bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinicopathologic Diagnosis of Differentiated Vulvar Intraepithelial Neoplasia and Vulvar Aberrant Maturation
Authors: Day Tania , Marzol Alexandra , Pagano Ross , Jaaback Ken , Scurry James
Published: September 2020

Objective

The aim of the study was to describe the demographic, clinical, and histopathologic features of differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar aberrant maturation (VAM).

Methods

Specimens from 2010 to 2020 reported as dVIN or VAM were reviewed. Clinical data included age, rurality, symptoms, and evidence of lichen sclerosus (LS). Histopathologic data included epithelial thickness, keratinization, architectural and dyskeratotic features, stroma, p16, and p53. Differentiated vulvar intraepithelial neoplasia and VAM were distinguished by assessment of basal nuclear chromatin, enlargement, pleomorphism, and mitoses.

Results

One hundred twenty women with a median age of 71 years had 179 examples of dVIN and VAM. Squamous cell carcinoma was concurrent in 66% and associated with rurality. Ten percent were asymptomatic, and all but 3 had evidence of LS. Differentiated vulvar intraepithelial neoplasia showed a range of thickness, architecture, and dyskeratosis; its unifying !feature was basal atypia. Differentiated vulvar intraepithelial neoplasia displayed hyperchromasia in 83% and easily observed mitoses in 70%. Nonkeratinizing morphology, subcategorized into basaloid and intermediate, occurred in 24% of women with dVIN. Traditional dVIN represented 62% of keratinizing cases; the remainder were atrophic (13%), hypertrophic (13%), acantholytic (8%), or subtle (5%). Vulvar aberrant maturation had abnormal stratum corneum, acanthosis, premature maturation, and enlarged vesicular nuclei. Null p53 helped distinguish dVIN from VAM and dermatoses.

Conclusions

The morphology of dVIN encompasses nonkeratinizing and keratinizing types, the latter subdivided into traditional, acantholytic, atrophic, hypertrophic, and subtle. Diagnosis relies on basal atypia with supportive p16 and p53. Atypia exists on a biologic spectrum with mild abnormalities of VAM and reactive change. Identification of dVIN and VAM requires collaboration between clinicians and pathologists experienced in vulvar disorders.
Curvilinear Multiplanar Reconstruction to Predict Useful Length and Diameter of Cochlear Lumen for Cochlear Implantation
Authors: Guigou Caroline , Schein Antoine , Trouilloud Pierre , Lalande Alain , Hussain Raabid , Bozorg Grayeli Alexis
Published: September 2020

Objective:

Evaluate the useful length and the diameter of the cochlear lumen (CL) using routine imaging before cochlear implantation to study inter-individual variability and its impact on the insertion depth of the electrode carrier (EC).

Study design:

Prospective cross-sectional study.

Setting:

Tertiary referral center.

Patients:

Thirty-one preoperative and postimplantation temporal bone CT scans were analyzed by two investigators.

Intervention:

Images were analyzed via orthogonal multiplanar reconstruction (Osirix) to measure the lengths of the entire CL and the basal turn. By means of curvilinear reconstruction, the CL was unfolded and the diameters of the CL and of the EC were measured every 2 mm from the round window (RW) to the apex.

Results:

Very high-inter individual variability was found for the length of the basal turn (RSD > 1000%), the entire CL length (RSD > 800%), and the CL diameter at the RW (RSD > 600%). CL diameter was not correlated to the CL length. The inserted EC/total visible CL length ratio was 1.0 ± 0.12. Reliability of the measures was acceptable for the CL length and the diameter at 16 mm from the RW (Crohnbach's alpha > 0.7, n = 31).

Conclusion:

CL length and diameter can be directly measured in a reliable manner by commercially available tools. These parameters potentially influence the EC insertion and should be assessed before cochlear implant surgery.
Conversion of Propranolol to Carvedilol Improves Renal Perfusion and Outcome in Patients With Cirrhosis and Ascites
Authors: Kalambokis Georgios N. , Christaki Maria , Tsiakas Ilias , Despotis Grigorios , Fillipas-Ntekouan Sempastien , Fotopoulos Andreas , Tsiouris Spyridon , Xourgia Xanthi , Lakkas Lampros , Pappas Konstantinos , Michalis Lampros K. , Sergianiti Fotini , Baltayiannis Gerasimos , Christodoulou Dimitrios , Koustousi Christina , Aggelis Nikolaos , Milionis Haralampos
Published: September 2020

Background:

In recent years, concerns have been raised on the potential adverse effects of nonselective beta-blockers, and particularly carvedilol, on renal perfusion and survival in decompensated cirrhosis with ascites. We investigated the long-term impact of converting propranolol to carvedilol on systemic hemodynamics and renal function, and on the outcome of patients with stable cirrhosis and grade II/III nonrefractory ascites.

Patients and Methods:

Ninety-six patients treated with propranolol for esophageal varices’ bleeding prophylaxis were prospectively evaluated. These patients were randomized in a 2:1 ratio to switch to carvedilol at 12.5 mg/d (CARVE group; n=64) or continue propranolol (PROPRA group; n=32). Systemic vascular resistance, vasoactive factors, glomerular filtration rate, and renal blood flow were evaluated at baseline before switching to carvedilol and after 6 and 12 months. Further decompensation and survival were evaluated at 2 years.

Results:

During a 12-month follow-up, carvedilol induced an ongoing improvement of systemic vascular resistance (1372±34 vs. 1254±33 dynes/c/cm5; P=0.02) along with significant decreases in plasma renin activity (4.05±0.66 vs. 6.57±0.98 ng/mL/h; P=0.01) and serum noradrenaline (76.7±8.2 vs. 101.9±10.5 pg/mL; P=0.03) and significant improvement of glomerular filtration rate (87.3±2.7 vs. 78.7±2.3 mL/min; P=0.03) and renal blood flow (703±17 vs. 631±12 mL/min; P=0.03); no significant effects were noted in the PROPRA group. The 2-year occurrence of further decompensation was significantly lower in the CARVE group than in the PROPRA group (10.5% vs. 35.9%; P=0.003); survival at 2 years was significantly higher in the CARVE group (86% vs. 64.1%; P=0.01, respectively).

Conclusion:

Carvedilol at the dose of 12.5 mg/d should be the nonselective beta-blocker treatment of choice in patients with cirrhosis and nonrefractory ascites, as it improves renal perfusion and outcome.
Cost-effectiveness of tofacitinib for the treatment of moderate to severe active ulcerative colitis in Greece
Authors: Vellopoulou Katerina , Stefanou Garyfallia , Tzanetakos Charalampos , Boubouchairopoulou Nantia , Nakou Magdalini , Gourzoulidis George , Kourlaba Georgia
Published: September 2020

Objective

To evaluate the cost-effectiveness of tofacitinib versus other treatment options currently available for the management of adult patients with moderate-to-severe ulcerative colitis, who have had an inadequate response, loss of response, or were intolerant to conventional therapy or a biologic agent, in Greece.

Methods

A Markov model was adapted for projecting lifetime costs and outcomes, for a cohort of patients with moderate-to-severe ulcerative colitis from a Greek payer perspective. Patients entered the model in the active ulcerative colitis state and transitioned to a remission or response state or they underwent colectomy. Following an initial 8-week induction treatment period, patients received maintenance therapy until loss of response. Nonresponders could switch to up to two subsequent biologic lines. Clinical efficacy, adverse event rates and utilities derived from OCTAVE trials and a network-meta-analysis (NMA), while adverse event-related disutilities were obtained from the literature. Information on treatment pathways and resource use was provided by an advisory board due to a lack of local data. Unit costs derived from official national sources (€, 2018).

Results

Over a life-time horizon, treating moderate-to-severe active ulcerative colitis with tofacitinib resulted in additional quality-adjusted life-years (QALYs) and lower total costs compared to vedolizumab (0.018; €6408), infliximab (biosimilar) (0.009; €3031), golimumab (0.042; €1988) and infliximab (originator) (0.009; €6724). Hence, tofacitinib was estimated to be dominant over all comparators.

Conclusion

The results of the analysis suggest that in the Greek setting, tofacitinib could be considered a cost-effective (dominant) treatment option for the treatment of patients with moderate-to-severe active ulcerative colitis.
High Dose of Pegylated Interferon for the Treatment of Chronic Hepatitis B in Children Infected With Genotype C
Authors: Komatsu Haruki , Inui Ayano , Yoshio Sachiyo , Kanto Tatsuya , Umetsu Shuichiro , Tsunoda Tomoyuki , Fujisawa Tomoo
Published: September 2020

Objectives:

Chronic hepatitis B virus (HBV) genotype C infection is unlikely to show a good response to interferon (IFN). However, it is unknown whether a high dose of pegylated IFN (PEG-IFN) treatment would be effective for hepatitis B e antigen (HBeAg)-positive children with chronic HBV genotype C infection.

Methods:

HBeAg-positive children and adolescents with chronic HBV genotype C infection were eligible for this study. To increase the dose of PEG-IFN, all patients received PEG-IFN-α-2a (180 μg) without dose adjustment on the basis of body surface area for 48 weeks and were followed up for 24 weeks after the completion of treatment.

Results:

Thirteen patients (median age, 9 years) were enrolled prospectively for this study. One patient dropped out, and the remaining 12 patients were evaluated. Of the 12 patients, 11 received PEG-IFN of 180 μg/1.73 m2 or more (median, 287 μg/1.73 m2). Eight (67%) experienced HBeAg seroconversion, and 1 (8%) achieved hepatitis B surface antigen (HBsAg) loss at the end of follow-up. There was a significant difference in the decrease of hepatitis B surface antigen levels from the baseline to week 24 of treatment between the responders and the nonresponders. Serum cytokines and chemokines were measured in 10 patients. The levels of C-X-C motif chemokine ligand 9, 10, 11, and 13 in the responders tended to be higher than those in the nonresponders during the first 24 weeks of treatment.

Conclusions:

A high dose of PEG-IFN treatment was effective and safe. A decrease in the hepatitis B surface antigen level from baseline to week 24 of treatment might be a predictor of HBeAg seroconversion.
Chronic Recurrent Multifocal Osteomyelitis in Pediatric Crohn Disease, A Paradoxical Effect to Antitumor Necrosis Factor Alpha
Authors: Cordesse Anne , Ecochard-Dugelay Emmanuelle , Melki Isabelle , Caseris Marion , Belarbi Nadia , Hugot Jean-Pierre , Viala Jerome , Martinez-Vinson Christine
Published: September 2020

Tumor necrosis factor-α (TNF-α) inhibitors have resulted in significant progress in the treatment of chronic inflammatory diseases. However, these therapies can lead to paradoxical immune-mediated inflammatory diseases with unknown physiopathology. For the first time, we report 3 cases of paradoxical chronic recurrent multifocal osteomyelitis after infliximab or adalimumab therapy during the course of Crohn disease. The patients complained of bone pain without joint involvement. At the time of diagnosis of paradoxical reaction, all patients were in remission due to anti-TNFα efficiency. Trough levels of anti-TNFα were in the expected range, and there were no anti–anti-TNFα antibodies. The duration of treatment was between 2 and 26 months. Other causes of CRMO were excluded. All patients recovered after discontinuation of infliximab (n = 2) or adalimumab (n = 1). The increasing use of these therapies leads to new descriptions of paradoxical effects, which clinicians should be aware of.
Implementing a behavioral medicine approach in physiotherapy for patients with musculoskeletal pain: a scoping review
Authors: Söderlund Anne , Elvén Maria , Sandborgh Maria , Fritz Johanna
Published: September 2020

In intervention research on musculoskeletal pain, physiotherapists often study behavioral and cognitive components. Evidence on applying these components has increased during the past decade. However, how to effectively integrate behavioral and cognitive components in the biopsychosocial management of musculoskeletal pain is challenging. The aim was to study the intervention components and patient outcomes of studies integrating behavioral and cognitive components in physiotherapy, to match the interventions with a definition of behavioral medicine in physiotherapy and to categorize the behavior change techniques targeted at patients with musculoskeletal pain in (1) randomized controlled effect trials or (2) implementation in clinical practice trials. A scoping review was used to conduct this study, and the PRISMA-ScR checklist was applied. Relevant studies were identified from the PubMed, MEDLINE, PsycINFO, CINAHL Plus, and Web of Science Core databases separately for the (1) randomized controlled effect trials and (2) implementation in clinical practice trials. Synthesis for the matching of the patient interventions with the existing definition of behavior medicine in physiotherapy showed that the interventions mostly integrated psychosocial, behavioral, and biomedical/physical aspects, and were thus quite consistent with the definition of behavioral medicine in physiotherapy. The reported behavior change techniques were few and were commonly in categories such as “information of natural consequences,” “feedback and monitoring,” and “goals and planning.” The patient outcomes for long-term follow-ups often showed positive effects. The results of this scoping review may inform future research, policies, and practice.
Parental Alcohol Problems, Parental Divorce, and Type 2 Diabetes in Adulthood: A Longitudinal Prospective Cohort Study in Middle-Aged Men
Authors: Upadhyaya Subina , Tolmunen Tommi , Elomaa Antti-Pekka , Ruohomäki Aleksi , Kraav Siiri-Liisi , Kauhanen Laura , Kaplan George , Kauhanen Jussi , Lehto Soili M.
Published: September 2020

Objective

Type 2 diabetes is a chronic disease and a serious global public health concern increasing both mortality and morbidity. Previous studies have found evidence for an association between early psychological stress and diabetes later in life.

Methods

This study examined the association between parental alcohol problems and parental divorce and the incidence of type 2 diabetes in Finnish men aged 42 to 61 years (n = 754) in a prospective setting. Information on parental alcohol problems and parental divorce was derived from school records and subjective experiences of the same events from self-rated questionnaires. The average follow-up time for the participants until the first type 2 diabetes diagnosis was 23.3 years (25th–75th percentile, 21.2–27.9 years).

Results

Cox regression analyses revealed that parental alcohol problems (hazard ratio = 3.09, 95% confidence interval = 1.38–6.88) were associated with an increased risk of type 2 diabetes during the follow-up, even after adjustment for age, marital status, education, Human Population Laboratory Depression Scale scores, smoking, alcohol consumption, body mass index, and serum high-sensitivity C-reactive protein. In a similar model, parental divorce (hazard ratio = 1.69, 95% confidence interval = 0.40–7.05) was not associated with an increased risk of type 2 diabetes during the follow-up.

Conclusions

Our findings suggest that not all adverse childhood experiences contribute equally to the risk of type 2 diabetes. Parental alcohol problems, but not parental divorce, were associated with an increased risk of type 2 diabetes in men. These findings highlight the need for early interventions targeting parents with excessive alcohol consumption to reduce their offspring’s risk of life-style–related disorders.
Prenatal and Postnatal Imaging Findings After Fetal Repair of Spinal Dysraphisms Using Cryopreserved Human Umbilical Cord Patch: A Case Series of 4 Patients
Authors: Calle Susana , Papanna Ramesha , Hughes Katrina , Aein Azin , Riascos Roy , Johnson Anthony , Tsao KuoJen , Moise Kenneth J. , Fletcher Stephen , Patel Rajan
Published: September 2020

We describe a case series of imaging findings of 4 patients who underwent spinal dysraphisms repair in utero with novel patch material, cryopreserved human umbilical cord, in our institution. In our study, the prenatal and postnatal magnetic resonance imaging and ultrasound are reviewed and showed cord tethering and syrinx progression in all cases. Our report is the first description of magnetic resonance imaging and ultrasound findings in the context of using this novel patch in severe cases of spinal dysraphisms.
Noncontrast Magnetic Resonance Angiography in the Era of Nephrogenic Systemic Fibrosis and Gadolinium Deposition
Authors: Lim Ruth P. , Hecht Elizabeth M. , Desmond Patricia M.
Published: September 2020

Gadolinium-based contrast agents for clinical magnetic resonance imaging are overall safe. However, the discovery of nephrogenic systemic fibrosis in patients with severe renal impairment and gadolinium deposition in patients receiving contrast have generated developments in contrast-free imaging of the vasculature, that is, noncontrast magnetic resonance angiography. This article presents an update on noncontrast magnetic resonance angiography techniques, with comparison to other imaging alternatives. Potential benefits and challenges to implementation, and evidence to date for various clinical applications are discussed.
Decisional Conflict in Percutaneous Gastrostomy Tube Placement in Adults
Authors: Muoki Deltra C.
Published: September 2020

Percutaneous endoscopic gastrostomy tubes are placed when individuals are unable to orally consume adequate nutrition and require an alternative method to meet their daily nutritional needs. This decision is multifactorial and depends on the prognosis of the illness, patients' wishes, and weighing risks versus benefits. The recent movement toward patient-centered care supports open communication and shared decision-making that have the potential to mitigate decisional conflict. The aim of this literature review was to identify factors associated with the decision-making process for gastrostomy tube placement for adults. Three quantitative, 4 qualitative, and 1 Q-methodology study were analyzed. Social life, body image and intimacy, uncertainty and fear, complications, and burden to caregiver were central factors that influenced decision making. Social life and body image associated with intimacy were found to be the most prevalent themes in the review. This review indicates that decision making for gastrostomy tube placement is highly individualized. Patients need adequate information to make informed decisions that are congruent with their healthcare goals. Nurses should act as patient advocates and must have candid discussions to ensure that patients have received thorough and adequate information regarding gastrostomy tube placement and management.
Women's Experience With Celiac Disease
Authors: Foley Linda
Published: September 2020

The purpose of this qualitative study was to explore the lived experience of women who have been diagnosed with celiac disease. Celiac disease is a multisystem autoimmune disease and affects approximately 1% of the population. In addition, celiac disease is seen 1–2 times more often in women and they tend to have more severe disease and treatment burden. Quantitative research has been completed on celiac disease, but there remains a gap related to the implications of the disease from a qualitative perspective. The research tradition used for this qualitative study was phenomenology. Interviews were audio-recorded using a developed questionnaire. Saturation of the data occurred after 12 participant interviews. Following the analysis, 5 themes resulted: (a) Who am I? (b) medical aspects; (c) challenges; (d) daily living; and (e) facing the challenges. There remains a gap in the education, support, advocacy, and follow-up care of this population.
A Conceptual Framework for Rescheduling Elective Pediatric Gastroenterology Procedures Following COVID-19 Pandemic Lockdown
Authors: Kaur Panamdeep , Attard Thomas M. , Fishman Douglas S. , Zapata Fernando , Ditsch Donna , Thomson Mike , Schurman Jennifer V.
Published: September 2020

Elective surgical and endoscopic procedures were suspended nationwide during the March 2020 COVID-19 pandemic to minimize exposure and healthcare resource utilization. This resulted in an unprecedented backlog of procedures in most clinical practices including pediatrics. Our group developed an internal process toward the rational development of an algorithm prioritizing elective procedures. This was based on patient disease severity defined by the presence of alert symptoms, symptom severity for dysphagia and abdominal pain, and diagnostic investigation findings. The underlying rationale is to prioritize patients in whom suspected disease course would be greatest impacted by endoscopy. We developed a nurse phone call-based process utilizing REDCap®, identifying relevant symptoms categorized by severity, and a validated functional impairment questionnaire for abdominal pain. We abstracted key laboratory and radiological findings also categorized by severity. The order of priority of procedures was established on the basis of a 4-tiered system factoring both presence and severity of symptoms or prior diagnostic testing results. We present the framework that we have adopted toward prioritizing procedures with the assumption that it offers an objective methodology and that can be efficiently and more broadly applied to other similar practice scenarios. Our tool may have wide-ranging implications both in the current COVID-19 pandemic and in other scenarios of limited resource allocation and deserves further investigation.
Increase in Pediatric Perforated Appendicitis in the New York City Metropolitan Region at the Epicenter of the COVID-19 Outbreak
Authors: Fisher Jason C. , Tomita Sandra S. , Ginsburg Howard B. , Gordon Alex , Walker David , Kuenzler Keith A.
Published: September 2020

Objective:

The aim of the study was to determine whether perforated appendicitis rates in children were influenced by the Coronavirus disease 2019 (COVID-19) surge.

Background:

Disruption of care pathways during a public health crisis may prevent children from obtaining prompt assessment for surgical conditions. Progression of appendicitis to perforation is influenced by timeliness of presentation. In the context of state-mandated controls and public wariness of hospitals, we investigated the impact of the COVID-19 outbreak on perforated appendicitis in children.

Study Design:

We conducted an analysis of all children presenting to 3 hospital sites with acute appendicitis between March 1 and May 7, 2020, corresponding with the peak COVID-19 outbreak in the New York City region. Control variables were collected from the same institutions for the preceding 5 years. The primary outcome measure was appendiceal perforation.

Results:

Fifty-five children presented with acute appendicitis over 10 weeks. Compared to a 5-year control cohort of 1291 patients, we observed a higher perforation rate (45% vs 27%, odds ratio 2.23, 95% confidence interval 1.29–3.85, P = 0.005) and longer mean duration of symptoms in children with perforations (71 ± 39 vs 47 ± 27 h, P = 0.001) during the COVID-19 period. There were no differences in perforation rates (55% vs 59%, P = 0.99) or median length of stay (1.0 vs 3.0 days, P = 0.58) among children screening positive or negative for SARS-CoV-2.

Conclusions:

Children in the epicenter of the COVID-19 outbreak demonstrated higher rates of perforated appendicitis compared to historical controls. Preoperative detection of SARS-CoV-2 was not associated with inferior outcomes. Although children likely avoid much of the morbidity directly linked to COVID-19, disruption to local healthcare delivery systems may negatively impact other aspects of pediatric surgical disease.
Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study
Authors: Goodall J. W. , Reed T. A. N. , Ardissino M. , Bassett P. , Whittington A. M. , Cohen D. L. , Vaid N.
Published: September 2020

COVID-19 has caused a major global pandemic and necessitated unprecedented public health restrictions in almost every country. Understanding risk factors for severe disease in hospitalized patients is critical as the pandemic progresses.

This observational cohort study aimed to characterize the independent associations between the clinical outcomes of hospitalized patients and their demographics, comorbidities, blood tests and bedside observations. All patients admitted to Northwick Park Hospital, London, United Kingdom between 12 March and 15 April 2020 with COVID-19 were retrospectively identified. The primary outcome was death. Associations were explored using Cox proportional hazards modelling.

The study included 981 patients. The mortality rate was 36.0%. Age (adjusted hazard ratio (aHR) 1.53), respiratory disease (aHR 1.37), immunosuppression (aHR 2.23), respiratory rate (aHR 1.28), hypoxia (aHR 1.36), Glasgow Coma Score <15 (aHR 1.92), urea (aHR 2.67), alkaline phosphatase (aHR 2.53), C-reactive protein (aHR 1.15), lactate (aHR 2.67), platelet count (aHR 0.77) and infiltrates on chest radiograph (aHR 1.89) were all associated with mortality.

These important data will aid clinical risk stratification and provide direction for further research.
Interpretable network-guided epistasis detection
Authors: Duroux Diane , Climente-González Héctor , Azencott Chloé-Agathe , Steen Kristel Van
Published: September 2020

Detecting epistatic interactions at the gene level is essential to understanding the biological mechanisms of complex diseases. Unfortunately, genome-wide interaction association studies (GWAIS) involve many statistical challenges that make such detection hard. We propose a multi-step protocol for epistasis detection along the edges of a gene-gene co-function network. Such an approach reduces the number of tests performed and provides interpretable interactions, while keeping type I error controlled. Yet, mapping gene-interactions into testable SNP-interaction hypotheses, as well as computing gene pair association scores from SNP pair ones, is not trivial. Here we compare three SNP-gene mappings (positional overlap, eQTL and proximity in 3D structure) and use the adaptive truncated product method to compute gene pair scores. This method is non-parametric, does not require a known null distribution, and is fast to compute. We apply multiple variants of this protocol to a GWAS inflammatory bowel disease (IBD) dataset. Different configurations produced different results, highlighting that various mechanisms are implicated in IBD, while at the same time, results overlapped with known disease biology. Importantly, the proposed pipeline also differs from a conventional approach were no network is used, showing the potential for additional discoveries when prior biological knowledge is incorporated into epistasis detection.
MSH2knock-down shows CTG repeat stability and concomitant upstream demethylation at theDMPKlocus in myotonic dystrophy type 1 human embryonic stem cells
Authors: Franck Silvie , Barbé Lise , Ardui Simon , De Vlaeminck Yannick , Allemeersch Joke , Dziedzicka Dominika , Spits Claudia , Vanroye Fien , Hilven Pierre , Duqué Geoffrey , Vermeesch Joris R. , Gheldof Alexander , Sermon Karen
Published: September 2020

Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in theDMPKgene, where expansion size and somatic mosaicism correlates with disease severity and age of onset. While it is known that the mismatch repair protein MSH2 contributes to the unstable nature of the repeat, its role on other disease-related features, such as CpG methylation upstream of the repeat, is unknown. In this study, we investigated the effect of anMSH2knock-down (MSH2KD) on both CTG repeat dynamics and CpG methylation pattern in human embryonic stem cells (hESC) carrying the DM1 mutation. Repeat size in MSH2 wild type (MSH2WT) andMSH2KDDM1 hESC was determined by PacBio sequencing and CpG methylation by bisulfite massive parallel sequencing. We found stabilization of the CTG repeat concurrent with a gradual loss of methylation upstream of the repeat in MSH2KD cells, while the repeat continued to expand and upstream methylation remained unchanged in MSH2WT control lines. Repeat instability was re-established and biased towards expansions uponMSH2transgenic re-expression in MSH2KD lines while upstream methylation was not consistently re-established. We hypothesize that the hypermethylation at the mutant DM1 locus is promoted by the MMR machinery and sustained by a constant DNA repair response, establishing a potential mechanistic link between CTG repeat instability and upstream CpG methylation. Our work represents a first step towards understanding how epigenetic alterations and repair pathways connect and contribute to the DM1 pathology.
Shelf-based scarcity as a cue of luxuriousness: an application of psychophysiology
Authors: Sung Billy , Hatton-Jones Siobhan , Teah Min , Cheah Isaac , Phau Ian
Published: September 2020

Purpose

The purpose of this paper is to examine the perception of luxuriousness as a novel underlying mechanism of the shelf-based scarcity effect by using both psychophysiological measures (Study 1) and self-reported measures (Study 2).

Design/methodology/approach

Two within-subject experimental designs were conducted to examine the effects of low, medium and high stock depletion levels (i.e. shelf-based scarcity) on consumer responses. In Study 1, facial expression analysis was used to examine consumers’ liking, and left frontal asymmetry brainwaves were used to examine consumers’ approach motivation as a proxy for purchase intention. Study 2 extended the findings with self-reported measures.

Findings

In Study 1, perceived product luxuriousness was found to underlie the shelf-based scarcity effect on facial expressions and left frontal asymmetry brainwaves after controlling for other previously proposed mediators (i.e. product popularity and quality). The shelf-based scarcity effect is only observed between low vs high stock levels, whereas moderate stock level depletion does not evoke the shelf-based scarcity effect. Study 2 used self-reported measures to replicate the effect of shelf-based scarcity on product luxuriousness. However, the findings demonstrated the limitation of self-reported measures to identify a significant spill-over effect of perceived luxuriousness to attitude.

Research limitations/implications

Extending previous literature that relied heavily on self-reported measures, the current research used psychophysiological methods to uncover perceived luxuriousness as a novel underlying mechanism for the shelf-based scarcity effect. Thus, the findings are not only the first to provide psychophysiological evidence of the shelf-based scarcity effect but also to validate perceived luxuriousness as an underlying mechanism of the shelf-based scarcity effect.

Practical implications

The current findings suggest that the shelf-based scarcity effect is only evoked by high (instead of moderate) levels of stock depletion. The study also shows that shelf-based scarcity does not necessarily signal product popularity, but instead it may serve as a cue of product luxuriousness. Adding to other manipulations of retail spaces that elicit luxury perception (e.g. artwork, sensory delight and themed store atmospherics), this implies that businesses are able to use shelf-based scarcity as a cue to enhance or complement the luxury image or the perception of the brand or product.

Originality/value

The current research is the first study to use psychophysiological techniques to examine perceived luxuriousness as an underlying mechanism of shelf-based scarcity. It also demonstrates that self-report measures are not sensitive to such an effect in comparison to psychophysiological techniques, explaining why perceived luxuriousness has not been previously found to be an underlying mechanism of shelf-based scarcity.
Premature frailty, geriatric conditions and multimorbidity among people experiencing homelessness: a cross-sectional observational study in a London hostel
Authors: Rogans-Watson Raphael , Shulman Caroline , Lewer Dan , Armstrong Megan , Hudson Briony
Published: September 2020

Purpose

The purpose of this paper is to assess frailty, geriatric conditions and multimorbidity in people experiencing homelessness (PEH) using holistic evaluations based on comprehensive geriatric assessment (CGA) and draw comparisons with general population survey data.

Design/methodology/approach

Cross-sectional observational study conducted in a London-based hostel for single PEH over 30 years old in March–April 2019. The participants and key workers completed health-related questionnaires, and geriatric conditions were identified using standardised assessments. Frailty was defined according to five criteria in Fried’s phenotype model and multimorbidity as the presence of two or more long-term conditions (LTCs). Comparisons with the general population were made using data from the English Longitudinal Study of Ageing and the Health Survey for England.

Findings

A total of 33 people participated with a mean age of 55.7 years (range 38–74). Frailty was identified in 55% and pre-frailty in 39%. Participants met an average of 2.6/5 frailty criteria, comparable to 89-year-olds in the general population. The most common geriatric conditions were: falls (in 61%), visual impairment (61%), low grip strength (61%), mobility impairment (52%) and cognitive impairment (45%). All participants had multimorbidity. The average of 7.2 LTCs (range 2–14) per study participant far exceeds the average for even the oldest people in the general population.

Originality/value

To the best of authors’ knowledge, this is the first UK-based study measuring frailty and geriatric conditions in PEH and the first anywhere to do so within a CGA-type evaluation. It also demonstrates the feasibility of conducting holistic evaluations in this setting, which may be used clinically to improve the health outcomes for PEH.
Technical innovation: trigger or threat for organizational learning? A curvilinear relationship revisited
Authors: Ortega Egea M. Teresa , Roldán Bravo María Isabel , Ruiz Moreno Antonia , Haro Domínguez Carmen , Cabeza Pullés Dainelis
Published: September 2020

Purpose

Although most research considers organizational learning as an antecedent of innovation, the relationship is complex and could be reciprocal. Therefore, more research is needed on the profit gained from the learning and organization acquires from its innovation activities. Using the concept of fit, this paper aims to investigate whether organizational learning increases when an organization’s technical innovation level exceeds that of its competitors (positive misfit), theorizing the curvilinear effect of positive technical innovation misfit on organizational learning.

Design/methodology/approach

This paper uses regression analysis with survey data gathered from 202 European firms.

Findings

The findings support the argument that positive technical innovation misfit has an inverted-U shaped effect on organizational learning.

Practical implications

The findings obtained should orient firm managers to developing a work environment that enables optimal levels of technical innovation and learning – levels at which the technical innovation developed drives learning among the organization’s members but avoids becoming trapped in the organizational complexity involved in very high levels of positive technical innovation misfit.

Originality/value

This study resolves conflicting views of the relationship between organizational learning and technical innovation and adds to the existing literature that indicates that proactive innovative firms can fail when becoming learners.
A comprehensive model for assessing the quality in higher education institutions
Authors: Dwaikat Nidal Yousef
Published: September 2020

Purpose

This study aims to propose a comprehensive model for assessing the quality of academic programs in higher education institutions (HEIs) by adopting the TQM philosophy.

Design/methodology/approach

Based on a sample of 377 responses from higher education academics, experts and professionals in Sweden, partial least squares structural equation modeling (PLS-SEM) technique was used to empirically test the proposed hypotheses and validate the model.

Findings

The model reveals that the input-based factors have a stronger impact on the process-based factors; while process-based factors have less impact on the output-based factors. The input-based factors: adoption of international pedagogy standards (IPS), education infrastructure (EDI), and work/study environment (WSE) through the process-based factors quality of students (QOS) and quality of faculty staff (QFS) is found to have a significant impact on output-based factor quality of academic programs (QAP).

Research limitations/implications

This study has been conducted in Sweden. Inclusion of other countries provides opportunities for further analysis by conducting cross-comparison between different cultures in higher education, and including additional stakeholders such as policymakers, parents and students.

Practical implications

This research also contributes to practice by providing an in-depth understanding of the relationships among variables that affect the quality of academic programs in HEIs, and provides insights to internally assess the quality levels of their academic programs

Originality/value

This study contributes to the knowledge by providing a holistic view in which it integrates input, process and output perspectives in a conceptual model to assess the quality of academic programs at the higher education level.
Dark septate endophytes and arbuscular mycorrhizal fungi (Paris‐morphotype) affect the stable isotope composition of ‘classically’ non‐mycorrhizal plants
Authors: Giesemann Philipp , Eichenberg David , Stöckel Marcus , Seifert Lukas F. , Gomes Sofia I. F. , Merckx Vincent S. F. T. , Gebauer Gerhard
Published: September 2020

The vast majority of terrestrial plants exchange nutrients with fungal partners forming different mycorrhizal types. The minority of plants considered as non‐mycorrhizal, however, are not necessarily free of any fungi, but are frequently colonized by elusive fungal endophytes, such as dark septate endophytes (DSE) or fine root endophytes (FRE). While a functional role of FRE in the improvement of nutrient gain was recently elucidated, the function of DSE is still in discussion and was here addressed for 36 plant species belonging to the families Equisetaceae, Cypereaceae and Caryophyllaceae.

Molecular and microscopic staining approaches were conducted to verify the presence of DSE in the investigated species. Stable isotope natural abundances of the elements carbon, nitrogen, hydrogen and oxygen and total nitrogen concentrations were analysed for the respective species of the target plant families and accompanying mycorrhizal and non‐mycorrhizal (Brassicaceae) plant species.

Staining approaches confirmed the presence of DSE in all investigated species within the families Equisetaceae, Cyperaceae and Caryophyllaceae. A co‐colonization with Paris‐type arbuscular mycorrhiza (AM) was occasionally found by staining and molecular approaches in species of the Equisetaceae. Species of the Equisetaceae, Cyperaceae and Caryophyllaceae were significantly 15N‐enriched in comparison to accompanying plants. In addition, a significant 13C and 2H enrichment and increased total nitrogen concentrations were found for representatives of the Equisetaceae.

The 15N enrichment found here for representatives of Equisetaceae, Cyperaceae and Caryophyllaceae provides evidence for a functional role of the ubiquitous DSE fungi. DSE fungi obviously provide access to 15N‐enriched soil organic compounds probably in exchange for organic carbon compounds from plant photosynthesis. As indicated by additional 13C and 2H enrichments, representatives of the Equisetaceae apparently gain simultaneously organic carbon compounds from their AM fungi of the Paris‐morphotype. Thus, species of the Equisetaceae have to be considered as partially, or in case of the achlorophyllous fertile Equisetum arvense, as fully mycoheterotrophic at least in some stages of their life cycle.

So far, mostly underappreciated fungi classified as DSE are suggested to occupy an ecologically relevant role similar to mycorrhizae and the occurrence of simultaneous functions of DSE and AM fungi in Equisetaceae is proposed.

A free Plain Language Summary can be found within the Supporting Information of this article.
Functional and taxonomic diversity of grasshoppers differentially shape above‐ and below‐ground communities and their function
Authors: Lucas Jane M. , Jonas Jayne , Laws Angela N. , Branson David H. , Pennings Steven C. , Prather Chelse M. , Strickland Michael S.
Published: September 2020

Herbivores are important drivers in both above‐ and below‐ground ecosystems. Despite their importance, studies of herbivores often focus on the effects of individual species, potentially missing the effects of herbivore diversity.

Here we examine how orthopteran herbivore species and functional (i.e. diet) diversity interact with nutrient availability to shape above‐ and below‐ground ecosystems. We stocked six species of grasshoppers (Orthoptera) with two different feeding modes (i.e. grass‐only or grass‐ and forb‐feeders) at varying taxonomic compositions (0, 1 or 6 species) in field enclosures and measured their effects on above‐ground plant biomass, chemistry and richness, as well as below‐ground microbial community composition and function. We treated half the cages with nitrogen fertilizer to examine how herbivore effects may be mitigated by soil nutrient availability.

Above‐ground, we predicted that grasshoppers would decrease plant biomass and richness, and increase the %N of the plant community. We also predicted that high diversity cages would have the largest decreases in plant biomass and richness, but these effects would be offset by fertilizer additions.

Below‐ground, we predicted that herbivore taxonomic composition and diet would differentially shift soil microbial community composition and function. We also predicted that fertilization would decrease the soil pH and increase nutrient availability creating an interaction with herbivores that leads to shifts below‐ground community composition.

We found that grasshoppers decreased plant biomass and richness, and this effect was not dependent on nutrient additions. Contrary to our predictions, we did not see the largest above‐ground changes in high diversity cages.

Below‐ground, herbivore diet and fertilization, but not their interaction, shifted bacterial communities. Grasshopper taxonomic composition did not influence bacterial communities. Grasshopper taxonomic composition and diet interacted with fertilizer to increase below‐ground levels of bioavailable C and microbial biomass. Fungal communities did not respond to any treatments.

The differing effects of herbivore diet versus taxonomic composition highlight the need for studies that examine multiple diversity metrics when exploring herbivore‐meditated effects on above‐ and below‐ground ecosystems. Combined, our results suggest that bottom‐up and top‐down controls are important factors to consider when studying the composition and function of grassland ecosystems.

A free Plain Language Summary can be found within the Supporting Information of this article.
Dark Nudges and Sludge in Big Alcohol: Behavioral Economics, Cognitive Biases, and Alcohol Industry Corporate Social Responsibility
Authors: PETTICREW MARK , MAANI NASON , PETTIGREW LUISA , RUTTER HARRY , VAN SCHALKWYK MAY CI
Published: September 2020

Policy Points

Nudges steer people toward certain options but also allow them to go their own way. “Dark nudges” aim to change consumer behavior against their best interests. “Sludge” uses cognitive biases to make behavior change more difficult.

We have identified dark nudges and sludge in alcohol industry corporate social responsibility (CSR) materials. These undermine the information on alcohol harms that they disseminate, and may normalize or encourage alcohol consumption.

Policymakers and practitioners should be aware of how dark nudges and sludge are used by the alcohol industry to promote misinformation about alcohol harms to the public.

Context

“Nudges” and other behavioral economic approaches exploit common cognitive biases (systematic errors in thought processes) in order to influence behavior and decision‐making. Nudges that encourage the consumption of harmful products (for example, by exploiting gamblers’ cognitive biases) have been termed “dark nudges.” The term “sludge” has also been used to describe strategies that utilize cognitive biases to make behavior change harder. This study aimed to identify whether dark nudges and sludge are used by alcohol industry (AI)–funded corporate social responsibility (CSR) organizations, and, if so, to determine how they align with existing nudge conceptual frameworks. This information would aid their identification and mitigation by policymakers, researchers, and civil society.

Methods

We systematically searched websites and materials of AI CSR organizations (e.g., IARD, Drinkaware, Drinkwise, Éduc'alcool); examples were coded by independent raters and categorized for further analysis.

Findings

Dark nudges appear to be used in AI communications about “responsible drinking.” The approaches include social norming (telling consumers that “most people” are drinking) and priming drinkers by offering verbal and pictorial cues to drink, while simultaneously appearing to warn about alcohol harms. Sludge, such as the use of particular fonts, colors, and design layouts, appears to use cognitive biases to make health‐related information about the harms of alcohol difficult to access, and enhances exposure to misinformation. Nudge‐type mechanisms also underlie AI mixed messages, in particular alternative causation arguments, which propose nonalcohol causes of alcohol harms.

Conclusions

Alcohol industry CSR bodies use dark nudges and sludge, which utilize consumers’ cognitive biases to promote mixed messages about alcohol harms and to undermine scientific evidence. Policymakers, practitioners, and the public need to be aware of how such techniques are used to nudge consumers toward industry misinformation. The revised typology presented in this article may help with the identification and further analysis of dark nudges and sludge.