bluuebunny/crossref_metadata_2025 huggingface dataset:
Residential aged care homes: Why do they call ‘000’? A study of the emergency prehospital care of older people living in residential aged care homes
Authors: Dwyer Rosamond A , Gabbe Belinda J , Tran Thach , Smith Karen , Lowthian Judy A
Published: October 2020

Objective

To describe the clinical characteristics, medical interventions and patterns of ambulance service use related to the emergency, prehospital care of older people living in residential aged care (RAC) homes.

Methods

Retrospective cohort study using secondary analyses of routinely collected clinical and administrative data from Ambulance Victoria and population data from the Australian Bureau of Statistics for the state of Victoria, Australia. Participants included people aged 65 years and over, attended by emergency ambulances from 2008 to 2013, with data captured in the Ambulance Victoria electronic record.

Results

The mean (standard deviation) age of RAC residents attended by emergency ambulance was 85 (7.3) years and 63% were women. Common comorbidities included dementia (32.7%), ischaemic heart disease (27.7%) and osteoarthritis (24.6%). Polypharmacy was prevalent with 70% currently prescribed antibiotics, over 20% prescribed sedatives and a further 14.9% antipsychotics. Fifteen percent of attendances were for falls, which were more frequent among women than men. Other common reasons for ambulance call‐out included uncontrolled pain, respiratory tract infection, non‐specific febrile illness and altered conscious state. Almost 90% of people were transported to hospital from the RAC, with just over half of call‐outs occurring out‐of‐hours.

Conclusion

This is the first study to describe emergency prehospital care, case‐mix and intervention of frail, older people living in RAC. These results demonstrate a clinically complex group of people with high rates of comorbidity, cognitive impairment and polypharmacy. These valuable data will inform education and training of prehospital clinicians, assist in targeting preventative medicine and primary care programmes and further development of alternate, acute and emergency care pathways for this unique patient group.
Novel coronavirus disease in patients with end‐stage kidney disease
Authors: Shimada Noriaki , Shimada Hiroaki , Itaya Yoshiaki , Tomino Yasuhiko
Published: October 2020

The novel coronavirus disease outbreak started in Wuhan, China, in December 2019 and has since spread rapidly worldwide. As almost all patients with end‐stage kidney disease have been treated with HD in Japan, they have a higher risk of infection than the healthy population. Moreover, the complications of renal failure, such as hypertension and cardiovascular diseases, appear to be a risk factor of death owing to novel coronavirus disease. The reported morbidity and mortality rates of novel coronavirus disease are significantly higher in dialysis patients than in the healthy population. No treatment for novel coronavirus disease has yet been developed; thus, countermeasures to prevent the spread of coronavirus disease in dialysis facilities must be rapidly established. The latest findings on novel coronavirus disease in patients with end‐stage kidney disease and the guidelines for countermeasures against the spread of novel coronavirus disease worldwide are summarized in this review.
Parametric Insurance for Solar Geoengineering: Insights from the Pacific Catastrophe Risk Assessment and Financing Initiative
Authors: Horton Joshua B. , Lefale Penehuro , Keith David
Published: October 2020

Solar geoengineering (SG) entails using technology to modify the Earth's radiative balance to offset some of the climate changes caused by long‐lived greenhouse gases. Parametric insurance, which delivers payouts when specific physical indices (such as wind speed) cross predefined thresholds, was recently proposed by two of us as a compensation mechanism for SG with the potential to ease disagreements about the technology and to facilitate cooperative deployment; we refer to this proposal as reduced‐rate climate risk insurance for solar geoengineering, or ‘RCG’. Here we probe the plausibility of RCG by exploring the Pacific Catastrophe Risk Assessment and Financing Initiative (PCRAFI), a sovereign risk pool providing parametric insurance coverage against tropical cyclones and earthquakes/tsunamis to Pacific island countries since 2013. Tracing the history of PCRAFI and considering regional views on insurance as compensation necessitates reconfiguring RCG in a way that shifts the focus away from bargaining between developed and developing countries toward bargaining among developed countries. This revised version of RCG is challenged by an assumption of broad developed country support for sovereign climate insurance in the developing world, but it also better reflects the underlying incentive structure and distribution of power.
Elevated miR‐124‐3p in the aging colon disrupts mucus barrier and increases susceptibility to colitis by targeting T‐synthase
Authors: Huang Li , Sun Ting‐yi , Hu Liang‐jun , Hu Shi‐long , Sun Hai‐mei , Zhao Fu‐qian , Wu Bo , Yang Shu , Ji Feng‐qing , Zhou De‐shan
Published: October 2020

The risk of colitis and colorectal cancer increases markedly throughout adult life, endangering the health and lives of elderly individuals. Previous studies have proposed that bacterial translocation and infection are the main risk factors for these diseases. Therefore, in the present study, we aimed to identify the underlying mechanism by focusing on the mucus barrier function and mucin‐type O‐glycosylation. We evaluated alterations in the colon mucus layer in 2‐, 16‐, and 24‐month‐old mice and aged humans. Aged colons showed defective intestinal mucosal barrier and changed mucus properties. The miR‐124‐3p expression level was significantly increased in the aged distal colonic mucosa, which was accompanied by an increase in pathogens and bacterial translocation. Meanwhile, T‐synthase, the rate‐limiting enzyme in O‐glycosylation, displayed an age‐related decline in protein expression. Further experiments indicated that miR‐124‐3p modulated O‐glycosylation by directly targeting T‐synthase. Moreover, young mice overexpressing miR‐124‐3p exhibited abnormal glycosylation, early‐onset, and more severe colitis. These data suggest that miR‐124‐3p predisposes to senile colitis by reducing T‐synthase, and the miR‐124‐3p/T‐synthase/O‐glycans axis plays an essential role in maintaining the physiochemical properties of colonic mucus and intestinal homeostasis.
Understanding people’s responses toward predators in the Indian Himalaya
Authors: Bhatia S. , Suryawanshi K. , Redpath S. M. , Mishra C.
Published: October 2020

Research on human–wildlife interactions has largely focused on the magnitude of wildlife‐caused damage, and the patterns and correlates of human attitudes and behaviors. We assessed the role of five pathways through which various correlates potentially influence human responses toward wild animals, namely, value orientation, social interactions (i.e. social cohesion and support), dependence on resources such as agriculture and livestock, risk perception and nature of interaction with the wild animal. We specifically evaluated their influence on people’s responses toward two large carnivores, the snow leopard Panthera uncia and the wolf Canis lupus in an agropastoral landscape in the Indian Trans‐Himalaya. We found that the nature of the interaction (location, impact and length of time since an encounter or depredation event), and risk perception (cognitive and affective evaluation of the threat posed by the animal) had a significant influence on attitudes and behaviors toward the snow leopard. For wolves, risk perception and social interactions (the relationship of people with local institutions and inter‐community dynamics) were significant. Our findings underscore the importance of interventions that reduce people’s threat perceptions from carnivores, improve their connection with nature and strengthen the conservation capacity of local institutions especially in the context of wolves.
Cutaneous mastocytosis: A dermatological perspective
Authors: Di Raimondo Cosimo , Del Duca Ester , Silvaggio Dionisio , Di Prete Monia , Lombardo Paolo , Mazzeo Mauro , Spallone Giulia , Campione Elena , Botti Elisabetta , Bianchi Luca
Published: October 2020

Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and gastrointestinal tract. The prevalence of mastocytosis has been estimated to be one in 10 000, while the estimated incidence is one per 100 000 people per year. Cutaneous mastocytosis is classified into (i) maculopapular cutaneous mastocytosis, also known as urticaria pigmentosa; (ii) diffuse cutaneous mastocytosis; and (iii) mastocytoma of the skin. In adults, cutaneous lesions are usually associated with indolent systemic mastocytosis and have a chronic evolution. Paediatric patients, on the contrary, have often cutaneous manifestations without systemic involvement and usually experience a spontaneous regression. Diagnosis of cutaneous mastocytosis may be challenging due to the rarity of the disease and the overlap of cutaneous manifestations. This short review describes pathogenesis and clinical aspects of cutaneous mastocytosis with a focus on diagnosis and currently available therapies.
Commentary on Dermoscopy as a complementary tool for positive margin demarcation on the Mohs' map
Authors: Ocampo‐Garza Sonia Sofía , Ocampo‐Candiani Jorge , Orizaga‐Y‐Quiroga Thelma Laura , Garza‐Rodríguez Verónica
Published: October 2020

Mohs micrographic surgery (MMS) is a technique that allows removal of complex or ill‐defined skin cancer, combining tissue preservation and complete microscopic margin control. One of the main challenges of Mohs surgery is to illustrate the exact location of the tumour detected by light microscope. Using a dermoscope allows a fast, easy, reproducible way to accurately illustrate the location of a positive tumour on the Mohs map and ultimately transpose it to the surgical defect of the patient in a more precise way.
Voluntary Audit Committees and Financial Reporting: Korean Evidence*
Authors: Doo Seoyoung , Yoon Sung‐Soo
Published: October 2020

This study investigates whether and how a regulatory change in the appointment procedure of audit committees affects firms’ choice of an auditor or a voluntary audit committee. It also investigates whether voluntary audit committees improve earnings quality. We find that relatively larger medium‐sized firms with high ownership concentration establish voluntary audit committees to reinforce the control of major shareholders and that these audit committees do not improve financial reporting. Our result that audit committees do not necessarily improve financial reporting calls for policymakers and capital market participants to devote greater attention to audit committee appointments.
Extracellular vesicles and their potential role inducing changes in maternal insulin sensitivity during gestational diabetes mellitus
Authors: Nair Soumyalekshmi , Ormazabal Valeska , Lappas Martha , McIntyre H. David , Salomon Carlos
Published: October 2020

Gestational diabetes mellitus (GDM) is one of the most common endocrine disorders during gestation and affects around 15% of all pregnancies worldwide, paralleling the global increase in obesity and type 2 diabetes. Normal pregnancies are critically dependent on the development of maternal insulin resistance balanced by an increased capacity to secrete insulin, which allows for the allocation of nutrients for adequate foetal growth and development. Several factors including placental hormones, inflammatory mediators and nutrients have been proposed to alter insulin sensitivity and insulin response and underpin the pathological outcomes of GDM. However, other factors may also be involved in the regulation of maternal metabolism and a complete understanding of GDM pathophysiology requires the identification of these factors, and the mechanisms associated with them. Recent studies highlight the potential utility of tissue‐specific extracellular vesicles (EVs) in the diagnosis of disease onset and treatment monitoring for several pregnancy‐related complications, including GDM. To date, there is a paucity of data defining changes in the release, content, bioactivity and diagnostic utility of circulating EVs in pregnancies complicated by GDM. Placental EVs may engage in paracellular interactions including local cell‐to‐cell communication between the cell constituents of the placenta and contiguous maternal tissues, and/or distal interactions involving the release of placental EVs into biological fluids and their transport to a remote site of action. Hence, the aim of this review is to discuss the biogenesis, isolation methods and role of EVs in the physiopathology of GDM, including changes in maternal insulin sensitivity during pregnancy.
Adult‐onset eosinophilic airway diseases
Authors: Asano Koichiro , Ueki Shigeharu , Tamari Mayumi , Imoto Yoshimasa , Fujieda Shigeharu , Taniguchi Masami
Published: October 2020

Eosinophilic airway inflammation is one of the cardinal features of allergic airway diseases such as atopic asthma and allergic rhinitis. These childhood‐onset conditions are mediated by allergen and allergen‐specific IgE and often accompanied by other allergic diseases including food allergy and eczema. They can develop consecutively in the same patient, which is referred to as an allergic march. In contrast, some phenotypes of asthma, nonsteroidal anti‐inflammatory drugs‐exacerbated airway disease (N‐ERD), chronic rhinosinusitis with nasal polyps (CRSwNP)/eosinophilic CRS and allergic bronchopulmonary aspergillosis/mycosis (ABPA/ABPM) are adult‐onset airway diseases, which are characterized by prominent peripheral blood eosinophilia. Most of these conditions, except for ABPA/ABPM, are nonatopic, and the coexistence of multiple diseases, including an adult‐onset eosinophilic systemic disease, eosinophilic granulomatosis with polyangiitis (EGPA), is common. In this review, we focus on eosinophil biology, genetics and clinical characteristics and the pathophysiology of adult‐onset eosinophilic asthma, N‐ERD, CRSwNP/eosinophilic CRS, ABPA/ABPM and EGPA, while exploring the common genetic, immunological and pathological conditions among these adult‐onset eosinophilic diseases.
Longitudinal egg‐specific regulatory T‐ and B‐cell development: Insights from primary prevention clinical trials examining the timing of egg introduction
Authors: Lai Catherine L. , Campbell Dianne E. , Palmer Debra J. , Makrides Maria , Santner‐Nanan Brigitte , Gold Michael , Tan John Wei‐Liang , Valerio Carol , Nanan Ralph , Prescott Susan L. , Hsu Peter S.
Published: October 2020

Background

Egg allergy affects almost 1 in 10 Australian infants. Early egg introduction has been associated with a reduced risk in developing egg allergy; however, the immune mechanisms underlying this protection remain unclear.

Objective

To examine the role of regulatory immune cells in tolerance induction during early egg introduction.

Methods

Cryopreserved peripheral blood mononuclear cells (PBMC) were obtained from infants from 2 randomized controlled trials of early introduction of egg for the primary prevention of egg allergy; BEAT (at 12 months, n = 42) and STEP (at 5 months n = 82; 12 months n = 82) study cohorts. In vitro ovalbumin‐stimulated PBMC were analyzed by flow cytometry for presence of ovalbumin‐specific regulatory T cells, using activation markers, FoxP3, and IL‐10 expression. Ovalbumin‐specific regulatory B cells were identified by co‐expression of fluorescence‐conjugated ovalbumin and IL‐10.

Results

Specific, age‐dependent expansion of ovalbumin‐specific regulatory T cells was only observed in infants who (a) had early egg introduction and (b) did not have egg allergy at 12 months. This expansion was blunted or impaired in children who did not undergo early egg introduction and in those with clinical egg allergy at 12 months. Infants with egg allergy at 12 months of age also had reduced frequency of ovalbumin‐specific regulatory B cells compared to egg‐tolerant infants.

Conclusion

Early egg introduction and clinical tolerance to egg were associated with expansion of ovalbumin‐specific T and B regulatory cells, which may be an important developmental process for tolerance acquisition to food allergens.
Antibody dynamics to SARS‐CoV‐2 in asymptomatic COVID‐19 infections
Authors: Lei Qing , Li Yang , Hou Hong‐yan , Wang Feng , Ouyang Zhu‐qing , Zhang Yandi , Lai Dan‐yun , Banga Ndzouboukou Jo‐Lewis , Xu Zhao‐wei , Zhang Bo , Chen Hong , Xue Jun‐biao , Lin Xiao‐song , Zheng Yun‐xiao , Yao Zong‐jie , Wang Xue‐ning , Yu Cai‐zheng , Jiang He‐wei , Zhang Hai‐nan , Qi Huan , Guo Shu‐juan , Huang Sheng‐hai , Sun Zi‐yong , Tao Sheng‐ce , Fan Xiong‐lin
Published: October 2020

Background

The missing asymptomatic COVID‐19 infections have been overlooked because of the imperfect sensitivity of the nucleic acid testing (NAT). Globally understanding the humoral immunity in asymptomatic carriers will provide scientific knowledge for developing serological tests, improving early identification, and implementing more rational control strategies against the pandemic.

Measure

Utilizing both NAT and commercial kits for serum IgM and IgG antibodies, we extensively screened 11 766 epidemiologically suspected individuals on enrollment and 63 asymptomatic individuals were detected and recruited. Sixty‐three healthy individuals and 51 mild patients without any preexisting conditions were set as controls. Serum IgM and IgG profiles were further probed using a SARS‐CoV‐2 proteome microarray, and neutralizing antibody was detected by a pseudotyped virus neutralization assay system. The dynamics of antibodies were analyzed with exposure time or symptoms onset.

Results

A combination test of NAT and serological testing for IgM antibody discovered 55.5% of the total of 63 asymptomatic infections, which significantly raises the detection sensitivity when compared with the NAT alone (19%). Serum proteome microarray analysis demonstrated that asymptomatics mainly produced IgM and IgG antibodies against S1 and N proteins out of 20 proteins of SARS‐CoV‐2. Different from strong and persistent N‐specific antibodies, S1‐specific IgM responses, which evolved in asymptomatic individuals as early as the seventh day after exposure, peaked on days from 17 days to 25 days, and then disappeared in two months, might be used as an early diagnostic biomarker. 11.8% (6/51) mild patients and 38.1% (24/63) asymptomatic individuals did not produce neutralizing antibody. In particular, neutralizing antibody in asymptomatics gradually vanished in two months.

Conclusion

Our findings might have important implications for the definition of asymptomatic COVID‐19 infections, diagnosis, serological survey, public health, and immunization strategies.
False individual patient data and zombie randomised controlled trials submitted to Anaesthesia
Authors: Carlisle J. B.
Published: October 2020

Concerned that studies contain false data, I analysed the baseline summary data of randomised controlled trials when they were submitted to Anaesthesia from February 2017 to March 2020. I categorised trials with false data as ‘zombie’ if I thought that the trial was fatally flawed. I analysed 526 submitted trials: 73 (14%) had false data and 43 (8%) I categorised zombie. Individual patient data increased detection of false data and categorisation of trials as zombie compared with trials without individual patient data: 67/153 (44%) false vs. 6/373 (2%) false; and 40/153 (26%) zombie vs. 3/373 (1%) zombie, respectively. The analysis of individual patient data was independently associated with false data (odds ratio (95% credible interval) 47 (17–144); p = 1.3 × 10−12) and zombie trials (odds ratio (95% credible interval) 79 (19–384); p = 5.6 × 10−9). Authors from five countries submitted the majority of trials: China 96 (18%); South Korea 87 (17%); India 44 (8%); Japan 35 (7%); and Egypt 32 (6%). I identified trials with false data and in turn categorised trials zombie for: 27/56 (48%) and 20/56 (36%) Chinese trials; 7/22 (32%) and 1/22 (5%) South Korean trials; 8/13 (62%) and 6/13 (46%) Indian trials; 2/11 (18%) and 2/11 (18%) Japanese trials; and 9/10 (90%) and 7/10 (70%) Egyptian trials, respectively. The review of individual patient data of submitted randomised controlled trials revealed false data in 44%. I think journals should assume that all submitted papers are potentially flawed and editors should review individual patient data before publishing randomised controlled trials.
Infections and nutritional status of internationally adopted children in France
Authors: Goutines Juliette , Miller Laurie C. , Sorge Frederic
Published: October 2020

Aim

In the context of global changes in the epidemiology of internationally adopted children (IACs), the prevalence of infectious diseases and nutritional impairment has not been recently reviewed. Moreover, in France, these characteristics of the children according to their continents of origin and preadoption special needs (SN) status have been incompletely explored.

Methods

Demographic, infectious data and anthropometric of all the newly arrived IACs seen in a specialised clinic for international adoptees in Paris, France, between 2013 and 2016 were retrospectively reviewed.

Results

Three hundred and fifty IACs [mean age: 3.4 years (±2.7), 204 male] from 39 countries were included; 55% had SN. Ninety‐nine patients had at least one infection, 42% being classified as ‘serious’ (chronic viral infection, tuberculosis or malaria). Chronic viral infection was diagnosed in 26 (7%) patients (HIV: 16 cases, HBV: 5, HCV: 4) and affected especially Asian children (P < .001). The prevalence of stunting, underweight, wasting and microcephaly was, respectively, 25%, 22%, 15% and 8%. Stunting was more frequent in children from Eastern Europe (P = .02), while SN children were more often microcephalic or underweight (respectively P = .03 and .02).

Conclusion

The prevalence of serious infections and nutritional impairment remains high in IACs and requires early detection and careful follow‐up.
Letrozole targets the human ether‐a‐go‐go–related gene potassium current in glioblastoma
Authors: Shugg Tyler , Dave Nimita , Amarh Enoch , Assiri Abdullah A. , Pollok Karen E. , Overholser Brian R.
Published: October 2020

Aberrant expression of human ether‐a‐go‐go–related gene (hERG) potassium channels has been implicated in the pathophysiology of glioblastoma (GBM). Letrozole has demonstrated efficacy in pre‐clinical GBM models. The objective of this research was to assess the potential for hERG inhibition by letrozole to mediate efficacy in GBM. hERG currents were assessed using patch‐clamp electrophysiology in an overexpression system during treatment with letrozole, exemestane or vehicle (dimethyl sulphoxide). Relative to vehicle, peak hERG tail current density was reduced when treated with 300 nmol/L and 1 µmol/L letrozole but not when treated with exemestane (up to 1 µmol/L). Cell proliferation was assessed in cultured glioblastoma cell lines (U87 and U373) treated with letrozole, exemestane, doxazosin (hERG blocker) or vehicle. Letrozole, but not exemestane, reduced cell proliferation relative to vehicle in U87 and U373 cells. The associations between expression of hERG (KCNH2), aromatase (CYP19A1) and the oestrogen receptors (ESR1 and ESR2) and time to all‐cause mortality were assessed in GBM patients within The Cancer Genome Atlas (TCGA) database. hERG expression was associated with reduced overall survival in the TCGA GBM cohort. Future work is warranted to investigate hERG expression as a potential biomarker to predict the therapeutic potential of hERG inhibitors in GBM.
Rejoinder to Discussions on “Approval policies for modifications to machine learning‐based software as a medical device: A study of bio‐creep”
Authors: Feng Jean , Emerson Scott , Simon Noah
Published: October 2020

We thank the discussants for sharing their unique perspectives on the problem of designing automatic algorithm change protocols (aACPs) for machine learning‐based software as a medical device. Both Pennello et al. and Rose highlighted a number of challenges that arise in real‐world settings, and we whole‐heartedly agree that substantial extensions of our work are needed to understand if and how aACPs can be safely deployed in practice. Our work demonstrated that aACPs that appear to be harmless may allow for biocreep, even when the data distribution is assumed to be representative and stationary over time. While we investigated two solutions that protect against this specific issue, many more statistical and practical challenges remain and we look forward to future research on this topic.
Family carers managing personal budgets for adults with learning disabilities or autism
Authors: Turnpenny Agnes , Rand Stacey , Whelton Beckie , Beadle‐Brown Julie , Babaian Jacinta
Published: October 2020

Accessible summary

Direct payments can help people with learning disabilities or autism to have good support. Often, family carers manage the direct payments for people who would find this very difficult.

We asked family carers who managed direct payments to tell us why they decided to do this and what their experiences were.

Family carers told us they found managing direct payments difficult and stressful at first, but this got easier over time.

They also said that direct payments helped their family members to have more person‐centred support.

Background

There are a growing number of people with learning disabilities and autism who access personal budgets in the form of direct payments in England. Although they are often involved in decisions about their support, personal budgets are usually managed by someone else, typically a parent. This study examined the experiences of carers who manage personal budgets for adults with learning disabilities or autism with a particular focus on the challenges of securing suitable support and implications for their own well‐being.

Methods

This was a qualitative study using a descriptive phenomenological approach to investigate the lived experiences of family carers who manage personal budgets. We conducted semi‐structured interviews with 13 family carers. Interview transcripts were thematically analysed using the framework approach.

Results

Our analysis identified five main themes. The first theme relates to why carers decide to take up a personal budget in the first place and their initial expectations. The second theme, restricted choice, highlights the difficulties in securing adequate support and services in the context of what are often described as “complex needs.” The third and fourth themes relate to the tasks involved in managing a personal budget and the challenges associated with the dual role of the carer as a parent and a “professional.” The fifth and final theme, mixed emotions, describes the impact on the subjective well‐being of carers.

Conclusions

Family carers indicated that the benefits of personal budgets outweighed the difficulties and stress inherent in managing them. They need adequate support to ensure that personal budgets deliver personalised and self‐directed support and greater well‐being, and are sustainable arrangements.
Human papillomavirus vaccine to prevent cervical intraepithelial neoplasia in Japan: A nationwide case‐control study
Authors: Ikeda Sayaka , Ueda Yutaka , Hara Megumi , Yagi Asami , Kitamura Tetsuhisa , Kitamura Yuri , Konishi Hiroshi , Kakizoe Tadao , Sekine Masayuki , Enomoto Takayuki , Sobue Tomotaka
Published: October 2020

Cervical cancer remains among the most common cancers in women worldwide and can be prevented by vaccination. The Ministry of Health, Labour and Welfare of Japan suspended active recommendation of regular human papillomavirus (HPV) vaccines in 2013 because of various symptoms including chronic pain and motor impairment. This nationwide case‐control study from April 2013 to March 2017 targeted women aged 20‐24 years old at cervical screening. We compared HPV vaccination exposure between those with abnormal and normal cytology. Abnormal cytology was classified based on the results of histological test and we calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 – OR) × 100. A total of 2483 cases and 12 296 controls (one‐to‐five matching) were eligible in 31 municipalities in Japan. The distribution of histological abnormalities among cases was 797 CIN1 (including dysplasia) (32.1%), 165 CIN2 (6.7%), 44 CIN3 (1.8%), and eight squamous cell carcinoma (SCC) (0.3%). The OR of HPV vaccination compared with no vaccination for abnormal cytology, CIN1+, CIN2+, and CIN3+ versus controls was 0.42 (95% CI, 0.34‐0.50), 0.42 (95% CI, 0.31‐0.58), 0.25 (95% CI, 0.12‐0.54), and 0.19 (95% CI, 0.03‐1.15), respectively, equating to a vaccine effectiveness of 58.5%, 57.9%, 74.8%, and 80.9%, respectively. Eight patients had SCC, none was vaccinated. This nationwide case‐control study in Japan demonstrated a substantial risk reduction in abnormal cytology and CIN among women who did versus those who did not receive HPV vaccination.
Whole-exome sequencing of T-B+ severe combined immunodeficiency in Egyptian infants, JAK3 predominance and novel variants
Authors: El Hawary R , Meshaal S , Mauracher A A , Opitz L , Abd Elaziz D , Lotfy S , Eldash A , Boutros J , Galal N , Pachlopnik Schmid J , Elmarsafy A
Published: October 2020

Severe combined immunodeficiency (SCID) is fatal if not treated with immune reconstitution. In Egypt, T-B+ SCID accounts for 38·5% of SCID diagnoses. An accurate genetic diagnosis is essential for choosing appropriate treatment modalities and for offering genetic counseling to the patient's family. The objectives of this study were to describe the clinical, immunological and molecular characteristics of a cohort of twenty Egyptian patients with T-B+ SCID. The initial diagnosis (based on clinical features and flow cytometry) was followed by molecular investigation (whole-exome sequencing). All patients had the classic clinical picture for SCID, including failure to thrive (n = 20), oral candidiasis (n = 17), persistent diarrhea (n = 14), pneumonia (n = 13), napkin dermatitis (n = 10), skin rash (n = 7), otitis media (n = 3) and meningitis (n = 2). The onset of manifestations was at the age of 2·4 ± 1·6 months and diagnosis at the age of 6·7 ± ·5 months, giving a diagnostic delay of 4·3 months. JAK3 gene variants were most frequent (n = 12) with three novel variants identified, followed by IL2Rγ variants (n = 6) with two novel variants. IL7Rα and CD3ε variants were found once, with a novel variant each. T-B+NK− SCID accounted for approximately 90% of the Egyptian patients with T-B+SCID. Of these T-B+NK− SCID cases, 60% were autosomal recessive syndromes caused by JAK3 mutations and 30% were X-linked syndromes. It might be useful to sequence the JAK3 gene (i.e. targeted Sanger sequencing) in all T-B+ SCID patients, especially after X-linked SCID has been ruled out. Hence, no more than 10% of T-B+ SCID patients might require next-generation for a molecular diagnosis.
Precise variant interpretation, phenotype ascertainment, and genotype–phenotype correlation of children in the EARLY PRO‐TECT Alport trial
Authors: Boeckhaus Jan , Hoefele Julia , Riedhammer Korbinian M. , Tönshoff Burkhard , Ehren Rasmus , Pape Lars , Latta Kay , Fehrenbach Henry , Lange‐Sperandio Baerbel , Kettwig Matthias , Hoyer Peter , Staude Hagen , Konrad Martin , John Ulrike , Gellermann Jutta , Hoppe Bernd , Galiano Matthias , Gessner Michaela , Pohl Michael , Bergmann Carsten , Friede Tim , Gross Oliver ,   for the GPN Study Group and EARLY PRO‐TECT Alport Investigators
Published: October 2020

Early initiation of therapy in patients with Alport syndrome (AS) slows down renal failure by many years. Genotype–phenotype correlations propose that the location and character of the individual's variant correlate with the renal outcome and any extra renal manifestations. In‐depth clinical and genetic data of 60/62 children who participated in the EARLY PRO‐TECT Alport trial were analyzed. Genetic variants were interpreted according to current guidelines and criteria. Genetically solved patients with X‐linked inheritance were then classified according to the severity of their COL4A5 variant into less‐severe, intermediate, and severe groups and disease progress was compared. Almost 90% of patients were found to carry (likely) pathogenic variants and classified as genetically solved cases. Patients in the less‐severe group demonstrated a borderline significant difference in disease progress compared to those in the severe group (p = 0.05). While having only limited power according to its sample size, an obvious strength is the precise clinical and genetic data of this well ascertained cohort. As in published data differences in clinical progress were shown between patients with COL4A5 less‐severe and severe variants. Therefore, clinical and segregational data are important for variant (re)classification. Genetic testing should be mandatory allowing early diagnosis and therapy of AS.
Determinants of the grant lag and the surrender lag of horticultural crop plant breeders’ rights applications: Survival analysis with competing risks
Authors: Meng Ting , Carew Richard , Florkowski Wojciech J.
Published: October 2020

Obtaining a Plant Breeders’ Rights (PBR) certificate provides horticultural institutions the exclusive right to produce and reproduce new varieties, which directly motivate new plant variety innovations. This study investigates how the grant and surrender lag of PBR certificates is influenced by the crop type and applicant characteristics using the Canadian Food Inspection Agency horticultural crop PBR application data for the period 1992–2014. Results from the Fine and Gray subdistribution hazard model reveal that the grant lag and surrender lag of Canadian PBR applications significantly vary by the country of origin of the applicant, whether the applicant is a public institution or private company/individual, horticultural crop types, and the decades when applications are filed. The policy implications of the results provide useful information to stakeholders of the Canadian Plant Breeders’ Rights System regarding how the lifespan of PBRs is influenced by crop type and applicant characteristics.
The effect of the Canada–China canola trade dispute on canola prices
Authors: Wells Jacob , Slade Peter
Published: October 2020

In March 2019, China revoked the canola export licenses of two major Canadian exporters. We estimate the impact of these restrictions on Canadian canola prices. Using a vector error correction model to generate counterfactual prices, we estimate that between March 2019 and February 2020 canola prices were 3.6% lower than would have been expected in the absence of the import restrictions. We discuss the implications of our finding for both the ongoing negotiations between Canada and China and producer support in Canada.
Application of multicolour flow cytometry in the detection of metastatic carcinoma in serous effusions: Special emphasis in atypical cytology
Authors: Sahu Saumya , Gupta Parikshaa , Susheilia Shaily , Gautam Upasana , Dey Pranab
Published: October 2020

Introduction

We evaluated the role of simultaneous use of multiple antibodies in flow cytometry (FCM) to detect metastatic carcinomas in effusion samples.

Methods

Cytological examination of 75 successive cases of effusion samples was performed. There were 48 peritoneal, 26 pleural and one pericardial fluid. Multi‐coloured FCM examination was undertaken using a cocktail of CD45, CD14 and epithelial cell adhesion molecule (EpCAM), antibodies tagged with different fluorochromes. The percentage of EpCAM positivity was calculated in the CD45 and CD14 dual negative population by selective gating. The EpCAM value was correlated with the cytological findings, follow‐up data and MOC‐31 immunostaining.

Results

There were 20 benign, 35 malignant and 20 atypical cases diagnosed on cytomorphology. The primary sources of carcinomas were mainly from the ovary, followed by lung, gall bladder, intestine and other areas. Out of 20 cytologically benign cases, there were two malignant cases on the final follow‐up, and EpCAM on FCM picked up all 18 benign cases and one malignant case. Out of 35 cytologically detected malignant cases, EpCAM picked up 32 malignant cases. The EpCAM detected 15/18 malignant and both benign cases out of 20 cytological atypical cases. EpCAM antibody by FCM showed 87% sensitivity, 100% specificity, 100% positive predictive value and 74% negative predictive value.

Conclusion

This comprehensive study highlights the potential use of multi‐coloured FCM along with cytological examination to diagnose metastatic carcinoma in effusion samples. Multi‐coloured FCM is rapid and quantitative and is helpful in atypical cases.
Cytology of a temporal swelling in a young adult with unilateral conductive hearing loss
Authors: Kumar Pankaj , Gupta Parikshaa , Sharma Neeraj , Kamal Ahuja Chirag , Rajwanshi Arvind
Published: October 2020

Giant‐cell tumour involving the calvarial bones is extremely rare. This case of a young man with unilateral hearing loss and earache associated with a mass over the temporal region was accurately diagnosed pre‐operatively by fine needle aspiration cytology. Knowledge of the characteristic cytological features can help to distinguish it pre‐operatively from its radiological mimics.
Artificial intelligence for the management of pancreatic diseases
Authors: Gorris Myrte , Hoogenboom Sanne A. , Wallace Michael B. , van Hooft Jeanin E.
Published: October 2020

Novel artificial intelligence techniques are emerging in all fields of healthcare, including gastroenterology. The aim of this review is to give an overview of artificial intelligence applications in the management of pancreatic diseases. We performed a systematic literature search in PubMed and Medline up to May 2020 to identify relevant articles. Our results showed that the development of machine‐learning based applications is rapidly evolving in the management of pancreatic diseases, guiding precision medicine in clinical, endoscopic and radiologic settings. Before implementation into clinical practice, further research should focus on the external validation of novel techniques, clarifying the accuracy and robustness of these models.
Dual language statistical word segmentation in infancy: Simulating a language‐mixing bilingual environment
Authors: Tsui Angeline Sin Mei , Erickson Lucy C. , Mallikarjunn Amritha , Thiessen Erik D. , Fennell Christopher T.
Published: October 2020

Infants are sensitive to syllable co‐occurrence probabilities when segmenting words from fluent speech. However, segmenting two languages overlapping at the syllabic level is challenging because the statistical cues across the languages are incongruent. Successful segmentation, thus, relies on infants’ ability to separate language inputs and track the statistics of each language. Here, we report three experiments investigating how infants statistically segment words from two overlapping languages in a simulated language‐mixing bilingual environment. In the first two experiments, we investigated whether 9.5‐month‐olds can use French and English phonetic markers to segment words from two overlapping artificial languages produced by one individual. After showing that infants could segment the languages when the languages were presented in isolation (Experiment 1), we presented infants with two interleaved languages differing in phonetic cues (Experiment 2). Both monolingual and bilingual infants successfully segmented words from one of the two languages—the language heard last during familiarization. In Experiment 3, a conceptual replication, we replicated the findings of Experiment 2 with a different population and with different cues. As before, when 12‐month‐old monolingual infants heard two interleaved languages differing in English and Finnish phonetic cues, they learned only the last language heard during familiarization. Together, our findings suggest that segmenting words in a language‐mixing environment is challenging, but infants possess a nascent ability to recruit phonetic cues to segment words from one of two overlapping languages in a bilingual‐like environment. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=92pNcpxZguw.
Unicuspid aortic valve: Case series and review
Authors: Suraci Nicholas , Lo Presti Saberio , D’Mello Jayanand , Xydas Steve , Mihos Christos G.
Published: October 2020

A unicuspid aortic valve is a very rare valvular lesion. Its physical manifestations vary and are associated with other cardiovascular abnormalities such as aortic stenosis/insufficiency and aortopathy. Echocardiography remains the modality of choice, with computerized tomography or cardiac magnetic resonance used as adjunctive imaging. Herein, we present a case series of three patients with unicuspid aortic valves treated at our institution, with a focus on 2D and 3D echocardiographic imaging.
Revealing hidden plant diversity in arid environments
Authors: Carrasco‐Puga Gabriela , Díaz Francisca P. , Soto Daniela C. , Hernández‐Castro Catalina , Contreras‐López Orlando , Maldonado Antonio , Latorre Claudio , Gutiérrez Rodrigo A.
Published: October 2020

Estimating total plant diversity in extreme or hyperarid environments can be challenging, as adaptations to pronounced climate variability include evading prolonged stress periods through seeds or specialized underground organs. Short‐term surveys of these ecosystems are thus likely poor estimators of actual diversity. Here we develop a multimethod strategy to obtain a more complete understanding of plant diversity from a community in the Atacama Desert. We explicitly test environmental DNA‐based techniques (eDNA) to see if they can reveal the observed and ‘hidden' (dormant or locally rare) species.

To estimate total plant diversity, we performed long‐term traditional surveys during eight consecutive years, including El Niño and La Niña events, we then analyzed eDNA from soil samples using high‐throughput sequencing. We further used soil pollen analysis and soil seed bank germination assays to identify ‘hidden' species. Each approach offers different subsets of current biodiversity at different taxonomic, spatial and temporal resolution, with a total of 92 taxa identified along the transect. Traditional field surveys identified 77 plant species over eight consecutive years. Observed community composition greatly varies interannually, with only 22 species seen every year. eDNA analysis revealed 37 taxa, eight of which were ‘hidden' in our field surveys. Soil samples contain a viable seed bank of 21 taxa. Soil pollen (27 taxa) and eDNA analysis show affinities with vegetation at the landscape scale but a weak relationship to local plot diversity.

Multimethod approaches (including eDNA) in deserts are valuable tools that add to a comprehensive assessment of biodiversity in such extreme environments, where using a single method or observations over a few years is insufficient. Our results can also explain the resilience of Atacama plant communities as ‘hidden' taxa may have been active in the recent past or could even emerge in the future as accelerated global environmental change continues unabated.
Sex differences in social functioning of patients with schizophrenia depending on the age of onset and severity of the disease
Authors: Zorkina Yana , Morozova Anna , Abramova Olga , Reznik Alexander , Kostyuk Georgiy
Published: October 2020

Aim

Schizophrenia manifests differently in women and men. This disease starts at a young age, leads to disability at working age. The aim of our work was to study sex differences, association between social factors and different parameters of the clinical picture and the course of the disease.

Methods

This study was performed using population of Russian patients (men: 345, women: 310). Patients were examined using DSM‐V, Bush‐Francis catatonia rating scale (BFCRS), Positive and Negative Syndrome Scale (PANSS), 4‐Items Negative Symptoms Assessment (NSA‐4) and Frontal Assessment Battery (FAB).

Results

Sex differences were mainly shown through negative symptoms, which were more severe in male patients. Men were shown to experience a decrease in social functioning and earlier age of onset. A positive family history further influenced negative symptoms and age of onset. When comparing scores before and after inpatient treatment (4 weeks), sex differences were not so pronounced. Female patients and patients with high levels of education, no conflictual relationship with family and active labour activity showed a later age of onset of the prodromal events and manifestation age. The decrease in the number of social contacts correlated with lower age of disability. The association between social factors and the severity of psychotic symptoms was shown across DSM‐V, PANSS, NSA‐4 and FAB, but not for BFCRS. Social factors were associated with negative symptoms of schizophrenia, but not with positive.

Conclusion

For successful treatment of patients with schizophrenia, the discussed factors must be considered and schizophrenia treatment methods should be primarily aimed at improving social functioning.
Transesophageal Echocardiography – Dysphagia Risk in Acute Stroke (TEDRAS): a prospective, blind, randomized and controlled clinical trial
Authors: Hamzic S. , Braun T. , Butz M. , Khilan H. , Weber S. , Yeniguen M. , Gerriets T. , Schramm P. , Juenemann M.
Published: October 2020

Background and purpose

Dysphagia is common in acute stroke and leads to worse overall outcome. Transesophageal echocardiography (TEE) is used in the diagnostic evaluation of stroke with regard to its etiology and is a known cause of postoperative dysphagia in cardiac surgery. The prevalence of dysphagia in acute stroke patients undergoing TEE remains unknown. The aim of the Transesophageal Echocardiography – Dysphagia Risk in Acute Stroke (TEDRAS) study was to assess the influence of TEE on swallowing among patients who have experienced acute stroke.

Methods

The TEDRAS study was a prospective, blind, randomized, controlled trial that included two groups of patients with acute stroke. Simple unrestricted randomization was performed, and examiners were blinded to each other's results. Swallowing was tested using flexible endoscopic evaluation of swallowing (FEES) at three different time points in the intervention group (24 h before, immediately after and 24 h after TEE) and in the control group (FEES on three consecutive days and TEE earliest after the third FEES). Validated scales were used to assess dysphagia severity for all time points as primary outcome measures.

Results

A total of 34 patients were randomized: 19 to the intervention group and 15 to the control group. The key findings of the repeated‐measures between‐group comparisons were significant increases in the intervention group for the following dysphagia measures: (1) secretion severity score (immediately after TEE: P < 0.001; 24 h after TEE: P < 0.001) and (2) Penetration‐Aspiration Scale score for saliva (immediately after TEE: P < 0.001; 24 h after TEE: P = 0.007), for small (immediately after TEE: P = 0.009) and large liquid boli (immediately after TEE: P = 0.009; 24 h after TEE: P = 0.025).

Conclusion

The results indicate a negative influence of TEE on swallowing in acute stroke patients for at least 24 hours.