bluuebunny/crossref_metadata_2025 huggingface dataset:
E-Government and Social Media: The Impact on Accessibility
Authors: Sonnenberg Christian
Published: March 2020

Social media is a valuable tool, providing a means of instruction, communication, and collaboration to many organizations including the government institutions that citizens rely upon. However, while important for distributing information, social media has not historically prioritized accessibility. The federal government has a duty to provide fair and usable information access for those with disabilities, but the delineation between where this responsibility lies becomes blurred when third-party platforms like social media are utilized. The extent to which social media pervades government sites and causes accessibility issues is one that is not well understood. This article presents an overview of the current state of affairs for Section 508, the implications it has for social media, and a study to evaluate the potential impact it has on all users.
Compressive behaviors of ultra-low-weight foamed cement-based composite reinforced by polypropylene short fibers
Authors: Yang Yuanyi , Zhou Qi , Deng Yi , Lin Jinhui
Published: March 2020

With advantages in sustainability, low thermal conductivity, and self-weight, the foamed cement-based composites have captured tremendous attention in various low strength structural and nonstructural applications. This paper aimed to investigate the effects of the short polypropylene fibers on the quasi-static compression performance of the ultra-low-weight foamed cement-based composites. The results show that the elasticity modulus, peak strength, and ultimate linear strength of the fiber-reinforced composites are increased by 208%, 42%, and 71%, respectively. The plateau stress and the densification strain energy of fiber-reinforced composites are improved by up to 49% and 47%. Simultaneously, the failure mode of the fibrous sample is altered from a brittle behavior to plastic behavior. The significance of this work shows that short synthetic fibers can improve the compressive capacity considerably, turning out to be an effective strategy for obtaining higher mechanical strengths associated with ultra-low-weight typical cement-based elements. According to the experiment results, a constructive damage model is carried out to describe the compressive properties of short PP fiber-reinforced composites. Thus, such theoretical curves can describe the compression behavior successfully and can be potentially applied in practical project and numerical simulation. This work can also be useful toward the foundation of optimal design for toughening behavior in fiber-reinforced lightweight cement elements.
How to Correct for Computer Experience in Online Cognitive Testing?
Authors: Lee Meeuw Kjoe Philippe R. , Agelink van Rentergem Joost A. , Vermeulen Ivar E. , Schagen Sanne B.
Published: March 2020

Objective: Since computerized cognitive test performance may be influenced by computer experience, correction for this measure might be needed. This study examined how to correct for computer experience by examining its influence on online and traditional tests. Method: 248 healthy adults completed an online neuropsychological test battery and 70 adults completed traditional equivalents of the tests. Computer experience was assessed by a performance-based and a self-report measure. Regression analyses were applied to examine their influence on the online and traditional tests. Results: After correction for demographics, the performance-based measure was associated with online and traditional, predominantly speed-based, tests. The self-report measure was also associated with speed-based online tests but not with most traditional tests. Conclusions: Correcting computerized neuropsychological tests using a performance-based measure of computer experience would be unwise, because this measure also seems to tap into cognitive functions. A correction using a self-report measure might be better and is appropriate.
Predictors of High Grade and Other Clinically Significant Placental Findings by Indication for Submission in Singleton Placentas From Term Births
Authors: Zhou Yi Yuan , Ravishankar Sanjita , Luo Guangju , Redline Raymond W
Published: March 2020

Indications for placental submission are variable. Established guidelines are largely based on expert opinion, and there is a need for more evidence-based criteria. A 10-year database of term placentas was used to evaluate indications significantly associated with placental pathology. Lesions in 5 categories were separated into high- and low-grade subgroups. Two additional high-grade lesions were also evaluated. Indications associated with high-grade placental lesions were chronic monitoring abnormalities, severe preeclampsia, pregestational diabetes, maternal signs of infection, postdates pregnancy, artificial reproductive technology, drug abuse, umbilical cord entanglements, selected gross placental abnormalities, stillbirth, Apgar 5 minutes <6, small-for-gestational age infant, and macrosomia. Indications for which placental findings did not differ from the population as a whole were acute monitoring abnormalities, chronic hypertension, maternal obesity, vaginal bleeding, accessory lobe/multilobed placenta, meconium-stained fluid, single umbilical artery, and borderline large-for-gestational age infant. Other indications for submission were intermediate showing significant or borderline elevations in the prevalence of low- and high-grade lesions combined. We suggest on the basis of this study that guidelines for the submission of singleton term placentas could be modified to exclude cases with clinical indications that lack a significant association with placental lesions.
“They are mar-vel-ous, and they all want me!”: Gay Brazilian tourists and global geographies of desire
Authors: Jarrin Alvaro , Pitts Bryan
Published: March 2020

This article explores the geographies of desire that inform contact between gay Brazilian tourists and the men they encounter abroad. It argues that Brazilian men largely embrace the sexualized image of themselves that circulates globally and value foreign men according to their proximity to whiteness. By studying tourists who hail from the Global South, their imaginings of the Global North, and the ways they exoticize themselves, the article brings a new perspective to the scholarship on tourism, which usually focuses on North-to-South travel.
“If somebody could just understand what I am going through, it would make all the difference”: Conceptualizations of trauma in homeless populations experiencing severe mental illness
Authors: Gilmoor Andrew , Vallath Smriti , Regeer Barbara , Bunders Joske
Published: March 2020

Exposure to violence, vulnerability due to lack of shelter, alienation due to stigma, the experiences of severe mental illness (SMI) and subsequent institutionalization, make homeless persons with SMI uniquely susceptible to trauma exposure and subsequent mental health consequences. This study aims to contribute to the development of culturally sensitive interventions for identifying and treating trauma in a population of homeless persons with SMI in Tamil Nadu, India by understanding the manifestations of trauma and its associated consequences in this population. Free-listing exercises followed by in-depth interviews were conducted with a convenience sample of 26 user-survivors who have experienced homelessness or were at risk of homelessness, and suffered from SMI. Topics explored included events considered to be traumatic, pathways to trauma, associated emotional, physical and social complaints, and coping strategies. Results indicate discrepancies in classification of traumatic events between user-survivors and the Diagnostic and Statistical Manual of Mental Disorders. Traumatic experiences, particularly relating to social relationships and poverty, mentioned by user-survivors did not match traditional conceptualizations of trauma. Positive coping strategies for trauma included being mentally strong, knowledge and awareness, whereas the main negative coping strategy is avoidance. User-survivors attributed their experiences of homelessness and SMI to past traumas. Differing views of trauma between user-survivors and mental health professionals can lead to misdiagnosis and under-recognition of trauma in this population of homeless persons with SMI.
Global Stroke Statistics 2019
Authors: Kim Joosup , Thayabaranathan Tharshanah , Donnan Geoffrey A , Howard George , Howard Virginia J , Rothwell Peter M , Feigin Valery , Norrving Bo , Owolabi Mayowa , Pandian Jeyaraj , Liu Liping , Cadilhac Dominique A , Thrift Amanda G
Published: March 2020

Background

Data on stroke epidemiology and availability of hospital-based stroke services around the world are important for guiding policy decisions and healthcare planning.

Aims

To provide the most current incidence, mortality and case–fatality data on stroke and describe current availability of stroke units around the world by country.

Methods

We searched multiple databases (based on our existing search strategy) to identify new original manuscripts and review articles published between 1 June 2016 and 31 October 2018 that met the ideal criteria for data on stroke incidence and case–fatality. For data on the availability of hospital-based stroke services, we searched PubMed for all literature published up until 31 June 2018. We further screened reference lists, citation history of manuscripts and gray literature for this information. Mortality codes for International Classification of Diseases-9 and International Classification of Diseases-10 were extracted from the World Health Organization mortality database for each country providing these data. Population denominators were obtained from the World Health Organization, and when these were unavailable within a two-year period of mortality data, population denominators within a two-year period were obtained from the United Nations. Using country-specific population denominators and the most recent years of mortality data available for each country, we calculated both the crude mortality from stroke and mortality adjusted to the World Health Organization world population.

Results

Since our last report in 2017, there were two countries with new incidence studies, China ( n = 1) and India ( n = 2) that met the ideal criteria. New data on case–fatality were found for Estonia and India. The most current mortality data were available for the year 2015 (39 countries), 2016 (43 countries), and 2017 (7 countries). No new data on mortality were available for six countries. Availability of stroke units was noted for 63 countries, and the proportion of patients treated in stroke units was reported for 35/63 countries.

Conclusion

Up-to-date data on stroke incidence, case–fatality, and mortality statistics provide evidence of variation among countries and changing magnitudes of burden among high and low–middle income countries. Reporting of hospital-based stroke units remains limited and should be encouraged.
Pregnancy outcomes from the global pharmacovigilance database on interferon beta-1b exposure
Authors: Hellwig Kerstin , Duarte Caron Fernando , Wicklein Eva-Maria , Bhatti Aasia , Adamo Alessandra
Published: March 2020

Background:

The goal of the present cohort study was to review outcomes of patients exposed to interferon beta-1b during pregnancy.

Methods:

Pregnancy cases with exposure to interferon beta-1b reported to Bayer’s pharmacovigilance (PV) database from worldwide sources from January 1995 through February 2018 were retrieved for evaluation. Only cases where pregnancy outcomes were unknown at the time of reporting (i.e. prospective cases) were included in the analysis of this retrospective cohort study.

Results:

As of February 2018, 2581 prospective pregnancies exposed to interferon beta-1b were retrieved from the database; 1348 pregnancies had documented outcomes. The majority of outcomes [1106 cases (82.0%)] were live births. Health status was known for 981 live births (no known health status for 125). Most of the prospective pregnancies with known outcomes corresponded to live births with no congenital anomalies [896 cases (91.3%)]. Spontaneous abortion occurred in 160 cases (11.9%). Congenital birth defects were observed in 14/981 live births with known health status [1.4%, 95% confidence interval (CI) 0.78–2.38]. No consistent pattern in the type of birth defect was identified. Rates of both spontaneous abortion and birth defects were not higher than the general population.

Conclusions:

These PV data, the largest sample of interferon beta-1b-exposed patients reported to date, suggest no increase in risk of spontaneous abortion or congenital anomalies in women exposed during pregnancy.
An Acute, Severe Axonal Sensorimotor Polyneuropathy in the Setting of Nitrous Oxide Abuse
Authors: Beal Jules C. , Cheng Yishan , Merchant Sabiha , Zarnegar Reza
Published: March 2020

Nitrous oxide, often used as an anesthetic agent, is also increasingly a drug of abuse due to its euphoric and anxiolytic effects. Frequent exposure to nitrous oxide can lead to neurologic complications, including B12 deficiency and resultant subacute myeloneuropathy, as well as direct neurotoxicity. A clinical presentation of acute sensorimotor polyneuropathy mimicking Guillain-Barré syndrome after chronic nitrous oxide abuse has been reported only rarely. Here we present a 17-year-old previously healthy girl presented with 10 days of progressive ascending sensory loss and weakness in the legs. She admitted to heavy nitrous oxide abuse over a period of a year or more. Laboratory evaluation was significant for normal vitamin B12 level with elevated homocysteine. A magnetic resonance imaging (MRI) of her spine showed abnormal signal involving the bilateral dorsal columns. Nerve conduction studies were suggestive of severe axonal sensorimotor polyneuropathy. This patient demonstrates concurrent multifactorial neurologic injury as a result of nitrous oxide abuse. She had a functional vitamin B12 deficiency as indicated by the elevated homocysteine, leading to a subacute combined degeneration that was evident on the MRI. In addition, she had evidence of direct neurotoxicity leading to axonal injury and sensorimotor polyneuropathy reminiscent of Guillain-Barré syndrome. This clinical picture is a serious but seldom reported possible complication if nitrous oxide abuse and should be considered in patients presenting with a clinical picture suspicious for Guillain-Barré syndrome or its variants.
Patient and physician preferences for multiple sclerosis treatments in Germany: A discrete-choice experiment study
Authors: Poulos Christine , Wakeford Craig , Kinter Elizabeth , Mange Brennan , Schenk Thomas , Jhaveri Mehul
Published: March 2020

Objective

To assess heterogeneity in patient and physician preferences for multiple sclerosis treatment features and outcomes via a discrete-choice experiment.

Method

Patients with self-reported multiple sclerosis and treating physicians participated in an online discrete-choice experiment. Patients, each considering a better or worse reference condition, and physicians, each considering two patient profiles, chose between hypothetical treatment profiles defined by seven attributes with varying levels: years until disability progression, number of relapses in the decade, mode of administration, dosing frequency, and risks of mild, moderate, and severe side effects. Latent class analysis was used to measure respondent preferences and identify potential subgroups with distinct preferences.

Results

Distinct treatment preferences emerged among subgroups of patients ( n = 301) and physicians ( n = 308). Patients in class 1 (43% of sample) were most concerned about side effects; chief concerns of class 2 patients (57%) were delaying disability progression and avoiding severe side-effect risks. The most important attributes for physicians (by class) were delaying disability (class 1, 45%), avoiding severe side-effect risks and (class 2, 33%), and avoiding all side-effect risks (class 3, 22%).

Conclusion

Patients and physicians have diverse preferences for multiple sclerosis treatments, reflecting heterogeneity in the disease course and available therapies and the need for shared decision making.
Triage in primary healthcare
Authors: Göransson Malin , Persson Anna-Carin , Abelsson Anna
Published: March 2020

The majority of healthcare visits in Sweden are within the primary healthcare centres with a wide variety of patients, ranging from children to the elderly, varying from trivial to the most acute. The aim was to describe nurses’ experiences of triaging patients at walk-in clinics at primary healthcare centres. Semi-structured interviews with 12 nurses, analysed using qualitative analysis, were used. The overall understanding was that a physical meeting with the patient gave the opportunity for eye contact and physical examination of the patient’s body. With broad expertise and experience, the informants felt more confident in their assessment. Cooperation between colleagues meant always having someone to consult when the informants felt unsure. The result highlight that triage is a challenging and complex task for informants. In order to be able to triage in an effective way, the informant must possess broad competence through solid knowledge and experience.
CLL intraclonal fractions exhibit established and recently acquired patterns of DNA methylation
Authors: Bartholdy Boris A. , Wang Xiahoua , Yan Xiao-Jie , Pascual Marién , Fan Manxia , Barrientos Jacqueline , Allen Steven L. , Martinez-Climent Jose Angel , Rai Kanti R. , Chiorazzi Nicholas , Scharff Matthew D. , Roa Sergio
Published: March 2020

Intraclonal subpopulations of circulating chronic lymphocytic leukemia (CLL) cells with different proliferative histories and reciprocal surface expression of CXCR4 and CD5 have been observed in the peripheral blood of CLL patients and named proliferative (PF), intermediate (IF), and resting (RF) cellular fractions. Here, we found that these intraclonal circulating fractions share persistent DNA methylation signatures largely associated with the mutation status of the immunoglobulin heavy chain locus (IGHV) and their origins from distinct stages of differentiation of antigen-experienced B cells. Increased leukemic birth rate, however, showed a very limited impact on DNA methylation of circulating CLL fractions independent of IGHV mutation status. Additionally, DNA methylation heterogeneity increased as leukemic cells advanced from PF to RF in the peripheral blood. This frequently co-occurred with heterochromatin hypomethylation and hypermethylation of Polycomb-repressed regions in the PF, suggesting accumulation of longevity-associated epigenetic features in recently born cells. On the other hand, transcriptional differences between paired intraclonal fractions confirmed their proliferative experience and further supported a linear advancement from PF to RF in the peripheral blood. Several of these differentially expressed genes showed unique associations with clinical outcome not evident in the bulk clone, supporting the pathological and therapeutic relevance of studying intraclonal CLL fractions. We conclude that independent methylation and transcriptional landscapes reflect both preexisting cell-of-origin fingerprints and more recently acquired hallmarks associated with the life cycle of circulating CLL cells.
Cortical potentiation induced by calcitonin gene-related peptide (CGRP) in the insular cortex of adult mice
Authors: Liu Yinglu , Chen Qi-Yu , Lee Jung Hyun , Li Xu-Hui , Yu Shengyuan , Zhuo Min
Published: March 2020

Recent studies demonstrate that calcitonin gene-related peptide (CGRP) plays critical roles in migraine. Immunohistochemistry and in situ hybridization studies have shown that CGRP and its receptors are expressed in cortical areas that are critical for pain perception including the anterior cingulate cortex (ACC) and insular cortex (IC). Recent studies reported that CGRP enhanced excitatory transmission in the ACC. However, little is known about the possible effect of CGRP on excitatory transmission in the IC. In the present study, we investigated the role of CGRP on synaptic transmission in the IC slices of adult male mice. Bath application of CGRP produced dose-dependent potentiation of evoked excitatory postsynaptic currents (eEPSCs). This potentiation was NMDA receptor (NMDAR) independent. After application of CGRP1 receptor antagonist CGRP8–37 or BIBN 4096, CGRP produced potentiation was significantly reduced. Paired-pulse facilitation was significantly decreased by CGRP, suggesting possible presynaptic mechanisms. Consistently, bath application of CGRP significantly increased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. Finally, adenylyl cyclase subtype 1 (AC1) and protein kinase A (PKA) are critical for CGRP-produced potentiation, since both selective AC1 inhibitor NB001 and the PKA inhibitor KT5720 completely blocked the potentiation. Our results provide direct evidence that CGRP contributes to synaptic potentiation in the IC, and the AC1 inhibitor NB001 may be beneficial for the treatment of migraine in the future.
Low prevalence of organic pathology in a predominantly black population with premature adrenarche: need to stratify definitions and screening protocols
Authors: Foster Christy , Diaz-Thomas Alicia , Lahoti Amit
Published: March 2020

Background

Premature adrenarche has been described as clinical and biochemical hyperandrogenism before the age of 8 years in girls and 9 years in boys and absence of signs of true puberty. Adrenal pathology such as adrenal tumors or non-classical congenital adrenal hyperplasia (NCCAH) and exogenous androgen exposure need to be excluded prior to diagnosing (idiopathic) premature adrenarche. Premature adrenarche is more common among black girls compared to white girls and other racial groups. Adrenal pathology such as NCCAH is less common as a cause for premature adrenarche compared with idiopathic premature adrenarche. The evaluation guidelines for premature adrenarche however are not individualized based on racial/ethnic differences. Few studies have been done to evaluate a largely black population with premature adrenarche to assess the incidence of adrenal pathology.

Methods

This cross-sectional retrospective study evaluated characteristics of prepubertal patients seen in an endocrine clinic for premature adrenarche.

Results

Two hundred and seventy three subjects had signs of early adrenarche. Three subjects were found to have CAH (2 with NCCAH and 1 with late diagnosis classical CAH). None were black. Exogenous androgen exposure was etiology in 4 additional subjects. These 7 patients were excluded from further analysis. The remaining subjects had idiopathic PA (n = 266); 76.7% were females. The mean age at initial visit was 6.42 +/− 1.97 years (with no racial difference) although black subjects were reported symptom onset at a significantly younger age compared to non-Hispanic white patients.

Conclusions

Our study showed organic pathology was very uncommon in a predominantly black population with premature adrenarche. Patient factors that influence the probability of an underlying organic pathology including race/ ethnicity should be considered to individualize evaluation.
Effects of sustainable land management interventions on selected soil properties in Geda watershed, central highlands of Ethiopia
Authors: Terefe Hailu , Argaw Mekuria , Tamene Lulseged , Mekonnen Kindu , Recha John , Solomon Dawit
Published: March 2020

Background

Land degradation through soil erosion by water is severe in the highlands of Ethiopia. In order to curb this problem, the government initiated sustainable land management interventions in different parts of the country since 2008, and in Geda watershed since 2012. However, the impacts of the interventions on soil properties were not assessed so far. Thus, this study investigated the impacts of sustainable land management interventions on selected soil properties in Geda watershed. Soil samples were collected from treated and untreated sub-watersheds at the upper and lower landscape positions, from cropland and grazing lands at two soil depths (0–15 cm and 15–30 cm). Selected soil physicochemical properties were assessed with respect to landscape position, land-use type, and soil depth in both treated and untreated sub-watersheds.

Results

Generally, most of the soil physicochemical properties differed greatly across sub-watersheds, land-use types, and soil depths. Clay, electrical conductivity, total N, available P, exchangeable K, and organic carbon were higher in the treated sub-watershed, whereas sand, silt, bulk density, and pH were higher in the untreated sub-watershed. The higher sand, silt, and bulk density could be attributed to erosion, while the higher pH could be due to the higher exchangeable Na in the untreated sub-watershed. Most of the selected soil chemical properties were not affected by landscape position, but land-use type affected available P and organic carbon with higher mean values at croplands than at grazing lands, which could be ascribed to the conservation structure and tillage of the soils in that conservation structures trap and accumulate transported organic materials from the upper slope, while tillage facilitates aeration and decomposition processes.

Conclusion

Sustainable land management interventions improved soil physicochemical properties and brought a positive restoration of the soil ecosystem. Maintaining the soil conservation measures and enhancing community awareness about the benefits, coupled with management of livestock grazing are required to sustain best practices.
Low-grade developmental and epilepsy associated brain tumors: a critical update 2020
Authors: Slegers Rutger Juriaan , Blumcke Ingmar
Published: March 2020

Brain tumors represent the second most frequent etiology in patients with focal seizure onset before 18 years of age and submitted to epilepsy surgery. Hence, this category of brain tumors, herein defined as low-grade, developmental, epilepsy-associated brain tumors (LEAT) is different from those frequently encountered in adults as (A): 77% of LEAT occur in the temporal lobe; (B): the vast majority of LEAT are of low malignancy and classified as WHO I°; (C): LEAT are often composed of mixed glial and neuronal cell components and present with variable growth patterns including small cysts or nodules; (D): LEAT do not share common gene driving mutations, such as IDH1 or 1p/19q co-deletions. Characteristic entities comprise the ganglioglioma (GG), the dysembryoplastic neuroepithelial tumor (DNT), the angiocentric glioma (AG), the isomorphic diffuse glioma (IDG) and the papillary glio-neuronal tumor (PGNT), representing 73.2% of 1680 tumors collected in a large German series of 6747 patients submitted to epilepsy surgery. In the realm of exciting discoveries of genetic drivers of brain tumors new genes have been also reported for LEAT. BRAF V600E mutations were linked to GG with CD34 expression, FGFR1 mutations to DNT, MYB alterations to AG and also IDG and PRKCA fusions to PGNT, suggesting the possibility to also develop a genetically driven tumor classification scheme for LEAT. Rare availability of LEAT in a single center is a challenging obstacle, however, to systematically unravel the neurobiological nature and clinical behavior of LEAT. Other challenges in need of clarification include malignant tumor progression of LEAT entities, seizure relapse in patients following bulk tumor resection and the controversial issue of associated focal cortical dysplasia as additional pathomechanism. In order to advance our understanding and promote reliable diagnostic work-up of LEAT, we recommend, therefore, international collaboration to achieve our goals.
Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients
Authors: Rydbirk Rasmus , Folke Jonas , Busato Florence , Roché Elodie , Chauhan Alisha Shahzad , Løkkegaard Annemette , Hejl Anne-Mette , Bode Matthias , Blaabjerg Morten , Møller Mette , Danielsen Erik Hvid , Brudek Tomasz , Pakkenberg Bente , Tost Jorg , Aznar Susana
Published: March 2020

Multiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological brain processes in MSA patients to improve distinction from similar diseases. In the current study, we investigated DNA methylation changes in brain samples from 41 MSA patients and 37 healthy controls. We focused on the prefrontal cortex, a moderately affected area in MSA. Using Illumina MethylationEPIC arrays, we investigated 5-methylcytosine (5mC) as well as 5-hydroxymethylcytosine (5hmC) changes throughout the genome. We identified five significantly different 5mC probes (adj.P < 0.05), of which one probe mapping to theAREL1gene involved in antigen presentation was decreased in MSA patients. This decrease correlated with increased 5hmC levels. Further, we identified functional DNA methylation modules involved in inflammatory processes. As expected, the decreased 5mC levels onAREL1was concordant with increased gene expression levels of bothAREL1as well as MHC Class IHLAgenes in MSA brains. We also investigated whether these changes in antigen-related processes in the brain associated with changes in peripheral mononuclear cells. Using flow cytometry on an independent cohort of MSA patients, we identified a decrease in circulating non-classical CD14+CD16++blood monocytes, whereas T and NK cell populations were unchanged. Taken together, our results support the view of an active neuroimmune response in brains of MSA patients.
Family related variables effect on later educational outcome: a further geospatial analysis on TIMSS 2015 Finland
Authors: Harju-Luukkainen H. , Vettenranta J. , Wang J. , Garvis S.
Published: March 2020

Family-related factors, like parent’s educational level, their values and expectations have a significant impact on child’s early skills and later educational outcomes. Further, parents provide their child, alongside with other learning environments, a broad mathematical and early literacy input. This study investigates the relationship between family-related socio-economic and other factors like, parental education, amount of books at home, parental attitudes towards mathematics and science, parental perception of child’s early skills and student’s later academic achievement. This is studied in the light of the Finnish data collected for Trends in International Mathematics and Science Study (TIMSS) 2015. The results are presented with the help of a geospatial method called Kriging that reveals regional variance. The results indicate that family-related background variables have different effects on child’s later achievement in mathematics across Finland. The results suggest, that some areas in Finland are better in ‘levelling the playing field’ for children and minimising the effect of family related variables on educational outcomes than others.
Modelling shares choice to enter in a portfolio using artificial neural networks (ANN)
Authors: Manurung Adler Haymans , Natasha Christina , Budiharto Widodo
Published: March 2020

Shares choice to enter a portfolio is a good topic in finance and management, as it affects the portfolio performance which is managed by a Fund Manager. In this research, we aim to create an artificial neural network model to choose a share to enter a portfolio based on its financial factors and big data about the financial condition of companies. The artificial neural network model has 15 input nodes of attributes associated with a company’s financial situation, 8 hidden layer nodes, and 1 output node. The accuracy of the model is 85.71%, with a learning rate of 0.05 trained over 2000 iterations.
Sleep disturbances and predictors of nondeployability among active-duty Army soldiers: an odds ratio analysis of medical healthcare data from fiscal year 2018
Authors: Devine Jaime K. , Collen Jacob , Choynowski Jake J. , Capaldi Vincent
Published: March 2020

Background

The impact of sleep disorders on active-duty soldiers’ medical readiness is not currently quantified. Patient data generated at military treatment facilities can be accessed to create research reports and thus can be used to estimate the prevalence of sleep disturbances and the role of sleep on overall health in service members. The current study aimed to quantify sleep-related health issues and their impact on health and nondeployability through the analysis of U.S. military healthcare records from fiscal year 2018 (FY2018).

Methods

Medical diagnosis information and deployability profiles (e-Profiles) were queried for all active-duty U.S. Army patients with a concurrent sleep disorder diagnosis receiving medical care within FY2018. Nondeployability was predicted from medical reasons for having an e-Profile (categorized as sleep, behavioral health, musculoskeletal, cardiometabolic, injury, or accident) using binomial logistic regression. Sleep e-Profiles were investigated as a moderator between other e-Profile categories and nondeployability.

Results

Out of 582,031 soldiers, 48.4% (n = 281,738) had a sleep-related diagnosis in their healthcare records, 9.7% (n = 56,247) of soldiers had e-Profiles, and 1.9% (n = 10,885) had a sleep e-Profile. Soldiers with sleep e-Profiles were more likely to have had a motor vehicle accident (pOR (prevalence odds ratio) =4.7, 95% CI 2.63–8.39, P ≤ 0.001) or work/duty-related injury (pOR = 1.6, 95% CI 1.32–1.94, P ≤ 0.001). The likelihood of nondeployability was greater in soldiers with a sleep e-Profile and a musculoskeletal e-Profile (pOR = 4.25, 95% CI 3.75–4.81, P ≤ 0.001) or work/duty-related injury (pOR = 2.62, 95% CI 1.63–4.21, P ≤ 0.001).

Conclusion

Nearly half of soldiers had a sleep disorder or sleep-related medical diagnosis in 2018, but their sleep problems are largely not profiled as limitations to medical readiness. Musculoskeletal issues and physical injury predict nondeployability, and nondeployability is more likely to occur in soldiers who have sleep e-Profiles in addition to these issues. Addressing sleep problems may prevent accidents and injuries that could render a soldier nondeployable.
The novel coronavirus outbreak: what can be learned from China in public reporting?
Authors: Li Hao , Chen Xinguang , Huang Hao
Published: March 2020

The new coronavirus outbreak gets everyone’s attention. China’s national actions against the outbreak have contributed great contributions to the world. China has been learning from practice for better reporting and is fast to adapt itself. In this article we discuss China’s practice in public reporting and its implications to global health. Confirmed cases, dynamic suspected cases, recovered cases, and deaths have been reported both in accumulative numbers and their daily updates. Some ratio indictors reporting (fatality rate, recovery rate, etc.), trend reporting, and global surveillance have been applied as well. Some improvements can still be made. It is necessary to further explore the influential factors behind the indicators for interventions. Recommendations are made to the World Health Organization and other countries for better public reporting and surveillance.
Arterial CO2 pressure changes during hypercapnia are associated with changes in brain parenchymal volume
Authors: van der Kleij Lisa A. , De Vis Jill B. , de Bresser Jeroen , Hendrikse Jeroen , Siero Jeroen C. W.
Published: March 2020

The Monro-Kellie hypothesis (MKH) states that volume changes in any intracranial component (blood, brain tissue, cerebrospinal fluid) should be counterbalanced by a co-occurring opposite change to maintain intracranial pressure within the fixed volume of the cranium. In this feasibility study, we investigate the MKH application to structural magnetic resonance imaging (MRI) in observing compensating intracranial volume changes during hypercapnia, which causes an increase in cerebral blood volume. Seven healthy subjects aged from 24 to 64 years (median 32), 4 males and 3 females, underwent a 3-T three-dimensional T1-weighted MRI under normocapnia and under hypercapnia. Intracranial tissue volumes were computed. According to the MKH, the significant increase in measured brain parenchymal volume (median 6.0 mL; interquartile range 4.5, 8.5; p = 0.016) during hypercapnia co-occurred with a decrease in intracranial cerebrospinal fluid (median -10.0 mL; interquartile range -13.5, -6.5; p = 0.034). These results convey several implications: (i) blood volume changes either caused by disorders, anaesthesia, or medication can affect outcome of brain volumetric studies; (ii) besides probing tissue displacement, this approach may assess the brain cerebrovascular reactivity. Future studies should explore the use of alternative sequences, such as three-dimensional T2-weighted imaging, for improved quantification of hypercapnia-induced volume changes.
Microsatellite instability predicts improved response to adjuvant therapy with irinotecan, 5-fluorouracil and leucovorin in stage III colon cancer
Authors: Bertagnolli M. M. , Compton C. C. , Niedzwiecki D. , Warren R. S. , Jewell S. , Bailey G. P. , Mayer R. J. , Goldberg R. , Saltz L. , Redston M.
Published: March 2020

10003

Background: Colon cancers exhibiting a high level of microsatellite instability (MSI-H) show distinct clinicopathological features, including both better prognosis and reduced response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the impact of adjuvant chemotherapy containing irinotecan in patients with MSI-H colon cancers. Methods: CALGB protocol 89803 randomized 1264 patients with resected stage III colon cancer to receive post-operative 5-FU and leucovorin (LV) with or without irinotecan. Paraffin blocks containing primary tumor and normal tissue were collected. Microsatellite instablility was assessed using a panel of mono- and di-nucleotide markers. Disease free survival (DFS) was measured from trial entry until documented disease progression or death from any cause. A statistical significance level of 0.2 was used in screening to generate hypotheses regarding MSI status and outcome. Median follow-up at analysis was 3.8 years. Overall C89803 showed no advantage for addition of irinotecan to 5-FU/LV. Results: Patients with and without tumor samples analyzed did not differ by treatment, age, gender, primary site, T-stage, differentiation, # positive nodes, or mucinous type. Of 482 tumors analyzed, 75 (16%) demonstrated MSI-H. MSI-H cancers were more likely to be located in the proximal colon (p<0.0001), of high histologic grade (p<0.0001) and mucinous histology (p<0.0001), and also had increased numbers of tumor-containing lymph nodes (mean # positive nodes/case = 3.5 for MSI Low/Stable vs. 4.7 for MSI-H; p = 0.04). At the time of analysis 143 of 482 patients (36%) analyzed experienced tumor recurrence and/or death due to any cause. For patients with MSI-H tumors, DFS was better in those treated with irinotecan in addition to 5-FU/LV (logrank p=0.18). Among patients with MSI Low/Stable tumors there was no difference in DFS between those treated with and without irinotecan (logrank p =0.39). Conclusions: Early results from CALGB protocol 89803 indicate that addition of postoperative irinotecan to 5-FU/LV may improve DFS in patients with stage III colon cancers that exhibit MSI-H. Longer follow-up is required to confirm this finding.

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Is mammography adequate for screening BRCA mutation carriers with low breast density?
Authors: Bigenwald R. , Warner E. , Gunasekara A. , Hill K. , Causer P. , Messner S. , Eisen A. , Plewes D. , Narod S. , Yaffe M.
Published: March 2020

10014

Background: Several large observational studies have demonstrated that magnetic resonance imaging (MRI) is much more sensitive than M (sensitivity 71–96% vs. 28–43%) for screening women > age 25 at high risk for hereditary breast cancer. However, MRI is much more costly and less specific than M. The extent to which the low sensitivity of M in these studies is due to the greater average breast density of younger women is unknown. Accordingly, we sought to determine the sensitivity of M and MRI according to breast density for the detection of breast cancer in a screening study of BRCA mutation carriers. Methods: Breast density was measured on the screening mammogram of the contralateral breast for all women who developed in-situ or invasive breast cancer on study. Density was measured in 2 ways: qualitatively according to the four categories characterized by the BIRADS system: 1) mostly fatty, 2) scattered fibroglandular tissue, 3) heterogeneously dense, 4) extremely dense; and semi-quantitatively using computer-aided techniques with subsequent classification as: A) ≤10%, B) 11–25%, C) 26%-50%, or D) >50% density. Results: Between 11/97 and 06/05 a total of 39 cases (12 in-situ and 27 invasive) were found in 36 mutation carriers (19 BRCA1 and 17 BRCA2). Mean age of the women with cancer was 48 (range 34 to 64). Average semi-quantitative breast density for BRCA1 mutation carriers was 28% and for BRCA2 was 27%. Sensitivity of M vs. MRI for in-situ cases was 25% vs. 83%, and for invasive cases was 30% vs. 93%. Sensitivities for BRCA1 and BRCA2 mutation carriers were similar. For BIRADS 1 to 4 respectively M detected 1/3 (33%), 5/11 (45%), 4/22 (18%), and 1/3 (33%) of cases; and for density groups A to D respectively detected 2/6 (33%), 7/15 (47%), 1/11 (9%) and, 1/7 (14%). Conclusion: Although there was a trend towards decreasing mammographic sensitivity with increasing density, even among BRCA mutation carriers with low breast density mammography is an inadequate screening tool.

No significant financial relationships to disclose.
Phase I study of CNF1010 (lipid formulation of 17-(allylamino)-17-demethoxygeldanamycin: 17-AAG) in patients with advanced solid tumors
Authors: Saif M. W. , Erlichman C. , Dragovich T. , Mendelson D. , Toft D. , Timony G. , Burrows F. , Padgett C. , De Jager R. , Von Hoff D.
Published: March 2020

10062

Background: 17-AAG is a benzoquinone ansamycin that binds to and inhibits the HSP90 family of molecular chaperones leading to the proteasomal degradation of client proteins critical in malignant cell proliferation and survival. We have undertaken a Phase 1 trial of CNF1010, an oil-in-water nanoemulsion of 17-AAG. Methods: Patients (pts) with advanced solid tumors, ECOG PS 0–2, and adequate hematologic, hepatic, renal and cardiac functions received CNF1010 by 1 h intravenous infusion, twice-a-week, three weeks out of four, starting at 6 mg/m2 per dose. Doses were escalated sequentially in single pts (6 and 12 mg/m2) and 3–6 pts (≥ 25 mg/m2) cohorts according to a modified Fibonacci’s schema. Plasma pharmacokinetic (PK) profiles were obtained on days 1 and 18. Biomarkers were measured in PBMC’s (HSP70) and plasma (HER-2 ectodomain (HER-2 ECD)). Results: 30 pts (M/F: 14/16; median age 63, range 48–78) with colorectal cancer (11), pancreatic cancer (5), melanoma (5), ovarian (2), others (7) were treated with a median of 2 courses (range: 1–10). There was no dose-limiting toxicity up to 175 mg/m2. One pt at 175 mg/m2 died on study, but drug relation was unclear. Grade 1–2 gastrointestinal toxicities (nausea, vomiting, diarrhea) and serum creatinine elevation were observed. Severe toxicities (grade 3 but no grade 4) consisted of reversible hepatic enzyme elevation, hyperbilirubinemia, fatigue, anemia and hyperglycemia. There were no hematological toxicities. Plasma 17-AAG PK appeared dose-proportional (AUC, Cmax); CL (17 L/h/m2) and t1/2 (5.2 h) were dose independent and unchanged after repeated dosing (day 18). Post-treatment increases in HSP70 were observed in PBMCs and decreases in plasma HER-2 ECD were observed at doses ≥ 83 mg/m2. Minor tumor regressions were seen in 1 pt with duodenal cancer (83 mg/m2), 1 pt with gastric carcinoid (175 mg/m2) and 1 pt with melanoma (175 mg/m2). Conclusion: The threshold of biologic activity for CNF1010 administered by a twice a week schedule appears to be 83 mg/m2. This dosing regimen appears to be optimal and supported by the pharmacokinetic and pharmacodynamic data. The MTD has not yet been determined. Dose escalation of CNF1010 continues at 225 mg/m2.

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The mutation status of the epidermal growth factor receptor (EGFR) as a selection criterion for therapy with EGFR tyrosine kinase inhibitors (TKI’s) in non-small cell lung cancer (NSCLC)
Authors: Mathy A. , Nederlof P. , Boerrigter L. , Van ’t Veer L. , De Jong D. , Baas P. , Burgers S. , Van Zandwijk N.
Published: March 2020

10073

Background: Somatic mutations in the EGFR gene have been shown to be closely associated with a favorable response to small-molecule TKI’s, while K-ras mutations seem to be associated with primary resistance. We present an exploratory study confirming the importance of mutation status for response on anti EGFR therapy. Methods: Mutations in the EGFR TK domain were looked for in tumor material extracted from two series of patients with advanced NSCLC. In the first series, mutations were determined in patients with an objective response or clearly progressive under gefitinib therapy. In the second series, EGFR mutations were determined prospectively in an enriched population (two of three characteristics: female gender, non-smoking status, bronchoalveolar -or adenocarcinoma pathology). The presence of a mutation was the criterion for treatment with TKI’s. Response assessment was done according to RECIST. K-Ras mutations were determined retrospectively. Results: In the retrospective series, 15 biopsies were analyzed, belonging to 3 complete responders and 12 non-responders (gefitinib). All three responders harbored an EGFR mutation, none had a K-ras mutation. None of the non-responders had an EGFR mutation. Three of them had a K-ras mutation. In the prospective (enriched) series, 13 out of 41 patients (tumors) possessed an EGFR mutation. Eleven of them swiftly responded on erlotinib or gefitinib, 1 had stable disease, 1 stopped treatment due to severe toxicity. K-ras mutations were not found in this set. In a single EGFR mutation positive patient survival has extended over 40 months since start of therapy. Conclusions: Our findings corroborate other groups’ conclusions that EGFR mutations are a powerful indicator of response to TKI’s and that K-ras mutations are associated with resistance.

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