bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of CS2 Absorption Cross-Sections in the 188–215 nm Region at Room Temperature and Atmospheric Pressure
Authors: Zhang Yungang , Wang Yongda , Liu Yunjie , Ai Xinyu , Zhang Zhiguo , Li Jimeng
Published: September 2020

Carbon disulfide, an important sulfur-containing species, has strong absorption lines in the wavelength range of 188 nm to 215 nm. It is difficult to accurately measure the absorption cross sections of carbon disulfide because carbon disulfide will be easily converted into carbon sulfide when it is exposed to ultraviolet light. In this study, the absorption cross sections of carbon disulfide were measured by reducing carbon disulfide conversion. The factors affecting carbon disulfide conversion, including gas flow rate, ultraviolet light intensity, and duration of illumination, were studied to reduce the conversion of carbon disulfide by controlling experimental conditions in the experiment. Finally, the absorption cross sections of carbon disulfide at room temperature and atmospheric pressure were calculated using the absorption spectrum and the carbon disulfide concentration in the absence of carbon disulfide conversion. The wavelengths of 16 absorption peaks on the carbon disulfide absorption cross sections of the vibration change were marked. Carbon disulfide has the maximum absorption cross section of 4.5 × 10–16 cm2/molecule at a wavelength of 198.10 nm.
Considerations for Continuing Semielective and Emergency Otolaryngological Procedures During the COVID-19 Pandemic
Authors: Mueller Sarina K. , Traxdorf Maximilian , Mantsopoulos Konstantinos , Gostian Antoniu-Oreste , Sievert Matti , Koch Michael , Huebner Matthias J. , Iro Heinrich
Published: September 2020

Introduction:

During the COVID-19 pandemic, worldwide over 600,000 human beings died due to the cause of the disease. In order to deescalate the transmission rate and to avoid crush loading the countries medical health systems social distancing, face masks, and lockdowns have been considered essential by the majority of governments. Whereas some countries have highly reduced or completely stopped otorhinolaryngological procedures, other countries have continued selected surgeries. The objective of this study was to analyze procedures and outcomes of continuing semielective and emergency surgeries during the COVID-19 pandemic.

Methods:

Retrospective analysis of n = 750 patients who received semi-elective or emergency surgery between March 26 and June 16, 2020, in the Otolaryngology Department of the Friedrich-Alexander-University of Erlangen-Nürnberg. All patients were screened for COVID symptoms and swabbed for SARS-CoV-2 prior to surgery.

Results:

Of the n = 750 patients, n = 699 patients received semielective surgery and n = 51 emergency surgery. For 27 patients, the swab result could not be awaited due to a life-threatening condition. In these cases, surgery was performed in full protective equipment. No patient was tested positive during or after the surgery (follow-up 45 to 127 days). No member of the medical personnel showed symptoms or was tested positive after contact with patients. Due to the continuation of surgeries, patients’ lives were saved and improvement of long-term quality-of-life and outcomes is anticipated.

Conclusions:

Continuing selected otorhinolaryngological surgeries is crucial for patients’ health, survival, and long-time quality of life, yet, the protection of the medical personnel has to be granted.
ADHD in Adolescents: Commentary on the Special Issue of Ripple Effects in Self-Perceptions and Social Relationships
Authors: Becker Stephen P.
Published: September 2020

Adolescence is a developmental period that affords both risk as well as enormous opportunity. Ripple effects can extend far and wide and speak to the nuance and complexity in understanding and treating ADHD during the adolescent period. The studies in this special issue provide novel and important insights into the lives of adolescents with ADHD, and they collectively point to important areas for both research and clinical attention. Further, each of the studies underscore the importance of soliciting the perspective of adolescents with ADHD. In this commentary, I consider the value of self-report when working with adolescents with ADHD, the possibility of a self-perception bias in youth with ADHD, challenges in assessing social functioning in adolescence, and implications for school-based assessments and interventions. For treatment specifically, I raise the possibility of a modular intervention approach for adolescents with ADHD and shared decision making that solicits and incorporates the adolescent perspective. The voices of adolescents with ADHD may be crucial for understanding how to lower risk, promote resilience, reduce stigma, and improve our assessments and interventions.
Cognitive stimulation therapy for dementia: Provision in National Health Service settings in England, Scotland and Wales
Authors: Holden Ellen , Stoner Charlotte R , Spector Aimee
Published: September 2020

Objectives: Cognitive stimulation therapy (CST) is a brief, non-pharmacological intervention for people with dementia, with an established evidence base for improving cognition and quality of life. It is widely implemented in National Health Service (NHS) settings, but little is known about its naturalistic use. The aim of this survey was to identify and explore inclusion criteria, dose and quality of CST across services in Great Britain (England, Scotland and Wales).Methods: All NHS memory clinics and services for people with dementia were contacted and asked to complete a mixed methods online survey on CST delivery in their service. Questions were centred on who provided CST, who received CST, the dose of CST and any outcomes that were routinely measured.Results: A total of 57/186 services responded, giving a response rate of 30.7%. While the majority reported offering CST (87.7%), there was variability in how this was delivered. Differing inclusion criteria included the use of varying cognitive and behavioural outcome measures, and CST was reported as being offered once and twice weekly. Services also differed in how they evaluated the quality of CST and how this evidence was incorporated for future sessions.Conclusion: While there was a low response rate, this survey indicates that there is significant variability in how CST is used in clinical practice, with many trusts not adhering to the evidence base. To ensure that people with dementia are consistently offered evidence-based, high-quality CST across NHS settings, further standardisation of inclusion criteria, dose and outcomes is needed.
Caring for a violent relative with severe mental illness: a qualitative study
Authors: Paradis-Gagné Etienne , Holmes Dave , Jacob Jean Daniel
Published: September 2020

Background:

According to the literature reviewed, although families living with a mentally ill relative often face violence, this issue has been little studied in nursing.

Methods:

We conducted a qualitative research study to explore the experience of families dealing with this complex reality. We adopted Jacques Donzelot’s theory of the government of family as our theoretical framework and used grounded theory as our research methodology. In total, 14 participants who had been victims of violence perpetrated by relatives with severe mental illness were interviewed.

Findings:

Qualitative analysis led to the identification of five themes: (a) medico-legal apparatus; (b) experience of violence; (c) the family’s responsibility toward the violent relative; (d) exclusion and stigmatisation; and (e) suffering and resilience. The present paper focuses on the study’s central theme: the family’s responsibility toward the violent relative.
Risk Assessment of Heavy Metal Concentrations in Sediments of Matang Mangrove Forest Reserve
Authors: Khan Waseem Razzaq , Zulkifli Syaizwan Zahmir , bin Mohamad Kasim Mohamad Roslan , Zimmer Martin , Pazi Ahmad Mustapha , Kamrudin Nur Amira , Rasheed Fahad , Zafar Zikria , Mostapa Roslan , Nazre M.
Published: September 2020

Matang Mangrove Forest Reserve (MMFR) is one of the most productive and managed forests in the world. On the other hand, it has become a concern whether MMFR is being degraded as a result of exposure to industrial pollution. Industries located around MMFR dispose effluents contaminated by heavy metals. This study was conducted to analyze heavy metal contamination and risk assessment status in MMFR sediments. Sediment samples from six compartments were collected based on age and location of the mangrove plantation. Total metal digestion and modified sequential extraction were performed to estimate the concentration of heavy metals. Based on the estimation, risk assessment code, geo-accumulation index, pollution load index, and contamination factor were computed to classify the compartments according to their contamination and pollution levels. Organic matter and sediment texture (silt, clay, and sand content) were also analyzed to find its correlation with heavy metals. According to the results, high concentrations for Copper, Nickel, and Cadmium were observed in Compartment 42, while Compartment 18 and Compartment 74 showed higher concentrations for Zinc and Lead. Heavy metals showed weak positive correlation with clay and silt, but weak negative correlation with sand. For organic matter, only Zinc showed statistically significant but weak negative correlation. Risk assessment code, geo-accumulation index, pollution load index, and contamination factor categorized the compartments into unpolluted to moderately polluted. Based on the study outcomes, it can be concluded that MMFR, although acquiring industrial discharge, is not with a high risk of heavy metal contamination.
International Migration amid a World in Crisis
Authors: Chamie Joseph
Published: September 2020

Executive Summary

This article comprehensively examines international migration trends and policies in light of the coronavirus disease 2019 (COVID-19) pandemic. It begins by reviewing migration developments throughout the past 60 years. It then examines pandemic-related migration trends and policies. It concludes with a series of general observations and insights that should guide local, national, regional, and international policymakers, moving forward. In particular, it proposes the following: National measures to combat COVID-19 should include international migrants, irrespective of their legal status, and should complement regional and international responses. Localities, nations, and the international community should prioritize the safe return and reintegration of migrants. States and international agencies should plan for the gradual re-emergence of large-scale migration based on traditional push and pull forces once a COVID-19 vaccine is widely available. States should redouble their efforts to reconcile national border security concerns and the basic human rights of migrants, refugees, and asylum seekers. States and the international community should accelerate their efforts to address climate-related migration. States of origin, transit, and destination should directly address the challenges of international migration and not minimize them.
Quantifying the streamflow response to groundwater abstractions for irrigation or drinking water at catchment scale using SWAT and SWAT–MODFLOW
Authors: Liu Wei , Park Seonggyu , Bailey Ryan T. , Molina-Navarro Eugenio , Andersen Hans Estrup , Thodsen Hans , Nielsen Anders , Jeppesen Erik , Jensen Jacob Skødt , Jensen Jacob Birk , Trolle Dennis
Published: September 2020

Background

Groundwater abstraction can cause a decline in the water table, and thereby affects surface streamflow connected to the aquifer, which may impair the sustainability of both the water resource itself and the ecosystem that it supports. To quantify the streamflow response to groundwater abstractions for either irrigation or drinking water at catchment scale and compared the performance of the widely used semi-distributed hydrological model SWAT and an recently integrated surface–subsurface model SWAT–MODFLOW, we applied both SWAT and SWAT–MODFLOW to a groundwater-dominated catchment in Denmark and tested a range of groundwater abstraction scenarios.

Results

To accommodate the study area characteristics, the SWAT–MODFLOW model complex was further developed to enable the Drain package and an auto-irrigation routine to be used. A PEST (parameter estimation by sequential testing)-based approach which enables simultaneous calibration of SWAT and MODFLOW parameters was developed to calibrate SWAT–MODFLOW. Both models demonstrated generally good statistical performance for the temporal pattern of streamflow, with better R2 and NSE (Nash–Sutcliffe efficiency) for SWAT–MODFLOW but slightly better PBIAS (percent bias) for SWAT. Both models indicated that drinking water abstractions caused some degree of streamflow depletion, while abstractions for returned irrigation led to a slight total flow increase, but may influence the hydrology outside the catchment. However, the streamflow decrease caused by drinking water abstractions simulated by SWAT was unrealistically low, and the streamflow increase caused by irrigation abstractions was exaggerated compared with SWAT–MODFLOW.

Conclusion

We conclude that the SWAT–MODFLOW model produces much more realistic signals relative to the SWAT model when quantifying the streamflow response to groundwater abstractions for irrigation or drinking water; hence, it has great potential to be a useful tool in the management of water resources in groundwater-dominated catchments. With further development of SWAT–MODFLOW and the PEST-based approach developed for its calibration, this study would broaden the SWAT–MODFLOW application and benefit catchment managers.
A LINE-1 insertion situated in the promoter of IMPG2 is associated with autosomal recessive progressive retinal atrophy in Lhasa Apso dogs
Authors: Hitti-Malin Rebekkah J. , Burmeister Louise M. , Ricketts Sally L. , Lewis Thomas W. , Pettitt Louise , Boursnell Mike , Schofield Ellen C. , Sargan David , Mellersh Cathryn S.
Published: September 2020

Background

Canine progressive retinal atrophies are a group of hereditary retinal degenerations in dogs characterised by depletion of photoreceptor cells in the retina, which ultimately leads to blindness. PRA in the Lhasa Apso (LA) dog has not previously been clinically characterised or described in the literature, but owners in the UK are advised to have their dog examined through the British Veterinary Association/ Kennel Club/ International Sheep Dog Society (BVA/KC/ISDS) eye scheme annually, and similar schemes that are in operation in other countries. After the exclusion of 25 previously reported canine retinal mutations in LA PRA-affected dogs, we sought to identify the genetic cause of PRA in this breed.

Results

Analysis of whole-exome sequencing data of three PRA-affected LA and three LA without signs of PRA did not identify any exonic or splice site variants, suggesting the causal variant was non-exonic. We subsequently undertook a genome-wide association study (GWAS), which identified a 1.3 Mb disease-associated region on canine chromosome 33, followed by whole-genome sequencing analysis that revealed a long interspersed element-1 (LINE-1) insertion upstream of the IMPG2 gene. IMPG2 has previously been implicated in human retinal disease; however, until now no canine PRAs have been associated with this gene. The identification of this PRA-associated variant has enabled the development of a DNA test for this form of PRA in the breed, here termed PRA4 to distinguish it from other forms of PRA described in other breeds. This test has been used to determine the genotypes of over 900 LA dogs. A large cohort of genotyped dogs was used to estimate the allele frequency as between 0.07–0.1 in the UK LA population.

Conclusions

Through the use of GWAS and subsequent sequencing of a PRA case, we have identified a LINE-1 insertion in the retinal candidate gene IMPG2 that is associated with a form of PRA in the LA dog. Validation of this variant in 447 dogs of 123 breeds determined it was private to LA dogs. We envisage that, over time, the developed DNA test will offer breeders the opportunity to avoid producing dogs affected with this form of PRA.
An RTM-GWAS procedure reveals the QTL alleles and candidate genes for three yield-related traits in upland cotton
Authors: Su Junji , Wang Caixiang , Ma Qi , Zhang Ai , Shi Chunhui , Liu Juanjuan , Zhang Xianliang , Yang Delong , Ma Xiongfeng
Published: September 2020

Background

Cotton (Gossypium spp.) fiber yield is one of the key target traits, and improved fiber yield has always been thought of as an important objective in the breeding programs and production. Although some studies had been reported for the understanding of genetic bases for cotton yield-related traits, the detected quantitative trait loci (QTL) for the traits is still very limited. To uncover the whole-genome QTL controlling three yield-related traits in upland cotton (Gossypium hirsutum L.), phenotypic traits were investigated under four planting environments and 9244 single-nucleotide polymorphism linkage disequilibrium block (SNPLDB) markers were developed in an association panel consisting of 315 accessions.

Results

A total of 53, 70 and 68 significant SNPLDB loci associated with boll number (BN), boll weight (BW) and lint percentage (LP), were respectively detected through a restricted two-stage multi-locus multi-allele genome-wide association study (RTM-GWAS) procedure in multiple environments. The haplotype/allele effects of the significant SNPLDB loci were estimated and the QTL-allele matrices were organized for offering the abbreviated genetic composition of the population. Among the significant SNPLDB loci, six of them were simultaneously identified in two or more single planting environments and were thought of as the stable SNPLDB loci. Additionally, a total of 115 genes were annotated in the nearby regions of the six stable SNPLDB loci, and 16 common potential candidate genes controlling target traits of them were predicted by two RNA-seq data. One of 16 genes (GH_D06G2161) was mainly expressed in the early ovule-development stages, and the stable SNPLDB locus (LDB_19_62926589) was mapped in its promoter region.

Conclusion

This study identified the QTL alleles and candidate genes that could provide important insights into the genetic basis of yield-related traits in upland cotton and might facilitate breeding cotton varieties with high yield.
The application of CRISPR/Cas9 in hairy roots to explore the functions of AhNFR1 and AhNFR5 genes during peanut nodulation
Authors: Shu Hongmei , Luo Ziliang , Peng Ze , Wang Jianping
Published: September 2020

Background

Peanut is an important legume crop growing worldwide. With the published allotetraploid genomes, further functional studies of the genes in peanut are very critical for crop improvement. CRISPR/Cas9 system is emerging as a robust tool for gene functional study and crop improvement, which haven’t been extensively utilized in peanut yet. Peanut plant forms root nodules to fix nitrogen through a symbiotic relationship with rhizobia. In model legumes, the response of plants to rhizobia is initiated by Nod factor receptors (NFRs). However, information about the function of NFRs in peanut is still limited. In this study, we applied the CRISPR/Cas9 tool in peanut hairy root transformation system to explore the function of NFR genes.

Results

We firstly identified four AhNFR1 genes and two AhNFR5 genes in cultivated peanut (Tifrunner). The gene expression analysis showed that the two AhNFR1 and two AhNFR5 genes had high expression levels in nodulating (Nod+) line E5 compared with non-nodulating (Nod-) line E4 during the process of nodule formation, suggesting their roles in peanut nodulation. To further explore their functions in peanut nodulation, we applied CRISPR technology to create knock-out mutants of AhNFR1 and AhNFR5 genes using hairy root transformation system. The sequencing of these genes in transgenic hairy roots showed that the selected AhNFR1 and AhNFR5 genes were successfully edited by the CRISPR system, demonstrating its efficacy for targeted mutation in allotetraploid peanut. The mutants with editing in the two AhNFR5 genes showed Nod- phenotype, whereas mutants with editing in the two selected AhNFR1 genes could still form nodules after rhizobia inoculation.

Conclusions

This study showed that CRISPR-Cas9 could be used in peanut hairy root transformation system for peanut functional genomic studies, specifically on the gene function in roots. By using CRISPR-Cas9 targeting peanut AhNFR genes in hairy root transformation system, we validated the function of AhNFR5 genes in nodule formation in peanut.
Maternal sciatic nerve administered bupivacaine induces hippocampal cell apoptosis in offspring
Authors: Mirkheshti Alireza , Shakeri Alireza , Memary Elham , Baniasadi Mansoureh , Zaringhalam Jalal , Tajbakhsh Ardeshir , Mirzaei Marzieh , Lak Elena
Published: September 2020

Background

Bupivacaine, an amid-type local anesthetic, is widely used for clinical patients especially in pregnant women. In addition to neurotoxicity effect of bupivacaine, it can cross the placenta, accumulates in this tissue and retained in fetal tissues. Nevertheless, whether bupivacaine can cause neurotoxicity in fetus remains unclear. Hence, this study was design to investigate the effects of maternal bupivacaine use on fetus hippocampal cell apoptosis and the possible related mechanism.

Methods

On day 15 of pregnancy, sciatic nerve of pregnant wistar rat (180–200 g) were exposed by lateral incision of the right thigh and 0.2 ml of bupivacaine was injected. After their delivery, we randomly selected one male offspring of every mother. On day 30 after of their birth, the rat’s hippocampi were isolated for molecular studies. Western blotting was used to examine the expression of cleaved caspase-3, caspase-8 and p-Akt in fetal hippocampus.

Results

Our results showed that maternal bupivacaine use caused a significant increment of cleaved caspase-3 and caspase-8 expression in fetal hippocampus compared with the sham group. In addition, maternally administered bupivacaine could significantly decrease hippocampal P.Akt/T.Akt ratio which was concurrent with an increment of cleaved caspase-3 and caspase-8 expression.

Conclusion

Our data suggest that maternal bupivacaine use increases fetal hippocampal cell apoptosis markers such as caspase 8 and cleaved caspase 3, at least in part, via inhibiting the Akt activation.
Effect of sedation with dexmedetomidine or propofol on gastrointestinal motility in lipopolysaccharide-induced endotoxemic mice
Authors: Chang Haiqing , Li Shuang , Li Yansong , Hu Hao , Cheng Bo , Miao Jiwen , Gao Hui , Ma Hongli , Gao Yanfeng , Wang Qiang
Published: September 2020

Background

Sepsis often accompanies gastrointestinal motility disorder that contributes to the development of sepsis in turn. Propofol and dexmedetomidine, as widely used sedatives in patients with sepsis, are likely to depress gastrointestinal peristalsis. We queried whether propofol or dexmedetomidine, at sedative doses, aggravated sepsis-induced ileus.

Methods

Sedative/Anesthetic Scores and vital signs of lipopolysaccharide (LPS)-induced endotoxemic mice were measured during sedation with propofol or dexmedetomidine. Endotoxemic mice were divided into 10% fat emulsion, propofol, saline, and dexmedetomidine group. The gastric emptying, small intestinal transit, tests of colonic motility, gastrointestinal transit and whole gut transit were evaluated at 15 mins and 24 h after intraperitoneal injection of sedatives/vehicles respectively.

Results

40 mg·kg− 1propofol and 80 μg·kg− 1 dexmedetomidine induced a similar depth of sedation with comparable vital signs except that dexmedetomidine strikingly decreased heart rate in endotoxemic mice. Dexmedetomidine markedly inhibited gastric emptying (P = 0.006), small intestinal transit (P = 0.006), colonic transit (P = 0.0006), gastrointestinal transit (P = 0.0001) and the whole gut transit (P = 0.034) compared with the vehicle, whereas propofol showed no depression on all parts of gastrointestinal motility 15 mins after administration. The inhibitive effects of dexmedetomidine in these tests vanished 24 h after the administration.

Conclusions

Deep sedation with dexmedetomidine, but not propofol, significantly inhibited gastrointestinal peristalsis in endotoxemic mice while the inhibitory effect disappeared 24 h after sedation. These data suggested that both propofol and dexmedetomidine could be applied in septic patients while dexmedetomidine should be used cautiously in patients with cardiac disease or ileus.
Suitability of administrative claims databases for bariatric surgery research – is the glass half-full or half-empty?
Authors: Li Xiaojuan , Lewis Kristina H. , Callaway Katherine , Wharam J. Frank , Toh Sengwee
Published: September 2020

Background

Claims databases are generally considered inadequate for obesity research due to suboptimal capture of body mass index (BMI) measurements. This might not be true for bariatric surgery because of reimbursement requirements and changes in coding systems. We assessed the availability and validity of claims-based weight-related diagnosis codes among bariatric surgery patients.

Methods

We identified three nested retrospective cohorts of adult bariatric surgery patients who underwent adjusted gastric banding, Roux-en-Y gastric bypass, or sleeve gastrectomy between January 1, 2011 and June 30, 2018 using different components of OptumLabs® Data Warehouse, which contains linked de-identified claims and electronic health records (EHRs). We measured the availability of claims-based weight-related diagnosis codes in the 6-month preoperative and 1-year postoperative periods in the main cohort identified in the claims data. We created two claims-based algorithms to classify the presence of severe obesity (a commonly used cohort selection criterion) and categorize BMI (a commonly used baseline confounder or postoperative outcome). We evaluated their performance by estimating sensitivity, specificity, positive predictive value, negative predictive value, and weighted kappa in two sub-cohorts using EHR-based BMI measurements as the reference.

Results

Among the 29,357 eligible patients identified using claims only, 28,828 (98.2%) had preoperative weight-related diagnosis codes, either granular indicating BMI ranges or nonspecific denoting obesity status. Among the 27,407 patients with granular preoperative codes, 12,346 (45.0%) had granular codes and 9355 (34.1%) had nonspecific codes in the 1-year postoperative period. Among the 3045 patients with both preoperative claims-based diagnosis codes and EHR-based BMI measurements, the severe obesity classification algorithm had a sensitivity 100%, specificity 71%, positive predictive value 100%, and negative predictive value 78%. The BMI categorization algorithm had good validity categorizing the last available preoperative or postoperative BMI measurements (weighted kappa [95% confidence interval]: preoperative 0.78, [0.76, 0.79]; postoperative 0.84, [0.80, 0.87]).

Conclusions

Claims-based weight-related diagnosis codes had excellent validity before and after bariatric surgical operation but suboptimal availability after operation. Claims databases can be used for bariatric surgery studies of non-weight-related effectiveness and safety outcomes that are well-captured.
The protocol of a clinical quality registry for dementia and mild cognitive impairment (MCI): the Australian dementia network (ADNeT) Registry
Authors: Lin Xiaoping , Wallis Kasey , Ward Stephanie A. , Brodaty Henry , Sachdev Perminder S. , Naismith Sharon L. , Krysinska Karolina , McNeil John , Rowe Christopher C. , Ahern Susannah
Published: September 2020

Background

Dementia was identified as a priority area for the development of a Clinical Quality Registry (CQR) in Australia in 2016. The Australian Dementia Network (ADNeT) Registry is being established as part of the ADNeT initiative, with the primary objective of collecting data to monitor and enhance the quality of care and patient outcomes for people diagnosed with either dementia or Mild Cognitive Impairment (MCI). A secondary aim is to facilitate the recruitment of participants into dementia research and trials. This paper describes the Registry protocol.

Methods

The ADNeT Registry is a prospective CQR of patients newly diagnosed with either dementia or MCI. Eligible patients will be identified initially from memory clinics and individual medical specialists (e.g., geriatricians, psychiatrists and neurologists) involved in the diagnosis of dementia. Participants will be recruited using either an opt-out approach or waiver of consent based on three key determinants (capacity, person responsible, and communication of diagnosis). Data will be collected from four sources: participating sites, registry participants, carers, and linkage with administrative datasets. It is anticipated that the Registry will recruit approximately 10,000 participants by the end of 2023. The ADNeT registry will be developed and implemented to comply with the national operating principles for CQRs and governed by the ADNeT Registry Steering Committee.

Discussion

The ADNeT Registry will provide important data on current clinical practice in the diagnosis, treatment and care of people with dementia and MCI in Australia as well as long-term outcomes among these people. These data will help to identify variations in clinical practice and patient outcomes and reasons underlying these variations, which in turn, will inform the development of interventions to improve care and outcomes for people with dementia and MCI.
Spatio-temporal impact of self-financed rotavirus vaccination on rotavirus and acute gastroenteritis hospitalisations in the Valencia region, Spain
Authors: López-Lacort Mónica , Orrico-Sánchez Alejandro , Martínez-Beneito Miguel Ángel , Muñoz-Quiles Cintia , Díez-Domingo Javier
Published: September 2020

Background

Several studies have shown a substantial impact of Rotavirus (RV) vaccination on the burden of RV and all-cause acute gastroenteritis (AGE). However, the results of most impact studies could be confused by a dynamic and complex space-time process. Therefore, there is a need to analyse the impact of RV vaccination on RV and AGE hospitalisations in a space-time framework to detect geographical-time patterns while avoiding the potential confusion caused by population inequalities in the impact estimations.

Methods

A retrospective population-based study using real-world data from the Valencia Region was performed among children aged less than 3 years old in the period 2005–2016. A Bayesian spatio-temporal model was constructed to analyse RV and AGE hospitalisations and to estimate the vaccination impact measured in averted hospitalisations.

Results

We found important spatio-temporal patterns in RV and AGE hospitalisations, RV vaccination coverage and in their associated adverted hospitalisations. Overall, ~ 1866 hospital admissions for RV were averted by RV vaccination during 2007–2016. Despite the low-medium vaccine coverage (~ 50%) in 2015–2016, relevant 36 and 20% reductions were estimated in RV and AGE hospitalisations respectively.

Conclusions

The introduction of the RV vaccines has substantially reduced the number of RV hospitalisations, averting ~ 1866 admissions during 2007–2016 which were space and time dependent. This study improves the methodologies commonly used to estimate the RV vaccine impact and their interpretation.
Histological diagnosis of immune checkpoint inhibitor induced acute renal injury in patients with metastatic melanoma: a retrospective case series report
Authors: Hultin Sebastian , Nahar Kazi , Menzies Alexander M. , Long Georgina V. , Fernando Suran L. , Atkinson Victoria , Cebon Jonathan , Wong Muh Geot
Published: September 2020

Background

Immune checkpoint inhibitors (ICI) have become the standard of care in many oncological conditions but are associated with a spectrum of renal immune-related adverse events (IrAEs). We aimed to describe the spectrum, histology, management and outcomes of renal IrAE in patients with metastatic melanoma undergoing ICI therapy.

Methods

We conducted a retrospective review of 23 patients with a diagnosis of metastatic melanoma treated with ICI between January 2017 and April 2019 who developed a renal IrAE. Baseline demographic data, biochemical and histopathological results, management and outcomes were analyzed.

Results

The majority of patients who developed renal irAE were male and received combination immunotherapy. The median time of onset from initiation of ICI therapy to renal IrAE was 4 months. 52% of the treated renal IrAE had histopathologically confirmed renal IrAE. The most common histological pattern of injury was acute tubulo-interstitial nephritis (92%). One patient developed anti-GBM disease with non-dialysis dependent stage 5 CKD. In tubulointerstitial injury, there was no association between peak creatinine, renal recovery and histologically reported inflammation or fibrosis. Patients with renal IrAE demonstrated persisting renal dysfunction at 3, 6 and 12 months with a mean baseline, 3 and 12 month creatinine of 90.0 μmol/L, 127.0 μmol/L and 107.5 μmol/L respectively.

Conclusion

Renal IrAE is most commonly attributable to steroid responsive acute tubulointerstitial nephritis. The outcome of rarer pathologies such as anti-GBM disease may be adversely affected by a delayed diagnosis. There is persisting renal dysfunction following an episode of renal IrAE that may have impact on future renal and overall survival outcomes.
IgM nephropathy complicated by cerebral venous sinus thrombosis: a case study
Authors: Downie Elizabeth , Diep Jason , Sungala Nagendraprasad , Wong Jeffrey
Published: September 2020

Background

IgM nephropathy is a rare disease with variable clinical presentations and is an unusual cause of nephrotic syndrome. Histopathological findings typically include mesangial hypercellularity with IgM and complement deposition, though the spectrum may range from normal glomeruli through to focal and segmental glomerulosclerosis. Thromboembolism is a well recognised complication of nephrotic syndrome, but cerebral venous sinus thrombosis is rarely described.

Case presentation

This is the case of a 23-year-old male presenting with the nephrotic syndrome, whose initial renal biopsy was consistent with minimal change disease. Complete remission was achieved with prednisone, however multiple relapses and steroid dependence prompted re-biopsy, the results of which were more consistent with IgM nephropathy. His last relapse was complicated by cerebral venous sinus thrombosis. He then received rituximab and a weaning course of prednisone to again enter remission.

Conclusions

This case highlights the need to consider IgM nephropathy in the differential diagnosis of nephrotic syndrome. Additionally, it emphasises the risk of thrombosis in patients with severe nephrosis.
A rare case of anti-LGI1 limbic encephalitis with concomitant positive NMDAR antibodies
Authors: Ji Tuo , Huang Zhi , Lian Yajun , Wang Chengze , Zhang Qiaoman , Li Jinghong
Published: September 2020

Background

N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) antibodies define the most prevalently recognized autoimmune encephalitis syndromes, while the simultaneous occurrence of both conditions has hardly been published before.

Case presentation

We report the case of a 67-year-old patient who presented with generalized tonic–clonic seizures (GTCS) followed by behavioral changes, psychosis, sleep disorders, decreased consciousness, and faciobrachial dystonic seizures. Ancillary findings included serum hyponatremia and imaging evidence of high-intensity lesions within bilateral medial temporal lobes on T2-weighted fluid attenuation inversion recovery. Both LGI1 and NMDAR antibodies were positive in serum and cerebral spinal fluid using transfected cell based assays. Despite prominent clinical features of anti-LGI1 limbic encephalitis (LGI1-LE), the patient also exhibited overlapping symptoms of anti-NMDAR encephalitis, like early-onset GTCS, which might be related to the concomitant positive NMDAR antibodies.

Conclusions

We report a rare case of LGI1-LE with overlapping symptoms and simultaneous positive NMDAR antibodies. It is necessary to evaluate the presence of NMDAR antibodies in certain LGI1-LE patients with unusual symptoms. However, caution should be exercised in interpreting the observation, given the fact of a single-case study.
First trimester anomaly scan using virtual reality (VR FETUS study): study protocol for a randomized clinical trial
Authors: Pietersma C. S. , Mulders A. G. M. G. J. , Moolenaar L. M. , Hunink M. G. M. , Koning A. H. J. , Willemsen S. P. , Go A. T. J. I. , Steegers E. A. P. , Rousian M.
Published: September 2020

Background

In recent years it has become clear that fetal anomalies can already be detected at the end of the first trimester of pregnancy by two-dimensional (2D) ultrasound. This is why increasingly in developed countries the first trimester anomaly scan is being offered as part of standard care. We have developed a Virtual Reality (VR) approach to improve the diagnostic abilities of 2D ultrasound. Three-dimensional (3D) ultrasound datasets are used in VR assessment, enabling real depth perception and unique interaction. The aim of this study is to investigate whether first trimester 3D VR ultrasound is of additional value in terms of diagnostic accuracy for the detection of fetal anomalies. Health-related quality of life, cost-effectiveness and also the perspective of both patient and ultrasonographer on the 3D VR modality will be studied.

Methods

Women in the first trimester of a high risk pregnancy for a fetus with a congenital anomaly are eligible for inclusion. This is a randomized controlled trial with two intervention arms. The control group receives ‘care as usual’: a second trimester 2D advanced ultrasound examination. The intervention group will undergo an additional first trimester 2D and 3D VR ultrasound examination. Following each examination participants will fill in validated questionnaires evaluating their quality of life and healthcare related expenses. Participants’ and ultrasonographers’ perspectives on the 3D VR ultrasound will be surveyed. The primary outcome will be the detection of fetal anomalies. The additional first trimester 3D VR ultrasound examination will be compared to ‘care as usual’. Neonatal or histopathological examinations are considered the gold standard for the detection of congenital anomalies. To reach statistical significance and 80% power with a detection rate of 65% for second trimester ultrasound examination and 70% for the combined detection of first trimester 3D VR and second trimester ultrasound examination, a sample size of 2800 participants is needed.

Discussion

First trimester 3D VR detection of fetal anomalies may improve patients’ quality of life through reassurance or earlier identification of malformations. Results of this study will provide policymakers and healthcare professionals with the highest level of evidence for cost-effectiveness of first trimester ultrasound using a 3D VR approach.

Trial registration

Dutch Trial Registration number NTR6309, date of registration 26 January 2017.
Measurement of maternal functioning during pregnancy and postpartum: findings from the cross-sectional WHO pilot study in Jamaica, Kenya, and Malawi
Authors: Cresswell Jenny A. , Barbour Kelli D. , Chou Doris , McCaw-Binns Affette , Filippi Veronique , Cecatti Jose Guilherme , Barreix Maria , Petzold Max , Kostanjsek Nenad , Cottler-Casanova Sara , Say Lale
Published: September 2020

Background

The World Health Organization’s definition of maternal morbidity refers to “a negative impact on the woman’s wellbeing and/or functioning”. Many studies have documented the, mostly negative, effects of maternal ill-health on functioning. Although conceptually important, measurement of functioning remains underdeveloped, and the best way to measure functioning in pregnant and postpartum populations is unknown.

Methods

A cross-sectional study among women presenting for antenatal (N = 750) and postpartum (N = 740) care in Jamaica, Kenya and Malawi took place in 2015–2016. Functioning was measured through the World Health Organization Disability Assessment Schedule (WHODAS-12). Data on health conditions and socio-demographic characteristics were collected through structured interview, medical record review, and clinical examination. This paper presents descriptive data on the distribution of functioning status among pregnant and postpartum women and examines the relationship between functioning and health conditions.

Results

Women attending antenatal care had a lower level of functioning than those attending postpartum care. Women with a health condition or associated demographic risk factor were more likely to have a lower level of functioning than those with no health condition. However, the absolute difference in functioning scores typically remained modest.

Conclusions

Functioning is an important concept which integrates a woman-centered approach to examining how a health condition affects her life, and ultimately her return to functioning after delivery. However, the WHODAS-12 may not be the optimal tool for use in this population and additional components to capture pregnancy-specific issues may be needed. Challenges remain in how to integrate functioning outcomes into routine maternal healthcare at-scale and across diverse settings.
Bayesian copy number detection and association in large-scale studies
Authors: Cristiano Stephen , McKean David , Carey Jacob , Bracci Paige , Brennan Paul , Chou Michael , Du Mengmeng , Gallinger Steven , Goggins Michael G. , Hassan Manal M. , Hung Rayjean J. , Kurtz Robert C. , Li Donghui , Lu Lingeng , Neale Rachel , Olson Sara , Petersen Gloria , Rabe Kari G. , Fu Jack , Risch Harvey , Rosner Gary L. , Ruczinski Ingo , Klein Alison P. , Scharpf Robert B.
Published: September 2020

Background

Germline copy number variants (CNVs) increase risk for many diseases, yet detection of CNVs and quantifying their contribution to disease risk in large-scale studies is challenging due to biological and technical sources of heterogeneity that vary across the genome within and between samples.

Methods

We developed an approach called CNPBayes to identify latent batch effects in genome-wide association studies involving copy number, to provide probabilistic estimates of integer copy number across the estimated batches, and to fully integrate the copy number uncertainty in the association model for disease.

Results

Applying a hidden Markov model (HMM) to identify CNVs in a large multi-site Pancreatic Cancer Case Control study (PanC4) of 7598 participants, we found CNV inference was highly sensitive to technical noise that varied appreciably among participants. Applying CNPBayes to this dataset, we found that the major sources of technical variation were linked to sample processing by the centralized laboratory and not the individual study sites. Modeling the latent batch effects at each CNV region hierarchically, we developed probabilistic estimates of copy number that were directly incorporated in a Bayesian regression model for pancreatic cancer risk. Candidate associations aided by this approach include deletions of 8q24 near regulatory elements of the tumor oncogene MYC and of Tumor Suppressor Candidate 3 (TUSC3).

Conclusions

Laboratory effects may not account for the major sources of technical variation in genome-wide association studies. This study provides a robust Bayesian inferential framework for identifying latent batch effects, estimating copy number, and evaluating the role of copy number in heritable diseases.
Identification of a novel subgroup of endometrial cancer patients with loss of thyroid hormone receptor beta expression and improved survival
Authors: Piqué Daniel G. , Greally John M. , Mar Jessica C.
Published: September 2020

Background

Endometrial cancer (EC) is the most common gynecologic cancer in women, and the incidence of EC has increased by about 1% per year in the U. S over the last 10 years. Although 5-year survival rates for early-stage EC are around 80%, certain subtypes of EC that lose nuclear hormone receptor (NHR) expression are associated with poor survival rates. For example, estrogen receptor (ER)-negative EC typically harbors a worse prognosis compared to ER-positive EC. The molecular basis for the loss of NHR expression in endometrial tumors and its contribution to poor survival is largely unknown. Furthermore, there are no tools to systematically identify tumors that lose NHR mRNA expression relative to normal tissue. The development of such an approach could identify sets of NHR-based biomarkers for classifying patients into subgroups with poor survival outcomes.

Methods

Here, a new computational method, termedreceptLoss, was developed for identifying NHR expression loss in endometrial cancer relative to adjacent normal tissue. When applied to gene expression data from The Cancer Genome Atlas (TCGA),receptLossidentified 6 NHRs that were highly expressed in normal tissue and exhibited expression loss in a subset of endometrial tumors.

Results

Three of the six identified NHRs – estrogen, progesterone, and androgen receptors – that are known to lose expression in ECs were correctly identified byreceptLoss. Additionally, a novel association was found between thyroid hormone receptor beta (THRB) expression loss, increased expression of miRNA-146a, and increased rates of 5-year survival in the EC TCGA patient cohort.THRBexpression loss occurs independently of estrogen and progesterone expression loss, suggesting the discovery of a distinct, clinically-relevant molecular subgroup.

Conclusion

ReceptLossis a novel, open-source software tool to systematically identify NHR expression loss in cancer. The application ofreceptLossto endometrial cancer gene expression data identifiedTHRB, a previously undescribed biomarker of survival in endometrial cancer. ApplyingreceptLossto expression data from additional cancer types could lead to the development of biomarkers of disease progression for patients with any other tumor type.ReceptLosscan be applied to expression data from additional cancer types with the goal of identifying biomarkers of differential survival.