bluuebunny/crossref_metadata_2025 huggingface dataset:
PP117 Isosorbide And Nifedipine In Chagas Patients: A Systematic Review
Authors: Cruz Luciane , Migliavaca Celina Borges , Stein Cinara , Colpani Verônica , Miguel Sandro , Falavigna Maicon
Published: January 2018

INTRODUCTION:

Chagas disease, caused by the parasite Trypanosoma cruzi, affects more than seven million people worldwide and it is considered by the World Health Organization (WHO) a neglected tropical disease (1). About one third of Chagas patients develop gastrointestinal disorders, such as dysphagia and achalasia. Management of the disease focuses on symptom improvement and drugs that relax the lower esophageal sphincter pressure (LESP), such as isosorbide and nifedipine. However, the use of these therapies is doubtful because of their side effects and palliative approach (2). The objective of this systematic review is to assess the effectiveness of isosorbide and nifedipine on gastrointestinal manifestation of Chagas disease.

METHODS:

We searched MEDLINE, EMBASE and LILACS databases to retrieve potentially relevant articles from inception to December 2016. Inclusion criteria: clinical trials, cohorts or cross-sectional design; adults (>18 years old); assessment of effects of isosorbide or nifedipine on gastrointestinal symptoms in Chagas patients. Two reviewers independently screened titles and abstracts, selected eligible studies and extracted data from each study. PROSPERO registration number: CRD42017055143.

RESULTS:

Eight studies were included (two case series, two clinical trials and four crossovers). Three studies evaluated the effect of isosorbide in LESP and three in esophageal emptying. All of them found that isosorbide rapidly reduces LESP and increases esophageal emptying rates, improving dysphagia. However, several patients reported collateral effects, such as gastroesophageal reflux, headaches and dizziness. One study evaluated the effect of nifedipine on LESP and one on esophageal emptying. Nifedipine decreased LESP, but there was no effect on esophageal emptying.

CONCLUSIONS:

The available evidence shows isosorbide is effective in the management of gastrointestinal symptoms. Frequently health care of Chagas disease patients is delivered by primary care physicians. So, information on effectiveness of interventions can be aggregated to clinical guidelines, having an important value to inform general practitioners on the decision-making process regarding treatment of this group of patients, avoiding referencing to a specialized care.
PP124 The HTAi Vortal: A Comparative Analysis
Authors: Chalon Patrice
Published: January 2018

INTRODUCTION:

The HTAi Vortal is a product of the HTAi Information Retrieval Group (IRG) which has collected resources in the field of Health Technology Assessment (HTA) since 2005.

In 2011, a new technical platform was set up and the legacy Vortal content was split in three sections: HTA producers and networks, Selected references and Career development (including trainings). The same year, a fourth section was created to host a new product of the IRG: SuRe.info.

In 2014, the Vortal added a new service to other Interest sub groups of HTAi: the hosting of “Custom bibliographies”. But while the Vortal was probably quite unique in 2005, other Websites have been developed since then to offer quite similar functionalities.

The present communication aims at evaluating how the Vortal compares with similar tools existing on the Web.

METHODS:

Vortal competitors have been identified using a quick empirical search of the Web.

Functionalities have been identified by testing the website or their archive; maintainers have been sometimes contacted to ask for complementary information. A grid listing all functionalities has been established and filled in with the collected information.

RESULTS:

Several competitors have been identified. The Vortal presents functionalities similar to online tools, but detailing level is different. Also, the Vortal provides a better integration resulting in more efficiency. And, the Vortal is the only Web platform to offer a service of publication of custom bibliographies to the different HTAi Interest Sub Groups.

CONCLUSIONS:

After 12 years of existence, the HTAi Vortal is still a recognized online resource about HTA. While some existing functionalities are to be found in other online tools, some remain unique to the Vortal. Further research is needed to evaluate the preferences of people with interest in HTA.
PP172 Recruiting Academic Physicians Without Financial Conflict Of Interest
Authors: Belghiti Jacques , Luzio Stéphanie , Fuks David , Emery Gregory
Published: January 2018

INTRODUCTION:

To minimize the potential impact of conflicts of interest on health recommendations, several health institutions may be reluctant to recruit academic physicians due to their potential close relationship with industry. The present study aimed at evaluating the influence of academic physicians (AP) on the “rate of deport” due to financial support in the national commission of the HAS assessing medical devices.

METHODS:

After the renewal of this commission in November 2015, introducing patients representatives and more academic physicians, two periods of 12 months immediately before and after that date have been compared regarding the rate of deport during the sessions. Deport were decided by the legal section of our institution one week before each meeting according to a complete analysis of potential financial conflict of interest related to the medical device assessed. Only members without significant financial conflicts were allowed to participate to the discussion and the vote. The assessment of potential conflict of interest of all members followed the same criteria during the two periods.

RESULTS:

The number of physicians increased in the second period (nineteen versus twenty-three) with a significant higher rate of academic physicians (63 percent versus 82 percent, p = .001). The mean attendance of physicians was significantly lower during the second period (80 percent versus 65 percent, p = .03). During the two periods, the number of meetings (n = 22) was similar and the number of dossiers assessing new products was comparable (96 versus 104, p = .872). The decision to reimburse the medical devices was similar in the two periods (78 percent versus 73 percent, p = .681). The number of cases when physicians’ members were deported for conflict of interest was similar during the two periods (30 versus 28, p = .482) with not any increase among academic physicians.

CONCLUSIONS:

This study showed that it is possible to recruit several academic physicians without major financial conflicts of interest providing that their status could alter their assiduity.
VP09 Arthroplasty Registers As A Tool For Health Technology Assessment
Authors: Domingo Laia , Martínez Olga , Arias Jorge , Nardi Joan , Puig Lluís , Espallargues Mireia
Published: January 2018

INTRODUCTION:

Our purpose is to present the potential for health technology assessment that arthroplasty registers may offer.

METHODS:

A revision of the health assessment uses and information collected by arthroplasty registers was made. The information provided from international networks like NORE, ISAR and ICOR was also considered. Arthroplasty registers collect data of patients undergoing joint replacement surgery (mainly hip and knee) along with implant information. They provide longitudinal information useful to assess implant survival (expressed as revision rate and calculated from the primary surgery to implant revision). They also data from the surgical procedure and, more recently, a number of registries incorporate patient reported outcomes (PROMs) information.

RESULTS:

Arthroplasty registers provide information from multiple perspectives:

(i)

Decision-makers and healthcare providers/authorities: the comparison of revision rates by using funnel plots is a useful methodology to benchmark implants and to identify outliers, or models with significantly different revision rate in comparison to their peers. Besides, data available in registers has proven to be useful to define sets of indicators related to safety, effectiveness, efficiency, patient-centered healthcare and perceived health outcomes.

(ii)

Surgeons: Some ongoing initiatives, like ODEP, aiming at providing a benchmark rating for implant survivorship, are gaining interest by professionals promoting an evidence-based clinical practice.

(iii)

Industry: the large amount of data recorded so far may allow obtaining robust information of prosthesis behavior.

(iv)

Patients: there is an increasing number of registers that incorporate PROMs. Moreover, a growing interest to promote patient engagement in arthroplasty decision making has been observed.

CONCLUSIONS:

Long-standing arthroplasty registries have untapped potential. Beyond the assessment of implant survival, they have been consolidated as a useful tool for decision-makers, professionals, and patients. Next steps will be to promote joint analysis of national/regional registries to explore uncommon practices or new medical devices, and also to adapt to future regulations on implant traceability.
VP36 Cost-Effectiveness Of Non-Invasive Prenatal Testing For Down Syndrome
Authors: Orruño Estibalitz , Bayón Juan Carlos , Portillo Isabel , Asua José
Published: January 2018

INTRODUCTION:

The analysis of cell-free fetal DNA in maternal blood, also called Non-Invasive Prenatal Testing (NIPT), represents an emerging technology and a possible alternative/complement to current prenatal screening based on biochemical and sonographic markers for Down Syndrome (DS) detection.

The aim of the study was to compare the application of NIPT with the prenatal diagnosis/screening procedures currently applied in the Basque Country.

METHODS:

An analytical decision model was developed to assess the costs and consequences, comparing current prenatal screening, NIPT as a contingency test in high-risk cases and NIPT as a first-line screening test. An economic analysis was conducted to determine which strategy was more cost-effective. Sensitivity analyses were performed (1).

RESULTS:

For a population of 97,074 pregnant women in gestational week 14 and a cut-off point of 1:270, NIPT as a contingent test was not cost-effective, detecting two cases less of DS and causing a lower number of miscarriages related to invasive-testing (4 versus 23) at a slightly lower cost (EUR8,111,351 versus EUR8,901,872).

For risk cut-off points of 1:500 or 1:1000 for contingent NIPT, the number of DS cases detected increased, as did the cost. It could be cost-effective compared with current prenatal screening, (EUR61,763 or EUR256,123 per extra DS case detected, respectively).

Using the NIPT as a primary test detected more DS cases (296 versus 271) and caused less miscarriages (5 versus 23), at a substantially higher cost (EUR41,395,645 versus EUR8,901,872). Cost-effectiveness analysis indicated that it was more expensive and more effective.

Univariant sensitivity-analysis showed that when the price of the NIPT as primary test was EUR76, it was dominant compared with current prenatal screening. It was also cost-effective compared with the NIPT as a contingent test (EUR9,869 per extra DS case detected).

CONCLUSIONS:

The study shows that NIPT had higher detection rates for DS in different scenarios, but the cost constitutes a limiting factor for implementation in the Basque Health System.
VP64 Post-Graduation Selection Using Multi-Criteria Decision Analysis
Authors: Santos Marisa , Senna Kátia , Magliano Carlos , Baldissara Jessica
Published: January 2018

INTRODUCTION:

Selecting candidates for graduate programs is considered to be a complex task, often subject to failures, especially regarding to the appraisal of non-cognitive (1,2) skills (for example, Motivation). Identifying suitable candidates is important for the overall success of the graduate programs, since dropouts and low productivity negatively affect the program classification by the Brazilian Governmental Agency.

This study aims to describe the use of Multicriteria Decision Analysis (3) in the selection of candidates for a master degree program in Health Technology Assessment (HTA).

METHODS:

The Multicriteria Decision Analysis (MCDA) technique was used to measure value in the selection of students applying for a masters degree program, in 2017, using Multi-Attribute Value Theory methods (MAVT) method. The examiners group consisting of full-time professors who selected the criteria, blinded ranked and assigned weight relative to each criterion, using swing weights technique, normalized to 100 percent. During the face to face interview with the students, each evaluator professor filled an individual spreadsheet based on pre-defined questions and curriculum analysis. The results were summarized with a mean. For criterion performance, a value from 0 until 3 was assigned if the candidate didn't meet the criterion, partially meet and fully meet. The performance scores were multiplied by the weight of each criterion, the results were summarized by simple additive model, and the candidates were ranked.

RESULTS:

An interview was conducted with the examining group evaluating MCDA asking for difficulties, time consumed and if the result was considered fair. Seven criteria were listed: “Comprehension of HTA”, “Motivation”, “Ability to disseminate information”, “Availability to attend the course”, “Scientific production”, “Potential to work in HTA area” and “Scientific writing skills”.

The highest weight (24 percent) was attributed to the “Potential to work in HTA area” and “Scientific writing skills” (20 percent). The evaluating group was unanimous in considering the process easy, fast and fair.

CONCLUSIONS:

The MCDA technique was applied successfully in student selection. Further prospective studies are needed.
VP100 Disease Modelling Approaches In Multiple Sclerosis
Authors: Cortesi Paolo , Uzman Nilhan , Ferrario Matteo , Mantovani Lorenzo Giovanni
Published: January 2018

INTRODUCTION:

In the past decades the cost-effectiveness of new effective disease-modifying therapies (DMTs) for Relapsing Remitting Multiple Sclerosis (RRMS) form was assessed through decision analytical models. Recently, new treatment option for the Primary Progressive (PPMS) form was developed. Aim of this work was assessing the similarities and differences of PPMS and RRMS and their impact in the development of decision analytical model for PPMS.

METHODS:

Literature review was performed to retrieve information on natural history of PPMS and RRMS and impact of DMTs agents on the progression of these conditions. Further, a review of the published cost-effectiveness models for RRMS was performed. Based on these data, an analysis on the difference and similarities between the two MS forms that could have an impact on the development of decision analytical model for PPMS was performed.

RESULTS:

Based on the analysis, similar structure model used for RRMS could be applied for PPMS. Health states of the model could be based on Expanded Disability Status Scale score as already done for RRMS. The relapse events considered for RRMS should not be included in PPMS model, and no possibility to develop another form, as the Secondary Progressive, should be included. While RRMS models should include at least a second line treatment option due to alternative DMTs available, only first treatment line should be considered for PPMS. Assessing data available to populate the model, poor data on the natural history, utility and cost associated to PPMS were available and assumption or expert opinions will be needed to overcome the lack of robust data.

CONCLUSIONS:

A decision analytical model for PPMS can use a similar structure used in the models for RRMS. However, more robust data on PPMS and some structural change are needed to provide a good tool to assess cost-effectiveness of DMTS in PPMS.
VP103 Health Technology Assessment Of Genetic Tests For Cystic Fibrosis Carrier Screening In Italy
Authors: Vukovic Vladimir , Agodi Antonella , Assael Baroukh , Calabro' Giovanna Elisa , Campanella Paolo , Castellani Carlo , Coviello Domenico , Di Pietro Maria Luisa , Favaretti Carlo , Gurrieri Fiorella , Ripabelli Giancarlo , Sbrogio' Luca , Teleman Adele Anna , Boccia Stefania
Published: January 2018

INTRODUCTION:

Cystic Fibrosis (CF) is a genetic disorder caused by mutations in CFTR gene. In Italy, reported prevalence is approximately .70 per 10,000 inhabitants (1). The practice and recommendations for Cystic Fibrosis carrier screening are very heterogeneous in Europe. A proposal of a carrier genetic test in the general population raises many questions. Health Technology Assessment (HTA) could offer a sound methodological basis for this evaluation. The aim of this work was to summarize the available evidence, using the HTA approach, on the genetic tests for Cystic Fibrosis carrier screening.

METHODS:

A systematic literature search was used to find the best available international and national evidence on genetics test for CF carrier screening. In this report, we specifically addressed the health problem of disease, description and technical characteristics of tests – its analytic and clinical validity, and clinical utility. Economic evaluation of different scenarios was synthesized from the literature. Ethical, organizational, and social aspects of CF and genetic screening were also considered.

RESULTS:

Several screening strategies have been evaluated in the literature and screening options can be characterized by different timing, model and place of screening (2). The reported cost of a screening test ranged from EUR25 to EUR212 (3). Estimated life time cost of care for CF patients ranged from EUR291,048 to EUR1,105,452. Ethical analysis emphasized that the use of these tests is an advantage in terms of the acquisition of knowledge and of responsible management of choices, but at the same time raises many ethical questions. Social considerations reported among patients and their families an overall positive attitude toward population CF carrier screening.

CONCLUSIONS:

The advances in the molecular genetics technology have made CF carrier testing reliable and affordable. The multidisciplinary approach of this HTA provided an evidence-based evaluation of genetic tests and offers a firm scientific background for the decision-makers to consider the implementation of a screening for Cystic Fibrosis carriers into the Italian health care system.
VP116 Comparison Between Time To Off Treatment And Italian Medicines Agency Registries Treatment Duration
Authors: Vittoria Gabriele , Fascì Antonio , Ferrario Matteo , Giuliani Giovanni
Published: January 2018

INTRODUCTION:

The Italian Medicines Agency Registry represents a tool that could be a precious source of information regarding the mean treatment duration of a drug in a real world context. Monitoring registries are applied at the national level after market authorization and are designed not only to apply the Managed Entry Agreements (MEAs) but also to collect Real World Data on drugs safety, effectiveness and real life utilization. The purpose of this analysis was to compare the treatment duration from clinical trials and the mean treatment duration calculated using data from monitoring registries (1).

METHODS:

For each drug included in the analysis it was collected the treatment duration from Time To Off Treatment curves for the experimental drug (eTTOT) from Phase III clinical trials and the mean treatment duration data calculated by using the number of cycles (converted in months of treatment) of all treated patients extracted from AIFA registries (TTAR). The mean ratios between the Time of Treatment of Italian Medicines Agency and Experimental arm time to off treatment were calculated to identify potential correlations. High level of correlation was expected if Time to Payment By Result /Time To Off Treatment ratio was close to 1 (±.2).

RESULTS:

Six Roche products or different indications of the same product were identified as candidates for the analysis from 2013 to 2016. The mean TTAR/eTTOT ratio observed in patients treated from 2013 to 2016 was .97 (±.10), meaning that the mean treatment duration calculated from AIFA Registries is strongly comparable with the treatment duration observed in clinical trials. In one case the TTAR is even more major than eTTOT.

CONCLUSIONS:

A high level of correlation between TTAR and eTTOT was found. Additional analyses considering different cohorts of patients over time could be useful to have a more precise estimate of real world drug utilization. Even though RCTs remain the gold standard for demonstrating clinical efficacy in restricted trial setting, Real World Evidence from AIFA registries can contribute to the evidence base needed for healthcare decisions.
VP131 Comparison Of Variation Methods For One-Way Sensitivity Analyses
Authors: McQueen Robert , Campbell Jonathan
Published: January 2018

INTRODUCTION:

A common approach to one-way sensitivity analysis is to vary inputs by a constant percentage. An alternative is to derive ranges using evidence-based probability distributions from published sources. Our objective was to compare one-way sensitivity analysis results when using these two approaches for a reference case model, along with two additional case studies.

METHODS:

For the reference case, we replicated a published Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) cost-effectiveness Markov model (zidovudine versus zidovudine plus lamivudine in the UK) using TreeAge®. Health states included three HIV/AIDS states and death. We generated one-way sensitivity analyses by varying inputs in two ways: (i) using ±15 percent for all inputs, and (ii) using the 2.5 and 97.5 percentile values of the evidence-based probability distributions for all inputs. Our outcome was the mean difference between lower and upper incremental cost-effectiveness ratios (ICERs) for each variation method for the ten most influential inputs. We assessed the number of inputs with a mean difference between lower and upper ICERs of >10 percent of the deterministic ICER.

RESULTS:

The deterministic ICER was GBP7,654/QALY (quality adjusted life year) for combination therapy versus monotherapy. The mean difference in ICER uncertainty for the evidence-based vs. ±15 percent variation method was GBP3,251/QALY (p = .0096). Six inputs had a mean difference in ICER uncertainty of >10 percent of GBP7,654/QALY (that is, mean difference in ICER uncertainty > GBP765) for the evidence-based variation method, compared to only two inputs for the constant percentage variation method.

CONCLUSIONS:

For the reference case, the magnitude of uncertainty in the outcome was larger for the evidence-based variation method compared to the constant percentage variation method. Evidence-based uncertainty in inputs should be used in all sensitivity analyses to reflect realistic uncertainty in an outcome and aid decision-making about future research strategies. Additional case studies will be presented using validated models in diabetes and asthma.
VP166 Selecting Rapid Review Methods For Health Technology Assessment
Authors: Kaltenthaler Eva , Cooper Katy , Martyn-St James Marrissa , Pandor Abdullah , Wong Ruth
Published: January 2018

INTRODUCTION:

Rapid reviews are of increasing importance within Health Technology Assessment (HTA) due to the need for timely evidence to underpin the assessment of new technologies as well as financial constraints. There are many rapid review methods available (1) although there is little guidance as to the most suitable methods (2). A recent paper outlines issues to consider when selecting rapid review methods (3). The aim of this presentation is to present key aspects to consider when selecting rapid review methods.

METHODS:

We searched the evidence base for guidance on the selection of rapid review methods. We also examined three recently completed systematic reviews to identify rapid review methods used, the reasons for selection and the strengths and weaknesses of each method. Finally we identified key aspects to consider when selecting rapid review methods.

RESULTS:

The evidence on guidance identified for the selection of rapid review methods was very limited. The analysis of the three reviews found that each review had distinctly different challenges, such as large numbers of relevant trials and heterogeneity in terms of populations, interventions, comparators and outcomes. All reviews included at least ten randomized controlled trials and numerous outcome measures. Three different approaches to the rapid review of the evidence were used in the three reviews. Key themes to consider when selecting rapid review methods were identified. These include: the size and nature of the evidence base, the characteristics of included studies and the expectations of those commissioning the review.

CONCLUSIONS:

Rapid review methods need to be chosen to fit the needs of the review, each of which may have different challenges. Collaboration between those producing rapid reviews and commissioners is crucial when choosing methods to ensure that the needs of commissioners are met and limitations associated with the chosen methods are understood.
VP177 Older People With Cancer: To Treat Or Not To Treat With Chemotherapy?
Authors: Boland Angela , Pilkington Gerlinde , Greenhalgh Janette , Dickson Rumona
Published: January 2018

INTRODUCTION:

Older people with cancer are less likely to receive radical treatment for cancer. We conducted a series of systematic reviews to explore the effectiveness and tolerability of systemic anti-cancer therapy for older people with cancer. The reviews were conducted on behalf of the National Cancer Equality Initiative to establish an understanding of the current body of research and to enable the development of more personalized treatment protocols for elderly patients that take into account fitness and personal choice.

METHODS:

We conducted six systematic reviews that considered the effectiveness and tolerability of treatment for older people with cancer (breast, colorectal, lung, renal cell, chronic myeloid leukaemia and non-Hodgkin's lymphoma). Four electronic databases were searched from 2010 to 2013. Data were extracted on a range of outcomes from published studies (randomised controlled trials, subgroup analyses, pooled analyses, cohort studies and retrospective studies).

RESULTS:

We found a large quantity of published research from a wide range of study types. We included a total of 490 studies (64 randomized controlled trials, 30 subgroup analyses, 24 pooled analyses, 255 cohort studies, and 117 retrospective studies).

Most of the randomized controlled trials enrolled fitter and healthier patients than those seen in routine clinical practice. The evidence indicates that older patients with good performance status can, and do, respond well to chemotherapy, frequently achieving similar survival benefit to younger patients.

We found no consistent definitions of ‘old’ or ‘elderly’ and these varied from 50 years to 85 years across studies.

The study results demonstrate that comprehensive geriatric assessment has not been routinely conducted in clinical cancer studies and that readily available assessment tools were not used by study investigators.

CONCLUSIONS:

Age should not be a barrier to treatment for the older population. Research is needed to determine which treatment regimens offer the appropriate balance of clinical effect and likelihood of adverse events within older populations. Future randomized controlled trials could be designed to include either higher proportions of older people, or only older people.
The Best Breakfast in Town: A Comprehensive Research Methods Project
Authors: Rosen Amanda M.
Published: January 2018

When instructors are first tasked with teaching the research methods course for their department, a common reaction is frustration and panic. Although all political scientists are trained in research methods, few besides methodologists view it as their primary or strongest area of expertise, and they are aware that the course rarely returns high teaching evaluations (Fletcher and Painter-Main 2014). Likewise, students approach their required research methods course with extreme anxiety, viewing it as the math class they were trying to avoid by majoring in political science (Bernstein and Allen 2013; Coleman and Conrad 2007). With instructors unhappily teaching the class and students dreading taking it, there is a “perfect storm” of attitudes and beliefs that is hardly likely to lead to a productive learning environment. The challenge driving this article is how to teach research methods in a rigorous, engaging way that promotes student learning without tanking scores on teaching evaluations.
Undergraduate Moot Court: Student Expectations and Perspectives
Authors: Kammerer Edward F.
Published: January 2018

Moot court is a common practice in law schools and growing in popularity at the undergraduate level. As part of the move to incorporate more active learning elements, instructors in a variety of courses include moot court elements in their syllabi. Courses, however, are not the only place where undergraduate students encounter moot court. Increasingly, students compete in moot court at the intercollegiate level. This paper examines those students who compete in moot court tournaments sponsored by the American Moot Court Association to determine what motivates these students and what benefits these students believe they receive from their participation. Survey results show that students are motivated to participate in moot court for academic reasons, that they believe their critical thinking and public speaking skills improve, and that, despite its heavy work load and difficulty, moot court is also fun.
Solar system expansion and strong equivalence principle as seen by the NASA MESSENGER mission
Authors: Genova Antonio , Mazarico Erwan , Goossens Sander , Lemoine Frank G. , Neumann Gregory A. , Smith David E. , Zuber Maria T.
Published: January 2018

The NASA MESSENGER mission explored the innermost planet of the solar system and obtained a rich data set of range measurements for the determination of Mercury’s ephemeris. Here we use these precise data collected over 7 years to estimate parameters related to general relativity and the evolution of the Sun. These results confirm the validity of the strong equivalence principle with a significantly refined uncertainty of the Nordtvedt parameter η = (−6.6 ± 7.2) × 10−5. By assuming a metric theory of gravitation, we retrieved the post-Newtonian parameter β = 1 + (−1.6 ± 1.8) × 10−5 and the Sun’s gravitational oblateness, $${{J}}_{2 \odot }$$

J

2
⊙

 = (2.246 ± 0.022) × 10−7. Finally, we obtain an estimate of the time variation of the Sun gravitational parameter, $$\dot{{G} {{M}}_ \odot} {\mathrm{/}}{{G}}{{M}}_ \odot$$

G

M

⊙

°

∕
G

M

⊙

 = (−6.13 ± 1.47) × 10−14, which is consistent with the expected solar mass loss due to the solar wind and interior processes. This measurement allows us to constrain $$\left| {{\dot{ G}}} \right|{\mathrm{/}}{{G}}$$

G

°

∕
G
to be <4 × 10−14 per year.
Bimolecular recombination in methylammonium lead triiodide perovskite is an inverse absorption process
Authors: Davies Christopher L. , Filip Marina R. , Patel Jay B. , Crothers Timothy W. , Verdi Carla , Wright Adam D. , Milot Rebecca L. , Giustino Feliciano , Johnston Michael B. , Herz Laura M.
Published: January 2018

Photovoltaic devices based on metal halide perovskites are rapidly improving in efficiency. Once the Shockley–Queisser limit is reached, charge-carrier extraction will be limited only by radiative bimolecular recombination of electrons with holes. Yet, this fundamental process, and its link with material stoichiometry, is still poorly understood. Here we show that bimolecular charge-carrier recombination in methylammonium lead triiodide perovskite can be fully explained as the inverse process of absorption. By correctly accounting for contributions to the absorption from excitons and electron-hole continuum states, we are able to utilise the van Roosbroeck–Shockley relation to determine bimolecular recombination rate constants from absorption spectra. We show that the sharpening of photon, electron and hole distribution functions significantly enhances bimolecular charge recombination as the temperature is lowered, mirroring trends in transient spectroscopy. Our findings provide vital understanding of band-to-band recombination processes in this hybrid perovskite, which comprise direct, fully radiative transitions between thermalized electrons and holes.
CA1 and CA3 differentially support spontaneous retrieval of episodic contexts within human hippocampal subfields
Authors: Dimsdale-Zucker Halle R. , Ritchey Maureen , Ekstrom Arne D. , Yonelinas Andrew P. , Ranganath Charan
Published: January 2018

The hippocampus plays a critical role in spatial and episodic memory. Mechanistic models predict that hippocampal subfields have computational specializations that differentially support memory. However, there is little empirical evidence suggesting differences between the subfields, particularly in humans. To clarify how hippocampal subfields support human spatial and episodic memory, we developed a virtual reality paradigm where participants passively navigated through houses (spatial contexts) across a series of videos (episodic contexts). We then used multivariate analyses of high-resolution fMRI data to identify neural representations of contextual information during recollection. Multi-voxel pattern similarity analyses revealed that CA1 represented objects that shared an episodic context as more similar than those from different episodic contexts. CA23DG showed the opposite pattern, differentiating between objects encountered in the same episodic context. The complementary characteristics of these subfields explain how we can parse our experiences into cohesive episodes while retaining the specific details that support vivid recollection.
BLM helicase suppresses recombination at G-quadruplex motifs in transcribed genes
Authors: van Wietmarschen Niek , Merzouk Sarra , Halsema Nancy , Spierings Diana C. J. , Guryev Victor , Lansdorp Peter M.
Published: January 2018

Bloom syndrome is a cancer predisposition disorder caused by mutations in the BLM helicase gene. Cells from persons with Bloom syndrome exhibit striking genomic instability characterized by excessive sister chromatid exchange events (SCEs). We applied single-cell DNA template strand sequencing (Strand-seq) to map the genomic locations of SCEs. Our results show that in the absence of BLM, SCEs in human and murine cells do not occur randomly throughout the genome but are strikingly enriched at coding regions, specifically at sites of guanine quadruplex (G4) motifs in transcribed genes. We propose that BLM protects against genome instability by suppressing recombination at sites of G4 structures, particularly in transcribed regions of the genome.
Cytogenomic identification and long-read single molecule real-time (SMRT) sequencing of a Bardet–Biedl Syndrome 9 (BBS9) deletion
Authors: Reiner Jennifer , Pisani Laura , Qiao Wanqiong , Singh Ram , Yang Yao , Shi Lisong , Khan Wahab A. , Sebra Robert , Cohen Ninette , Babu Arvind , Edelmann Lisa , Jabs Ethylin Wang , Scott Stuart A.
Published: January 2018

Bardet–Biedl syndrome (BBS) is a recessive disorder characterized by heterogeneous clinical manifestations, including truncal obesity, rod-cone dystrophy, renal anomalies, postaxial polydactyly, and variable developmental delays. At least 20 genes have been implicated in BBS, and all are involved in primary cilia function. We report a 1-year-old male child from Guyana with obesity, postaxial polydactyly on his right foot, hypotonia, ophthalmologic abnormalities, and developmental delay, which together indicated a clinical diagnosis of BBS. Clinical chromosomal microarray (CMA) testing and high-throughput BBS gene panel sequencing detected a homozygous 7p14.3 deletion of exons 1–4 of BBS9 that was encompassed by a 17.5 Mb region of homozygosity at chromosome 7p14.2–p21.1. The precise breakpoints of the deletion were delineated to a 72.8 kb region in the proband and carrier parents by third-generation long-read single molecule real-time (SMRT) sequencing (Pacific Biosciences), which suggested non-homologous end joining as a likely mechanism of formation. Long-read SMRT sequencing of the deletion breakpoints also determined that the aberration included the neighboring RP9 gene implicated in retinitis pigmentosa; however, the clinical significance of this was considered uncertain given the paucity of reported cases with unambiguous RP9 mutations. Taken together, our study characterized a BBS9 deletion, and the identification of this shared haplotype in the parents suggests that this pathogenic aberration may be a BBS founder mutation in the Guyanese population. Importantly, this informative case also highlights the utility of long-read SMRT sequencing to map nucleotide breakpoints of clinically relevant structural variants.
NIPBL+/− haploinsufficiency reveals a constellation of transcriptome disruptions in the pluripotent and cardiac states
Authors: Mills Jason A. , Herrera Pamela S , Kaur Maninder , Leo Lanfranco , McEldrew Deborah , Tintos-Hernandez Jesus A , Rajagopalan Ramakrishnan , Gagne Alyssa , Zhang Zhe , Ortiz-Gonzalez Xilma R. , Krantz Ian D.
Published: January 2018

Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural and developmental defects caused by mutations in structural and regulatory proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein, has been identified as a critical protein responsible for the orchestration of transcriptomic regulatory networks necessary for embryonic development. Mutations in NIPBL are responsible for the majority of cases of CdLS. Through RNA-sequencing of human induced pluripotent stem cells and in vitro-derived cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs with altered expression in NIPBL+/− patient-derived cells. We demonstrate that NIPBL haploinsufficiency leads to upregulation of gene sets identified in functions related to nucleosome, chromatin assembly, RNA modification and downregulation of Wnt signaling, cholesterol biosynthesis and vesicular transport in iPSC and cardiomyocytes. Mutations in NIPBL result in the dysregulation of many genes responsible for normal heart development likely resulting in the variety of structural cardiac defects observed in the CdLS population.
Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein
Authors: Pandey Rajan Kumar , Bhatt Tarun Kumar , Prajapati Vijay Kumar
Published: January 2018

Malaria fever has been pervasive for quite a while in tropical developing regions causing high morbidity and mortality. The causal organism is a protozoan parasite of genus Plasmodium which spreads to the human host by the bite of hitherto infected female Anopheles mosquito. In the course of biting, a salivary protein of Anopheles helps in blood feeding behavior and having the ability to elicit the host immune response. This study represents a series of immunoinformatics approaches to design multi-epitope subunit vaccine using Anopheles mosquito salivary proteins. Designed subunit vaccine was evaluated for its immunogenicity, allergenicity and physiochemical parameters. To enhance the stability of vaccine protein, disulfide engineering was performed in a region of high mobility. Codon adaptation and in silico cloning was also performed to ensure the higher expression of designed subunit vaccine in E. coli K12 expression system. Finally, molecular docking and simulation study was performed for the vaccine protein and TLR-4 receptor, to determine the binding free energy and complex stability. Moreover, the designed subunit vaccine was found to induce anti-salivary immunity which may have the ability to prevent the entry of Plasmodium sporozoites into the human host.
Increased diversity with reduced “diversity evenness” of tumor infiltrating T-cells for the successful cancer immunotherapy
Authors: Hosoi Akihiro , Takeda Kazuyoshi , Nagaoka Koji , Iino Tamaki , Matsushita Hirokazu , Ueha Satoshi , Aoki Shin , Matsushima Kouji , Kubo Masato , Morikawa Teppei , Kitaura Kazutaka , Suzuki Ryuji , Kakimi Kazuhiro
Published: January 2018

To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy. Increased CD8+ T cell effector function and TCR diversity with enrichment of certain TCR clonotypes in the tumor was associated with anti-tumor effects. In contrast, polyclonal activation of T-cells in the periphery was associated with tissue damage. Thus, optimal combination therapy increases TCR diversity with extended activation of selective CD8+ T-cells specifically in the tumor but not in the periphery. Incorporation of the concept of evenness for the TCR diversity is proposed.
Patients over 40 years old with precursor T-cell lymphoblastic lymphoma have different prognostic factors comparing to the youngers
Authors: Dong Meng , Zhang Xudong , Yang Zhenzhen , Wu Shaoxuan , Ma Mijing , Li Zhaoming , Chang Yu , Wang Xinhua , Li Ling , Li Xin , Zhang Mingzhi , Chen Qingjiang
Published: January 2018

This study aimed to analyze the clinical characteristics and prognostic factors of patients, divided into over 40-year-old group or not, with precursor T-cell lymphoblastic lymphoma (Pre-T-LBL). Based on the retrospective analysis of the clinical data of 59 patients with Pre-T-LBL during the period from December 2010 to December 2015, albumin level, anemia, pleural or pericardial effusion, protocol, therapy response, mediastinal mass, lactate dehydrogenase (LDH), and international prognostic index (IPI) or age-adjusted international prognostic index (aaIPI) were summarized. For patients aged <40 years, factors correlating with poor progression-free survival (PFS) were pleural or pericardial effusion, regimen, albumin level and therapy response. Pleural or pericardial effusion, aaIPI score, regimen, LDH increased, albumin level, therapy response and mediastinal mass were all related with poor overall survival (OS). In the patients aged ≥40 years, only anemia associated with PFS. However, anemia, involvement of bone marrow and therapeutic response were all related with poor OS. In conclusion, the patients with Pre-T-LBL are characterized by a low incidence and bad prognosis. Different prognostic factors can be discovered for patients over 40-year-old with Pre-T-LBL comparing to the youngers. New prognostic evaluation factors should be explored for patients ≥40 years old.
Identification of isoforms of aspartic acid residues in peptides by 2D UV-MS fingerprinting of cold ions
Authors: Kopysov Vladimir , Gorshkov Mikhail V. , Boyarkin Oleg V.
Published: January 2018

We use 2D UV-MS cold-ion spectroscopy for the identification ofl-Asp,d-Asp,l-isoAsp andd-isoAsp residues in a fragment peptide derived from the hormone protein amylin.
Enhancing the photoluminescence of surface anchored metal–organic frameworks: mixed linkers and efficient acceptors
Authors: Oldenburg M. , Turshatov A. , Busko D. , Jakoby M. , Haldar R. , Chen K. , Emandi G. , Senge M. O. , Wöll C. , Hodgkiss J. M. , Richards B. S. , Howard I. A.
Published: January 2018

Photoluminescence quantum yield enhancement based on energy transfer in surface-anchored metal–organic frameworks.
Association of fatty acids and lipids metabolism in placenta with early spontaneous pregnancy loss in Chinese women
Authors: Li Kelei , Zhang Xiaotian , Chen Gong , Pei Lijun , Xiao Hailong , Jiang Jiajing , Li Jiaomei , Zheng Xiaoying , Li Duo
Published: January 2018

Abnormal fatty acids and lipids metabolism in the placenta is associated with early spontaneous pregnancy loss.
In vitro digestion with bile acids enhances the bioaccessibility of kale polyphenols
Authors: Yang Isabelle , Jayaprakasha Guddarangavvanahally K. , Patil Bhimanagouda
Published: January 2018

Kale (Brassica oleracea) polyphenols and dietary fiber have key roles in bile acid binding, and these bile acids enhanced significanlty higher (69.4%) bioaccessibility of certain health-promoting polyphenolics.
Biocatalysis of carboxylic acid reductases: phylogenesis, catalytic mechanism and potential applications
Authors: Qu Ge , Guo Jinggong , Yang Dameng , Sun Zhoutong
Published: January 2018

Recent advances in carboxylic acid reductases and their practical applications in bio-cascade processes.
Autoantibodies against angiotensin and adrenergic receptors: more than a biomarker?
Authors: Neuman Rugina , Danser A.H. Jan
Published: January 2018

Agonistic autoantibodies (AAs) directed against receptors of the sympathetic nervous system and the renin–angiotensin system have been suggested to contribute to cardiovascular and renal disease, in particular hypertension, preeclampsia, and graft failure in kidney transplantation patients. Consequently, they are now also being studied as biomarker for these conditions. This commentary summarizes our current understanding of these AAs, critically discussing whether they truly act as agonist, and focusing on the wide array of assays that are currently used for their quantification.
On a population dynamic model of active cells with direct interaction
Authors: Noussair Ahmed
Published: January 2018

Through two case studies, this paper deals with a new class of population dynamic models inspired from the kinetic theory for active particles modelling cell to cell interactions with a transfer processes between cells. The first case study problem is related to the transfer of proteins motivated by advantages of cell transfer therapies for the treatment of cancers. The second case concerns the activity transfer between immune and tumor cells. We provide some numerical tests and we prove the convergence of the solutions from the discrete model to the continuous model.