Unraveling treatment response in multiple sclerosis: A clinical and MRI challenge

Over the last few decades, the improved diagnostic criteria, the wide use of MRI, and the growing availability of effective pharmacologic treatments have led to substantial advances in the management of multiple sclerosis (MS). The importance of early diagnosis and treatment is now well-Established, but there is still no consensus on how to define and monitor response to MS treatments. In particular, the clinical relevance of the detection of minimal MRI activity is controversial and recommendations on how to define and monitor treatment response are warranted. An expert panel of the Magnetic Resonance Imaging in MS Study Group analyzed and discussed published studies on treatment response in MS. The evolving concept of no evidence of disease activity and its effect on predicting long-term prognosis was examined, including the option of defining a more realistic target for daily clinical practice: minimal evidence of disease activity. Advantages and disadvantages associated with the use of MRI activity alone and quantitative scoring systems combining on-treatment clinical relapses and MRI active lesions to detect treatment response in the real-world setting were also discussed. While most published studies on this topic involved patients treated with interferon-\u3b2, special attention was given to more recent studies providing evidence based on treatment with other and more efficacious oral and injectable drugs. Finally, the panel identified future directions to pursue in this research field

Pneumococcal carriage in sub-Saharan Africa--a systematic review.

BACKGROUND: Pneumococcal epidemiology varies geographically and few data are available from the African continent. We assess pneumococcal carriage from studies conducted in sub-Saharan Africa (sSA) before and after the pneumococcal conjugate vaccine (PCV) era. METHODS: A search for pneumococcal carriage studies published before 2012 was conducted to describe carriage in sSA. The review also describes pneumococcal serotypes and assesses the impact of vaccination on carriage in this region. RESULTS: Fifty-seven studies were included in this review with the majority (40.3%) from South Africa. There was considerable variability in the prevalence of carriage between studies (I-squared statistic = 99%). Carriage was higher in children and decreased with increasing age, 63.2% (95% CI: 55.6-70.8) in children less than 5 years, 42.6% (95% CI: 29.9-55.4) in children 5-15 years and 28.0% (95% CI: 19.0-37.0) in adults older than 15 years. There was no difference in the prevalence of carriage between males and females in 9/11 studies. Serotypes 19F, 6B, 6A, 14 and 23F were the five most common isolates. A meta-analysis of four randomized trials of PCV vaccination in children aged 9-24 months showed that carriage of vaccine type (VT) serotypes decreased with PCV vaccination; however, overall carriage remained the same because of a concomitant increase in non-vaccine type (NVT) serotypes. CONCLUSION: Pneumococcal carriage is generally high in the African continent, particularly in young children. The five most common serotypes in sSA are among the top seven serotypes that cause invasive pneumococcal disease in children globally. These serotypes are covered by the two PCVs recommended for routine childhood immunization by the WHO. The distribution of serotypes found in the nasopharynx is altered by PCV vaccination

Radiologically isolated syndrome or subclinical multiple sclerosis: MAGNIMS consensus recommendations

The widespread use of brain magnetic resonance imaging (MRI) has greatly increased findings of unanticipated asymptomatic intracranial abnormalities of uncertain clinical significance. These incidental findings on brain MRI are of various nature and origin and only rarely include abnormalities that could be interpreted as inflammatory or demyelinating lesions(1). However, the increase of unexpected MRI alterations has overall augmented the awareness for findings that have the morphology, size, location and distribution highly suggestive of a demyelinating disease. This has led to the definition of "radiologically isolated syndrome" (RIS), which was recently introduced to describe those asymptomatic subjects with brain MRI abnormalities suggestive of multiple sclerosis (MS) and lacking historical accounts of prior demyelinating events or an identifiable better reason for the observed changes(2). Since its first description, RIS has been widely debated and the risk of RIS evolving into MS has been investigated. According to existing data, a number of RIS subjects evolve to MS over time, demonstrating that RIS, at least in some cases, represents a preclinical stage of MS. RIS, however, is an entity that still needs to be better defined, with a number of issues needing to be addressed. These include the lack of expert guidelines on the management of RIS subjects and criteria that can establish the extent to which MRI lesions fulfilling the RIS criteria in asymptomatic subjects may represent subclinical MS or may be related to abnormalities that are not related to MS. We provide here expert recommendations that can help distinguish between subjects with low risk of developing MS and those that can be diagnosed with subclinical MS. Suggestions for the management of subjects stratified by risk for a future demyelinating event will also be provided. A summary of the main proposed recommendations is given in Table 1

Adipose tissue concentrations of non-persistent environmental phenols and local redox balance in adults from Southern Spain

The aim was to evaluate the associations of environmental phenol and paraben concentrations with the oxidative microenvironment in adipose tissue. This study was conducted in a subsample (n=144) of the GraMo cohort (Southern Spain). Concentrations of 9 phenols and 7 parabens, and levels of oxidative stress biomarkers were quantified in adipose tissue. Associations were estimated using multivariable linear regression analyses adjusted for potential confounders. Benzophenone-3 (BP-3) concentration was borderline associated with enhanced glutathione peroxidase (GPx) activity [exp(β)=1.20, p=0.060] and decreased levels of reduced glutathione (GSH) [exp(β)=0.55, p=0.070]. Concentrations of bisphenol A (BPA) and methylparaben (MeP) were associated to lower glutathione reductase (GRd) activity [exp(β)=0.83, exp(β)=0.72, respectively], and BPA was borderline associated to increased levels of oxidized glutathione (GSSG) [exp(β)=1.73, p-value=0.062]. MeP was inversely associated to both hemeoxygenase-1 (HO-1) and superoxide dismustase (SOD) activity, as well as to the levels of thiobarbituric acid reactive substances (TBARS) [0.75 < exp(β) < 0.79]. Our results suggest that some specific non-persistent pollutants may be associated with a disruption of the activity of relevant antioxidant enzymes, in addition to the depletion of the glutathione stock. They might act as a tissue-specific source of free radicals, contributing to the oxidative microenvironment in the adipose tissue.This research was supported in part by research grants from the European Union Commission (H2020-EJP-HBM4EU and SOE1/P1/F0082), Biomedical Research Networking Center-CIBER de Epidemiología y Salud Pública (CIBERESP), from the Institute of Health Carlos III, supported by European Regional Development Fund/FEDER (FIS-PI13/02406, FISPI14/ 00067, FIS-PI16/01820, FIS-PI16/01812, FIS-PI16/01858 and FIS-PI17/01743), and from the Consejería de Salud, Junta de Andalucía (PS-0506-2016). Funding for the equipment used was provided by Velux Fonden, Augustinus Fonden and Svend Andersen Fonden. The authors thank Kirsten og Freddy Johansens Fond and the International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC, Rigshospitalet, Copenhagen University) for economic support. Dr. Juan Pedro Arrebola is under contract within Ramón y Cajal Program (Ministerio de Economía, Industria y Competitividad de España, RYC-2016-20155)

Late Paleocene Flora of the Northern Alaska Peninsula: The Role of Transberingian Plant Migrations and Climatic Change

For the first time, the Late Sagwon Flora is described from the upper beds of the Prince Creek Formation (Upper Paleocene) at the Sagavanirktok River (northern Alaska Peninsula). The flora is dominated by the angiosperm Tiliaephyllum brooksense Moiseeva et Herman sp. nov. and conifer Metasequoia occidentalis (Newb.) Chaney. The Late Sagwon Flora is most similar to the Danian or Danian-Selandian flora from the middle part of the Upper Tsagayan Subformation (Amur Region) and lower part of the Wuyun Formation (Heilongjiang Province, China). This similarity allows us to hypothesize that the genus Tiliaephyllum, which dominated in the Late Tsagayan Flora, migrated via the Bering Land Bridge from southern paleolatitudes of the Far East to high latitudes of the Arctic Pacific, due to the progressively warming climate of the Paleocene. Additional new angiosperm species are described from the Late Sagwon Flora: Archeampelos mullii Moiseeva et Herman sp. nov., Tiliaephyllum brooksense Moiseeva et Herman sp. nov., and Dicotylophyllum sagwonicum Moiseeva et Herman sp. nov

Type-Ia Supernova Rates to Redshift 2.4 from Clash: The Cluster Lensing and Supernova Survey with Hubble

We present the supernova (SN) sample and Type-Ia SN (SN Ia) rates from the Cluster Lensing And Supernova survey with Hubble (CLASH). Using the Advanced Camera for Surveys and the Wide Field Camera 3 on the Hubble Space Telescope (HST), we have imaged 25 galaxy-cluster fields and parallel fields of non-cluster galaxies. We report a sample of 27 SNe discovered in the parallel fields. Of these SNe, approximately 13 are classified as SN Ia candidates, including four SN Ia candidates at redshifts z greater than 1.2.We measure volumetric SN Ia rates to redshift 1.8 and add the first upper limit on the SN Ia rate in the range z greater than 1.8 and less than 2.4. The results are consistent with the rates measured by the HST/ GOODS and Subaru Deep Field SN surveys.We model these results together with previous measurements at z less than 1 from the literature. The best-fitting SN Ia delay-time distribution (DTD; the distribution of times that elapse between a short burst of star formation and subsequent SN Ia explosions) is a power law with an index of 1.00 (+0.06(0.09))/(-0.06(0.10)) (statistical) (+0.12/0.08) (systematic), where the statistical uncertainty is a result of the 68% and 95% (in parentheses) statistical uncertainties reported for the various SN Ia rates (from this work and from the literature), and the systematic uncertainty reflects the range of possible cosmic star-formation histories. We also test DTD models produced by an assortment of published binary population synthesis (BPS) simulations. The shapes of all BPS double-degenerate DTDs are consistent with the volumetric SN Ia measurements, when the DTD models are scaled up by factors of 3-9. In contrast, all BPS single-degenerate DTDs are ruled out by the measurements at greater than 99% significance level

2021 MAGNIMS–CMSC–NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis

The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centres guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial relevant advances in knowledge, including the 2017 revisions of the McDonald diagnostic criteria, renewed safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MRI for diagnostic, prognostic, and monitoring purposes. These developments suggest a changing role of MRI for the management of patients with multiple sclerosis. This 2021 revision of the previous guidelines on MRI use for patients with multiple sclerosis merges recommendations from the Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centres, and North American Imaging in Multiple Sclerosis Cooperative, and translates research findings into clinical practice to improve the use of MRI for diagnosis, prognosis, and monitoring of individuals with multiple sclerosis. We recommend changes in MRI acquisition protocols, such as emphasising the value of three dimensional-fluid-attenuated inversion recovery as the core brain pulse sequence to improve diagnostic accuracy and ability to identify new lesions to monitor treatment effectiveness, and we provide recommendations for the judicious use of gadolinium-based contrast agents for specific clinical purposes. Additionally, we extend the recommendations to the use of MRI in patients with multiple sclerosis in childhood, during pregnancy, and in the post-partum period. Finally, we discuss promising MRI approaches that might deserve introduction into clinical practice in the near future

Long term productivity and collaboration in information science

This is an accepted manuscript of an article published by Springer in Scientometrics on 02/07/2016, available online: https://doi.org/10.1007/s11192-016-2061-8 The accepted version of the publication may differ from the final published version.Funding bodies have tended to encourage collaborative research because it is generally more highly cited than sole author research. But higher mean citation for collaborative articles does not imply collaborative researchers are in general more research productive. This article assesses the extent to which research productivity varies with the number of collaborative partners for long term researchers within three Web of Science subject areas: Information Science & Library Science, Communication and Medical Informatics. When using the whole number counting system, researchers who worked in groups of 2 or 3 were generally the most productive, in terms of producing the most papers and citations. However, when using fractional counting, researchers who worked in groups of 1 or 2 were generally the most productive. The findings need to be interpreted cautiously, however, because authors that produce few academic articles within a field may publish in other fields or leave academia and contribute to society in other ways