bluuebunny/crossref_metadata_2025 huggingface dataset:
PP93 Efficacy Of Pharmacological Treatments For Type 2 Diabetes In China
Authors: Gu Shuyan , Yu Hai , Li Yuanyuan , Shen Yi , Zhen Xuemei , Gu Yuxuan , Wei Jingming , Shi Lizheng , Dong Hengjin
Published: December 2019

Introduction

There are multiple antidiabetic drugs available in China, which vary in their efficacy and safety. However, no study exists that compares all the classes of antidiabetic drugs simultaneously. This study aimed to estimate and compare the efficacy of alternative classes of antidiabetic drugs for Chinese patients with type 2 diabetes, either in a monotherapy regimen or combined with metformin.

Methods

A systematic literature review was conducted by searching various literature databases to identify relevant randomized controlled trials published from 1990 to 2016. A meta-analysis was conducted to compare the efficacy of antidiabetic drug monotherapy and placebo or lifestyle interventions (i.e., diet and exercise), and antidiabetic drug plus metformin versus metformin alone, in Chinese patients with type 2 diabetes. An indirect comparison was used to estimate the efficacy of antidiabetic drug plus metformin versus placebo or lifestyle-intervention using metformin as the common comparator.

Results

The database search identified 354 relevant studies. Compared with placebo or lifestyle interventions, combination therapies achieved greater reductions in hemoglobin A1c (HbA1c) level (1.9% versus 0.9%), body mass index (BMI) (2.66 versus 0.98 kg/m2), and total cholesterol level (1.07 versus 0.35 mmol/L) than monotherapies. For monotherapies, the top three treatments for reducing HbA1c level were insulin, sulfonylurea, and glucagon-like peptide-1 (GLP-1) receptor agonist. The top three monotherapies for reducing BMI level were metformin, GLP-1 receptor agonist, and α-glycosidase inhibitor. The top three monotherapies for reducing total cholesterol level were metformin, GLP-1 receptor agonist, and dipeptidyl peptidase-4 (DPP-4) inhibitor. For combination therapies, the top three treatments for reducing HbA1c level were GLP-1 receptor agonist plus metformin, insulin plus metformin, and glinide plus metformin. The top three combination therapies for reducing BMI level were glinide plus metformin, GLP-1 receptor agonist plus metformin, and DPP-4 inhibitor plus metformin. The top three combination therapies for reducing total cholesterol level were insulin plus metformin, GLP-1 receptor agonist plus metformin, and α-glycosidase inhibitor plus metformin.

Conclusions

Pharmacological treatments had better efficacy than placebo or lifestyle interventions, while combination drug therapies were superior to monotherapies.
PP128 Quantifying The Relative Importance Of Chronic Obstructive Pulmonary Disease Symptoms To Patients
Authors: Cook Nigel S. , Kostikas Konstantinos , Oezel Beyza , Tatlock Sophi , Mycock Katie , Gardner Tom , Criner Gerard J. , Burgel Pierre-Régis , Gutzwiller Florian S.
Published: December 2019

Introduction

Previous qualitative research analyzing social media and online community discussions highlighted the symptomatic burden of cough and mucus (sputum), alongside shortness of breath, in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to determine the relative importance of these symptoms and their consequences (for example, disturbed sleep) to COPD patients, compared with conventional COPD endpoints (lung function and exacerbations).

Methods

A total of 1,050 patients (at least 40 years of age) with moderate to severe COPD or chronic bronchitis, and regular symptoms of cough and excess mucus production, are to be recruited through patient advocacy groups (PAGs) from five countries (Australia, France, Japan, the United Kingdom, and the United States; 150 to 400 patients per country). A discrete choice experiment was designed with input from clinical experts and the PAGs, plus scientific advice from the National Institute for Health and Care Excellence (NICE) in the United Kingdom. Patients’ preferences for the conditional relative importance of symptoms and impact of COPD will be quantified based on trade-offs they are willing to make among hypothetical COPD disease state profiles, described by differing attributes and levels. Hierarchical Bayesian analysis with effect-coding parameterization will be undertaken on the choice data to estimate (using Gibbs sampling) the relative value each respondent places on an attribute level.

Results

The feedback from NICE informed the selection of screening criteria and the statistical analysis plan, as well as the inclusion of a health status measure, the EQ-5D-3L. Qualitative patient interviews and pilot testing of the attributes and levels grid have been completed, informing finalization of the online survey design.

Conclusions

Patient preference studies evaluating the relative importance of symptom burden through assessment of disease state preference values are an important new form of patient-based evidence for informing value-based decision making in HTA. The present study should facilitate a more patient-centered approach to developing new treatments for and improving the care of patients with COPD.
PP141 Functional Connectivity Magnetic Resonance Imaging To Detect Autism
Authors: Polo-DeSantos Mar , Pablo Juan , Orrego Chalco , Hijas-Gómez Ana Isabel , Luengo-Matos Setefilla , Sánchez-Gómez Luis María
Published: December 2019

Introduction

Autism is a neurodevelopmental disorder characterized by alterations in the intellectual, social, communication, and behavioral capabilities of an individual, and is rarely detected in children before 24 months of age. Early diagnosis and intervention may be more effective at a younger age. Functional connectivity magnetic resonance imaging (fcMRI) of 6-month old infants may be able to identify brain connection patterns related to at least one of the characteristics of autism, which normally appear at 24 months of age, by using a mathematical model to analyze the neuroimaging data.

Methods

Clinical studies published up to December 2018 that used fcMRI to detect autism in infants were reviewed. The literature databases searched included PubMed, Web of Science, the Trip Database, DynaMed, the Cochrane Library, the International Clinical Trials Registry Platform, and ClinicalTrials.gov. Early assessments of fcMRI analysis were identified through the Early Awareness and Alert System of the Agencia de Evaluación de Tecnologías Sanitarias.

Results

Only one prospective study of 59 infants at 6-months of age was retrieved. A fcMRI analysis was performed to identify 2,635 pairs of functional connections from 230 brain regions. The infants were subsequently assessed for autism at 24 months of age using gold standard tests. The functional connections correlated with at least one of the behaviors related to autism evaluated at 24 months of age. Eleven infants (19%) were diagnosed with autism at 24 months. Compared with the gold standard test results, the predictive model achieved the following: sensitivity 0.82 (95% confidence interval [CI]: 0.52 - 0.95); specificity 1.00 (95% CI: 0.93–1.00); positive predictive value 1.00 (95% CI: 0.70–1.00); negative predictive value 0.96 (95% CI: 0.87–0.99); and negative likelihood ratio 0.18 (95% CI: 0.05–0.64). Adverse effects were not reported in the study.

Conclusions

The fcMRI analysis could help in early detection of autism and the development of preventive interventions. However, the evidence is sparse and more well-designed studies are needed.
PP171 Cost And Effectiveness Of Chronic Hepatitis C Treatment In Brazil
Authors: Schwambach Karin Hepp , Farias Mareni Rocha , Neto Giacomo Balbinotto , Blatt Carine Raquel
Published: December 2019

Introduction

With the discovery of new direct-acting antivirals, the cure for hepatitis C appears to be a reality, but its high price and the availability of new antivirals are a major obstacle. In Brazil, treatments for hepatitis C have been available in the public health system since the 1990s, and in 2015 were made available the antivirals sofosbuvir, daclatasvir and simeprevir. The calculation of the budgetary impact of this merger estimated expenditures between 467 and 666 million Reais (USD 121 and 172 million) per year. This study aims to present and discuss the cost and effectiveness of hepatitis C treatment with direct-acting antivirals with or without alfapeginterferon and ribavirin, based on real-life data, and compare it with the world scenario.

Methods

We analyzed the treatment data and outcomes of 253 patients from a retrospective cohort performed in a Specialized Care Service, in the city of Porto Alegre. In relation to costs, the direct costs of antiviral drugs, per unit (tablet), were considered according to financial receipts from public purchases. The total cost of the medications used by each individual in each treatment and the cost per cure obtained, expressed in Sustained Viral Response (SVR), were calculated.

Results

Most patients (66.8 percent) had genotype 1 of the hepatitis virus and 92.9 percent achieved SVR. The mean total cost of treatment of patients with genotype 1 was USD 5,862.31 and USD 6,310.34 per cure; while in patients with genotype 3 the cost was USD 5,144.27 and USD 5,974.76 per cure. The cost with the most commonly used treatment regimen, sofosbuvir, daclatasvir and ribavirin was USD 5,961.25 and USD 6,536.46 per cure. These values were 30 percent lower than the values estimated at the time of drug incorporation.

Conclusions

Cost and effectiveness data contextualize a real-life scenario in Brazil. The evaluated treatments presented good effectiveness, but high costs.
PP185 Clinical Papers: Which Are Ongoing Studies To Assess MHealth In 2020?
Authors: Olivier Cyril , Piotto Estelle , Collignon Corinne , Galmiche Hubert , Bélorgey Chantal
Published: December 2019

Introduction

Mobile health systems (MHS) are one of the more spreading technologies in the field of medicine. However, identification of useful MHS is rather challenging. Few of them are, or could be, connected medical devices (cMD). Like other medical devices, cMD must be assessed to validate claimed benefits for reimbursement purposes. Clinical added value demonstration is a major criterion used to satisfy administrative requirements. With the increase of clinical studies that are including MHS, study registries can be used for insight into the type of evidence expected to become available in the near future.

Methods

In 2018, the French National Authority for Health (HAS) performed a review of registered MHS clinical study designs. The Clinicaltrials.gov database was consulted for all studies indexed with the terms “mHealth” and “mobile health” for the search fields “study title”, “conditions” and “interventions”.

Results

Four hundred and fifteen clinical studies were registered. Three hundred and eighty studies were interventional with most comprised of a randomized study design (75 percent). Fifteen had a crossover design. Only few observational studies (n = 35) were registered. These mainly concerned (59 percent) patient use of an app on a smartphone without any other device.

Conclusions

Patterns of clinical studies were not found to significantly differ between MHS and other medical devices. Most of the clinical studies were randomized and specific criteria to assess MHS could easily be identified. However, specific methodologies for clinical development are not used in practice for cMD health technology assessment. In the absence of validated and specific methodology for clinical development, current methods that are being used in these ongoing studies will nonetheless be generating evidence for the upcoming years.
VP31 Searching Non-English Literature For HTA Reports May Be Unnecessary
Authors: Schell Lisa , Hausner Elke , Rodenhäuser Lina , Assall Oliver , Schulz Anke , Sieben Wiebke , van der Leck Kerstin , Sauerland Stefan
Published: December 2019

Introduction

Currently, the Institute for Quality and Efficiency in Health Care (IQWiG) does not restrict literature searches by language. Given limited resources, it is unclear whether the effort put into screening and translating studies published in non-English and non-German (nEnG) languages yields much new information when compared to including only English and German literature. Therefore, we aimed to analyze the impact of nEnG literature on the conclusion of IQWiG's health technology assessments (HTAs).

Methods

We checked for seventy-two IQWiG HTAs (all non-drug intervention HTAs published until August 2018 and three additional HTAs on drugs) whether they included nEnG studies. For all HTAs including at least one nEnG study, we analyzed whether the statistical significance would have changed for any endpoint without the respective nEnG study(ies). If no endpoint was impacted by a nEnG study, we classified the study as non-relevant to the HTA's conclusion and specified a reason for this.

Results

Of seventy-two HTAs, twenty-nine (40 percent) included a total of eighty-three nEnG publications). Three HTAs were impacted by the inclusion of altogether seven Chinese publications. For one HTA on systemic therapy, five endpoints’ conclusions were changed; for the other two HTAs, the statistical significance would have changed for one endpoint each. The remaining seventy-six publications (included in sixty-nine HTAs) were judged as non-relevant to the HTA's conclusion, the most prominent reason being “meta-analysis would have had the same result without respective study” (44 percent of nEnG publications).

Conclusions

Only three of seventy-two HTAs (4 percent) were impacted by nEnG publications, the changes being minimal for two of these. When faced with limited time or personnel resources, searching only for English and German publications may be sufficient, especially when generalizability issues are a possible concern.
VP32 Incorporation Of The Only Drug For Primary Biliary Cholangitis Brazil
Authors: Silva Thales
Published: December 2019

Introduction

Primary biliary cholangitis (CBP) is a rare autoimmune cholestatic liver disease, inflammation and progressive destruction of small and medium-sized interlobular ducts, progressing to fibrosis, cirrhosis, and death. Currently, the Brazilian public health system (SUS) offers treatment of the symptoms of cirrhosis, and has no medication with indication for CBP.

Methods

Scientific technical opinion with systematic review (SR) of available evidence in the databases MEDLINE (Pubmed), LILACS and Cochrane Library (accessed July 2017) on ursodeoxycholic acid (AUDC). Methodological quality was evaluated with AMSTAR and Newcastle Ottawa tools. Meta-analyses were performed in Review Manager® 5.2 in the random effects model. Analysis of the budget impact calculation deterministic model, from the perspective of five years for the SUS.

Results

Ten SRs and three cohorts were included. There was no statistically significant difference between AUDC and placebo in outcome. Overall survival was significantly (P <0.001) higher in the AUDC group compared to that predicted by the Mayo model or placebo. Treatment with UCD showed an increase in the long-term transplant-free survival time from the fifth year of treatment, with statistically significant results for years five, eight and ten (p <0.01). There were no statistically significant differences for safety outcomes. Based on the assumptions adopted, the incremental budgetary impact with the incorporation of the AUDC into SUS would be BRL 11.77 million (EUR 2.68 million) in the first year and BRL 98.52 million (EUR 22.45 million) in the accumulated five years, considering a market share of 10 percent per year.

Conclusions

Despite the uncertainties in the evidence of effectiveness of the AUDC and the probably underestimated budgetary impact, AUDC was incorporated into the SUS because it is the only alternative with indication for CBP and in use for more than two decades, allowing everyone access to the medicine
VP46 German Claims Data In Rare Disease HTA: Diffuse Large B-cell Lymphoma
Authors: Neubauer Aljoscha , Guthoff-Hagen Susanne , Menzler Jacob , Schwenke Carsten , Rueckert Markus , Boehnke Axel
Published: December 2019

Introduction

In rare disease areas representative data are scarce. Routine sick fund claims data provide a meaningful and reliable base for the in- and outpatient treatment landscape. This real-world data (RWE) from Germany was used to describe treatment patterns for Diffuse Large B-cell Lymphoma (DLBCL), the most frequent and aggressive non-Hodgkin lymphoma type in adults.

Methods

Claims data from several sick funds of 4.8 Million insured were analyzed. Diagnosis of non-follicular Lymphoma (C83) was confirmed in 2.178 patients, DLBCL (C83.3) in 819 patients. The analysis was age- and gender-adjusted, observational period was 2014 and 2015. Treatments were analyzed for hospitalization and medication based on ATC-Code, Pharma Central Number and coded diagnoses (per ICD).

Results

Mean age of DLBCL patients was 60.3 years, with two peaks at 50-54 and 70-74 years. Total costs for patients with DLBCL averaged 25.048 EUR versus 1.259 EUR in healthy insured. Charlson comorbidity index (CCI) of 4.58 indicates clinical relevance and severity. Comorbidities included several psychiatric diagnoses such as depression in every fifth patient. Mean 3.2 hospitalizations with average 31.5 hospital days were observed in DLBCL patients. Forty-seven percent of patients during observational time-frame did not receive oncological treatment, including relapsed / refractory patients. Only few patients received stem cell transplantation (2.6 percent) or radiation (3.9 percent). Most pharmacological treatments were Rituximab (RTX) + CHOP (57 percent), followed by RTX mono therapy (25 percent) or RTX in combination with Bendamustine (8 percent).

Conclusions

Despite limitations in sick fund claims analyses, these provide a reasonable database for rare diseases. They allow standard treatment pathway- and longitudinal analyses. All DLBCL patients frequently required hospitalization and generated significant costs. A high unmet medical need exists for treatments other than palliative care, especially for a tolerable and effective outpatient therapy in elderly relapsed / refractory DLBCL.
VP63 EUnetHTA Planned And Ongoing Projects Database: Usage And Challenges
Authors: Erdos Judit , Chalon Patrice
Published: December 2019

Introduction

The European Network for Health Technology Assessment (EUnetHTA) Planned and Ongoing Projects (POP) database allows sharing information on projects of HTA organisations participating in EUnetHTA. It enables users identifying overlaps and therefore has the potential to reduce duplication of work on similar topics. The aim of our research was to examine the usage of the database, how it helps to reduce duplication, and identify challenges to be addressed.

Methods

We conducted a systematic data collection and analysis on the topic overlaps retrospectively and complemented it with an electronic survey aimed at database users. The dataset on the overlaps was collected between June 2016 and September 2017. The survey was conducted in October 2017.

Results

During the data collection period, the POP database contained on average 800 projects provided by around fifty percent of the EUnetHTA partner organisations. One hundred and sixty nine identical projects could be identified from which ninety-two percent had different starting dates. Twenty-five percent of the identical projects were elaborated on by three organisations, 10 percent by four, and 6.5 percent by five organisations. Analysis of the survey showed a pattern of “wait and see”: users are informed about what other EUnetHTA partners are working on, wait for a finalised HTA or exchange the project plan, search strategies, search results, extraction tables, etc. The data collection and survey could not provide a precise number of collaborations initiated based on information gathered from the database.

Conclusions

The POP database is suitable for information sharing and has the potential to save time and resources at EUnetHTA partners. The collaboration is hindered by differences in national processes, including the timing and scope of the assessments. The impact of the POP database on the facilitation of collaboration and reduction of duplication of HTAs produced by EUnetHTA partners is yet to be strengthened.
VP71 Barriers To Access Biologic Products: A Rapid Review
Authors: Silva Roberta Borges , Farinasso Cecilia , Rego Daniela , Gomes Dalila Fernandes , de Aguiar Aurelina Aguiar , Leite Betânia , Goncalves Lenilson , Simões Luciana , Leão Camara , Sachetti Camile Giaretta
Published: December 2019

Introduction

The elevated costs with biologic products threaten the sustainability of health services, and, therefore, the access to these medicines in the perspectives of user, health professional, health manager and system. The entry of biosimilar products in the market could be an option to subsidize the search for solutions to those problems.

Methods

We conducted a rapid review using the databases Medline (via PubMed), EMBASE, Cochrane Library and CRD. The eligibility criteria were HTAs, systematic reviews and cross-sectional studies.

Results

Literature search retrieved 640 registries and, after duplicate removal, screening of titles and abstracts and full text reading, nine cross-sectional studies were selected. From a user's point of view, the following barriers were identified: lack of knowledge about the medicine, distance between the place of living and the health service (especially in the rural area), long waiting periods for service, passivity in regard to treatment. From a health professional's point of view the barriers were: acceptability of the expert in regard to treatment, interchangeability and substitution, the perception of lack of data showing efficacy and safety. Finally, from the payer's (or health manager) point of view, the barriers were: high cost of medicine, problems with reimbursement and bureaucracy. We did not retrieve any barriers from the health system's perspective from the selected studies.

Conclusions

The entry of biosimilar medicines in the market can induce competition and, therefore, reduce prices of biologic treatments. It is necessary to search for potential solutions to the access barriers identified in this rapid review.
VP72 Impact Of Comparator Choice On Oncology Drugs’ Market Access
Authors: Marfin Henri , Grande Mathilde , Thuillez Christian , d'Andon Anne
Published: December 2019

Introduction

In France, drug assessment is performed by the Transparency Committee (TC) of the French National Authority for Health (HAS). It's based on two criteria: the clinical benefit (CB) for reimbursement recommendation and the clinical added value (CAV) serving the pricing decision. The CAV is rated on a 5-point scale, from I (major) to V (no CAV). A critical step in the CAV assessment is the identification of the clinically relevant comparators (CRC) serving the TC to recognize the appropriateness of the comparators chosen in the randomized controlled trials (RCT). The objective of this study is to investigate the comparator choice consequences on TC appraisals and pricing.

Methods

A retrospective, descriptive study included all oncology indications assessed by the TC between 2015 and 2017. Based on a pre-specified grid, items on the comparators were extracted from final TC's appraisals.

Results

Among the 135 indications included, the assessed drugs had no CRC in 20% of cases. A RCT was submitted for 89 indications (66%) whose 67 (76%) were conducted versus a CRC. A CRC was identified by the TC for 70% of the 46 indications without RCT. An important/moderate CAV (II-III) was granted when there was a RCT versus a CRC in 70% of cases, versus 50% and 43% for minor (IV) and no CAV respectively. The public price was reduced by 13.5% in average compared to the claimed price without impact of the CAV level (n = 18).

Conclusions

In oncology, comparative data assessed by the TC met its expectations (RCT versus CRC) in a majority of cases. When there is no RCT or a comparison versus a non-relevant comparator the CAV appraisal is decreased. Surprisingly this study hasn't shown any impact of this decrease on the public price. A wider analysis in different medical areas would need to be performed to better investigate these results.
Seasonality of the transmissibility of hand, foot and mouth disease: a modelling study in Xiamen City, China
Authors: Huang Zehong , Wang Mingzhai , Qiu Luxia , Wang Ning , Zhao Zeyu , Rui Jia , Wang Yao , Liu Xingchun , Hannah Mikah Ngwanguong , Zhao Benhua , Su Yanhua , Zhao Bin , Chen Tianmu
Published: December 2019

This study attempts to figure out the seasonality of the transmissibility of hand, foot and mouth disease (HFMD). A mathematical model was established to calculate the transmissibility based on the reported data for HFMD in Xiamen City, China from 2014 to 2018. The transmissibility was measured by effective reproduction number (Reff) in order to evaluate the seasonal characteristics of HFMD. A total of 43 659 HFMD cases were reported in Xiamen, for the period 2014 to 2018. The median of annual incidence was 221.87 per 100 000 persons (range: 167.98/100,000–283.34/100 000). The reported data had a great fitting effect with the model (R2 = 0.9212, P < 0.0001), it has been shown that there are two epidemic peaks of HFMD in Xiamen every year. Both incidence and effective reproduction number had seasonal characteristics. The peak of incidence, 1–2 months later than the effective reproduction number, occurred in Summer and Autumn, that is, June and October each year. Both the incidence and transmissibility of HFMD have obvious seasonal characteristics, and two annual epidemic peaks as well. The peak of incidence is 1–2 months later than Reff.
General Synod of the Scottish Episcopal Church
Authors: Stuart John F
Published: December 2019

The General Synod met at St Paul's and St George's church in Edinburgh from 6 to 8 June. In his opening charge to Synod, the Primus, the Most Revd Mark Strange, encouraged Synod members to listen to the voice of God and respond to the command ‘this is the way, walk in it’. The Scottish Episcopal Church needed to be able to respond to a society crying out for reconciliation, fairness and hope but could only do so if, inside the Church, such values marked the way in which members treated one another.
Phase connected X-ray light curve and He II radial velocity measurements of NGC 300 X-1
Authors: Carpano S. , Haberl F. , Crowther P. , Pollock A.
Published: December 2019

. NGC 300 X-1 and IC 10 X-1 are currently the only two robust extragalactic candidates for being Wolf-Rayet/black hole X-ray binaries, the Galactic analogue being Cyg X-3. These systems are believed to be a late product of high-mass X-ray binary evolution and direct progenitors of black hole mergers. From the analysis of Swift data, the orbital period of NGC 300 X-1 was found to be 32.8 h. We here merge the full set of existing data of NGC 300 X-1, using XMM-Newton, Chandra and Swift observations to derive a more precise value of the orbital period of 32.7932 ± 0.0029 h above a confidence level of 99.99%. This allows us to phase connect the X-ray light curve of the source with radial velocity measurements of He II lines performed in 2010. We show that, as for IC 10 X-1 and Cyg X-3, the X-ray eclipse corresponds to maximum of the blueshift of the He II lines, instead of the expected zero velocity. This indicates that for NGC 300 X-1 as well, the wind of the WR star is completely ionised by the black hole radiation and that the emission lines come from the region of the WR star that is in the shadow. We also present for the first time the light curve of two recent very long XMM-Newton observations of the source, performed on the 16th to 20th of December 2016.
Black hole high mass X-ray binary microquasars at cosmic dawn
Authors: Mirabel I. F.
Published: December 2019

Theoretical models and observations suggest that primordial Stellar Black Holes (Pop-III-BHs) were prolifically formed in HMXBs, which are powerful relativistic jet sources of synchrotron radiation called Microquasars (MQs).

Large populations of BH-HMXB-MQs at cosmic dawn produce a smooth synchrotron cosmic radio background (CRB) that could account for the excess amplitude of atomic hydrogen absorption at z∼17, recently reported by EDGES.

BH-HMXB-MQs at cosmic dawn precede supernovae, neutron stars and dust. BH-HMXB-MQs promptly inject into the IGM hard X-rays and relativistic jets, which overtake the slowly expanding HII regions ionized by progenitor Pop-III stars, heating and partially ionizing the IGM over larger distance scales.

BH-HMXBs are channels for the formation of Binary-Black-Holes (BBHs). The large masses of BBHs detected by gravitational waves, relative to the masses of BHs detected by X-rays, and the high rates of BBH-mergers, are consistent with high formation rates of BH-HMXBs and BBHs in the early universe.
Facilitating Respite, Communication, and Care for Children With Intellectual and Developmental Disabilities: Preliminary Evaluation of the Caregiver Pain Information Guide
Authors: Genik Lara M. , Millett Geneva E. , McMurtry C. Meghan
Published: December 2019

Background: Pain is common in children with intellectual and developmental disabilities (I/DD) and yet is an understudied issue. Respite workers commonly care for children with I/DD but are lacking in resources to assist in pain assessment and management for this population. Without adequate knowledge in this domain, children with I/DD are at risk of their pain being underrecognized and undermanaged. A resource for caregivers was developed to address this issue, facilitating communication between parents and respite workers and better addressing the complex pain-related needs of children with I/DD. The objective of this study was to solicit initial feedback on the content, feasibility, and usability of the resource. Method/Procedure: Semistructured individual interviews and questionnaires were completed with 7 parents of children with I/DD and 6 respite workers. Results: All participants viewed the resource as important and potentially useful. Content analyses indicated that participants appreciated the comprehensiveness and format of the resource, whereas the modifiability was identified as an area for improvement. Participants believed that the resource would be useful across settings with a variety of caregivers. Three categories of considerations were identified as potential facilitators and barriers for implementation: consideration of how the resource is being completed, who is completing it, and organization-based procedures. Discussion/Conclusions: Results from this study suggest that the Caregiver Pain Information Guide is a promising resource for helping respite workers better understand pain in children with I/DD. Future work is needed on implementation and impact of this resource in community settings.

Implications for Impact Statement

Children with intellectual and developmental disabilities experience pain frequently and are at risk of having their pain missed by caregivers. Parents would like to share pain-related knowledge and skills specific to their children with intellectual and developmental disabilities with those who support their child in other settings. The Caregiver Pain Information Guide was created to facilitate communication between parents and caregivers of these children. The current article discusses initial feedback from parents and respite workers regarding this new tool.
The transport of liquids in softwood: timber as a model porous medium
Authors: Burridge H. C. , Wu G. , Reynolds T. , Shah D. U. , Johnston R. , Scherman O. A. , Ramage M. H. , Linden P. F.
Published: December 2019

Timber is the only widely used construction material we can grow. The wood from which it comes has evolved to provide structural support for the tree and to act as a conduit for fluid flow. These flow paths are crucial for engineers to exploit the full potential of timber, by allowing impregnation with liquids that modify the properties or resilience of this natural material. Accurately predicting the transport of these liquids enables more efficient industrial timber treatment processes to be developed, thereby extending the scope to use this sustainable construction material; moreover, it is of fundamental scientific value — as a fluid flow within a natural porous medium. Both structural and transport properties of wood depend on its micro-structure but, while a substantial body of research relates the structural performance of wood to its detailed architecture, no such knowledge exists for the transport properties. We present a model, based on increasingly refined geometric parameters, that accurately predicts the time-dependent ingress of liquids within softwood timber, thereby addressing this long-standing scientific challenge. Moreover, we show that for the minimalistic parameterisation the model predicts ingress with a square-root-of-time behaviour. However, experimental data show a potentially significant departure from this $$\sqrt{{\boldsymbol{t}}}$$t behaviour — a departure which is successfully predicted by our more advanced parametrisation. Our parameterisation of the timber microstructure was informed by computed tomographic measurements; model predictions were validated by comparison with experimental data. We show that accurate predictions require statistical representation of the variability in the timber pore space. The collapse of our dimensionless experimental data demonstrates clear potential for our results to be up-scaled to industrial treatment processes.
Predicting Effective Diffusivity of Porous Media from Images by Deep Learning
Authors: Wu Haiyi , Fang Wen-Zhen , Kang Qinjun , Tao Wen-Quan , Qiao Rui
Published: December 2019

We report the application of machine learning methods for predicting the effective diffusivity (De) of two-dimensional porous media from images of their structures. Pore structures are built using reconstruction methods and represented as images, and their effective diffusivity is computed by lattice Boltzmann (LBM) simulations. The datasets thus generated are used to train convolutional neural network (CNN) models and evaluate their performance. The trained model predicts the effective diffusivity of porous structures with computational cost orders of magnitude lower than LBM simulations. The optimized model performs well on porous media with realistic topology, large variation of porosity (0.28–0.98), and effective diffusivity spanning more than one order of magnitude (0.1 ≲ De < 1), e.g., >95% of predicted De have truncated relative error of <10% when the true De is larger than 0.2. The CNN model provides better prediction than the empirical Bruggeman equation, especially for porous structure with small diffusivity. The relative error of CNN predictions, however, is rather high for structures with De < 0.1. To address this issue, the porosity of porous structures is encoded directly into the neural network but the performance is enhanced marginally. Further improvement, i.e., 70% of the CNN predictions for structures with true De < 0.1 have relative error <30%, is achieved by removing trapped regions and dead-end pathways using a simple algorithm. These results suggest that deep learning augmented by field knowledge can be a powerful technique for predicting the transport properties of porous media. Directions for future research of machine learning in porous media are discussed based on detailed analysis of the performance of CNN models in the present work.
A Study of the North Water Polynya Ice Arch using Four Decades of Satellite Data
Authors: Vincent R. F.
Published: December 2019

Polynyas are sections of the polar ocean that remain relatively ice-free during winter, imparting significant physical and biological impact on the region. The North Water polynya (NOW) situated between Ellesmere Island and Greenland is the largest recurring Arctic polynya. Historically, the NOW forms every season when Arctic Ocean floes moving southward through Nares Strait become congested and form an ice arch that defines the northern border of the polynya. This blockage usually forms during winter and breaks down in spring. It is conjectured that the polynya is maintained by latent heat of fusion from the continuous formation of new ice as floes are swept southward from the ice arch by wind and ocean currents. Analysis of four decades of satellite imagery indicates a growing instability in the location of the ice arch, challenging previous models of polynya maintenance. A linear trend of the data indicates the number of days of Nares Strait blockage has decreased 2.1 days/year between 1979 and 2019 with wide interannual variations. Prior to 2007, ice arches blocked Nares Strait an average of 177 days/year compared to 128 days/year since that time. The overall trend of reduced ice arch duration is a contributing factor to the dramatic loss of multiyear ice in the Arctic basin.
Response of Near-Inertial Shear to Wind Stress Curl and Sea Level
Authors: Gao Jing , Wang Jianing , Wang Fan
Published: December 2019

Near-inertial waves (NIWs) contain a pronounced portion of shear energy in the internal wave field and is of great importance to deep ocean mixing. However, accurate simulation of NIWs remains a challenge. Here we analyzed 3-year long mooring observation of velocity profiles over 80–800 m to study the responses of near-inertial downward shear to varying wind stress curls and sea level anomalies (SLAs). It is demonstrated that moderate (even weak) cyclone makes more contributions to enhanced shear below the pycnocline than very strong cyclone. Because very strong curl can stall the downward propagation of large shear. The large positive and negative SLAs cause the accumulation of large shear in the lower and upper parts of the pycnocline through inducing downwelling and upwelling motions, respectively. Time variation of near-inertial shear was strongly influenced by cases of large curls and interannual variation of SLA, and thus did not follow the seasonal variation of wind stress. Our analyses suggest that matched fields of wind stress curl and SLA, and well representing the ocean response to moderate cyclone are needed in simulating the role of NIWs on mixing.
Acquisition of chopstick-operation skills with the non-dominant hand and concomitant changes in brain activity
Authors: Sawamura Daisuke , Sakuraba Satoshi , Suzuki Yumi , Asano Masako , Yoshida Susumu , Honke Toshihiro , Kimura Megumi , Iwase Yoshiaki , Horimoto Yoshitaka , Yoshida Kazuki , Sakai Shinya
Published: December 2019

Despite their common use as eating utensils in East Asia, chopsticks require complex fine motor-skills for adequate operation and are thus most frequently used with the dominant hand; however, the effect of training time on the proficiency of using chopsticks with the non-dominant hand, as well as the brain activity underlying changes in skill, remain unclear. This study characterised the effect of time spent training in chopstick operation with the non-dominant hand on chopstick-use proficiency and the related brain activity to obtain data that may help individuals who are obliged to change handedness due to neurological disease to learn to use their non-dominant hand in performing daily activities. Thirty-two healthy right-handed students were randomly allocated to training (n = 16) or control (n = 16) groups; the former received 6 weeks of training in chopstick use with their non-dominant (left) hand, and the latter received none. After training, significant improvements in the execution speed and smoothness of upper extremity joints were observed in the training group. Moreover, left dorsolateral prefrontal cortex activity significantly decreased, and bilateral premotor cortex activity significantly increased across training. These results indicated that 6 weeks of chopstick training with the non-dominant hand effectively improved chopstick operation.
Protein-bound uremic toxins are associated with cognitive function among patients undergoing maintenance hemodialysis
Authors: Lin Yi-Ting , Wu Ping-Hsun , Liang Shih-Shin , Mubanga Mwenya , Yang Yuan-Han , Hsu Ya-Ling , Kuo Mei-Chuan , Hwang Shang-Jyh , Kuo Po-Lin
Published: December 2019

Patients with chronic kidney disease have a greater risk of cognitive impairment. Cerebral uremic solute accumulation causes uremic encephalopathy; however, the association of protein-bound uremic toxins on cognitive function remains unclear. The present study aimed to investigate the association of two protein-bound uremic toxins, namely indoxyl sulfate (IS) and p-cresyl sulfate (PCS), on cognitive function in patients receiving hemodialysis (HD) for at least 90 days. Circulating free form IS and PCS were quantified by liquid chromatography/mass spectrometry. Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) were used to evaluate cognitive function. In total, 260 HD patients were recruited with a mean age of 58.1 ± 11.3 years, of which, 53.8% were men, 40% had diabetes, and 75.4% had hypertension. The analysis revealed that both free IS and free PCS were negatively associated with the CASI score and MMSE. After controlling for confounders, circulating free IS levels persisted to be negatively associated with MMSE scores [β = −0.62, 95% confidence interval (CI): −1.16 to −0.08] and CASI scores (β = −1.97, 95% CI: −3.78 to −0.16), mainly in the CASI domains of long-term memory, mental manipulation, language ability, and spatial construction. However, there was no correlation between free PCS and total MMSE or total CASI scores after controlling for confounders. In conclusion, circulating free form IS, but not PCS is associated with lower cognitive function test scores in HD patients. Thus, a further study is needed to evaluate whether a decrease in free IS levels can slow down cognitive decline in HD patients.
Antifouling strategies in advanced electrochemical sensors and biosensors
Authors: Lin Pei-Heng , Li Bor-Ran
Published: December 2019

A review presented recent development of antifouling strategies in electrochemical sensors and biosensors based on the modification methods.
A shear-thinning electrostatic hydrogel with antibacterial activity by nanoengineering of polyelectrolytes
Authors: Zhu Yanhui , Luo Qiaojie , Zhang Hongjie , Cai Qiuquan , Li Xiaodong , Shen Zhiquan , Zhu Weipu
Published: December 2019

Nanoengineering of polyelectrolytes was employed to prepare shear thinning electrostatic (STES) hydrogel by avoiding complex coacervate.
High mobility in α-phosphorene isostructures with low deformation potential
Authors: Fang Ruhao , Cui Xiangyuan , Stampfl Catherine , Ringer Simon P. , Zheng Rongkun
Published: December 2019

The exceptionally low deformation potential is proposed as the key determinant for the high carrier mobility in ten possible α-phosphorene isostructures.
Characterising absorption and health-related properties of phytochemicals extracted from Malaysian palm fruit biomass after oil extraction
Authors: Selby-Pham Sophie N. B. , Siow Lee Fong , Bennett Louise E.
Published: December 2019

After oil extraction, palm fruit biomass contains abundant water-soluble phytochemicals (PCs) with proven bioactivity in regulating oxidative stress and inflammation (OSI).
The effects of surfactant in the sol–gel synthesis of CuO/TiO2 nanocomposites on its photocatalytic activities under UV-visible and visible light illuminations
Authors: Ravishankar T. N. , Vaz M. de O. , Teixeira S. R.
Published: December 2019

Effective and low-cost CuO/TiO2 nanocomposites were prepared at room temperature by a surfactant-assisted sol–gel method for photocatalytic activities under UV-visible and visible light irradiations.
Oxygen vacancies confined in nickel oxide nanoprism arrays for promoted electrocatalytic water splitting
Authors: Zhang Xiaoshuang , Du Xiaoqiang
Published: December 2019

Experimental and DFT calculation results show that the presence of oxygen vacancies can decrease the adsorption energy of intermediates at active sites and facilitate the adsorption of intermediates, thus improving the catalytic properties.
Printable CsPbBr3 perovskite quantum dot ink for coffee ring-free fluorescent microarrays using inkjet printing
Authors: Gao Aijing , Yan Jia , Wang Zhaojin , Liu Pai , Wu Dan , Tang Xiaobing , Fang Fan , Ding Shihao , Li Xiang , Sun Jiayun , Cao Meijuan , Wang Liduo , Li Luhai , Wang Kai , Sun Xiao Wei
Published: December 2019

Printable perovskite quantum dot (QD) ink is very important for achieving high quality coffee ring-free fluorescent microarrays for different kinds of emerging perovskite optoelectronic applications using inkjet printing.
Molecular recognition with soft biomaterials
Authors: Clegg John R. , Peppas Nicholas A.
Published: December 2019

This review and critique provides fundamental considerations and practical suggestions for fabricating new polymeric biosensors, drug delivery vehicles, and scaffolds for tissue regeneration with tunable molecular recognition properties.
Introducing Tween-curcumin niosomes: preparation, characterization and microenvironment study
Authors: Sahu Anand Kumar , Mishra Jhili , Mishra Ashok Kumar
Published: December 2019

Curcumin induced micelle to vesicle transition in Tween surfactants and temperature induced vesicle to micelle degradation of Tween-curcumin vesicles.
Elucidating the mechanisms underlying PCBM enhancement of CH3NH3PbI3 perovskite solar cells using GIXRD and XAFS
Authors: Liu Bing , Cui Rongli , Huang Huan , Guo Xihong , Dong Jinquan , Yao Huanli , Li Ying , Zhao Dangui , Wang Jiahao , Zhang Jing , Chen Yu , Sun Baoyun
Published: December 2019

In this study, the stability mechanism of the optimized methyl ammonium lead triiodide (CH3NH3PbI3, MAPbI3)/[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) perovskite active layer upon exposure to moisture, light, and heating was investigated.
Surface passivation of perovskite thin films by phosphonium halides for efficient and stable solar cells
Authors: He Qingquan , Worku Michael , Xu Liangjin , Zhou Chenkun , Lteif Sandrine , Schlenoff Joseph B. , Ma Biwu
Published: December 2019

A new class of materials, phosphonium halide salts, are used as surface passivation agents for efficient and stable PSCs.
Recent advances in heparinization of polymeric membranes for enhanced continuous blood purification
Authors: Shan Liang , Sun Yunbo , Shan Feng , Li Li , Xu Zhi Ping
Published: December 2019

Heparinization of polymeric filtration membranes enhances antithrombogenicity and anti-fouling while maintaining the permeable property, increasing the membrane life time and reducing the patients’ economic burden.