDo. Thirty-day mortality was 27.8% (25/90). Mortality was significantly lower in patients with P. aeruginosa strains with MIC ≤2 mg/L and receiving HDo compared with the groups with the same or higher MIC and dosage (16.2% vs 35.8%; P = .041). Multivariate analysis identified septic shock (P < .001), C/T MIC >2 mg/L (P = .045), and increasing Charlson Comorbidity Index (P = .019) as independent predictors of mortality.

Conclusions

The effectiveness of C/T in P. aeruginosa LRI was associated with an MIC ≤2 mg/L, and the lowest mortality was observed when HDo was administered for strains with C/T MIC ≤2 mg/L. HDo was not statistically associated with a better outcome.
Primary vaginal adenocarcinoma of intestinal-type: case report of a rare gynaecological tumour
Authors: Ugwu Aloy O , Haruna Muibat , Okunade Kehinde S , Ohazurike Ephraim , Anorlu Rose I , Banjo Aina A F
Published: September 2019

Vaginal cancer is rare and accounts for only 1 to 2% of all gynaecological malignancies. They arise as primary squamous cell cancers or are the result of extension from the cervix or vulva. Primary mucinous vaginal adenocarcinoma of intestinal-type is an extremely rare malignancy of unknown histogenesis with a diagnostic dilemma for the clinician and histopathologist. We presented the case of a 40-year-old Para 0+2 woman with the complaint of a mass in the vagina and recurrent vaginal bleeding who was evaluated and worked-up for examination under anaesthesia and biopsy of the vaginal mass. The histological examination revealed the unusual intestinal-type variant of adenocarcinoma of the vagina. Recognition of this rare entity is important, particularly to avoid the pitfall of misdiagnosing metastatic disease as primary vaginal cancer.
A misleading appearance of a common disease: tuberculosis with generalized lymphadenopathy—a case report
Authors: Bottineau Marie-Claude , Kouevi Kagni Ayekoué , Chauvet Eline , Garcia Daniel Martinez , Galetto-Lacour Annick , Wagner Noémie
Published: September 2019

Introduction: Tuberculosis is a common illness for vulnerable populations in resource-limited settings. Lymph nodes in tuberculosis represent the most frequent extra-pulmonary form of tuberculosis in children, but lymph nodes are rarely generalized and large. We report an atypical pediatric case of tuberculosis with lymphadenopathy. Patient concerns and findings: A two-year-old child with severe acute malnutrition presented with painless, generalized, and excessively large nodes which were not compressive and were without fistula. Main diagnoses, interventions, outcomes: Fine needle aspiration was performed and led to the detection of lymph node granulomatous lymphadenitis suggestive of tuberculosis. Conclusion: The child was immediately initiated on anti-tuberculosis therapy with a very successful outcome. Clinicians should be aware of atypical manifestations such as the one we describe in the interest of swift diagnosis and initiation of treatment.
A large superior mesenteric artery aneurysm and ileal obstruction: a rare presentation of polyarteritis nodosa in an infant
Authors: Shimizu Akihiko , Tanaka Kensuke , Takazawa Shinya , Nishi Akira , Shimoyama Shinya , Kobayashi Tomio , Imagawa Tomoyuki , Hirato Junko , Yamada Yoshiyuki
Published: September 2019

Polyarteritis nodosa (PAN) is a rare form of vasculitis that occurs in childhood and affects small- and medium-sized arteries. Large aneurysms due to PAN can induce fatal complications like rupturing or occlusion of the affected arteries. Here, we report a case of a 4-month-old girl with PAN complicated by a large superior mesenteric artery aneurysm and ileal obstruction. We controlled her blood pressure to prevent the artery from rupturing. A combination of prednisolone, intravenous cyclophosphamide, and plasma exchange reduced the inflammation. She developed mechanical ileus due to ileum stricture and underwent bowel resection. Histopathological examinations revealed reparative arteritis around the healed ulcer. Her postoperative course was uneventful without further dilatation of the aneurysm. This case highlights the importance of intensive immunosuppressive therapy and appropriate blood pressure control in pediatric patients with PAN complicated by large aneurysms. Mechanical ileus can develop and may require surgical management even after remission of vasculitis.
Pain-Relieving Effect of 4.4 MHz of Pulsed Radiofrequency on Acute Knee Arthritis in Rats
Authors: Moon Sun Wook , Park Eui Ho , Park Jin Sung , Lee Seung Won , Suh Hye Rim , Park Sang Hyun , Yoon Seung Zhoo , Park Kun Woo , Han Hee Chul
Published: September 2019

Objective

Drug injections and surgery are popular treatments for knee joint osteoarthritis. However, these treatments are invasive, and new noninvasive treatments with similar or better efficacy are needed. Here, we evaluated the application of 4.4 MHz of pulsed radiofrequency (PRF) as a new treatment.

Methods

Acute arthritis was induced by injection of carrageenan into the intra-articular space of the knee in male rats. At 4.5 hours after arthritis induction, PRF with the treatment protocol of three seconds on and off was applied to the affected knee joint for 20 minutes. The changes in pain behavior were evaluated by comparing the peak weight load values of both hind paws at pretreatment and four, six, seven, eight, and 24 hours after treatment. And we also used Western blotting and immunohistochemistry to measure the inflammatory changes in the synovial membrane of the inflamed knee.

Results

We found that the 20-minute application of PRF with the treatment protocol significantly recovered the weight load reduction at six-, seven-, and eight-hour time points after carrageenan injection. COX-2 and IL-1β levels were significantly reduced in the inflamed rats after PRF application at six and eight hours post–carrageenan injection. Immunohistochemistry showed that PRF significantly reduced inflammatory cell infiltration at six hours post–carrageenan injection.

Conclusions

. Our results indicate that noninvasive PRF application inhibited pain-related behavior and decreased inflammatory cytokine expression in the inflamed knee joints of rats. Accordingly, PRF application can serve as a potential therapeutic treatment to relieve pain associated with peripheral joint/tissue damage or inflammation.
Mobile Neurofeedback for Pain Management in Veterans with TBI and PTSD
Authors: Elbogen Eric B , Alsobrooks Amber , Battles Sara , Molloy Kiera , Dennis Paul A , Beckham Jean C , McLean Samuel A , Keith Julian R , Russoniello Carmen
Published: October 2019

Objective

Chronic pain is common in military veterans with traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Neurofeedback, or electroencephalograph (EEG) biofeedback, has been associated with lower pain but requires frequent travel to a clinic. The current study examined feasibility and explored effectiveness of neurofeedback delivered with a portable EEG headset linked to an application on a mobile device.

Design

Open-label, single-arm clinical trial.

Setting

Home, outside of clinic.

Subjects

N = 41 veterans with chronic pain, TBI, and PTSD.

Method

Veterans were instructed to perform “mobile neurofeedback” on their own for three months. Clinical research staff conducted two home visits and two phone calls to provide technical assistance and troubleshoot difficulties.

Results

N = 36 veterans returned for follow-up at three months (88% retention). During this time, subjects completed a mean of 33.09 neurofeedback sessions (10 minutes each). Analyses revealed that veterans reported lower pain intensity, pain interference, depression, PTSD symptoms, anger, sleep disturbance, and suicidal ideation after the three-month intervention compared with baseline. Comparing pain ratings before and after individual neurofeedback sessions, veterans reported reduced pain intensity 67% of the time immediately following mobile neurofeedback. There were no serious adverse events reported.

Conclusions

This preliminary study found that veterans with chronic pain, TBI, and PTSD were able to use neurofeedback with mobile devices independently after modest training and support. While a double-blind randomized controlled trial is needed for confirmation, the results show promise of a portable, technology-based neuromodulatory approach for pain management with minimal side effects.
Thermal Psychophysics and Associated Brain Activation Patterns Along a Continuum of Healthy Aging
Authors: Beach Paul A , Cowan Ronald L , Dietrich Mary S , Bruehl Stephen P , Atalla Sebastian W , Monroe Todd B
Published: October 2019

Objective

To examine psychophysical and brain activation patterns to innocuous and painful thermal stimulation along a continuum of healthy older adults.

Design

Single center, cross-sectional, within-subjects design.

Methods

Thermal perceptual psychophysics (warmth, mild, and moderate pain) were tested in 37 healthy older adults (65–97 years, median = 73 years). Percept thresholds (oC) and unpleasantness ratings (0–20 scale) were obtained and then applied during functional magnetic resonance imaging scanning. General linear modeling assessed effects of age on psychophysical results. Multiple linear regressions were used to test the main and interaction effects of brain activation against age and psychophysical reports. Specifically, differential age effects were examined by comparing percent-signal change slopes between those above/below age 73 (a median split).

Results

Advancing age was associated with greater thresholds for thermal perception (z = 2.09, P = 0.037), which was driven by age and warmth detection correlation (r = 0.33, P = 0.048). Greater warmth detection thresholds were associated with reduced hippocampal activation in “older” vs “younger” individuals (>/<73 years; beta < 0.40, P < 0.01). Advancing age, in general, was correlated with greater activation of the middle cingulate gyrus (beta > 0.44, P < 0.01) during mild pain. Differential age effects were found for prefrontal activation during moderate pain. In “older” individuals, higher moderate pain thresholds and greater degrees of moderate pain unpleasantness correlated with lesser prefrontal activation (anterolateral prefrontal cortex and middle–frontal operculum; beta < –0.39, P < 0.009); the opposite pattern was found in “younger” individuals.

Conclusions

Advancing age may lead to altered thermal sensation and (in some circumstances) altered pain perception secondary to age-related changes in attention/novelty detection and cognitive functions.
Destructive Creation at Work: How Financial Distress Spurs Entrepreneurship
Authors: Babina Tania
Published: September 2019

Using U.S. Census firm-worker data, I document that firms’ financial distress has an economically important effect on employee departures to entrepreneurship. The impact is amplified in the high-tech and service sectors, where employees are key assets. In states with enforceable noncompete contracts, the effect is mitigated. Compared to typical entrepreneurs, distress-driven entrepreneurs are high-wage workers who found better firms, as measured by jobs, pay, and survival. Startup jobs compensate for 33% of job losses at the constrained incumbents. Overall, the financial inability of incumbent firms to pursue productive opportunities increases the reallocation of economic activity into new firms.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Monetary Transmission through Shadow Banks
Authors: Xiao Kairong
Published: September 2019

I find that shadow bank money creation significantly expands during monetary-tightening cycles. This “shadow banking channel” offsets reductions in commercial bank deposits and dampens the impact of monetary policy. Using a structural model of bank competition, I show that the difference in depositor clienteles quantitatively explains banks’ different responses to monetary policy. Facing a more yield-sensitive clientele, shadow banks are more likely to pass through rate hikes to depositors, thereby attracting more deposits when the Federal Reserve raises rates. My results suggest that monetary tightening could unintentionally increase financial fragility by driving deposits into the uninsured shadow banking sector.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
P55 Improving parental knowledge and confidence in managing a child with JIA
Authors: Sheehan Joanna , Green Kate
Published: October 2019

Background

An MDT-led educational class for parents of children newly diagnosed with JIA was developed with the aims of improving parental knowledge and confidence in managing a child with JIA. Our clinical observations were that a number of our patients had inaccurate ideas of what JIA was, three to six months into treatment. This is in-line with studies indicating that memory for medical information is often poor and inaccurate especially when the patient is anxious. Research also indicates the importance of patients developing an understanding of the condition and treatment which can aid in a number of improved outcomes including adherence.

Our aim was to provide parents with an opportunity to increase their knowledge regarding JIA, addressing the medical and psychological management in a relaxed environment separate from a clinic appointment, without their children present. Several families had also requested to meet other parents for peer support and practical advice.

Methods

Parents of children newly diagnosed with JIA were invited to attend a session held in the evening at the NOC. Sessions were also conducted by the team at outreach clinics throughout the region. The programme was tailored to the child’s developmental stage and included information about JIA and its management from the advanced nurse specialist, physiotherapist, occupational therapist, paediatric psychologist and an experienced parent.

Prior to the session, parents completed a short questionnaire to assess their confidence in managing their child’s condition and their understanding of JIA and treatment. Responses were measured on a ten point VAS scale. This was then repeated on completion of the session. Qualitative data regarding parent experience was also captured.

Results

Due to the large geographical area, attendance was approximately 50%. Parents’ understanding about JIA and treatment on average increased 2.6 points on VAS scale, parent’s confidence in managing their child increased on average 2.9 points. Parents reported the sessions were useful to explore what support is available, information regarding future management, importance of exercise, the emotional and psychological impact of JIA and how to manage it. 100% of parents reported their pre session aims were met.

Conclusion

Parental knowledge and confidence in managing their child’s condition was shown to increase in all those who attended, demonstrated by increases in VAS scores. Sessions allowed parents to access information from specialist paediatric rheumatology professionals and meet with peers in a relaxed environment.

Consideration is currently being given to the use of social media to boost attendance through a virtual session. We are planning to follow-up parents to see if the increase in VAS scores is maintained

Conflicts of Interest

The authors declare no conflicts of interest.
An open-label randomized controlled trial of DMARD withdrawal in RA patients achieving therapeutic response with certolizumab pegol combined with DMARDs
Authors: Pope Janet , Rampakakis Emmanouil , Vaillancourt Julie , Bessette Louis , Lazovskis Juris , Haraoui Boulos , Sampalis John S
Published: September 2019

Objectives

The objective of this trial was to compare effectiveness of certolizumab pegol added to conventional synthetic DMARDs (csDMARDs) in RA patients, followed by continuing vs discontinuing background csDMARDs after treatment response.

Methods

Patients with active RA who had certolizumab pegol added to their existing csDMARD regimen due to inadequate response were eligible. At 3 or 6 months, patients who achieved a change (Δ) in DAS28 of ⩾1.2 were randomized to continue combination therapy (COMBO) or withdraw csDMARD therapy (MONO) (unblinded). The primary outcome was non-inferiority of stopping vs continuing csDMARD(s) in terms of maintaining ΔDAS28 ⩾ 1.2 or achieving DAS28 low disease activity at 18 months (non-inferiority margin: 15 percentile units).

Results

A total of 125 patients were enrolled, 88 randomized to COMBO (n = 43) or MONO (n = 45). No significant differences were observed between groups in baseline age, gender, race, RF status or prior biologics (16% vs 11%). Although the rate of ΔDAS28 ⩾ 1.2 and/or DAS28 low disease activity achievement at 18 months was clinically comparable between the two groups (72% vs 69%), non-inferiority assumptions were not met [absolute risk difference (upper limit of 90% CI): 2.6% (19.1%)]. Similar baseline-adjusted improvements were seen in DAS28 (COMBO vs MONO: −2.3 vs −2.1; P = 0.49) and all endpoints were not statistically different including 59% vs 56% achieved DAS28 low disease activity, 69% vs 59% ΔDAS28 ⩾ 1.2, and 41% each remission.

Conclusion

Among RA patients achieving a therapeutic response on combination therapy with certolizumab pegol and csDMARDs, withdrawing csDMARDs was not non-inferior to maintaining csDMARDs but improvements were sustained in both groups at 18 months.
Towards “Green” Trusteeship: new statutory amendments for occupational pension trustees
Authors: Brown Lloyd
Published: October 2019

This article looks at the amendments to occupational pension schemes that are brought in by the Pension Protection Fund (Pensionable Service) and the Occupational Pension Schemes (Investment and Disclosure) (Amendment and Modification) Regulations 2018. It is respectfully submitted that the named regulations are legally compelling because they amend the regulatory landscape in a manner to enforce greater consideration of Environmental Social Governance risks by UK pension funds. In particular, this article engages with how the amendments are going to increase the pension fund trustees’ appetite to consider environmental risks (including climate-related risks) when exercising their general duty of investment.