bluuebunny/crossref_metadata_2025 huggingface dataset:
Blinatumomab and inotuzumab for B cell precursor acute lymphoblastic leukaemia in children: a retrospective study from the Leukemia Working Group of the Spanish Society of Pediatric Hematology and Oncology (SEHOP)
Authors: Fuster José L. , Molinos‐Quintana Agueda , Fuentes Carolina , Fernández José M. , Velasco Pablo , Pascual Toñi , Rives Susana , Dapena José L. , Sisinni Luisa , López‐Godino Oriana , Palomo Pilar , Villa‐Alcázar Marta , Bautista Francisco , González‐Vicent Marta , López‐Duarte Mónica , García‐Morín Marina , Ramos-Elbal Eduardo , Ramírez Manuel ,   the Leukemia Working Group of the Spanish Society of Pediatric Hematology, Oncology (SEHOP)
Published: April 2020

Blinatumomab and inotuzumab ozogamycin represent promising alternatives to conventional chemotherapy in acute lymphoblastic leukaemia (ALL). We analysed data from 29 children with ALL treated under compassionate use with blinatumomab, inotuzumab or both. The complete remission (CR) rate in a heavily pretreated population with overt relapse was 47·6%. At earlier stages (first/second CR), both antibodies represented a useful tool to reduce minimal residual disease, and/or avoid further toxic chemotherapy until stem cell transplantation. Six patients developed grade 3 reversible non‐haematological toxicity. The 12‐month overall survival and event‐free survival rates were 50·8 ± 26·4% and 38·9 ± 25·3% with blinatumomab, 45·8 ± 26% and 27·5 ± 25% with inotuzumab.
Primary prevention of venous thromboembolism with apixaban for multiple myeloma patients receiving immunomodulatory agents
Authors: Cornell Robert F. , Goldhaber Samuel Z. , Engelhardt Brian G. , Moslehi Javid , Jagasia Madan , Harrell Shelton , Rubinstein Samuel M. , Hall Robert , Wyatt Houston , Piazza Gregory
Published: April 2020

Immunomodulatory drugs (IMiDs) have improved survival of patients with multiple myeloma (MM) and comprise the therapeutic backbone at all phases of therapy. Although well‐tolerated, IMiDs increase rates of venous thromboembolism (VTE). In this phase IV, single‐arm pilot study, fifty patients with MM on IMiDs received apixaban 2·5 mg orally twice daily for primary prevention of VTE and were prospectively monitored for six months. The primary safety outcomes were rates of major haemorrhage and clinically relevant non‐major haemorrhage over six months. The primary efficacy outcome was the rate of symptomatic VTE over six months. IMiDs used were lenalidomide (58%) or pomalidomide (42%). During the six‐month evaluation period, no patients experienced major haemorrhage or VTE. Three patients experienced clinically relevant, non‐major haemorrhage which was managed medically, and all were able to resume apixaban. One patient stopped therapy shortly after initiation due to an allergic reaction to apixaban. No patients experienced stroke, myocardial infarction, or death. In this pilot study, low‐dose apixaban was safe and well‐tolerated as a primary prevention therapy of VTE for patients with MM receiving IMiDs. Further studies are needed to validate low‐dose apixaban as a standard primary prevention anti‐thrombotic strategy for patients with MM receiving IMiDs.
Detection of clinically significant prostate cancer in biopsy‐naïve men: direct comparison of systematic biopsy, multiparametric MRI‐ and contrast‐ultrasound‐dispersion imaging‐targeted biopsy
Authors: Mannaerts Christophe K. , Engelbrecht Marc R.W. , Postema Arnoud W. , van Kollenburg Rob A.A. , Hoeks Caroline M.A. , Savci‐Heijink Cemile Dilara , Van Sloun Ruud J.G. , Wildeboer Rogier R. , De Reijke Theo M. , Mischi Massimo , Wijkstra Hessel
Published: April 2020

Objectives

To compare and evaluate a multiparametric magnetic resonance imaging (mpMRI)‐targeted biopsy (TBx) strategy, contrast‐ultrasound‐dispersion imaging (CUDI)‐TBx strategy and systematic biopsy (SBx) strategy for the detection of clinically significant prostate cancer (csPCa) in biopsy‐naïve men.

Patients and Methods

A prospective, single‐centre paired diagnostic study included 150 biopsy‐naïve men, from November 2015 to November 2018. All men underwent pre‐biopsy mpMRI and CUDI followed by a 12‐core SBx taken by an operator blinded from the imaging results. Men with suspicious lesions on mpMRI and/or CUDI also underwent MRI‐TRUS fusion‐TBx and/or cognitive CUDI‐TBx after SBx by a second operator. A non‐inferiority analysis of the mpMRI‐ and CUDI‐TBx strategies in comparison with SBx for International Society of Urological Pathology Grade Group [GG] ≥2 PCa in any core with a non‐inferiority margin of 1 percentage point was performed. Additional analyses for GG ≥2 PCa with cribriform growth pattern and/or intraductal carcinoma (CR/IDC), and GG ≥3 PCa were performed. Differences in detection rates were tested using McNemar’s test with adjusted Wald confidence intervals.

Results

After enrolment of 150 men, an interim analysis was performed. Both the mpMRI‐ and CUDI‐TBx strategies were inferior to SBx for GG ≥2 PCa detection and the study was stopped. SBx found significantly more GG ≥2 PCa: 39% (56/142), as compared with 29% (41/142) and 28% (40/142) for mpMRI‐TBx and CUDI‐TBx, respectively (P < 0.05). SBx found significantly more GG = 1 PCa: 14% (20/142) compared to 1% (two of 142) and 3% (four of 142) with mpMRI‐TBx and CUDI‐TBx, respectively (P < 0.05). Detection of GG ≥2 PCa with CR/IDC and GG ≥3 PCa did not differ significantly between the strategies. The mpMRI‐ and CUDI‐TBx strategies were comparable in detection but the mpMRI‐TBx strategy had less false‐positive findings (18% vs 53%).

Conclusions

In our study in biopsy‐naïve men, the mpMRI‐ and CUDI‐TBx strategies had comparable PCa detection rates, but the mpMRI‐TBX strategy had the least false‐positive findings. Both strategies were inferior to SBx for the detection of GG ≥2 PCa, despite reduced detection of insignificant GG = 1 PCa. Both strategies did not significantly differ from SBx for the detection of GG ≥2 PCa with CR/IDC and GG ≥3 PCa.
Teachers' concerns about pupils' mental health in a cross‐sectional survey of a population sample of British schoolchildren
Authors: Mathews Frances , Newlove‐Delgado Tamsin , Finning Katie , Boyle Christopher , Hayes Rachel , Johnston Patrick , Ford Tamsin
Published: April 2020

Background

Schools are becoming central to the identification and referral of children and young people with poor mental health. Understanding how well a teacher concern predicts mental disorder in a child or young person is important for mental health teams who need to respond to referrals.

Method

This secondary analysis of the 2004 British Child and Adolescent Mental Health Survey used the first item of the Strengths and Difficulties Questionnaire (SDQ) Impact subscale to indicate concern about a child or young person’s mental health. Mental disorder according to DSM IVR criteria was assessed using the multi‐informant Development and Well‐Being Assessment. We compared the proportion with and without mental disorder according to the presence or absence of teacher concern.

Results

Teacher concern was moderately predictive (49% with teacher concern had a disorder) and sensitive (teacher concern present among 56% with disorder), while lack of teacher concern was highly predictive (only 5% had disorder) and specific (94% no disorder). Teacher concern was associated with significantly poorer mental health (mean teacher SDQ total difficulty score 19.6, SD 5.6 with disorder, mean 15.0; SD 5.1 if no disorder) compared to children without teacher concern (mean 9.6, SD 5.5 with disorder, and 4.9; SD 4.3 if no disorder; F (3, 5,931) = 1527.228, p = .001). If both teacher and parents were concerned, the child or young person was much more likely to have a disorder.

Conclusion

A lack of teacher concern can reassure mental health practitioners in the vast majority of cases. While teacher concern does identify those with poorer mental health, it is only moderately predictive of a disorder. When concerned about a child or young person, discussions with parents or others who know them may help teachers identify those who most need support.

Key Practitioner Message

The emphasis on schools as a major setting to provide support and identify the need for referral to specialist mental health services means service commissioners, providers and practitioners could benefit from insight into how predictive a teacher’s concern is of childhood mental health conditions and how this may vary with the type of disorder

If teachers are not concerned about a child, practitioners can be reassured that there is unlikely to be a significant problem with their mental health, although this will be less certain in schools whose pupils are likely to have a higher than average levels of difficulty

Teacher concerns do not necessarily differentiate between clinically impairing and mild/ moderate mental health difficulties, but do identify children in poorer mental health

Asking for corroboration of concern from other sources increases the strength of the association to severe mental health disorders
Food supply chains during the COVID‐19 pandemic
Authors: Hobbs Jill E.
Published: April 2020

This paper provides an early assessment of the implications of the COVID‐19 pandemic for food supply chains and supply chain resilience. The effects of demand‐side shocks on food supply chains are discussed, including consumer panic buying behaviors with respect to key items, and the sudden change in consumption patterns away from the food service sector to meals prepared and consumed at home. Potential supply‐side disruptions to food supply chains are assessed, including labor shortages, disruptions to transportation networks, and “thickening” of the Canada–U.S. border with respect to the movement of goods. Finally, the paper considers whether the COVID‐19 pandemic will have longer‐lasting effects on the nature of food supply chains, including the growth of the online grocery delivery sector, and the extent to which consumers will prioritize “local” food supply chains.
Resilience test of the North American food system
Authors: Orden David
Published: April 2020

This article assesses the resilience of the North American food system in the context of the coronavirus pandemic in the immediate, medium, and long run. Focus is on the United States. The immediate consequence is substantial disruption of agricultural markets and falling prices, but systemic breakdown of the system is unlikely. Existing farm programs and emergency legislation will support U.S. farmers. Medium term, supply is likely to be strong, while pandemic‐related disruptions in the developing world remain uncertain. Long term, the path forward under the fragility the pandemic has underscored is stronger international institutions and cooperation.
UNEARTHING T. REX: THE LAW AND ECONOMICS OF PALEONTOLOGICAL FINDS
Authors: Hallwood Paul , Miceli Thomas J.
Published: April 2020

This paper assesses the economic aspects of the search for and recovery of fossils on U.S. lands. The objective is taken to be the maximization of the social value of these resources, including the market and scientific values. Because independent searchers may not internalize the scientific value, we develop a reward scheme that incentivizes both optimal recovery of finds, and optimal search. We then trace how U.S. federal and state laws have tried to strike a balance between search activity and scientific recovery. We argue that existing law deals well with recovery but does not generally promote optimal search. (JEL D83, H41, I23, K11, O32)
Phase I/II Study of Erlotinib to Determine the Optimal Dose in Patients With Non‐Small Cell Lung Cancer Harboring Only EGFR Mutations
Authors: Takeda Yuichiro , Ishizuka Naoki , Sano Kazumi , Hirano Satoshi , Suzuki Manabu , Naka Go , Sugiyama Haruhito
Published: April 2020

The recommended daily dose of erlotinib was determined for patients with all types of non‐small cell lung cancer (NSCLC). We determined the optimal dose (OD) in patients with NSCLC harboring only epidermal growth factor receptor (EGFR) sensitizing mutations. EGFR‐tyrosine kinase inhibitor‐naïve patients with sensitizing mutations were eligible. Clinical OD was determined in a phase I/II study based on the continual re‐assessment method (CRM) of both disease control and dose‐limiting toxicity, defined as any toxicity of grade 2 (G2) or higher within 8 weeks. We also determined the pharmacologic OD via a pharmacokinetic (PK) study. Thirty‐eight patients were enrolled. Clinical OD was 25 mg/day by the CRM. Median progression‐free survival (mPFS) was 9.3 months. In receiver operating characteristic (ROC) analysis of mPFS, the trough concentration (

) was ≥ 0.30 μg/mL. The area under the curve (AUC) and

were predicted via population PK (PopPK) or a bootstrap of 100 iterations (PopPK100). TOX20 was defined as < 20% duration of any toxicity ≥ G2 during the PFS period. In ROC analysis of mPFS and TOX20 in the PopPK100 study,

was ≥ 0.17 and < 0.32 μg/mL, respectively. In ROC analysis of mPFS and TOX20 in the PopPK100 study,

was ≥ 0.15 and < 0.31 μg/mL, AUC was ≥ 14.4 and < 14.5 μg/mL•hour, and the dosage was ≥ 58.4 and < 58.8 mg/day, respectively. Clinical and pharmacologic ODs were 25 by CRM and 50–60 mg/day by PK, respectively. The proposed starting OD is 50–60 mg/day, with personalized adjustment of 0.15–0.31 μg/mL based on

as determined by PopPK monitoring.
A study of dermal melanophages in childhood nevi. Reassessing so‐called “pigment incontinence”
Authors: Cramer Stewart F. , Salgado Cláudia M. , Reyes‐Múgica Miguel
Published: April 2020

In inflammatory dermatoses, dermal melanophages (MLP) are ascribed to “pigment incontinence,” with melanin “dropping down” from the epidermis. Although this is analogous to the “dropping down” of melanocytic nevus cells (Abtropfung), MLP in ordinary nevi have not been systematically studied—so “pigment incontinence” may not apply to MLP in nevi. A total of 31 childhood nevi identified by pediatricians and family practitioners were evaluated for the distribution of MLP. We tested the hypothesis that a dermal origin of the melanin in MLP is more likely than dropping down from the epidermis. In our cohort, 90.3% (28/31) of childhood nevi had dermal MLP, a significantly higher frequency, compared to 31/60 ordinary adult nevi (P < 0.0001). Superficial dermis was the most common location (P < 0.001). However, only six specimens had MLP restricted to the superficial dermis, significantly less than predicted by the theory that melanin drops down from the epidermis (P < 0.00001). We also evaluated perivascular MLP, since nerves run together with vessels in neurovascular bundles (NVB), and it has been showed that precursors of melanocytes migrate from the neural crest to the skin as nerve sheath stem cells. Superficial NVB MLP correlated with deep NVB bundle MLP (P < 0.05), suggesting that NVB MLP represent “tombstones” for superficial and deep dermal nevus cells. Deep dermal, deep NVB, and deep periadnexal MLP may be valid biological criteria for diagnosis of congenital type (prenatal) nevi. Viewing prenatal nevi in children as a neurocristopathy fits a major principle of pediatric pathology: childhood diseases should be studied and understood based on what happens during tissue development.
Look west for Australian evidence of the relationship between amphetamine‐type stimulant prescribing and meth/amphetamine use
Authors: Whitely Martin , Allsop Steve
Published: April 2020

Aims

To investigate Western Australian (WA) data on the relationship between the prescription of Amphetamine‐Type Stimulants (ATS), and the non‐medical use of prescription ATS and other forms of meth/amphetamine, for both adults (18+) and minors (<18).

Design and Methods

Two WA specific data sources were identified. The Stimulant Regulatory Scheme provided comprehensive ATS prescribing data from 2004 until 2017, and Australian Secondary School Alcohol and Drug (ASSAD) surveys provided details of non‐medical prescription ATS use by WA adolescents (12‐17). Other data sources included National Drug Strategy Household Surveys (NDSHS), the Pharmaceutical Benefits Scheme (PBS), and the National Wastewater Drug Monitoring Program (NWDMP).

Results

Over 95% of WA ATS prescribing has been for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). WA adults have consistently received prescription ATS at a much higher rate than other Australian adults. The most recent published data reported that in 2017 WA adults were 2.6 times as likely as other Australian adults to be supplied an ATS for ADHD. Drug treatment, NDSHS and NWDMP data indicate that WA adult rates of non‐medical meth/amphetamine use have also regularly exceeded the Australian rate. Furthermore, the little data that exist on the non‐medical use of prescription ATS by Australian adults suggests that it may also be disproportionately common in WA. From 1993 until 2002 the proportion of WA minors prescribed ATS grew rapidly and was the highest in Australia. Following regulatory reforms prescribing rates declined. By 2010 they were approximately half the 2002 rate. Over a similar timeframe there was a 72% fall in WA adolescent self‐reported, past‐week, non‐medical amphetamine use. Since 2011 WA minor ATS prescribing rates have rebounded significantly. Unfortunately, useful data on adolescent meth/amphetamine use since 2011 is not available. Nonetheless, two ASSAD snapshots, in 2005 and 2017, suggest that more WA adolescents use prescription ATS non‐medically than medically.

Discussion and Conclusion

The data for WA adults suggest a correlation, but does not establish a causal connection, between ATS prescribing and the non‐medical use of ATS and other forms of meth/amphetamine. Although it is clear that there is significant illicit prescription ATS use by WA adolescents, little is known about the contribution that the prescription of ATS makes to subsequent meth/amphetamine and other drug use. There is a critical need for research that investigates long‐term, population‐wide patterns and individual experiences of both those prescribed ATS and the broader population, to inform policy, prevention and treatment responses.
Bidirectional relationships in the development of internalising symptoms and alcohol use in adolescence
Authors: Birrell Louise , Slade Tim , Teesson Maree , Prior Katrina , Chapman Catherine , Hides Leanne , McBride Nyanda , Mewton Louise , Allsop Steve , Andrews Gavin , Newton Nicola C.
Published: April 2020

Introduction and Aims

Previous literature has demonstrated an inconsistent relationship between alcohol use and internalising symptoms (anxiety, depression) in youth. This study aimed to clarify this link examining the bidirectional relationships between internalising symptoms and alcohol use in a community sample of adolescents, taking into account the effect of gender and externalising symptoms.

Design and Methods

Parallel latent growth models were run to prospectively explore the bidirectional relationships between internalising symptoms and alcohol use when assessed five times over 2 years, among 1557 (67% female) adolescents from age 13.5 years.

Results

Results showed that higher initial levels of internalising symptoms predicted increasing alcohol use frequency; however, this association was no longer significant once externalising symptoms and gender were accounted for. No bidirectional associations between internalising symptoms and alcohol use were found.

Discussion and Conclusions

This study adds to the literature examining the bidirectional relationships between internalising symptoms and alcohol use in adolescence. Findings highlight the importance of both gender and externalising symptoms in the development of this type of comorbidity and may help explain discrepant findings in the existing literature. Future prevention efforts for internalising problems and alcohol use should consider gender and externalising symptoms.
Hyperglucosuria induced by dapagliflozin augments bacterial colonization in the murine urinary tract
Authors: Saenkham Panatda , Jennings‐Gee Jamie , Hanson Braden , Kock Nancy D. , Adams L. Garry , Subashchandrabose Sargurunathan
Published: April 2020

Aim

To test the effects of dapagliflozin‐induced hyperglucosuria on ascending bacterial urinary tract infection (UTI) in a mouse model.

Methods

Dapagliflozin or canagliflozin was used to induce hyperglucosuria in non‐diabetic adult female mice prior to transurethral inoculation with uropathogenic Escherichia coli (UPEC) or Klebsiella pneumoniae. Glucose, bacterial load, cytokines, neutrophil mobilization and inflammation during acute and chronic UTI were determined.

Results

Significant increase in UPEC load was observed in the urinary tract of hyperglucosuric mice compared with controls. Dapagliflozin‐treated mice developed bacteraemia resulting in UPEC colonization of the spleen and liver at a higher frequency than controls. Chronic UTI in hyperglucosuric mice resulted in an increased incidence of renal abscesses. Histopathological evaluation revealed only modest increases in tissue damage in the urinary bladders and kidneys of dapagliflozin‐treated mice, despite a profound increase in bacterial load. There was poor neutrophil mobilization to the urine of hyperglucosuric mice. We also observed a delayed increase of IL‐1β in urine, and bladders, and IL‐6 in urine of hyperglucosuric mice. Experimental inoculation with K. pneumoniae also revealed higher bacterial burden in the urinary bladder, spleen and liver from dapagliflozin‐treated mice compared with controls.

Conclusion

Collectively, our results indicate that dapagliflozin‐induced hyperglucosuria in non‐diabetic female mice leads to increased susceptibility to severe UTI, and bacteraemia of urinary tract origin.
Infectivity and virulence of Nosema ceranae (Microsporidia) isolates obtained from various Apis mellifera morphotypes
Authors: Porrini Leonardo P. , Porrini Martín P. , Garrido Melisa P. , Müller Fernando , Arrascaeta Luciana , Fernández Iriarte Pedro J. , Eguaras Martin J.
Published: April 2020

The infection of honey bees, Apis mellifera L. (Hymenoptera: Apidae), by the microsporidian Nosema ceranae is one of the factors related to the increase in colony losses and the decrease in honey production observed in recent years. However, these effects seem to differ depending on the climate zone. The range and prevalence of N. ceranae have increased significantly in the last decades, with different consequences in northern and southern temperate areas. The existence of various isolates of N. ceranae from distant geographical areas, which probably exhibit different degrees of virulence, could explain the different responses of the bee to the infection. The aim of this work was to compare the effects of two N. ceranae isolates from different host populations from Argentina on honey bee survival at two ages post‐eclosion. Using cage experiments, we compared the development of infection of worker bees through the estimation of daily bee mortality and spore counts. Host subspecies identity analysis showed a strong similarity with Apis mellifera scutellata morphotype for the northern region, with a greater hybridization between subspecies with European origin toward the central and southern regions. Genetic characterization of isolates from the three regions indicated only the presence of N. ceranae. Infected bees survived longer than control bees, and bees infected at 5 days had a lower survival than those infected at 72 h with isolates from the three regions. These differences in survival matched the development of the N. ceranae infection, with differences in spore loads for infected bees at 5 days. Our studies showed that Nosema infection and survival varied among the different ages post emergence of workers, and both increased as the honey bee aged. These differences in susceptibility to infection could be related to the immune response of bees of different ages or to changes in the composition and succession of the intestinal microbiota throughout its ontogeny.
Curriculum mapping of dental physiology curriculum: The path towards outcome‐based education
Authors: Vashe Asha , Devi Vasudha , Rao Raghavendra , Abraham Reem R.
Published: April 2020

Introduction

Curriculum mapping provides a clear picture of curriculum content, learning opportunities and assessment methods employed to measure the achievement of learning outcomes with their interrelationships. It facilitates educators and teachers to examine the extent to which the curricular components are linked and hence to find out gaps in the curriculum. The objective of the study was, therefore, to evaluate the physiology curriculum of Bachelor of Dental Surgery (BDS) programme through curriculum mapping.

Materials and Methods

In this study, mapping of the physiology curriculum of three batches of BDS programme was conducted retrospectively. The components of the curriculum used for mapping were expected learning outcomes, curriculum content, learning opportunities, assessments and learning resources. The data were gathered by reviewing office records.

Results

Descriptive analysis of the data revealed reasonable alignment between the curriculum content and questions asked in examinations for all three batches. It was found that all the expected learning outcomes were addressed in the curriculum and assessed in different assessments. Moreover, the study revealed that the physiology curriculum was contributing to majority of the programme outcomes. Nevertheless, the study could identify some gaps in the curriculum, as well.

Conclusion

This study revealed that majority of the components of the curriculum were linked and contributed to attaining the expected learning outcomes. It also showed that curriculum mapping was feasible and could be used as a tool to evaluate the curriculum.
EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke
Authors: Bassetti C. L. A. , Randerath W. , Vignatelli L. , Ferini‐Strambi L. , Brill A.‐K. , Bonsignore M. R. , Grote L. , Jennum P. , Leys D. , Minnerup J. , Nobili L. , Tonia T. , Morgan R. , Kerry J. , Riha R. , McNicholas W. T. , Papavasileiou V.
Published: April 2020

Background

Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality.

Aim

Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology to critically evaluate the evidence regarding potential links and the impact of therapy.

Materials and methods

Thirteen research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta‐analyses; second, primary studies post‐dating the systematic reviews/meta‐analyses. A total of 445 studies were evaluated and 88 were included. Statements were generated regarding current evidence and clinical practice.

Results

Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle‐aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment‐compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, whilst CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, whilst the pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post‐stroke insomnia and RLS and their association with a less favourable stroke outcome, whilst treatment data are scarce.

Discussion/Conclusion

Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke.
Development of microsatellite markers for an extremely limited distributed rare diving beetle species, Acilius kishii, and a widely distributed species, Acilius japonicus (Coleoptera: Dytiscidae)
Authors: Kato Masaya , Nakahama Naoyuki , Izuno Ayako , Hirai Norio , Ueda Shouhei , Isagi Yuji
Published: April 2020

Acilius kishii Nakane, 1963 (Coleoptera: Dytiscidae) is an endangered diving beetle species distributed in only one location, Lake Yashaga‐Ike, Honshu Island, Japan. Acilius japonicus, which is related to A. kishii, is distributed widely in northern Honshu Island and Hokkaido Island in Japan. In this study, we identified 14 microsatellite loci for A. kishii and A. japonicus, including both polymorphic and monomorphic loci, using the next‐generation sequencing method. We observed that 5 and 10 loci showed polymorphisms in 31 and 32 individuals of A. kishii and A. japonicus, respectively. The observed and expected heterozygosities were 0.00–1.00 and 0.00–0.74, respectively. These microsatellite loci could be useful for future conservation genetic studies, including monitoring of genetic diversity and extinction risk of A. kishii.
Coral reef resilience to thermal stress in the Eastern Tropical Pacific
Authors: Romero‐Torres Mauricio , Acosta Alberto , Palacio‐Castro Ana M. , Treml Eric A. , Zapata Fernando A. , Paz‐García David A. , Porter James W.
Published: April 2020

Coral reefs worldwide are threatened by thermal stress caused by climate change. Especially devastating periods of coral loss frequently occur during El Niño‐Southern Oscillation (ENSO) events originating in the Eastern Tropical Pacific (ETP). El Niño‐induced thermal stress is considered the primary threat to ETP coral reefs. An increase in the frequency and intensity of ENSO events predicted in the coming decades threatens a pan‐tropical collapse of coral reefs. During the 1982–1983 El Niño, most reefs in the Galapagos Islands collapsed, and many more in the region were decimated by massive coral bleaching and mortality. However, after repeated thermal stress disturbances, such as those caused by the 1997–1998 El Niño, ETP corals reefs have demonstrated regional persistence and resiliency. Using a 44 year dataset (1970–2014) of live coral cover from the ETP, we assess whether ETP reefs exhibit the same decline as seen globally for other reefs. Also, we compare the ETP live coral cover rate of change with data from the maximum Degree Heating Weeks experienced by these reefs to assess the role of thermal stress on coral reef survival. We find that during the period 1970–2014, ETP coral cover exhibited temporary reductions following major ENSO events, but no overall decline. Further, we find that ETP reef recovery patterns allow coral to persist under these El Niño‐stressed conditions, often recovering from these events in 10–15 years. Accumulative heat stress explains 31% of the overall annual rate of change of living coral cover in the ETP. This suggests that ETP coral reefs have adapted to thermal extremes to date, and may have the ability to adapt to near‐term future climate‐change thermal anomalies. These findings for ETP reef resilience may provide general insights for the future of coral reef survival and recovery elsewhere under intensifying El Niño scenarios.
Measurements of eftrenonacog alfa by 19 different combinations reagents/instrument: A single‐centre study
Authors: Sinegre Thomas , Trayaud Adeline , Tardieu Maryse , Fourneyron Virginie , Talon Laurie , Berger Marc G. , Tillier Maxence , Senectaire Stéphanie , Gembara Piotr , Barbin Anne‐Lise , Vaissade Aurélie , Lebreton Aurélien
Published: April 2020

Introduction

Recombinant factor IX Fc fusion protein (rFIXFc) is an extended half‐life concentrate for the treatment of haemophilia B (HB). rFIXFc activity monitoring is crucial in several clinical situations. However, differences were observed between one‐stage clotting (OSC) and chromogenic assays, but not for all factor IX (FIX) concentrations.

Aims

To compare rFIXFc measurements obtained using different instruments and common OSC and chromogenic asssays.

Methods

FIX:C measurements were performed in rFIXFc‐spiked plasma aliquots (targeted FIX levels of 1.5, 1, 0.5, 0.2, 0.05, 0.02 and 0.01 IU/mL) and plasma samples collected from two patients with HB at various time points after rFIXFc infusion, using three instruments (STA‐R MAX, ACLTOP700 and CS2100i) and common clotting and chromogenic FIX:C assays.

Results

The same reagent could give different FIX:C measurements when adapted to different instruments. Moreover, the same reagent/instrument combination could give different results depending of the FIX concentration. For OSC assays, only STA‐Cephascreen on STA‐R MAX and CS2100i, SynthAFax on ACLTOP 700 and Actin on CS2100i provided acceptable recoveries for all rFIXFc concentrations. The chromogenic assays ROX‐FIX and Biophen FIX:C underestimated rFIXFc for concentrations lower than 0.05 and 0.2 IU/mL, respectively.

Conclusions

Our study demonstrates that the same reagent adapted to different instruments could lead to different rFIXFc values. As rFIXFc under/overestimation could be associated with inappropriate treatment or biased calculation of pharmacokinetic parameters, the reagent/instrument combination used by haemostasis laboratories should be considered and regularly evaluated by external quality assessment programmes.
Rare genetic variants in systemic autoimmunity
Authors: Jiang Simon H , Stanley Maurice , Vinuesa Carola G
Published: April 2020

Autoimmune disease is a substantial cause of morbidity and is strongly influenced by genetic risk. Extensive efforts have characterized the overall genetic basis of many autoimmune diseases, typically by investigation of common variants. While these common variants have modest effects and may cumulatively predispose to disease, it is also increasingly apparent that rare variants have significantly greater effect on phenotype and are likely to contribute to autoimmune disease. Recent advances have illustrated the next fundamental step in elucidating the genetic basis of autoimmunity, moving beyond association to demonstrate the functional consequences of these variants.
Applicability of the post‐traumatic stress disorder gate criterion in people with mild to moderate intellectual disabilities: Do additional adverse events impact current symptoms of Post Traumatic Stress Disorder in people with intellectual disabilities?
Authors: Rittmannsberger Doris , Weber Germain , Lueger‐Schuster Brigitte
Published: April 2020

Background

Diagnostic manuals provide a strict definition of the PTSD gate criterion. Research on the adequacy of this definition in people with intellectual disabilities is lacking. This study aims to test the adequacy of the gate criterion for this population.

Method

Fourty nine adults with mild to moderate intellectual disabilities and 43 caregivers were questioned. Traumatic events included in the gate criterion definition and adverse events going beyond it were assessed. It was tested whether adverse events affect symptoms of PTSD additionally to traumatic events.

Results

The current data showed ambiguous findings in self‐ and informant report. Informant data suggested an additional impact of adverse events on PTSD symptoms. Self‐report data suggested the contrary.

Conclusion

Adverse events seem to have an impact on externalizing behavioural symptoms, such as hyperarousal. Self‐report assessment of more specific, intrapsychic PTSD symptoms, such as intrusions and avoidance, should be addressed in future studies.
Impact of previous left atrial ablation procedures on the mechanism of left atrial flutter: A single‐centre experience
Authors: Siebermair Johannes , Kochhäuser Simon , Kupusovic Jana , Köhler Miriam I. , Pesch Elena , Vonderlin Nadine , Kaya Elif , Janosi Rolf A. , Rassaf Tienush , Wakili Reza
Published: April 2020

Introduction

Left atrial flutter predominantly occurs after surgical or ablation procedures but this entity has also been recently reported in individuals without previous interventions. The use of high‐density electroanatomical mapping‐systems (HDM) has improved the understanding of underlying mechanisms beyond entrainment maneuvers and substrate analyses. We aimed to evaluate the mechanism of left atrial (LA) flutters in preablated vs ablation‐naïve individuals and sought to assess the efficacy of empiric ablations sets in these groups.

Methods and results

We included 55 patients admitted for ablation of LA flutter between July 2017 and August 2019. On the basis of HDM analyses the arrhythmia mechanism was determined with consecutive ablation targeting the suspected critical isthmus.

Mean age was 69.8 ± 10.7 years, with 26 of 55 (47.3%) male patients. Thirty‐nine (71%) patients had previously undergone LA ablation. Arrhythmia mechanisms differed between preablated and ablation‐naïve patients as anatomical structure‐related LA flutters (perimitral, roof‐dependent, within‐pulmonary veins) were more frequent in the preablated cohort compared to ablation‐naïve individuals (74.4% vs 43.8%; P = .03). In ablation‐naïve patients, most flutters (9 of 16, 56.3%) were related to low‐voltage areas at the anterior/posterior wall. Acute termination rates were high (>90%) in both groups. Empirical mitral isthmus or roof lines showed a potential higher success rate in preablated patients.

Conclusion

We identified different mechanisms of LA flutters in preablated vs ablation‐naïve patients. In ablation‐naïve patients, most tachycardias involved low‐voltage areas rather than anatomical structures. Using HDM, acute success rates were high. Hypothetical linear ablations were less successful in ablation‐naïve individuals, further highlighting the need to identify the specific individual tachycardia mechanism in these patients.
Sex differences in scores on standardized measures of autism symptoms: a multisite integrative data analysis
Authors: Kaat Aaron J. , Shui Amy M. , Ghods Sheila S. , Farmer Cristan A. , Esler Amy N. , Thurm Audrey , Georgiades Stelios , Kanne Stephen M. , Lord Catherine , Kim Young Shin , Bishop Somer L.
Published: April 2020

Background

Concerns have been raised that scores on standard measures of autism spectrum disorder (ASD) symptoms may differ as a function of sex. However, these findings are hindered by small female samples studied thus far. The current study evaluated if, after accounting for age, IQ, and language level, sex affects ASD severity estimates from diagnostic measures among children with ASD.

Methods

Data were obtained from eight sources comprising 27 sites. Linear mixed‐effects models, including a random effect for site, were fit for 10 outcomes (Autism Diagnostic Observation Schedule [ADOS] domain‐level calibrated severity scores, Autism Diagnostic Interview–Revised [ADI‐R] raw scores by age‐based algorithm, and raw scores from the two indices on the Social Responsiveness Scale [SRS]). Sex was added to the models after controlling for age, NVIQ, and an indicator for language level.

Results

Sex significantly improved model fit for half of the outcomes, but least square mean differences were generally negligible (effect sizes [ES] < 0.20), increasing to small to moderate in adolescence (ES < 0.40). Boys received more severe RRB scores than girls on both the ADOS and ADI‐R (age 4 + algorithm), and girls received more severe scores than boys on both SRS indices, which emerged in adolescence.

Conclusions

This study combined several available databases to create the largest sample of girls with ASD diagnoses. We found minimal differences due to sex beyond other known influences on ASD severity indicators. This may suggest that, among children who ultimately receive a clinical ASD diagnosis, severity estimates do not systematically differ to such an extent that sex‐specific scoring procedures would be necessary. However, given the limitations inherent in clinically ascertained samples, future research must address questions about systematic sex differences among children or adults who do not receive clinical diagnoses of ASD. Moreover, while the current study helps resolve questions about widely used diagnostic instruments, we could not address sex differences in phenotypic aspects outside of these scores.
Second primary melanoma: incidence rate and risk factors
Authors: Villani A. , Fabbrocini G. , Costa C. , Greco V. , Scalvenzi M.
Published: April 2020

Linked article: N. Pastor‐Tomás, et al. J Eur Acad Dermatol Venereol 2020; 34: 2295–2302. https://doi.org/10.1111/jdv.16341
Neuronal volume of the hippocampal regions in ageing
Authors: Delgado‐González José Carlos , de la Rosa‐Prieto Carlos , Tarruella‐Hernández Diana Lucía , Vallejo‐Calcerrada Nuria , Cebada‐Sánchez Sandra , Insausti Ricardo , Artacho‐Pérula Emilio
Published: April 2020

The hippocampal formation (HF) has an important role in different human capacities, such as memory processing and emotional expression. Both extensive changes and limited variations of its components can cause clinically expressed dysfunctions. Although there remains no effective treatment for diseases caused by pathological changes in this brain region, detection of these changes, even minimally, could allow us to develop early interventions and establish corrective measures. This study analysed the neuronal islands of layer II of the entorhinal cortex (EC), the neuronal clumps of the external principal layer of the presubiculum (PrS) and the dentate granule cells of the dentate gyrus (DG), which represent the prominent structural regions within the HF circuit. Subjects from two age groups (younger or older than 65 years) were studied and their neuronal size assessed by the point‐sampled intercepts stereological method. The quantitative estimate was a volume of roughly 8,500 µm3 for EC layer II neurons, and DG granule neurons and presubicular neurons were five and 10 times smaller, respectively. The older age group showed a increase of 2%, 18% and 28% with respect to the younger group in the PrS, DG and EC regions, respectively. None of these regions showed interhemispheric differences. This quantitative estimation is relevant because the observed variance in the estimates suggests that biological variation is the main contributory factor, with intercepts and measurements having a smaller impact. Therefore, we suggest that age has a limited influence on neuronal volume variation in these HF regions, which needs to be compared with similar measurements in neurodegenerative disorders such as Alzheimer’s.
Comparative growth in the olfactory system of the developing chick with considerations for evolutionary studies
Authors: Hogan Aneila V. C. , Watanabe Akinobu , Balanoff Amy M. , Bever Gabriel S.
Published: April 2020

Despite the long‐held assumption that olfaction plays a relatively minor role in the behavioral ecology of birds, crown‐group avians exhibit marked phylogenetic variation in the size and form of the olfactory apparatus. As part of a larger effort to better understand the role of olfaction and olfactory tissues in the evolution and development of the avian skull, we present the first quantitative analysis of ontogenetic scaling between olfactory features [olfactory bulbs (OBs) and olfactory turbinates] and neighboring structures (cerebrum, total brain, respiratory turbinates) based on the model organism Gallus gallus. The OB develops under the predictions of a concerted evolutionary model with rapid early growth that is quickly overcome by the longer, sustained growth of the larger cerebrum. A similar pattern is found in the nasal cavity where the morphologically simple (non‐scrolled) olfactory turbinates appear and mature early, with extended growth characterizing the larger and scrolled respiratory turbinates. Pairwise regressions largely recover allometric relationships among the examined structures, with a notable exception being the isometric trajectory of the OB and olfactory turbinate. Their parallel growth suggests a unique regulatory pathway that is likely driven by the morphogenesis of the olfactory nerve, which serves as a structural bridge between the two features. Still, isometry was not necessarily expected given that the olfactory epithelium covers more than just the turbinate. These data illuminate a number of evolutionary hypotheses that, moving forward, should inform tradeoffs and constraints between the olfactory and neighboring systems in the avian head.
Two‐stage surgical treatment of giant congenital melanocytic nevus around the auricle
Authors: Dong Weiwei , Song Yupeng , Jiang Haiyue , Pan Bo , He Leren , Yang Qinghua
Published: April 2020

Background

This study presents the results of complete excision of giant congenital melanocytic nevi (GCMN) on the auricle, forehead, or periorbital area combined with tissue expansion, and skin graft transplantation performed in two stages based on 10 years of experience.

Aims

To solve the giant congenital melanocytic nevi on the auricle, forehead, or periorbital area with two‐stage operation.

Patients/Methods

A total of 21 patients with GCMN were included in this study. The operation combined tissue expander and skin graft transplantation.

Result

All GCMNs were successfully and completely excised. No patient in the study group had experienced skin contraction or auricular deformation at 3 years after treatment.

Conclusion

Two‐stage operation is effective for removing GCMN on the auricle or face and can achieve good oncological and cosmetic results.
Gender‐related differences in the facial aging of Caucasian French subjects and their relations with perceived ages and tiredness
Authors: Flament Frederic , Belkebla Soraya , Adam Anne‐Sophie , Abric Aurelie , Amar David
Published: April 2020

Objectives

(a) To assess and compare the changes in five facial signs with age between genders of Caucasian subjects and (b) to evaluate their links with perceived ages and tiredness.

Material and Methods

Once zoomed from standardized digital photographs, five facial signs of 518 Caucasian French subjects of both genders and different ages (18‐69 years) were graded by 15 experts, using a referential Skin Aging Atlas. A large naïve panel of 1000 French subjects (500 men and 500 women) was asked to attribute a perceived age and a degree of tiredness to 200 subjects (among the 518).

Results

The severity of the facial signs increases with time at a linear‐like rate. The changes in marionette lines significantly differ between genders, much more pronounced in women, and nasolabial fold was found more pronounced in men at older ages (>50 years). Before 50's, Forehead wrinkles present a slightly higher severity in men whereas at 50's women present more severe ptosis. Crow's feet wrinkles did not show significant changes. Perceived ages were found significantly correlated with the severities of the facial signs and the perception of tiredness was associated with perceived ages in men, but not in women older than 40 years. The gender‐related perceptions from the naïve panel in both perceived ages and tiredness showed a low discrepancy. Interestingly, as for changes in facial signs, the upper‐half face seems more affected for men and lower‐half face for women; after 40 years, the naïve panel seems more focusing on the same areas to predict a perceived age.

Conclusion

As compared to the previous Chinese study, the present work reveals some slight ethnical‐related differences, indicating that the facial signs of the lower face play a major role in the assessment of perceived age of both genders from different ethnicity.