bluuebunny/crossref_metadata_2025 huggingface dataset:
The quality of care in outpatient primary care in public and private sectors in Malaysia
Authors: Chin May Chien , Sivasampu Sheamini , Wijemunige Nilmini , Rannan-Eliya Ravindra P , Atun Rifat
Published: September 2019

In Malaysia, first-contact, primary care is provided by parallel public and private sectors, which are completely separate in organization, financing and governance. As the country considers new approaches to financing, including using public schemes to pay for private care, it is crucial to examine the quality of clinical care in the two sectors to make informed decisions on public policy. This study intends to measure and compare the quality of clinical care between public and private primary care services in Malaysia and, to the extent possible, assess quality with the developed economies that Malaysia aspires to join. We carried out a retrospective analysis of the National Medical Care Survey 2014, a nationally representative survey of doctor–patient encounters in Malaysia. We assessed clinical quality for 27 587 patient encounters using data on 66 internationally validated quality indicators. Aggregate scores were constructed, and comparisons made between the public and private sectors. Overall, patients received the recommended care just over half the time (56.5%). The public sector performed better than the private sector, especially in the treatment of acute conditions, chronic conditions and in prescribing practices. Both sectors performed poorly in the indicators that are most resource intensive, suggesting that resource constraints limit overall quality. A comparison with 2003 data from the USA, suggests that performance in Malaysia was similar to that a decade earlier in the USA for common indicators. The public sector showed better performance in clinical care than the private sector, contrary to common perceptions in Malaysia and despite providing worse consumer quality. The overall quality of outpatient clinical care in Malaysia appears comparable to other developed countries, yet there are gaps in quality, such as in the management of hypertension, which should be tackled to improve overall health outcomes.
Content of Brazilian supermarket circulars do not reflect national dietary guidelines
Authors: Camargo Anice Milbratz de , Farias Júlia Pitsch de , Mazzonetto Ana Claudia , Dean Moira , Fiates Giovanna Medeiros Rataichesck
Published: September 2019

Previous research on foods advertised in supermarket circulars revealed that advertisement for foods at promotional prices influence food choices and shopping behaviour, but no paper reporting the Latin American context was identified. Furthermore, most studies only assessed the products advertised on the front pages and not in the entire circulars. This paper quantifies and categorizes, according to level of processing, the foods advertised in circulars from four Brazilian supermarket chains in order to assess their compatibility with the national dietary guidelines issued by the Ministry of Health. Printed and online circulars were collected between June and July 2016. Foods items advertised were identified and classified into one of four categories using the NOVA classification as unprocessed or minimally processed, processed culinary ingredient, processed or ultra-processed. Sixteen documents were analysed, and 1786 food items identified, where 23% were categorized as unprocessed or minimally processed, and 63% as ultra-processed foods. While the mean proportion of ultra-processed and unprocessed or minimally processed foods advertised on circular covers was similar (p = 0.49), the mean proportion of ultra-processed foods advertised in the entire circular was significantly higher than unprocessed or minimally processed foods (p < 0.001). Brazilian supermarket circulars are stimulating the acquisition of ultra-processed foods, which does not encourage food choices to be in line with what is recommended by the Dietary Guidelines for the Brazilian Population.
Congruence between fine-scale genetic breaks and dispersal potential in an estuarine seaweed across multiple transition zones
Authors: Nicastro Katy R , Assis Jorge , Serrão Ester A , Pearson Gareth A , Neiva João , Valero Myriam , Jacinto Rita , Zardi Gerardo I
Published: September 2019

Genetic structure in biogeographical transition zones can be shaped by several factors including limited dispersal across barriers, admixture following secondary contact, differential selection, and mating incompatibility. A striking example is found in Northwest France and Northwest Spain, where the estuarine seaweed Fucus ceranoides L. exhibits sharp, regional genetic clustering. This pattern has been related to historical population fragmentation and divergence into distinct glacial refugia, followed by post-glacial expansion and secondary contact. The contemporary persistence of sharp ancient genetic breaks between nearby estuaries has been attributed to prior colonization effects (density barriers) but the effect of oceanographic barriers has not been tested. Here, through a combination of mesoscale sampling (15 consecutive populations) and population genetic data (mtIGS) in NW France, we define regional genetic disjunctions similar to those described in NW Iberia. Most importantly, using high resolution dispersal simulations for Brittany and Iberian populations, we provide evidence for a central role of contemporary hydrodynamics in maintaining genetic breaks across these two major biogeographic transition zones. Our findings further show the importance of a comprehensive understanding of oceanographic regimes in hydrodynamically complex coastal regions to explain the maintenance of sharp genetic breaks along continuously populated coastlines.
A multi-stock harvest control rule based on “pretty good yield” ranges to support mixed-fisheries management
Authors: Garcia Dorleta , Dolder Paul J , Iriondo Ane , Moore Claire , Prellezo Raúl , Urtizberea Agurtzane
Published: September 2019

Advice for commercially exploited fish stocks is usually given on a stock-by-stock basis. In light of the ecosystem-based fisheries management, the need to move towards a holistic approach has been largely acknowledged. In addition, the discard bans in some countries requires consistent catch advice among stocks to mitigate choke species limiting fisheries activity. In this context, in 2015, the European Commission proposed the use of fishing mortality ranges around fishing mortality targets to give flexibility to the catch advice system and improve the use of fishing opportunities in mixed-fisheries. We present a multi-stock harvest control rule (HCR) that uses single stock assessment results and fishing mortality ranges to generate a consistent catch advice among stocks. We tested the performance of the HCR in two different case studies. An artificial case study with three stocks exploited simultaneously by a single fleet and the demersal mixed-fishery operating in Bay of Biscay and Celtic Sea. The HCR produced consistent catch advice among stocks when there was only a single fleet exploiting them. Even more, the HCR removed the impact of the discard ban. However, in a multi-fleet framework the performance of the HCR varied depending on the characteristics of the fleets.
Hotspots of childhood obesity in a large metropolitan area: does neighbourhood social and built environment play a part?
Authors: Ribeiro Ana Isabel , Santos Ana Cristina , Vieira Verónica M , Barros Henrique
Published: September 2019

Background

Effective place-based interventions for childhood obesity call for the recognition of the high-risk neighbourhoods and an understanding of the determinants present locally. However, such an approach is uncommon. In this study, we identified neighbourhoods with elevated prevalence of childhood obesity (‘hotspots’) in the Porto Metropolitan Area and investigated to what extent the socio-economic and built environment characteristics of the neighbourhoods explained such hotspots.

Methods

We used data on 5203 7-year-old children from a population-based birth cohort, Generation XXI. To identify hotspots, we estimated local obesity odds ratios (OR) and 95% confidence intervals (95%CI) using generalized additive models with a non-parametric smooth for location. Measures of the socio-economic and built environment were determined using a Geographic Information System. Associations between obesity and neighbourhood characteristics were expressed as OR and 95%CI after accounting for individual-level variables.

Results

At 7 years of age, 803 (15.4%) children were obese. The prevalence of obesity varied across neighbourhoods and two hotspots were identified, partially explained by individual-level variables. Adjustment for neighbourhood characteristics attenuated the ORs and further explained the geographic variation. This model revealed an association between neighbourhood socio-economic deprivation score and obesity (OR = 1.014, 95%CI 1.004–1.025), as well as with the presence of fast-food restaurants at a walkable distance from the residence (OR = 1.37, 1.06–1.77).

Conclusions

In our geographic area it was possible to identify neighbourhoods with elevated prevalence of childhood obesity and to suggest that targeting such high-priority neighbourhoods and their environmental characteristics may help reduce childhood obesity.
The association of birthweight with age at natural menopause: a population study of women in Norway
Authors: Bjelland Elisabeth K , Gran Jon M , Hofvind Solveig , Eskild Anne
Published: September 2019

Background

Previous studies suggest that birthweight may influence age at natural menopause, but the evidence remains inconclusive. Thus, we aimed to estimate the association of birthweight with age at natural menopause.

Methods

A retrospective population study of 164 608 women in Norway, aged 48–71 years. Data were obtained by two self-administered questionnaires among participants in BreastScreen Norway during 2006–2014. We used Cox proportional hazard models to estimate hazard ratios and logistic regression models to estimate odds ratios of menopause according to birthweight. Restricted cubic splines were applied to allow for possible non-linear associations, and adjustments were made for year and country of birth.

Results

Women with birthweight <2500 g were median 51 years at menopause (interquartile range 49–54 years), whereas women with birthweight 3500–3999 g were median 52 years at menopause (interquartile range 49–54 years). The hazard ratio of menopause decreased with increasing birthweight up until 3500 g. At birthweights >3500 g, we estimated no further decrease (P for non-linearity = 0.007). Birthweight at 2500 g increased the odds ratios of menopause before the age of 45 [1.20; 95% confidence interval (CI): 1.14–1.25] and the age of 40 (1.26; 95% CI: 1.15–1.38) compared with birthweight at 3500 g. At birthweights 4000 g and 4500 g, the odds ratio estimates were very similar to the reference group and the CIs overlapped 1.00.

Conclusions

We found a non-linear dose-relationship of birthweight with age at natural menopause, and low birthweight was associated with early natural menopause. Our findings suggest that growth restriction during fetal life may influence the timing of natural menopause.
Charlotte Tilbury succeeds on copyright claim against Aldi lookalike
Authors: Fairhurst Oliver
Published: September 2019

Islestarr Holdings Ltd v Aldi Stores Ltd [2019] EWHC 1473 (Ch)

The High Court of England and Wales has found that discount supermarket Aldi had copied claimant Charlotte Tilbury’s artistic works in creating its cheaper make-up product. The case demonstrates the tools available to brands in tackling lookalikes (or ‘dupes’) and may provide lessons on how designers can build into their products certain protectable features that increase the chances of being able to repress unauthorized imitations.
Lyme Disease Risk of Exposure to Blacklegged Ticks (Acari: Ixodidae) Infected with Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in Pittsburgh Regional Parks
Authors: Simmons Alison E , Manges Anna B , Bharathan Tashi , Tepe Shannon L , McBride Sara E , DiLeonardo Matthew Q , Duchamp Joseph E , Simmons Thomas W
Published: September 2019

Lyme disease is the most commonly reported vector-borne illness and sixth most commonly reported notifiable infectious disease in the United States. The majority of cases occur in the Northeast and upper-Midwest, and the number and geographic distribution of cases is steadily increasing. The blacklegged tick (Ixodes scapularis Say) is the principal vector of the Lyme disease spirochete (Borrelia burgdorferi sensu stricto) in eastern North America. Although Lyme disease risk has been studied in residential and recreational settings across rural to urban landscapes including metropolitan areas, risk within U.S. cities has not been adequately evaluated despite the presence of natural and undeveloped public parkland where visitors could be exposed to B. burgdorferi-infected I. scapularis. We studied the occurrence of I. scapularis and infection prevalence of B. burgdorferi in four insular regional parks within the city of Pittsburgh to assess Lyme disease risk of exposure to infected adults and nymphs. We found that the density of I. scapularis adults (1.16 ± 0.21 ticks/100 m2) and nymphs (3.42 ± 0.45 ticks/100 m2), infection prevalence of B. burgdorferi in adults (51.9%) and nymphs (19.3%), and density of infected adults (0.60 ticks/100 m2) and nymphs (0.66 ticks/100 m2) are as high in these city parks as nonurban residential and recreational areas in the highly endemic coastal Northeast. These findings emphasize the need to reconsider, assess, and manage Lyme disease risk in greenspaces within cities, especially in high Lyme disease incidence states.
Modelling the evolution of PAH abundance in galaxies
Authors: Rau Shiau-Jie , Hirashita Hiroyuki , Murga Maria
Published: September 2019

We investigate the evolution of polycyclic aromatic hydrocarbon (PAH) abundance in a galaxy, which is a crucial step to understand the evolution of bright emission features in the mid-infrared range. We calculate the evolution of dust grain size distribution in a manner consistent with the physical conditions of the interstellar medium by post-processing our previous hydrodynamical simulation of an isolated disc galaxy. We also differentiate between aromatic and non-aromatic grains for carbonaceous dust species and explicitly considered the aromatization process. As a consequence, our model explains the metallicity dependence of PAH abundances in nearby galaxies well. The PAH abundance increase is driven particularly by the interplay between shattering and accretion (dust growth). The fast aromatization guarantees that the small carbonaceous grains trace PAHs very well. Since shattering and accretion are sensitive to the dust abundance, we predict that the PAH-to-dust abundance ratio increases as the metallicity increases. This is consistent with the observation data of nearby galaxies.
Discrete star formation events in the central bar of the Small Magellanic Cloud
Authors: Strantzalis A , Hatzidimitriou D , Zezas A , Antoniou V , Lianou S , Tsilia S
Published: September 2019

We present the results of the photometric analysis of a large part of the main body of the Small Magellanic Cloud. Using the 6.5m Magellan Telescope at the Las Campanas Observatory in Chile, we have acquired deep B and I images in four fields (0.44 deg each in diameter), yielding accurate photometry for 1068 893 stars down to 24th magnitude, with a spatial resolution of 0.20 arcsec per pixel. Colour–magnitude diagrams and (completeness-corrected) luminosity functions have been constructed, yielding significant new results that indicate at least two discrete star formation events over a period from 2.7 to 4 Gyr ago. Also, we have derived star formation rates as a function of look-back time and have found enhancements of SF between 4 and 6 Gyr and at younger ages.
AGN radiative feedback in the early growth of massive black holes
Authors: Ishibashi W
Published: September 2019

Growing observational evidence confirms the existence of massive black holes ($M_{\rm BH} \sim 10^9 \, \mathrm{M}_{\odot }$), accreting at rates close to the Eddington limit, at very high redshifts ($z \gtrsim 6\!-\!7$) in the early Universe. Recent observations indicate that the host galaxies of the first quasars are chemically evolved systems, containing unexpectedly large amounts of dust. Such a combination of high luminosities and large dust content should form favourable physical conditions for radiative dusty feedback. We explore the impact of the active galactic nucleus (AGN) feedback, driven by radiation pressure on dust, on the early growth of massive black holes. Assuming Eddington-limited exponential black hole growth, we find that the dynamics and energetics of the radiation pressure-driven outflows also follow exponential trends at late times. We obtain modest outflow energetics (with momentum flux $\dot{p} \lesssim L/c$ and kinetic power $\dot{E}_{\rm k} \lesssim 10^{-3} L$), comparable with available observations of quasar-driven outflows at very high redshifts, but significantly lower than typically observed in local quasars and predicted by wind energy-driven models. AGN radiative dusty feedback may thus play an important role in powering galactic outflows in the first quasars in the early Universe.
Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells
Authors: Yang Changwon , Lim Whasun , Park Junghyun , Park Sunwoo , You Seungkwon , Song Gwonhwa
Published: September 2019

Human umbilical cord mesenchymal stem cells (MSCs) have been reported to improve the migration and invasion of trophoblast cells; however, little is known about whether MSC-derived exosomes and exosomal miRNAs can regulate trophoblast cell properties. In this study, we investigated whether exosomal miRNAs from amniotic fluid-derived MSC (AF-MSC) could regulate the inflammatory response of the human trophoblast cell line HTR8/SVneo. We verified the anti-inflammatory effects of AF-MSCs on lipopolysaccharide (LPS)-induced inflammatory trophoblast cells and found that miR-146a-5p and miR-548e-5p in the AF-MSC–derived exosomes regulate nuclear factor κB, AKT and mitogen-activated protein kinase protein phosphorylation. Furthermore, we found that the transfection of human trophoblast cells with miR-146a-5p and miR-548e-5p inhibitors reduced trophoblast migration (P < 0.05 vs control) and the expression of proliferating cell nuclear antigen, a protein essential for cell proliferation (P < 0.01 vs control). In particular, the miR-548e-5p inhibitor induced apoptosis, while tumor necrosis factor receptor–associated factor 6, a predicted target of miR-146a-5p and miR-548e-5p, was involved in the regulation of oxidative stress in the human trophoblast cells. In a mouse model of LPS-induced preterm birth (PB), miR-146a-5p expression was found to be relatively low in the group in which the effect of AF-MSCs was insignificant. However, this study is limited in that the changes in the expression of some genes in response to AF-MSCs differ between the cell line and mouse model. Collectively, these data show that exosomal miR-146a-5p and miR-548e-5p from AF-MSCs have anti-inflammatory effects on human trophoblast cells and may be novel targets for treating inflammatory diseases and associated problems that occur during pregnancy, such as PB.
Altered DNA ligase activity in human disease
Authors: Tomkinson Alan E , Naila Tasmin , Khattri Bhandari Seema
Published: September 2019

The joining of interruptions in the phosphodiester backbone of DNA is critical to maintain genome stability. These breaks, which are generated as part of normal DNA transactions, such as DNA replication, V(D)J recombination and meiotic recombination as well as directly by DNA damage or due to DNA damage removal, are ultimately sealed by one of three human DNA ligases. DNA ligases I, III and IV each function in the nucleus whereas DNA ligase III is the sole enzyme in mitochondria. While the identification of specific protein partners and the phenotypes caused either by genetic or chemical inactivation have provided insights into the cellular functions of the DNA ligases and evidence for significant functional overlap in nuclear DNA replication and repair, different results have been obtained with mouse and human cells, indicating species-specific differences in the relative contributions of the DNA ligases. Inherited mutations in the human LIG1 and LIG4 genes that result in the generation of polypeptides with partial activity have been identified as the causative factors in rare DNA ligase deficiency syndromes that share a common clinical symptom, immunodeficiency. In the case of DNA ligase IV, the immunodeficiency is due to a defect in V(D)J recombination whereas the cause of the immunodeficiency due to DNA ligase I deficiency is not known. Overexpression of each of the DNA ligases has been observed in cancers. For DNA ligase I, this reflects increased proliferation. Elevated levels of DNA ligase III indicate an increased dependence on an alternative non-homologous end-joining pathway for the repair of DNA double-strand breaks whereas elevated level of DNA ligase IV confer radioresistance due to increased repair of DNA double-strand breaks by the major non-homologous end-joining pathway. Efforts to determine the potential of DNA ligase inhibitors as cancer therapeutics are on-going in preclinical cancer models.
A single ChIP-seq dataset is sufficient for comprehensive analysis of motifs co-occurrence with MCOT package
Authors: Levitsky Victor , Zemlyanskaya Elena , Oshchepkov Dmitry , Podkolodnaya Olga , Ignatieva Elena , Grosse Ivo , Mironova Victoria , Merkulova Tatyana
Published: September 2019

Recognition of composite elements consisting of two transcription factor binding sites gets behind the studies of tissue-, stage- and condition-specific transcription. Genome-wide data on transcription factor binding generated with ChIP-seq method facilitate an identification of composite elements, but the existing bioinformatics tools either require ChIP-seq datasets for both partner transcription factors, or omit composite elements with motifs overlapping. Here we present an universal Motifs Co-Occurrence Tool (MCOT) that retrieves maximum information about overrepresented composite elements from a single ChIP-seq dataset. This includes homo- and heterotypic composite elements of four mutual orientations of motifs, separated with a spacer or overlapping, even if recognition of motifs within composite element requires various stringencies. Analysis of 52 ChIP-seq datasets for 18 human transcription factors confirmed that for over 60% of analyzed datasets and transcription factors predicted co-occurrence of motifs implied experimentally proven protein-protein interaction of respecting transcription factors. Analysis of 164 ChIP-seq datasets for 57 mammalian transcription factors showed that abundance of predicted composite elements with an overlap of motifs compared to those with a spacer more than doubled; and they had 1.5-fold increase of asymmetrical pairs of motifs with one more conservative ‘leading’ motif and another one ‘guided’.
RNAInter in 2020: RNA interactome repository with increased coverage and annotation
Authors: Lin Yunqing , Liu Tianyuan , Cui Tianyu , Wang Zhao , Zhang Yuncong , Tan Puwen , Huang Yan , Yu Jia , Wang Dong
Published: September 2019

Research on RNA-associated interactions has exploded in recent years, and increasing numbers of studies are not limited to RNA–RNA and RNA–protein interactions but also include RNA–DNA/compound interactions. To facilitate the development of the interactome and promote understanding of the biological functions and molecular mechanisms of RNA, we updated RAID v2.0 to RNAInter (RNA Interactome Database), a repository for RNA-associated interactions that is freely accessible at http://www.rna-society.org/rnainter/ or http://www.rna-society.org/raid/. Compared to RAID v2.0, new features in RNAInter include (i) 8-fold more interaction data and 94 additional species; (ii) more definite annotations organized, including RNA editing/localization/modification/structure and homology interaction; (iii) advanced functions including fuzzy/batch search, interaction network and RNA dynamic expression and (iv) four embedded RNA interactome tools: RIscoper, IntaRNA, PRIdictor and DeepBind. Consequently, RNAInter contains >41 million RNA-associated interaction entries, involving more than 450 thousand unique molecules, including RNA, protein, DNA and compound. Overall, RNAInter provides a comprehensive RNA interactome resource for researchers and paves the way to investigate the regulatory landscape of cellular RNAs.
VCAM-1 targeted alpha-particle therapy for early brain metastases
Authors: Corroyer-Dulmont Aurélien , Valable Samuel , Falzone Nadia , Frelin-Labalme Anne-Marie , Tietz Ole , Toutain Jérôme , Soto Manuel Sarmiento , Divoux Didier , Chazalviel Laurent , Pérès Elodie A , Sibson Nicola R , Vallis Katherine A , Bernaudin Myriam
Published: September 2019

Background

Brain metastases (BM) develop frequently in patients with breast cancer. Despite the use of external beam radiotherapy (EBRT), the average overall survival is short (6 months from diagnosis). The therapeutic challenge is to deliver molecularly targeted therapy at an early stage when relatively few metastatic tumor cells have invaded the brain. Vascular cell adhesion molecule 1 (VCAM-1), overexpressed by nearby endothelial cells during the early stages of BM development, is a promising target. The aim of this study was to investigate the therapeutic value of targeted alpha-particle radiotherapy, combining lead-212 (212Pb) with an anti–VCAM-1 antibody (212Pb-αVCAM-1).

Methods

Human breast carcinoma cells that metastasize to the brain, MDA-231-Br-GFP, were injected into the left cardiac ventricle of nude mice. Twenty-one days after injection, 212Pb-αVCAM-1 uptake in early BM was determined in a biodistribution study and systemic/brain toxicity was evaluated. Therapeutic efficacy was assessed using MR imaging and histology. Overall survival after 212Pb-αVCAM-1 treatment was compared with that observed after standard EBRT.

Results

212Pb-αVCAM-1 was taken up into early BM with a tumor/healthy brain dose deposition ratio of 6 (5.52e108 and 0.92e108) disintegrations per gram of BM and healthy tissue, respectively. MRI analyses showed a statistically significant reduction in metastatic burden after 212Pb-αVCAM-1 treatment compared with EBRT (P < 0.001), translating to an increase in overall survival of 29% at 40 days post prescription (P < 0.01). No major toxicity was observed.

Conclusions

The present investigation demonstrates that 212Pb-αVCAM-1 specifically accumulates at sites of early BM causing tumor growth inhibition.
Simulating Episode-Based Bundled Payments for Cranial Neurosurgical Procedures
Authors: Medress Zachary , Ugiliweneza Beatrice , Parker Jonathon , Wang Dengzhi , Burton Eric , Boakye Maxwell , Skirboll Stephen
Published: September 2019

BACKGROUND

Episode-based bundled payments were introduced by Medicare in 2013 as the Bundled Payments for Care Improvement (BPCI) in order to improve care coordination and cost efficiency. BPCI has not yet been applied to cranial neurosurgical procedures.

OBJECTIVE

To determine projected values of episode-based bundled payments when applied to common cranial neurosurgical procedures using retrospective data from a large database.

METHODS

We performed a large retrospective observational study using the MarketScan administrative database to project bundled payment payments for 4 groups of common cranial neurosurgical procedures.

RESULTS

We identified 15 276 procedures that met our inclusion criteria. We observed significant variability between groups, with 90-d bundle projected payments ranging from $ 58,200 for craniotomy for meningioma to $ 102,073 for craniotomy for malignant glioma. We also found significant variability in projected bundled payments within each class of operation. On average, payment for the index hospitalization accounted for 85% of projected payments for a 30-d bundle and 70.5% of projected payments for a 90-d bundle. Multivariable analysis showed that hospital readmission, discharge to postacute care facilities, venous-thrombo-embolism, medical comorbidities, adjuvant therapies, and payer status significantly contributed to projected cranial bundle payments.

CONCLUSION

For the first time, to our knowledge, we project the values of episode-based bundled payments for common vascular and tumor cranial operations. As previously identified in orthopedic procedures, there is significant variability in total bundle payments within each cranial procedure. Compared to spine and orthopedic procedures, postdischarge care significantly impacts total bundle payments in cranial neurosurgery.
Surgical Management of Primary Skull Base Osteosarcomas: Impact of Margin Status and Patterns of Relapse
Authors: Raza Shaan M , Habib Ahmed , Wang Wei-Lien , Gildey Paul W , Conley Anthony P , Nader Marc-Elie , Hanna Ehab Y , Su Shirley Y , DeMonte Franco
Published: September 2019

BACKGROUND

Skull base osteosarcomas are aggressive neoplasms characterized by bony invasion and extracompartmental/extra-osseous soft tissue extension that pose obstacles to achieving complete resection. Management is further complicated by the paucity of data regarding the efficacy of surgery within the treatment paradigm.

OBJECTIVE

To identify the impact of margin status on local progression free survival (PFS) and disease specific survival (DSS).

METHODS

A retrospective review was performed of 36 patients with osteosarcoma who underwent gross total resection with negative margins (R0), or positive margins (R1). Patient demographics, prior treatments, relapse patterns, and survival were collected. Univariate analysis was performed to determine the impact of margin status on the PFS (primary outcome) and DSS (secondary outcome).

RESULTS

R0 resection was achieved in 67%, 25% patients had local recurrence, and 19.4% patients had distant metastasis. In assessing the entire cohort, R0 resections had improved DSS (P = .002) and PFS (P = .04). In chemotherapy-naïve patients, R0 resections also had improved impact on PFS (P = .04) and DSS (P = .027). For radiation-naïve patients, improvements in PFS (P = .026) and DSS (P = .031) were also noted.

CONCLUSION

Skull base osteosarcomas present management challenges in which both local and systemic disease progression is the cause of mortality. Achieving R0 resections significantly improves PFS and DSS in treatment-naïve patients within multimodality treatment paradigms. Salvage surgery may benefit in patients after failing previous radiation and chemotherapy treatments. Further work is needed to determine optimal treatment strategies. These data represent the largest series reported to date.
Efficacy of a Texting Program to Promote Cessation Among Pregnant Smokers: A Randomized Control Trial
Authors: Pollak Kathryn I , Lyna Pauline , Gao Xiaomei , Noonan Devon , Bejarano Hernandez Santiago , Subudhi Sonia , Swamy Geeta K , Fish Laura J
Published: September 2019

Introduction

Smoking during pregnancy poses serious risks to baby and mother. Few disseminable programs exist to help pregnant women quit or reduce their smoking. We hypothesized that an SMS text-delivered scheduled gradual reduction (SGR) program plus support texts would outperform SMS support messages alone.

Methods

We recruited 314 pregnant women from 14 prenatal clinics. Half of the women received theory-based support messages throughout their pregnancy to promote cessation and prevent relapse. The other half received the support messages plus alert texts that gradually reduced their smoking more than 3–5 weeks. We conducted surveys at baseline, end of pregnancy, and 3 months postpartum. Our primary outcome was biochemically validated 7-day point prevalence abstinence at late pregnancy. Our secondary outcome was reduction in cigarettes per day.

Results

Adherence to the SGR was adequate with 70% responding to alert texts to smoke within 60 minutes. Women in both arms quit smoking at the same rate (9%–12%). Women also significantly reduced their smoking from baseline to the end of pregnancy from nine cigarettes to four; we found no arm differences in reduction.

Conclusions

Support text messages alone produced significant quit rates above naturally occurring quitting. SGR did not add significantly to helping women quit or reduce. Sending support messages can reach many women and is low-cost. More obstetric providers might consider having patients who smoke sign up for free texting programs to help them quit.

Implications

A disseminable texting program helped some pregnant women quit smoking.

Clinical Trial Registration number: NCT01995097.
Exercise for Smoking Cessation in Postmenopausal Women: A Randomized, Controlled Trial
Authors: Oncken Cheryl , Allen Sharon , Litt Mark , Kenny Anne , Lando Harry , Allen Alicia , Dornelas Ellen
Published: September 2019

Background

Postmenopausal smokers have difficulty quitting smoking and experience considerable weight gain with smoking cessation. We examined whether adjunctive smoking treatment with exercise, compared to a relaxation control condition, could improve cigarette abstinence, decrease cigarettes smoked per day (CPD), and ameliorate changes in body mass index (BMI) in postmenopausal smokers.

Methods

Women (N = 301) signed informed consent and were randomized to treatment at two sites (Universities of Connecticut and Minnesota). We randomized groups of participants to a comprehensive group treatment program that included 12 weeks of varenicline and either a moderate exercise or relaxation component for 6 months. Participants were followed for a year after medication treatment.

Results

Overall, 17.3% of patients reported carbon monoxide-verified continuous abstinence for the 9- to 12-week period, and 11.6% reported prolonged abstinence at 1 year, with no significant differences between treatment conditions. CPD reported at study visits showed significant main effects for time in weeks, for site, and for treatment. The Exercise condition reported smoking fewer CPD over time, and that advantage widened over time. In terms of BMI, significant effects for time in weeks, and for the interaction of Week × Treatment condition, reflected gradually increasing BMI in these women over time, but with the increase in BMI slower in the Exercise condition.

Conclusions

Exercise, compared to relaxation, was associated with a reduced BMI and CPD in postmenopausal women, but did not increase end of treatment or prolonged abstinence. Further research is needed to devise exercise programs that increase smoking cessation rates in postmenopausal women.

Implications

This study adds to the literature on the effectiveness of a moderate exercise intervention compared to a relaxation control condition as an adjunctive treatment for smoking cessation in postmenopausal women. Our exercise program did not increase end of treatment or prolonged abstinence rates in postmenopausal women; however, there was a beneficial effect on smoking reduction and reduced body mass index. Additional research is needed to devise exercise programs that increase smoking cessation rates in postmenopausal women.
Evaluation of Abuse and Route of Administration of Extended-Release Tapentadol Among Treatment-Seeking Individuals, as Captured by the Addiction Severity Index–Multimedia Version (ASI-MV)
Authors: Vosburg Suzanne K , Beaumont Jared , Dailey-Govoni S Taryn , Butler Stephen F , Green Jody L
Published: September 2019

Background

Tapentadol is a molecule incorporating mu opioid receptor agonism and norepinephrine reuptake inhibition to provide analgesia, with the potential for a lower incidence of gastrointestinal side effects than full mu opioid agonists. Postmarketing surveillance of tapentadol as an active pharmaceutical ingredient has consistently revealed low levels of abuse and diversion.

Objective

The purpose of the present study was to further characterize the abuse liability of tapentadol extended-release (ER) by evaluating the prevalence of past 30-day tapentadol ER abuse and reported routes of administration as compared with ER opioids with Food and Drug Administration (FDA) abuse-deterrent labeling (“ADF opioids”) and ER opioids without FDA abuse-deterrent labeling (“non-ADF opioids”).

Methods

Data were collected from January 2014 through December 2017 from 776 centers located in 43 states throughout the United States using the Addiction Severity Index–Multimedia Version (ASI-MV), an instrument that is integral to the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO, Inflexxion, an IBH Company, Costa Mesa, CA, USA).

Results

Tapentadol ER had lower rates of past 30-day abuse than ADF ER and non-ADF ER opioid comparators, both at a population level and when adjusted for drug utilization. Tapentadol ER was primarily abused orally, although it was also abused through alternate routes of administration. Cumulative rates of tapentadol ER abuse by alternative routes of administration were lower than both ADF and non-ADF ER opioid comparators, although large confidence intervals resulting from the small sample size of reported tapentadol ER use limit firm conclusions.

Conclusions

In summary, tapentadol ER was found to have lower rates of both past 30-day abuse and use via alternate routes of administration, specifically snorting and smoking, than ADF and non-ADF ER comparators.
UNCERTAINTY EVALUATION IN DOSE ASSESSMENT DUE TO SPATIAL DISTRIBUTION OF NORM IN BEACH SANDS OF SOUTHEAST COAST OF INDIA: A PROBABILISTIC APPROACH
Authors: Chandrasekaran S , Sankaran Pillai G , Baskaran R , Venkatraman B
Published: September 2019

A study on radionuclide distribution along coastal stretch in high background areas is constantly attracted to many researchers around the world. In the present study, the concentration of radionuclides in beach sands along the southeast coastal region of India has been studied in detail. Concentration of radionuclides is measured using gamma spectrometry at 148 pre-determined locations. It is found that 238U and 232Th concentrations are varying in the range from 3 (BDL) to 298.9 and 1150.2 Bq kg−1, respectively. Concentration of 40K in beach sand varied from 11 to 1743.4 Bq kg−1. The measured activity levels of radionuclides were compared with earlier studies carried out by various researchers in the same region under study. The related radiological parameters of interest were also determined and compared with the internationally recommended values. With an increase in emphasis on quality in dose assessment methods, dose to human population living in the vicinity requires uncertainty evaluation, which is carried out by taking into account variation in the activity values. This study would serve as a baseline radiological mapping for the southeast coast region of India for environmental impact assessment prior to plan of nuclear facility in the future.
Pilot testing an app-based stress management intervention for cancer survivors
Authors: Børøsund Elin , Varsi Cecilie , Clark Matthew M , Ehlers Shawna L , Andrykowski Michael A , Sleveland Hilde Renate Sætre , Bergland Anne , Nes Lise Solberg
Published: September 2019

Psychosocial eHealth intervention programs for cancer survivors are still in their infancy, with inconsistent findings so far in the scientific literature. The aim of this study was to explore system use, usefulness, ease of use, and preliminary effects of Stress Proffen, an app-based cognitive-behavioral stress management intervention for patients with cancer. A feasibility pilot project tested the intervention with cancer survivors (N = 25). The intervention contained (a) one face-to-face introduction session, (b) 10 app-based modules with stress management educational material and exercises, and (c) one follow-up phone call. Post-intervention interviews were conducted and user log-data were extracted. Outcome measures—Perceived Stress Scale (PSS), Anxiety and Depression (Hospital Anxiety and Depression Scale [HADS]), Health-Related Quality of Life (HRQoL; SF-36), and Self-Regulatory Fatigue (SRF-18)—were completed at baseline and post-intervention. Participants were primarily women (84%), age 34–71 (mean 48) and represented a variety of cancer diagnoses (majority breast cancer: 40%). Twenty-two participants completed all (pre–post) questionnaires. Sixteen participants (67%) completed at least 7 of 10 modules within the 8-week study period. Post-intervention interviews described StressProffen as providing a new, appreciated, and easily accessible stress management tool for the cancer survivors. Dependent/paired t-tests showed significant pre–post intervention effects with significant decrease in stress (p = .008), anxiety (p = .019), and self-regulatory fatigue (p = .025), and improved HRQoL (Role Physical, General Health, Vitality, and Role Emotional, all p’s <.01). App-based stress management interventions such as StressProffen can provide appreciated support for cancer survivors, should be easy to use, can provide significant stress reduction, and improve emotional well-being. Further testing in a randomized controlled trial is warranted and is in progress.

Clinicaltrials.gov: NCT0293961.
Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis
Authors: Colas Romain A. , Nhat Le Thanh Hoang , Thuong Nguyen Thuy Thuong , Gómez Esteban A. , Ly Lucy , Thanh Hai Hoang , Mai Nguyen Thi Hoang , Phu Nguyen Hoan , Thwaites Guy E. , Dalli Jesmond
Published: September 2019

Tuberculous meningitis (TBM) is the most lethal form of tuberculosis infection, characterized by a dysregulated immune response that frequently leads to neurologic injury and death despite the best available treatment. The mechanisms driving the inflammatory response in TBM are not well understood. To gain insights into these mechanisms, we used a lipid mediator–profiling approach to investigate the regulation of a novel group of host protective mediators, termed specialized proresolving mediators (SPMs), in the cerebrospinal fluid (CSF) of adults with TBM. Herein, using CSF from patients enrolled into a randomized placebo‐controlled trial of adjunctive aspirin treatment, we found distinct lipid mediator profiles with increasing disease severity. These changes were linked with an up‐regulation of inflammatory eicosanoids in patients with severe TBM and a decrease in the production of a number of SPMs. CSF proresolving mediator concentrations were also associated with 80‐d survival. In survivors, we found a significant increase in proresolving mediator concentrations, including the lipoxygenase 5‐derived 13‐series resolvin (RvT)2, RvT4, and 15‐epi‐lipoxin B4, compared with those who died. Of note, treatment of patients with high‐dose aspirin led to a decrease in the concentrations of the prothrombic mediator thromboxane A2, reduced brain infarcts, and decreased death in patients with TBM. Together, these findings identify a CSF SPM signature that is associated with disease severity and 80‐d mortality in TBM.—Colas, R. A., Nhat, L. T. H., Thuong N. T. T., Gómez, E. A., Ly, L., Thanh, H. H., Mai, N. T. H., Phu, N. H., Thwaites, G. E., Dalli, J. Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis. FASEB J. 33, 13028–13039 (2019). www.fasebj.org
Anesthesia-induced Recognition Deficit Is Improved in Postnatally Gonadectomized Male Rats
Authors: Sasaki Russell Jennifer M. , Hagelstein Marlous , Lee Bradley H. , Sall Jeffrey W.
Published: September 2019

Background:

Preclinical investigations of the effects of general anesthesia on the young brain show differences in vulnerability of males and females to anesthetic exposure at different times during development. However, the mechanism underlying this sex difference is poorly understood. Perinatal testosterone is the primary determinant of sexual differentiation and likely plays an important role in defining the period of susceptibility to anesthetic injury. We investigated whether the removal of testosterone through gonadectomy shortly after birth would improve cognitive outcomes in male rodents after early anesthesia exposure.

Methods:

Male Sprague Dawley rats underwent gonadectomy at postnatal day 2 (P2), followed by exposure to 6 hours of isoflurane at P7. A control cohort of gonad-intact male littermates was simultaneously exposed. All rats were subjected to a series of object recognition and association tasks beginning at P42. Cell death in the thalamus and hippocampus was assessed in a separate cohort.

Results:

All groups performed similarly on the Novel Object Recognition task; however, the gonad-intact isoflurane group exhibited decreased performance in the more difficult tasks. This deficit was ameliorated in the gonadectomized group. Cell death was similar between both isoflurane-exposed groups, regardless of gonadectomy.

Conclusions:

The absence of testosterone does not block cell death after anesthesia in specific brain regions of interest; however, does provide some neuroprotection as evidenced by the improved cognitive test performance during adulthood. These findings suggest that testosterone may be mechanistically involved in the sex-specific effects of anesthetic injury on the developing brain by extending the vulnerable period in male rats.
Maternal Immunization
Authors: Munoz Flor M. , Jamieson Denise J.
Published: September 2019

Vaccines administered to women during pregnancy can provide protection against serious infectious diseases for the mother, for the newborn, or both. Maternal immunization boosts the concentration of maternal antibodies that can be transferred across the placenta to directly protect infants too young to be immunized. In addition, indirect protection through prevention of maternal infection and through breast milk antibodies can be achieved through maternal immunization. In general, inactivated vaccines are considered safe for pregnant women and their fetuses, whereas live vaccines are avoided owing to the theoretical potential risk to the fetus. However, the risks and benefits of vaccination must be carefully weighed and whenever possible, protection to the mother and her infant should be prioritized. Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines are routinely recommended for all pregnant women in the United States. Seasonal inactivated influenza vaccine is recommended for all pregnant women in any trimester of pregnancy, mainly to protect the mother, but there is growing evidence that infants benefit from passive antibody protection against influenza complications. The Tdap vaccine is recommended during the third trimester of each pregnancy to provide optimal protection to infants who are at particularly high risk of pertussis complications and mortality in the first 3 months of life. The effects of maternal immunization on the prevention of maternal and infant disease have been demonstrated in observational and prospective studies of influenza and pertussis disease in the United States and worldwide. Maternal immunization has the potential to improve the health of mothers and young infants and therefore, other diseases of relevance during this period are now targets of active research and vaccine development, including group B streptococcus and respiratory syncytial virus. Similarly, several vaccines can be administered during pregnancy in special circumstances, when maternal health, travel, or other special situations arise. This article reviews the current recommendations for vaccination of women during pregnancy.